Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 19, 2026.

Anti-Fungal Efficacy and Mechanisms of Flavonoids

Mohammed Saleh Al Aboody, Suresh Mickymaray

Antibiotics · 2020 · Review · CC BY

doi:10.3390/antibiotics9020045

Abstract

The prevalence of fungal infections is growing at an alarming pace and the pathogenesis is still not clearly understood. Recurrence of these fungal diseases is often due to their evolutionary avoidance of antifungal resistance. The development of suitable novel antimicrobial agents for fungal diseases continues to be a major problem in the current clinical field. Hence, it is urgently necessary to develop surrogate agents that are more effective than conventional available drugs. Among the remarkable innovations from earlier investigations on natural-drugs, flavonoids are a group of plant-derived substances capable of promoting many valuable effects on humans. The identification of flavonoids with possible antifungal effects at small concentrations or in synergistic combinations could help to overcome this problem. A combination of flavonoids with available drugs is an excellent approach to reduce the side effects and toxicity. This review focuses on various naturally occurring flavonoids and their antifungal activities, modes of action, and synergetic use in combination with conventional drugs.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 19, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Fungal illness often can be fatal, killing more than 1.5 million a year, and such illnesses have an effect on over a billion peoples in a year. Nevertheless, public health authorities have continued to neglect the issue, although the majority of deaths are from fungal infectious diseases. The severe fungal infections often arise because of other health issues, including acquired immunodeficiency syndrome (AIDS), cancer, asthma, diabetes, organ transplantation, and treatment with corticosteroids. Fungal infections have augmented constantly in the current decennium, mainly in immunocompromised hosts or hospitalized individuals with severe underlying infections. Yeasts are large, widespread opportunistic agents in fungal infectious diseases, and various fungal pathogens have been developed in the past decennium. Among the fungal infections, Candida, Aspergillus, Pneumocystis, and Cryptococcus are the main threatening agents globally due to the severity and higher incidence of the diseases. It is projected worldwide that these fungal species produce, annually, at least 1.4 million fatalities. Candida spp. is the most isolated yeast among systemic fungal infections. Candida is a genus of eukaryotic fungus comprised of 17 species out of 150, which are well-known causative agents of candidiasis in humans. According to the National Network of Health Security, Candida spp. are the third most widespread causative agent of blood culture infections (15%) connected to intensive care units, after other common bacterial pathogens. Candida albicans is the most ubiquitous species globally (50–70%), which produces more infectious diseases than the total occurrence of infections produced by C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei. These yeasts primarily cause superficial and systemic fungal infections that include biofilm-associated infections candidaemia, and fungemia in patients with malignancies. Aspergillus infections are another foremost infection occurring in recipients of hematopoietic stem cell transplants. About 30% of individuals may die from invasive aspergillosis, and the remaining 50% of deaths may occur by candidemia. Cryptococcus spp. is another medically noteworthy yeast species, consisting of 40 species; among them, C. gattii, and C. neoformans are the most clinically applicable. In addition, C. albidus and C. laurentii are developing pathogens that are participated in various kinds of infectious diseases. Cryptococcosis is greatly connected with AIDS and meningitis. This infection normally takes place exogenously through breathing or by direct inoculation into the host tissue.

The growing resistance of microbes against exiting antifungal drugs is one of the main issues among researchers and clinicians. Pathogenic fungi, viruses, bacteria, and protozoa are more challenging to treat with the existing drugs due to the development of resistance. Numerous investigations related to antimicrobial resistance estimated that the mortality rate may go above 10 million by 2050, possibly leading to higher mortality when compared to malignancies and metabolic diseases. The resistance of pathogenic fungi to available antibiotics has developed into a global epidemic. Therapeutic agents for fungal infections are negligible when related to therapeutic agents for bacterial infections. In order to heal fungal infections, four categories of antifungal drugs are often offered; viz., polyenes (amphotericin B, nystatin, candicidin, pimaricin, methyl partricin, trichomycin), azoles (fluconazole, itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, posaconazole, ravuconazole), echinocandins (caspofungins, micafungin, and anidulafungin), and flucytosine (5-fluorocytosine). However, those antifungal agents are only partially effective, and many of them produce several complications to host tissues. Based on a recent therapeutic search, limited antifungal agents have only been structurally and systematically elucidated in the past 30 years.

The development of resistance is habitually occurring by antifungal agents that usually bind with cell walls or biosynthetic pathways. For instance, there has been elevated use of fluconazole and amphotericin B, owing to their effectiveness and low toxicity and binding potential toward the membranes of fungal pathogens, consequently stimulating drug resistance. A. fumigatus and C. krusei are fundamentally resistant to most azole class drugs; viz., fluconazole, itraconazole, voriconazole, and posaconazole. Similarly, Cryptococcus neoformans are resistant to fluconazole and echinocandins. Hence, it is an urgent need to investigate novel drugs that have greater anti-fungal activity. The approaches of traditional plant-based medicine or bioactive natural products are great, as such therapeutic medicine can better the prevailing fungal treatments with lesser side effects.

Medicinal plants with ethnopharmacological uses of crude material or pure compounds have been applied comprehensively for treating and preventing human diseases since time immemorium. These traditional plant approaches have been supported to produce bioactive compounds to recent medicine as therapeutic tools. Phytocompounds or bioactive compounds play a significant role in drug discovery by serving as compounds of interest in their natural form or as templates for synthetic changes. Numerous studies have demonstrated that natural phytocompounds have potential antifungal activities. The employment of phytochemicals alone or in combination with conventional drugs signifies a greater alternative to conventional therapy. The mixture of those drugs generally needs a smaller quantity of antimicrobials. Hence, this lesser quantity may lead to reducing the toxicity, resulting in great tolerance to the antifungal agents. Based on the available data, even there has been adequate literature concerning antifungal phytocompounds proceeding 2015; only a few studies have reviewed the antifungal flavonoids that were accounted for later in 2015. Hence, this review aimed to focus on the antifungal activities of flavonoids and their modes of action.

An electronic hunt was performed using Google Scholar, PubMed, and Science Direct, and by finding the keywords “Flavonoids” AND “antifungal agents” AND “flavones” or “flavonols” or “flavanones” or “isoflavones” or “flavones” or “flavane” or “anthocyanidins” in “Title/Abstract/Keywords,” with a date cutoff, and checking all available findings (case-control studies, placebo, clinical, in vitro, and in vivo) that examined the relationship between flavonoids and their antifungal effects. Each antifungal mechanism was collected and arranged in an appropriate place for the review.

2. Fungal Diseases and Their Complications

Fungal cells are eukaryotic, and similar to mammalian cells in that they possess nuclei containing DNA, cytoplasm, mitochondria, endoplasmic reticulum, and the Golgi apparatus. However, the fungal cell membrane is made up of ergosterol, which differs from the mammalian cell, which mainly contains cholesterol. The occurrence of ergosterol has been noted as the main drug target of interest in the investigation of antifungal drugs. Fungal cell walls are generally rigid and cover complex polysaccharides called chitin, which are mixtures of β-(1,3)-glucan and β-(1,6)-glucan. The pathogenesis of fungal infections is normally aid by adhesion factors of the cell surface, which initially bind to the host surface. Then, the pathogen secretes membrane discharging hydrolytic enzymes with virulence factors for the invasion that ultimately breaks the host tissues. The occurrence of fungal infections is swiftly growing, which creates significant issues for healthcare specialists. In addition, these infections are rapidly increasing in prevalence with the diseases of cancer, AIDS, and diabetes, and in immunocompromised individuals. They often affect the skin, keratinous tissues, and mucous membranes, which distresses millions of people globally. They ultimately cause devastating effects on the quality of an individual’s life and spread infections to other individuals to become invasiveness.

Early diagnosis permits rapid antifungal treatment; conversely, it is regularly deferred or unattainable, leading to chronic illness, impaired vision, or death. Since 2013, LIFE-Worldwide (Leading International Fungal Education) portal has initiated and enabled the assessment of the encumbrance of serious fungal infections worldwide since 2013. The annual global accounts have showed the numbers of affected individuals with various fungal infections; viz., skin, hair, nail infections (≈1,000,000,000), recurrent vulvovaginal candidiasis (≈134,000,000), rhinosinusitis (≈12,000,000), fungal asthma (≈10,000,000), allergic bronchopulmonary aspergillosis in bronchial asthma individuals (≈4,800,000), chronic pulmonary aspergillosis (3,000,000), oral candidiasis (≈2,000,000), oesophageal candidiasis (≈1,300,000), invasive candidiasis (≈750,000), Pneumocystis causing pneumonia (≈500,000 cases), invasive aspergillosis (≈250,000), cryptococcal meningitis connecting HIV/AIDS (≈223,100), disseminated histoplasmosis (≈100,000), and fungal keratitis (≈1,000,000).

C. albicans is a typically polymorphic fungus, which is the major cause of invasive candidiasis, a superficial or deep tissue fungal infection. Notably, this invasive candidiasis causes an undesirably high mortality rate worldwide. For instance, C. albicans causes the occurrence of oral candidiasis in 80–95% of HIV/AIDS individuals (with a minimum of one episode). Moreover, chemotherapy, certain steroid drugs, treatment with multiple antibiotics, immunosuppressive therapy, antiretroviral therapy, and removable partial dentures may also impact the severity of oral candidiasis. As a result, patients may experience weight loss, dysphagia, and disseminated candidiasis that can be life-threatening, with 35–60% mortality rates. There are numerous and different types of candidiasis; viz., mucosal, cutaneous, antibiotic, and systemic candidiasis. Candida spp. has known to be causative of severe candidaemia that can show reduced vulnerability to the existing antifungal drugs. Candida spp. causing candidaemia is the widespread nosocomial infection connected with an elevated mortality rate (>49%) in immunocompromised patients. In about 40% of cases, the patient with candidaemia has sepsis or septic shock. In tropical countries, Candida tropicalis (causing candidiasis) has spread intensely on a global scale, and thus, this microorganism has been declared as an emerging pathogenic fungus. There are numerous reports on resistance to azole and other agents in regard to C. albicans and C. tropicalis. Vulvovaginal candidiasis is another widespread cause of noteworthy morbidity (5–7%) in adult women and affects 70–75% of women at least one time in a lifetime, mostly between 25 and 34 years of age.

In immunocompromised patients, other often-isolated pathogenic organisms include Aspergillus spp., which are found with other common pathogenic organisms; viz., Candida spp., Cryptococcus spp., Fusarium spp., Trichophyton spp., Pneumocystis jirovecii, Histoplasma capsulatum, Zygomycete, Dematiaceous, and Mucormycetes. These infectious agents often cause endophthalmitis, fungemia, keratitis, onychomycosis, osteomyelitis, peritonitis, pneumonia, septic arthritis, sinusitis, thrombophlebitis, and vulvovaginitis to the host. Colonization of the mucosal surfaces in the lungs by A. fumigatus, A. flavus, A. niger, or A. terreus causes allergic bronchopulmonary aspergillosis, which leads to active disseminated infection. The mortality rates may rise from 50% to 90% based on the host’s immune health, site of infection, and treatment regimen. The recipient of a bone marrow transplant has a greater than 95% mortality rate. Other clinical manifestations of aspergillosis are asthma, cutaneous and wound infections, invasive pulmonary aspergillosis, and Aspergillus sinusitis. A study on population-based surveillance for cryptococcosis has shown that the higher densities of Cryptococcus neoformans in patients with AIDS produce severe forms of meningitis and meningoencephalitis.

Malassezia is a lipophilic fungal genus that encompasses 14 species found in human skin, which are principally involved in various skin diseases; viz., atopic eczema, dandruff, folliculitis, onychomycosis, pityriasis seborrheic dermatitis, sepsis of neonates, and versicolor. Various Malassezia species found at higher population densities, up to 10 million, are present on scalps with dandruff; some Malassezia species can produce hypo or hyperpigmentation on the trunk and other locations in human. Penicillium oxalicum is an anamorph plant pathogen found to cause opportunistic fungal infection in patients with acute myeloid leukemia, chronic obstructive pulmonary disease (COPD), and diabetes. Pneumocystis jirovecii pneumonia is developing as a foremost cause of infection in HIV individuals. The global incidence is believed to be greater than 400,000 individuals yearly. The mortality rate of Pneumocystis jirovecii pneumonia is about 30% and can be even greater if the diagnosis is overdue. Another significant fungal infection is mycotic keratitis, or keratomycosis, which is also caused by various fungal genuses; viz., Candida, Aspergillus, Fusarium, Phoma, Mucorales, and Basidiomycetes. It is a corneal infection. This infection remains a cause of severe corneal opacification and visual loss, with projected international trouble for approximately 1.2 million people yearly.

Zygomycosis is another fatal, opportunistic fungal infection, mainly among patients with hematological malignancies, diabetes, and patients treatedwith the drug deferoxamine. A case-control observational study conducted for 27 cases of mucormycosis patients showed that Rhizopus, Mucor, and Rhizomucor spp. caused up to 75% of cases. The infection affects the patient’s immune system, and thus, these infections can be fatal. Infection with Entomophthora species is overwhelmingly found with gastrointestinal basidiobolomycosis. Similarly, infection with Fusarium species has been described in immunocompetent patients, and causes a broad spectrum of superficial and disseminated infections which may cause 100% mortality rate. The ingestion of Fusarium-contaminated food produces hypersensitivity with mycotoxicosis in a healthy individual (Bennett, 2003). Tinea capitis is a widespread cutaneous infection of the scalp caused by Trichophyton violaceum, T. tonsurans, and Microsporum spp. that occurs predominantly in children. The burden of this infection is about 21 million school children of 16 countries. It is especially prominent in sub-Saharan Africans.

3. Flavonoids

Flavonoids are secondary metabolites, identified as broad classes of polyphenols that are found largely in plants. These natural compounds greatly exist in foods, including cocoa, onion, apples, bananas, all citrus fruits, grapes, berries, red wine, and sea-buckthorns; and beverages, including, red wine, black tea, green tea, oolong tea, and cider. Their broad structure of flavonoids is composed of two phenyl rings coupled together by a 3-carbonated heterocyclic ring (C6-C3-C6) and in total has a 15-C skeleton (Figure 1). According to the changes in the central carbon ring, they can be divided into following subclasses; viz., flavonols, flavanones, isoflavones, flavones, flavan, and anthocyanidins,). Non-cyclization of the C3-portion joints gives rise to chalcones, which along with an isoflavonoid unit, pertain to a diverse numbering system. Fl avonoids present along with glycosylated derivatives or acylated with phenolic acids, which have been found in more 6000 in plants. Flavanols and anthocyanidins are generally termed condensed tannins, which are highly complex subclasses and most copious among the flavonoids.

Several in vivo and clinical investigations have reported that the flavonoids show various pharmacological functions; viz., anti-oxidant, antidiabetic, anti-obesity, anti-hyperlipidemic, anti-inflammatory, antiosteoporotic effect, antiallergic and antithrombotic, hepatoprotective, neuroprotective, renoprotective, chemopreventive and anticancer, anti-bacterial, antifungal, and anti-viral activities. Flavonoids can inhibit the in vitro proliferation of various cancer cell lines, and decrease tumor growth in various animal models. They are recognized as antioxidants and possess free radical quenching properties. Thus, they exert themselves as chelators of divalent cation and free radical scavenger properties that inhibit lipid peroxidation, capillary permeability, and platelet aggregation and fragility. In addition, flavonoids regulate biological systems through the inhibition of range of enzymes; viz., hydrolase, lipase, α-glucosidase, aldose reductase, cycloxygenase, xanthine oxidase, hyaluronidase, alkaline phosphatase, arylsulphatase, lipoxygenase, Ca+2-ATPase, cAMP phosphodiesterase, and several kinases.

A higher amount or prolonged intake of flavonoids in the diet may cause lesser side effects due to the relatively low bioavailability, lesser intestinal permeability, and higher metabolism rate. Furthermore, flavonoids have only mild toxicity to humans and animals because of their poor absorption coefficient. All this information should aid the researcher to explore and investigate the attractive therapeutic indices of flavonoids regarding human wellness. The dietary consumption of flavonoids accounts for 1–2.5 gm/day. The regular consumption of flavonols and flavones has been found to be 23 mg/day, among which, quercetin supplies 16 mg/day. Catechins, quercetin, and isoflavones are measured as the top absorbed compounds; meanwhile tea catechins, condensed tannins, and anthocyanins are the negligibly absorbed compounds.

4. Antifungal Activities of Flavonoids

Flavonoids have been found to be effective antifungal agents against a wide range of pathogenic organisms represented in Table 1.

The screening of antifungal flavonoids from plants has been assayed by using broth dilution, spore germination, and agar well or the disk diffusion. Derrone and licoflavone C extracted from Retama raetam, which has potent antifungal effects against Candida spp. with minimum inhibitory concentrations (MIC) of 7.81 and 15.62 μg/mL, correspondingly. Papyriflavonol A acquired from Broussonetia papyrifera that verified as antifungal agents against C. albicans with a MIC of 25 μg/mL. A plant-derived flavonoid, Quercetin-3-O-rutinosides had beneficial effects on C. albicans and C. krusei that exhibited with MICs of 16 and 32 μg/mL respectively. Two distinguished flavonoids, 5,7,4′-trihydroxy-8-methyl-6-(3-methyl-[2-butenyl])-2S- flavanone and 7-hydroxy-3′,4′-methylene dioxy flavan obtained from Eysenhardtia texana and Termanalia bellerica, which possess potential antifungal properties against A. flavus with MICs of 256 and 64 μg/mL respectively. Renowned flavonoids such as quercetin, myricetin, baicalein (from Scutellaria baicalensis), gallotannin (from Syzygium cordatum), apigenin and kaempferol (from propolis) isolated and reported as potential anti-candidal properties. In addition, coumarins and lignans have also presented antifungal effects against numerous dermatophyte species. Flavonoids and catechins acquired from Brazilian traditional medicinal plants, Eugenia dysenterica, and Pouteria ramiflora that have shown potential antifungal activities against C. tropicalis, C. famata, C. krusei, C. guilliermondii, and C. parapsilosis.

Various folkloric medicinal plants contain various fractions of flavonoids that show antifungal properties. Ocotea odorifera contain ellagitannins, has reported as a fungistatic potential against C. parapsilosis. Sanguiin H-6 and lambertianin C and isolated from raspberry (Rubus idaeus L.) fruit reported as antifungal effects against Geotrichum candidum. Acacia mearnsii contains encapsulated tannins that inhibit the effects against A. niger and C. albicans. Propolis and its high flavonoid content have antifungal activity against dermatophytes and Candida spp. Exclusively, propolis contains a flavonol, galangin, which has been demonstrated to have antifungal activities against Cladosporium sphaerospermum, Penicillium digitatum, A. tamarii, A. flavus, and P. italicum.

Nobiletin, langeritin and hesperidin have extracted from the peels of tangerine oranges and assayed for the activity towards Deuterophoma tracheiphila that exhibits promising antifungal activities. The antifungal effects have also been reported in flavonoids extracted from citrus fruits after processing in industries and bergamot peel that averts the growth of S. cerevisiae. Quercetin, naringenin is recognized to be potent inhibitors of C. albicans, and S. cerevisiae. Chlorflavonin is the first chlorine-containing flavonoid type antifungal agent, produced by strains of A. candidus. A recognized flavone, baicalein; and flavonol, myricetin have greater inhibitory effects on Candida sp., with MICs of 1.9–21 and 3.9–64 μg/mL, correspondingly.

The antifungal activity of 40 coumarins have studied against C. albicans, A. fumigatus, and F. solani, among them, osthenol and 4-acetetatecoumarin have demonstrated higher antifungal effects. Petroleum ether extracts of Baccharis darwinii and Ferula foetida contain well-known coumarin, diversinin and 5, 8-dihydroxyumbelliprenin, which have confirmed antifungal activity against T. rubrum, T. interdigitale, T. mentagrophytes, and M. gypseum. Phenylpropanoids are natural compounds that classified as coumarins, lignans and phenylpropanoic acid, often investigated due to their anti-candidal nature. Scopoletin (coumarin), salicylaldehyde and anisyl alcohol (phenylpropanoic acids) have potential antifungal effects against C. albicans, with MICs of 25, 31, and 31 μg/mL correspondingly. Similarly, antifungal activities have been described in hesperidin, neohesperidin, naringin which are normally isolated from the citrus fruits. These compounds have strong fungal inhibitory activity against P. expansum, F. semitectum, A. parasiticus, A. flavus.

Grapes are a rich source of flavonoids, and their pomaces largely help to avert the growth of Zygosaccharomyces bailii and Zygosaccharomyces rouxii. Chilean grape pomace extract is recognized to have antifungal activity against Botrytus cinerea. The growth of C. albicans could be averted by flavonoid extracts from Brazilian grapes. Similarly, Eysenhardita texana has prenylated flavanones that have potential antifungal activity against C. albicans. Flavanol is generally found in propolis that is also suggested to be used as antifungal agents. Flavonoid extracts of Sida acuta Burm f. have shown a varying range of antifungal activity against C. albicans. The degree of MIC and Minimum fungicidal concentration of extracts have accounted for 0.078–0.625 mg/mL and 0.078–1.25 mg/mL, correspondingly. Bitencourt et al. demonstrated that the four flavonoids such as quercetin, ellagic acid, galangin, and genistein have shown the most potential antifungal property with MIC of 125, 250, 1000, 1000 µg/mL against Trichophyton rubrum, which is common species among the fungal associated dermatophytosis. This team has further reported the antifungal potential of flavonoids that have been recognized as FAS inhibitors which modulate the fatty acid synthesis gene expressions in T. rubrum. The crude and butanolic leaf extract of Terminalia catappa contain the active components of hydrolyzable tannins (punicalin, punicalagin), gallic acid, and flavonoid C-glycosides that exhibits antifungal activity against Candida sp.. Similarly, crude and ethanol leaf extracts of Carya illinoensis contain gallic acid, ellagic acid, rutin, catechins and epicatechins that exhibits antifungal activity against different Candida strains with MIC range of 6.25–25 mg/mL.

Gallic acid is established to have potent antifungal property against Candida spp., and T. rubrum. Gallic acid is isolated from acetone fraction of Buchenavia tomentosa that inhibits the proliferation rate and disrupts 48 h-biofilm abruptly in C. albicans. Ethyl acetate and butanolic extracts of Punica granatum contain ellagic acid, gallagic acid, punicalins, and punicalagins which show antifungal activities against C. albicans, C. neoformans, and A. fumigatus. Curcumin is a renowned flavonoid present in turmeric, which has potential anti-candidal activity against various clinical isolates of C. albicans and C. gattii. Curcumin can decrease the colony width, sprouting, and sporulation of A. flavus and C. albicans. Similarly, Curcumin-silver nanoparticles have also exhibited potential anti-candidal activity against Candida species acquired from clinical samples of infected HIV individuals with MIC range of 31.2–250 μg/mL. All these findings strongly recommend that flavonoids exhibit a broad spectrum of antifungal activity against Candida spp., Aspergillus spp., Geotrichum spp., Cladosporium spp., Penicillium spp., Deuterophoma spp., Trichophyton spp., Trichophyton spp., Dermatophyte spp., and Fusarium spp.

5. Mechanism of Actions of Antifungal Flavonoids

Flavonoids have been extensively used for many centuries in the treatment of the range of human diseases. Flavonoids often inhibit fungal growth with various underlying mechanisms, including plasma membrane disruption, the induction of mitochondrial dysfunction, and inhibiting the following: cell wall formation, cell division, RNA and protein synthesis, and the efflux mediated pumping system (Figure 2).

5.1. Induced Plasma Membrane Disruption

The ergosterols are a vital component for the manufacturing of cell membranes. Antifungal drugs normally inhibit the ergosterol biosynthesis, and the cell membrane’s integrity is perhaps disrupted, leading to leakage of intracellular components. This inadequate formation or disruption of the plasma membrane leads to a lesion or membrane permeability changes. Furthermore, excess production of reactive oxygen species (ROS) also causes severe oxidative stress to the cell, which results in the progressive membrane permeabilization, or injury to nucleic acids and oxidation of fatty acids and amino acids. ROS often encounter the membrane lipids in C. albicans and generate lipid hydroperoxides; this is known as lipid peroxidation.

Lipid peroxidation has been demonstrated to disturb the lipid bilayer and alter membrane potentials, resulting in reduced fluidity, increased permeability, and disruption of phospholipids. The relationship between ROS generation and the lipid bilayer leads to the synthesis of malondialdehyde, which is a chief marker of lipid peroxidation. Apigenin has exerted antioxidant and antifungal activity against C. albicans, C. parapsilosis, Malassezia furfur, T. rubrum, and T. beigelii all with the MIC of 5 µg/mL. Antioxidant potential of the flavonoid inhibits biofilm formation and stimulates membrane disturbances, resulting in the reduction of cell size and leakage of intracellular components. In the previous study, LicoA demonstrated antifungal activities against T. rubrum with MIC of 11.52 μM, and the orientation of genes connected to the pathway of ergosterol biosynthesis. In an earlier study, prenylflavanone 8PP obtained from Dalea elegans, had potential antifungal activity against C. albicans, C. glabrata, C. krusei, C. neoformans, and T. mentagrophytes. In this study, prenylflavanone 8PP potentially inhibited the biofilms of sensitive and azole-resistant C. albicans at 100 μM through the gathering and elevation of endogenous ROS and reactive nitrogen intermediates.

Similarly, Baicalein has been isolated from Scutellaria baicalensis, which shows inhibitory effects towards Candida spp. when used in synergetic mixture with flucanazole at MIC of 64 μg/mL. Baicalein has induced the apoptosis through alteration in the membrane potentials of mitochondria and elevates intracellular ROS and upstream regulation of redox-related genes. In another study, baicalein presented antifungal activities toward T. rubrum, C. albicans, T. mentagrophytes, and A. fumigatus with MICs of 120, 30, 60, and 230 μM respectively. Baicalein has induced concentration-dependent ROS generation, deformation of membrane structure, and efflux of a cotton-like constituents that are alleged to degenerate cytosol in fungal bodies of T. rubrum, T. mentagrophytes, A. fumigatus, and C. albicans. However, Kang et al. reported controversial outcomes, including that antifungal screening of baicalein in C. krusei isolates showed higher alteration in the mitochondrial homeostasis without elevating the intracellular ROS, thereby causing apoptosis. Antifungal activities of fisetin inhibit the growth of C. neoformans, C. gattii, M. gypseum, T. mentagrophytes, T. rubrum, and T. tonsurans with MIC range of 4–128 µg/mL. In this study, reductions of ergosterol levels and structural alterations were detected in C. gattii.

Fatty acid synthase is a significant enzyme essential for endogenous fatty acid synthesis in the membrane of fungi, indicating it as a potential target for novel antifungal drugs. Quercetin has been reported to have individual or synergic antifungal properties with flucanazole, which is recognized as an inhibitor of fatty acid synthase. The inhibitory effects of quercetin and fluconazole were reported as MICs of 125 and 63 μg/mL against T. rubrum. Likewise, catechin or epigallocatechin gallate have also shown synergic antifungal effects with the MIC values of 16 and 1 µg/mL respectively. These active flavonoids induce the activation of phosphatidylserine, which inhibits fatty acid synthase. In addition, they stimulate the intracellular accumulation of ROS, structural modifications, apoptosis, mitochondrial depolarization, and fragmentation of DNA in C. tropicalis. Isoquercitrin has also shown antifungal activities against C. albicans, M. furfur, C. parapsilosis, T. rubrum, and T. beigelii with MIC values of 2.5–5.0 μg/mL through inhibition of fatty acid synthase and plasma membrane disruption.

5.2. Inhibition of Cell Wall Formation

The cell walls of fungi are primarily composed of β-glucans and chitin. The antifungal mechanism has been based on cell wall deformation which is caused by the inhibition of the synthesis of those compounds. Glabridin is a chief active isoflavane isolated from Glycyrrhiza glabra, and has significant antifungal activities against C. albicans, C. tropicalis C. neoformans, and C. glabratas with MIC values ranging from 16 to 64 µg/mL. The antifungal process is achieved based on the cell wall deformation which includes the remarkable decreasing of cell size and increasing membrane permeability. Similarly, glabridin treatment enhances the expression of various genes in C. glabrata which participate in the fragmentation of DNA (chromatin condensation) resulting in apoptosis. These deformations of the cell wall normally occur due to the presence of the prenylation of glabridin. Antifungal effects of pedalitin (5,6,3′,4′-tetrahydroxy-7-methoxyflavone) have been reported against several strains of C. albicans and Cryptococcus spp.. An animal model study against disseminated Candidiasis showed epigallocatechin-o-gallate’s synergistic interaction with amphotericin B against C. albicans. Infected animals administered with mixed doses of epigallocatechin-o-gallate and amphotericin B exhibited an augmented survival rate compared to animals administered with amphotericin B. The results show that epigallocatechin-o-gallate exclusively inhibits the hyphal formation and ergosterol synthesis in C. albicans. The investigations of propidium iodide assay and artificial membrane permeability study specified that pedalitin stimulates the elevation of permeability and physical alarm of the plasma membrane, permitting the diffusion of molecules smaller than about 3.3 nm. These cell wall deformations and the membrane damage are generally promoted by pedalitin, which contributes to malfunctions of the membrane that causes depolarization, K+ leakage, and reduction in membrane fluidity, eventually leading to cell death.

5.3. Induced Mitochondrial Dysfunction

Inhibition of the mitochondrial electron transport chain (ETC) leads to diminishing membrane potential. This inhibition generally takes place in the ETC by inhibition of proton pumps, which reduces ATP synthesis, and thus, cell death. Wogonin (5,7-dihydroxy-8-methoxy flavone) showed antifungal activity against A. fumigates, T. rubrum, and T. mentagrophytes with MICs of 230, 60, and 60 µM respectively. The treatment with wogonin induces accumulation of ROS in mitochondria and causes a decreased membrane potential and reducing ATP synthesis and eventually contraction or cracking of fungal filaments. Baicalein inhibits biofilm formation in a dose-dependent manner from 4 to 32 µg/mL. The results of confocal scanning laser microscopy, flow cytometry, and transmission-electron-microscopy analysis have shown baicalein treatment reduces cell surface hydrophobicity and mRNA expression, and elevates apoptosis that is connected to the failure of mitochondrial membrane potential. Similarly, quercetin, resveratrol, and curcumin modulate mitochondrial functions by inhibiting oxidative phosphorylation through various mitochondrial enzymes, or by changing the generation of ROS in mitochondria and by modulating the activity of transcription factors which control mitochondrial proteins’ expression. All these compounds exhibit pro-apoptotic functions, mediated by the ability to discharge of cytochrome c from mitochondria, or indirectly by upregulating pro-apoptotic proteins of Bcl-2 expressions and downregulating anti-apoptotic proteins. Honey extract also contains a flavonoid that improves mitochondrial functions and decreases the vacuolization, adjusting the branching process connected with virulence. Honey extract induces alterations in the cell cycle, membrane integrity, functions of mitochondria, and biogenesis. A synergistic study has also investigated the synergy between epigallocatechin gallate and conventional antimycotics agents, such as miconazole, fluconazole, and amphotericin B, against biofilms of C. albicans, C. glabrata, C. parapsilosis, C. kefyr, C. tropicalis, and C. krusei. Similarly, epigallocatechin gallate has described as an anti-candidal agent, which has been demonstrated through the mechanism of mitochondrial membrane dysfunction. Likewise, Spondias tuberosa rich flavonoids elevate the levels of the superoxide anion via the lysosome, causing hyperpolarization in the mitochondrial membrane, so granting anti-Candida activity.

5.4. Inhibition of Cell Division

The inhibition of cell division generally causes inhibition of microtubule polymerization, which inhibits the mitotic spindle formation (. Honey flavonoid extract inhibits the proliferation of C. albicans phenotypes, diminishes the infection, and reduce the distressing membrane integrity. This inhibition is measured by using flow cytometry and scanning electron microscopy analyses. Honey flavonoid extract affects the hyphal transition by decreasing the G0/G1 phase and increasing the G2/M phase. Some flavonoids, such as apigenin, α-naphthoflavone, 3′-methoxy-4’-nitroflavone, and 2′-amino-3′-methoxy flavone, have various ligands of the aryl hydrocarbon receptor that inhibit the cell cycle. Studies show that alizarin and chrysazin suppress biofilm formation in C. albicans, and effectively inhibit hyphal formation and inhibit the cell cycle. Another study shows that magnolol and honokiol inhibit the growth of C. albicans through the Ras1-cAMP-Efg1 pathway. These compounds have potential inhibitory effects on the cell cycle and biofilm-formation-ability of C. albicans. Rubus chingii is a well-known traditional Chinese medicinal plant that possesses flavonoid-rich compounds, known to have significant antimicrobial and antifungal activities. The crude extract of this plant synergistically interacts with fluconazole to inhibit C. albicans. The probable mechanism behind this synergistic interaction could be the cell cycle arrest at S phase in C. albicans. The crude extract containing flavonoids reduce the efflux of Cdr1 ABC transporter, which may be the reason for fluconazole resistance. Similarly, daphnegiravone D, a prenylated flavonoid, has cytotoxic effects and significantly inhibits cell division. Systematically, daphnegiravone D arrests the G0/G1 phase and stimulates apoptosis, by reducing the expression of cyclin E1, CDK2, and CDK4, and promote the cleavage of caspase 3 and PARP.

5.5. Inhibition of Efflux Pumps

Efflux pumps are transporters present in most living cells, including fungi; they have the noteworthy function of removing toxic substances from the fungal body (Kang et al., 2010). This transporter can detoxify a fungal cell through the removal of a drug being accumulated. The high efflux pump’s expression can lead to drug-resistance. Hence, inhibiting the efflux pumps is a crucial aim for reducing drug resistance. A flavone, 7,4′-dimethoxy apigenin, inhibits the growth of C. albicans when synergistically combined with miconazole. This combination reduces ergosterol biosynthesis and inhibits drug efflux pumps with IC50 of 51.64 µg/mL. Baicalein (5,6,7-trihydroxy flavone) is a flavone, isolated from Scutellaria baicalens, that has significant anticandidal activity with a MIC value of 26 mg/mL. This compound is well recognized as a lipooxygenase inhibitor or efflux pump inhibitor when in combination with fluconazole; it decreases the capacity of the cells to efflux out drugs. Similarly, diorcinol D is another natural compound obtained from a lichen endophytic fungus, Aspergillus versicolor, that inhibits the efflux pump activity by decreasing the Cdr1 expression in C. albicans. Curcumin from rhizomes of Curcuma longa is also another natural polyphenolic compound that modulates the efflux pump activity in Saccharomyces cerevisiae, and overexpresses the C. albicans ATP binding cassette (ABC) multidrug transporters, Candida drug resistance protein 1, and Candida drug resistance protein 2. Similarly, the quorum-sensing molecule farnesol is drug efflux a modulator that mediates through ABC multidrug transporters and synergizes with fluconazole, ketoconazole, miconazole, and amphotericin B in C. albicans. This synergistic interaction of quorum-sensing molecule farnesol with those antifungal drugs leads to ROS generation, which causes early apoptosis. Naturally occurring flavones, such as apigenin, chrysin, baicalein, luteolin, tangeritin, scutellarein, 6-hydroxyflavone, and wogonin inhibit efflux mediated pumps that induce cell death in the fungi. An isoflavone, sedonan A extracted from Dalea formosa, also inhibits efflux pumps in C. albicans and C. glabrata, and disturbs various intracellular transcription genes with MIC of 15 and 7.6 mg/mL, respectively. Another isoflavone has been identified as dorsmanin isolated from dorstenia mannii that inhibits efflux pumps in C. albicans with a MIC of 64 mg/ml.

5.6. Inhibition of RNA/DNA and Protein Synthesis

The antifungal agent generally enters into the cell through active transport that reaches into the nucleus, and thus inhibits DNA, RNA, and protein synthesis. The inhibition of protein synthesis is well-recognized as an antifungal target. For instance, 5-flurocytosine inhibits nucleic acid synthesis by the formation of fluorinated pyrimidine metabolites, which can cause a deficit of cytosine deaminase, resulting in the deregulation of the pyrimidine biosynthesis. Similarly, Catechin inhibits C. albicans nucleic acid synthesis; analysis by flow cytometry shows that it exhibits the inhibition of FCS-induced hyphal formation; western blotting results also reveal that the treatment with catechin in the C. albicans reduces the hypha-specific gene expression in mitogen-activated protein kinase cascade and the cyclic adenosine 3,5-monophosphate pathway. Based on the findings, the team in question highlighted catechin as a potential antifungal candidate in clinical therapy for the management and prevention of candidosis. Similarly, flavonols (myricetin, kaempferol, fisetin, quercetin, 3-hydroxy flavone, and 3,7-dihydroxyflavone), a flavone (luteolin), a flavanone (naringenin), and isoflavones (genistein, biochanin A) inhibit filamentous fungus Cochliobolus lunatus through the inhibition of nucleic acid synthesis. Apigenin is a well-known flavone found in a wide variety of plants and herbs that interferes with the translational activity of fungal foot-and-mouth disease driven by the internal ribosome entry site, and was thus identified as a potential drug for foot-and-mouth disease infection. Carvacrol, a chalcone extracted from Lavandula multifida L. that inhibits the nucleic acid synthesis and disrupts the cellular cytoplasmic membrane, eventually causes apoptosis in various candida species. Gallic acid extracted from Paeonia rockii inhibits the protein synthesis of C. albicans, which has been shown to be involved in a decreasing number of hyphal cells and germ tubes with a MIC of 30 mg/mL. Similarly, gallotannin obtained from Syzygium cordatum inhibits RNA synthesis and possess antifungal activity against C. albicans with an MIC value of 0.195 mg/mL.

5.7. Synergistic Action between Flavonoids and Antifungals

The combination of natural products with antifungal drugs is recognized as an effective strategy to fight invasive fungal infections and microbial resistance. This combination is often beneficial and effective for both the rate and degree of microbial killing. Generally, each drug has a diverse mechanism of action, and two drugs may play on diverse targets, resulting in multi-targeting. Based on the multi-targeting strategy, the progress of drug resistance can be reduced. Toxicity and intolerance of the drug can also be evaded with the aid of two or more collective drug treatments. Several in vitro studies have shown a reduced inhibitory concentration of natural products with antifungal drugs. For instance, bioactive compounds help elevate the intracellular concentration of related antifungals by potentiating their action, inhibiting the efflux pumps, and inhibiting the morphogenesis of drug-resistant C. albicans.

Studies have exhibited that Brazilian Red Propolis and Acca sellowiana produce in vitro synergistic activity with fluconazole against resistant fungal isolates of C. parapsilosis and C. glabrata. Propolis offered action on the cell membrane, permitting fluconazole penetration into the cells. The synergistic effect accelerates between the extracts of Uncaria tomentosa and fluconazole against Candida non-albicans, and quite likely this effect is connected to teamwork events happening outside the cell membrane. For antifungal therapeutic approaches, a combination of antifungals with the host’s immune system is more essential. This combination may trigger the healing of lesions and control most of the symptoms connected to fungal infections. Hence, the phytotherapy adjuvant is the main healer for fungal infections exclusively for pharmaceutical companies.

Curcumin, when combined with fluconazole, miconazole, ketoconazole, nystatin, and amphotericin B in vitro, results in synergistic interaction against C. albicans. Curcumin elevates the level of ROS and regulation of expression of numerous genes related to fungal oxidative stress, including superoxide dismutase, catalase, and oxydoreductase. Chalcones are naturally occurring flavonoids that have been synthesized by aldol condensation, which possess significant antifungal properties when combined with fluconazole and resistant strains of C. albicans. Chalcones are the main inhibitors of the efflux pump, which in combination with fluconazole decrease the ability of cells to efflux out the drugs. Osthole is a natural methylated derivative of coumarin isolated from Candida fructus, which has been extensively used for the treatment of supportive dermatitis and vaginitis in China. It is synergistically combined with fluconazole and possesses significant antifungal effects through the generation of ROS. Similarly, eugenol-tosylate, a semi-synthetic analog of eugenol, has a synergistic interaction with fluconazole that exhibits antifungal activity against fluconazole-resistant C. albicans which occurs through the inhibiting of ergosterol biosynthesis. Glabridin exhibits a synergistic combination with fluconazole against resistant strains of C. albicans, causing cell wall alteration. Likewise, quercetin’s synergistic combination with fluconazole inhibits C. albicans biofilm, which is isolated from vulvovaginal candidiasis patients. These drugs combined, have the ability to avert the adhesion of cell-cell communication and disturb the expression of genes accountable for biofilm formation.

6. Conclusions

The elevation of fungal infections is alarming. They lead to high levels of morbidity and mortality globally. Emerging new fungal species and the incidence of elevated drug resistance for fungal diseases continues to rise. The scenario of the existing antifungal agents and their complications is quite critical. There are limitations manifest by antifungal agents: the lower fungistatic ability, high toxicity, and kidney failure. Hence, it is vital to search novel agents as alternative therapies that are potentially active against most fungal diseases. Medicinal plants containing flavonoids are recognized as safe and endowed with numerous biological functions. Various flavonoids have been extracted and investigated in association with their anti-fungal activities and can be promising, efficient, and cost-effective agents for the inhibition of fungal infections. They often inhibit fungal growth in various underlying mechanisms by enhancing the disruption of the plasma membrane and mitochondrial dysfunction; and inhibiting cell wall formation, cell division, protein synthesis, and the efflux-mediated pumping system. These flavonoids are capable and efficient in synergetic combination therapy with conventional drugs, which can be more appropriate and supportive for finding novel drug therapies against fungal pathogens.

References 234

  1. 1.
    Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision · 2017
    No notice
  2. 2.

    Lu M., Li T., Wan J., Li X., Yuan L., Sun S. Antifungal effects of phytocompounds on Candida species alone and in combination with fluconazole. Int. J. Antimicrobial. Agents. 2017;49:125-136.

    Not in our library10.1016/j.ijantimicag.2016.10.021

  3. 3.

    Vijayakumar R., Sandle T., Al-Aboody M.S., AlFonaisan M.K., Alturaiki W., Mickymaray S., Premanathan M., Alsagaby S.A. Distribution of biocide resistant genes and biocides susceptibility in multidrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii—A first report from the Kingdom of Saudi Arabia. J. Infect. Public Health. 2018;11:812-816.

    Not in our library10.1016/j.jiph.2018.05.011

  4. 4.
    Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes · 2018
    No notice
  5. 5.

    Ganesan K., Guo S., Fayyaz S., Zhang G., Xu B. Targeting Programmed Fusobacterium nucleatum Fap2 for Colorectal Cancer Therapy. Cancers. 2019;11:1592.

    Not in our library10.3390/cancers11101592

  6. 6.
    Emerging Threats in Antifungal-Resistant Fungal Pathogens · 2016
    No notice
  7. 7.

    de Almeida R.F.M., Santos F.C., Marycz K., Alicka M., Krasowska A., Suchodolski J., Panek J.J., Jezierska A., Starosta R. New diphenylphosphane derivatives of ketoconazole are promising antifungal agents. Sci. Rep. 2019;9.

    Not in our library10.1038/s41598-019-52525-7

  8. 8.

    Vinodhini R.M.K., Al Aboody M.S., Suresh M. Prevalence And Antifungal Susceptibility Pattern of Candida dubliniensis Isolated From Urine Samples. Int. J. Recent Sci. Res. 2016;7:13474-13480.

    Not in our library

  9. 9.

    Devi A.C.D.D., Suresh M., Thajuddin N. Diagnostic value of real time PCR and associated bacterial and fungal infections in female genital tuberculosis. Biomed. Pharmacol. J. 2015;3:73-79.

    Not in our library

  10. 10.
    Screening and antibacterial efficacy of selected Indian medicinal plants · 2016
    Not checked
  11. 11.

    Ng K.P., Kuan C.S., Kaur H., Na S.L., Atiya N., Velayuthan R.D. Candidaspecies epidemiology 2000-2013: a laboratory-based report. Trop. Med. Int. Health. 2015;20:1447-1453.

    Not in our library10.1111/tmi.12577

  12. 12.

    Wang Y. Looking intoCandida albicansinfection, host response, and antifungal strategies. Virulence. 2015;6:307-308.

    Not in our library10.1080/21505594.2014.1000752

  13. 13.

    Polke M., Hube B., Jacobsen I.D. Candida Survival Strategies. Advances in Applied Microbiology. 2015;139-235.

    Not in our library10.1016/bs.aambs.2014.12.002

  14. 14.

    Hurtado J.C., Castillo P., Fernandes F., Navarro M., Lovane L., Casas I., Quintó L., Marco F., Jordao D., Ismail M.R., et al. Mortality due to Cryptococcus neoformans and Cryptococcus gattii in low-income settings: an autopsy study. Sci.Rep. 2019;9.

    Not in our library10.1038/s41598-019-43941-w

  15. 15.

    Molina-Leyva A., Ruiz-Carrascosa J.C., Leyva-Garcia A., Husein-Elahmed H. Cutaneous Cryptococcus laurentii infection in an immunocompetent child. Int. J. Infect. Dis. 2013;17:e1232-e1233.

    Not in our library10.1016/j.ijid.2013.04.017

  16. 16.
    Perspectives on non-neoformans cryptococcal opportunistic infections · 2017
    Not checked
  17. 17.

    Calista F., Tomei F., Assalone P., Traficante D., Di Pilla G., Pepe C., Di Lullo L. Cryptococcus laurentii Diarrhea in a Neoplastic Patient. Case Rep. Oncol. Med. 2015;2015:216458.

    Not in our library10.1155/2015/216458

  18. 18.

    Rajasingham R., Smith R.M., Park B.J., Jarvis J.N., Govender N.P., Chiller T.M., Denning D.W., Loyse A., Boulware D.R. Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis. Lancet Infect. Dis. 2017;17:873-881.

    Not in our library10.1016/s1473-3099(17)30243-8

  19. 19.

    Kannaiyan M., Meseret Abebe G., Kanimozhi C., Thambidurai P., Ashokapuram Selvam S., Vinodhini R., Suresh M. Prevalence of extended-spectrum beta-lactamase producing enterobacteriaceae members isolated from clinically suspected patients. Asian J. Pharma. Clin. Res. 2018;11:364.

    Not in our library10.22159/ajpcr.2018.v11i5.19363

  20. 20.

    Sinaga M., Ganesan K., Kumar Nair S.K.P., Gani S.B. Preliminary Phytochemical Analysis and In Vitro Antibacterial Activity of Bark and Seeds of Ethiopian Neem (Azadirachta Indica A. Juss). World J. Pharmacy Pharma. Sci. 2016;5:1714-1723.

    Not in our library10.20959/wjpps20164-6479

  21. 21.

    Kriengkauykiat J., Ito J.I., Dadwal S.S. Epidemiology and treatment approaches in management of invasive fungal infections. Clin. Epidemiol. 2011;3:175.

    Not in our library10.2147/clep.s12502

  22. 22.

    Roemer T., Krysan D.J. Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches. Cold Spring Harbor Perspect. Med. 2014;4:a019703.

    Not in our library10.1101/cshperspect.a019703

  23. 23.

    Banu G.S., Kumar G. In-vitro antibacterial activity of flower extracts of Woodfordia fruticosa Kurz. Int. J. Curr. Res. Chem. Pharma. Sci. 2014;1:127-130.

    Not in our library

  24. 24.
    Antifungal Efficacy of Marine Macroalgae against Fungal Isolates from Bronchial Asthmatic Cases · 2018
    Not checked
  25. 25.

    Mickymaray S., Al Aboody M.S. In vitro antioxidant and bactericidal efficacy of 15 common spices: novel therapeutics for urinary tract infections? Medicina. 2019;55:289.

    Not in our library10.3390/medicina55060289

  26. 26.

    Mickymaray S. One-step Synthesis of Silver Nanoparticles Using Saudi Arabian Desert Seasonal Plant Sisymbrium irio and Antibacterial Activity Against Multidrug-Resistant Bacterial Strains. Biomolecules. 2019;9:662.

    Not in our library10.3390/biom9110662

  27. 27.

    Kumar G., Banu G.S., Murugesan A.G., Pandian M.R. Hypoglycaemic effect of Helicteres isora bark extract in rats. J. Ethnopharmacol. 2006;107:304-307.

    Not in our library10.1016/j.jep.2006.05.007

  28. 28.

    Moorthy K., Punitha T., Vinodhini R., Mickymaray S., Shonga A., Tomass Z., Thajuddin N. Efficacy of different solvent extracts of Aristolochia krisagathra and Thottea ponmudiana for potential antimicrobial activity. J. Pharmacy Res. 2015;9:35-40.

    Not in our library

  29. 29.

    Zhang T., Jayachandran M., Ganesan K., Xu B. Black Truffle Aqueous Extract Attenuates Oxidative Stress and Inflammation in STZ-Induced Hyperglycemic Rats via Nrf2 and NF-κB Pathways. Front. Pharmacol. 2018;9.

    Not in our library10.3389/fphar.2018.01257

  30. 30.

    Jayachandran M., Wu Z., Ganesan K., Khalid S., Chung S.M., Xu B. Isoquercetin upregulates antioxidant genes, suppresses inflammatory cytokines and regulates AMPK pathway in streptozotocin-induced diabetic rats. Chem. Biol. Interact. 2019;303:62-69.

    Not in our library10.1016/j.cbi.2019.02.017

  31. 31.

    Sukalingam K., Ganesan K., Xu B. Protective Effect of Aqueous Extract from the Leaves of Justicia tranquebariesis against Thioacetamide-Induced Oxidative Stress and Hepatic Fibrosis in Rats. Antioxidants. 2018;7:78.

    Not in our library10.3390/antiox7070078

  32. 32.
    The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens · 2019
    No notice
  33. 33.

    de Freitas M.A., Andrade J.C., Alves A.I.S., dos Santos F.d.A.G., Leite-Andrade M.C., Sales D.L., Nunes M., Ribeiro P.R.V., Melo Coutinho H.D., Morais-Braga M.F.B., et al. Use of the natural products from the leaves of the fruitfull tree Persea americana against Candida sp. biofilms using acrylic resin discs. Sci. Total Environ. 2020;703:134779.

    Not in our library10.1016/j.scitotenv.2019.134779

  34. 34.

    K Singla R., K Dubey A. Molecules and Metabolites from Natural Products as Inhibitors of Biofilm in Candida spp. pathogens. Curr. Topics Med. Chem. 2019;19.

    Not in our library10.2174/1568026619666191025154834

  35. 35.

    Seleem D., Pardi V., Murata R.M. Review of flavonoids: A diverse group of natural compounds with anti-Candida albicans activity in vitro. Archiv. Oral Biol. 2017;76:76-83.

    Not in our library10.1016/j.archoralbio.2016.08.030

  36. 36.

    Singh H., Mishra A., Mishra A.K. The chemistry and pharmacology of Cleome genus: A review. Biomed. Pharmacother. 2018;101:37-48.

    Not in our library10.1016/j.biopha.2018.02.053

  37. 37.

    El Moussaoui A., Jawhari F.Z., Almehdi A.M., Elmsellem H., Fikri Benbrahim K., Bousta D., Bari A. Antibacterial, antifungal and antioxidant activity of total polyphenols of Withania frutescens.L. Bioorg. Chem. 2019;93:103337.

    Not in our library10.1016/j.bioorg.2019.103337

  38. 38.

    de Andrade Monteiro C., Ribeiro Alves dos Santos J. Phytochemicals and Their Antifungal Potential Against Pathogenic Yeasts. Phytochemicals in Human Health. 2019.

    Not in our library10.5772/intechopen.87302

  39. 39.

    Lagrouh F., Dakka N., Bakri Y. The antifungal activity of Moroccan plants and the mechanism of action of secondary metabolites from plants. J. Mycol. Med. 2017;27:303-311.

    Not in our library10.1016/j.mycmed.2017.04.008

  40. 40.

    Gow N.A.R., Hube B. Importance of the Candida albicans cell wall during commensalism and infection. Curr. Opin. Microbiol. 2012;15:406-412.

    Not in our library10.1016/j.mib.2012.04.005

  41. 41.

    Veeraraghavan B., Jesudason M.R., Prakasah J.A.J., Anandan S., Sahni R.D., Pragasam A.K., Bakthavatchalam Y.D., Selvakumar R.J., Dhole T.N., Rodrigues C., et al. Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report. Indian J. Med. Microbiol. 2018;36:32-36.

    Not in our library10.4103/ijmm.ijmm_17_415

  42. 42.

    Brown G.D., Denning D.W., Gow N.A.R., Levitz S.M., Netea M.G., White T.C. Hidden Killers: Human Fungal Infections. Sci. Translat. Med. 2012;4:165rv113.

    Not in our library10.1126/scitranslmed.3004404

  43. 43.

    Limper A.H., Adenis A., Le T., Harrison T.S. Fungal infections in HIV/AIDS. Lancet Infect. Dis. 2017;17:e334-e343.

    Not in our library10.1016/s1473-3099(17)30303-1

  44. 44.

    Suresh M., Rath P.K., Panneerselvam A., Dhanasekaran D., Thajuddin N. Anti-mycobacterial effect of leaf extract of Centella asiatica. Res. J. Pharm. Technol. 2010;3:872-876.

    Not in our library

  45. 45.

    Suresh M., Rath P.K., Panneerselvam A., Dhanasekaran D., Thajuddin N. Antifungal activity of selected Indian medicinal plant salts. J.Glob. Pharm.Technol. 2010;2:71-74.

    Not in our library

  46. 46.

    Revathi P., Senthinath T.J., Vigneswari R. Antimicrobial resistance pattern of gram negative bacteria to 3rd and 4th generation cephalosporins. BMC Proceedings. 2011;5.

    Not in our library10.1186/1753-6561-5-s6-p146

  47. 47.

    Kannaiyan M., Manuel V.N., Raja V., Thambidurai P., Mickymaray S., Nooruddin T. Antimicrobial activity of the ethanolic and aqueous extracts of Salacia chinensis Linn. against human pathogens. Asian Pac. J. Trop. Dis. 2012;2:S416-S420.

    Not in our library10.1016/s2222-1808(12)60194-7

  48. 48.

    Kothavade R.J., Kura M.M., Valand A.G., Panthaki M.H. Candida tropicalis: its prevalence, pathogenicity and increasing resistance to fluconazole. J. Med. Microbiol. 2010;59:873-880.

    Not in our library10.1099/jmm.0.013227-0

  49. 49.

    Tobudic S., Kratzer C., Presterl E. Azole-resistant Candida spp.—Emerging pathogens? Mycoses. 2012;55:24-32.

    Not in our library10.1111/j.1439-0507.2011.02146.x

  50. 50.

    Gonçalves B., Ferreira C., Alves C.T., Henriques M., Azeredo J., Silva S. Vulvovaginal candidiasis: Epidemiology, microbiology and risk factors. Crit. Rev. Microbiol. 2015;42:905-927.

    Not in our library10.3109/1040841x.2015.1091805

  51. 51.

    Sobel J.D. Recurrent vulvovaginal candidiasis. Am. J. Obst. Gynecol. 2016;214:15-21.

    Not in our library10.1016/j.ajog.2015.06.067

  52. 52.

    Pana Z.D., Roilides E., Warris A., Groll A.H., Zaoutis T. Epidemiology of Invasive Fungal Disease in Children. J. Pediatr. Infect. Dis. Soc. 2017;6:S3-S11.

    Not in our library10.1093/jpids/pix046

  53. 53.

    Lin S.J., Schranz J., Teutsch S.M. Aspergillosis Case-Fatality Rate: Systematic Review of the Literature. Clin. Infect. Dis. 2001;32:358-366.

    Not in our library10.1086/318483

  54. 54.

    McCarthy K.M., Morgan J., Wannemuehler K.A., Mirza S.A., Gould S.M., Mhlongo N., Moeng P., Maloba B.R., Crewe-Brown H.H., Brandt M.E., et al. Population-based surveillance for cryptococcosis in an antiretroviral-naive South African province with a high HIV seroprevalence. AIDS. 2006;20:2199-2206.

    Not in our library10.1097/qad.0b013e3280106d6a

  55. 55.

    Gaitanis G., Magiatis P., Hantschke M., Bassukas I.D., Velegraki A. The Malassezia Genus in Skin and Systemic Diseases. Clin. Microbiol. Rev. 2012;25:106-141.

    Not in our library10.1128/cmr.00021-11

  56. 56.

    Prohic A., Jovovic Sadikovic T., Krupalija-Fazlic M., Kuskunovic-Vlahovljak S. Malasseziaspecies in healthy skin and in dermatological conditions. Int. J. Dermatol. 2015;55:494-504.

    Not in our library10.1111/ijd.13116

  57. 57.

    Olicón-Hernández D.R., Camacho-Morales R.L., Pozo C., González-López J., Aranda E. Evaluation of diclofenac biodegradation by the ascomycete fungus Penicillium oxalicum at flask and bench bioreactor scales. Sci. Total Environ. 2019;662:607-614.

    Not in our library10.1016/j.scitotenv.2019.01.248

  58. 58.

    Armstrong-James D., Meintjes G., Brown G.D. A neglected epidemic: fungal infections in HIV/AIDS. Trends Microbiol. 2014;22:120-127.

    Not in our library10.1016/j.tim.2014.01.001

  59. 59.

    Green M.D., Apel A.J.G., Naduvilath T., Stapleton F.J. Clinical outcomes of keratitis. Clin. Exp. Ophthalmol. 2007;35:421-426.

    Not in our library10.1111/j.1442-9071.2007.01511.x

  60. 60.

    Kontoyiannis D.P., Lionakis M.S., Lewis R.E., Chamilos G., Healy M., Perego C., Safdar A., Kantarjian H., Champlin R., Walsh T.J., et al. Zygomycosis in a Tertiary-Care Cancer Center in the Era ofAspergillus-Active Antifungal Therapy: A Case-Control Observational Study of 27 Recent Cases. J. Infect. Dis. 2005;191:1350-1360.

    Not in our library10.1086/428780

  61. 61.

    Geramizadeh B., Foroughi R., Keshtkar-Jahromi M., Malek-Hosseini S.A., Alborzi A. Gastrointestinal basidiobolomycosis, an emerging infection in the immunocompetent host: a report of 14 patients. J. Med. Microbiol. 2012;61:1770-1774.

    Not in our library10.1099/jmm.0.046839-0

  62. 62.

    Nucci M., Anaissie E. Fusarium Infections in Immunocompromised Patients. Clin. Microbiol. Rev. 2007;20:695-704.

    Not in our library10.1128/cmr.00014-07

  63. 63.
    Tinea Capitis: Current Status · 2016
    No notice
  64. 64.

    Nweze E.I., Eke I.E. Dermatophytes and dermatophytosis in the eastern and southern parts of Africa. Med. Mycol. 2017;56:13-28.

    Not in our library10.1093/mmy/myx025

  65. 65.
    The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids · 2017
    No notice
  66. 66.

    Oteiza P.I., Fraga C.G., Mills D.A., Taft D.H. Flavonoids and the gastrointestinal tract: Local and systemic effects. Mol. Aspects Med. 2018;61:41-49.

    Not in our library10.1016/j.mam.2018.01.001

  67. 67.

    Felice M.R., Giuffrè L., El Aamri L., Hafidi M., Criseo G., Romeo O., Scordino F. Looking for New Antifungal Drugs from Flavonoids: Impact of the Genetic Diversity of Candida albicans on the in-vitro Response. Curr. Med. Chem. 2019;26:5108-5123.

    Not in our library10.2174/0929867325666171226102700

  68. 68.
    Polyphenol-Rich Dry Common Beans (Phaseolus vulgaris L.) and Their Health Benefits · 2017
    No notice
  69. 69.

    Islam T., Ganesan K., Xu B. New Insight into Mycochemical Profiles and Antioxidant Potential of Edible and Medicinal Mushrooms: A Review. Int. J. Med. Mushrooms. 2019;21:237-251.

    Not in our library10.1615/intjmedmushrooms.2019030079

  70. 70.

    Ganesan K., Xu B. Polyphenol-Rich Lentils and Their Health Promoting Effects. Int. J. Mol. Sci. 2017;18:2390.

    Not in our library10.3390/ijms18112390

  71. 71.

    Ganesan K., Xu B. Anti-Obesity Effects of Medicinal and Edible Mushrooms. Molecules. 2018;23:2880.

    Not in our library10.3390/molecules23112880

  72. 72.

    Ganesan K., Xu B. A critical review on phytochemical profile and health promoting effects of mung bean (Vigna radiata). Food Sci. Hum. Wellness. 2018;7:11-33.

    Not in our library10.1016/j.fshw.2017.11.002

  73. 73.
    A Critical Review on Polyphenols and Health Benefits of Black Soybeans · 2017
    No notice
  74. 74.

    Hegarty V.M., May H.M., Khaw K.-T. Tea drinking and bone mineral density in older women. Am. J. Clin. Nutr. 2000;71:1003-1007.

    Not in our library10.1093/ajcn/71.4.1003

  75. 75.

    Bojić M., Maleš Ž., Antolić A., Babić I., Tomičić M. Antithrombotic activity of flavonoids and polyphenols rich plant species. Acta Pharma. 2019;69:483-495.

    Not in our library10.2478/acph-2019-0050

  76. 76.

    Ganesan K., Jayachandran M., Xu B. A critical review on hepatoprotective effects of bioactive food components. Crit. Rev. Food Sci. Nutr. 2017;58:1165-1229.

    Not in our library10.1080/10408398.2016.1244154

  77. 77.

    Abdulwanis Mohamed Z., Mohamed Eliaser E., Mazzon E., Rollin P., Cheng Lian Ee G., Abdull Razis A.F. Neuroprotective Potential of Secondary Metabolites from Melicope lunu-ankenda (Rutaceae). Molecules. 2019;24:3109.

    Not in our library10.3390/molecules24173109

  78. 78.

    Kumar G., Banu G.S., Murugesan A.G.A. Influence of Helicteres isora L. bark extracts on glycemic control and renoprotective activity in streptozotocin-induced diabetic rats. Int. J. Pharma Sci. Nanotechnol. 2008;1:275-280.

    Not in our library

  79. 79.

    Ganesan K., Xu B. Molecular targets of vitexin and isovitexin in cancer therapy: A critical review. Ann. N.Y. Acad. Sci. 2017;1401:102-113.

    Not in our library10.1111/nyas.13446

  80. 80.

    Ganesan K., Xu B. Telomerase Inhibitors from Natural Products and Their Anticancer Potential. Int. J. Mol. Sci. 2017;19.

    Not in our library10.3390/ijms19010013

  81. 81.

    Pandian M.R., Banu G.S., Kumar G. A study of the antimicrobial activity of Alangium salviifolium. Indian J. Pharmacol. 2006;38:203.

    Not in our library10.4103/0253-7613.25810

  82. 82.

    Mickymaray S. Efficacy and Mechanism of Traditional Medicinal Plants and Bioactive Compounds against Clinically Important Pathogens. Antibiotics. 2019;8:257.

    Not in our library10.3390/antibiotics8040257

  83. 83.

    Banu G.S., Kumar G. Preliminary Screening of Endophytic Fungi from Medicinal Plants in India for Antimicrobial and Antitumor Activity. Int. J. Pharma. Sci. Nanotechnol. 2009;2:566-571.

    Not in our library

  84. 84.

    Sukalingam K., Ganesan K., Xu B. Trianthema portulacastrum L. (giant pigweed): Phytochemistry and pharmacological properties. Phytochem. Rev. 2017;16:461-478.

    Not in our library10.1007/s11101-017-9493-5

  85. 85.

    Abd El Maksoud A.I., Taher R.F., Gaara A.H., Abdelrazik E., Keshk O.S., Elawdan K.A., Morsy S.E., Salah A., Khalil H. Selective Regulation of B-Raf Dependent K-Ras/Mitogen-Activated Protein by Natural Occurring Multi-kinase Inhibitors in Cancer Cells. Front. Oncol. 2019;9.

    Not in our library10.3389/fonc.2019.01220

  86. 86.

    Yang X., Jiang J., Zhang C., Li Y. Baicalein restrains proliferation, migration, and invasion of human malignant melanoma cells by down-regulating colon cancer associated transcript-1. Braz. J. Med. Biol. Res. 2019;52.

    Not in our library10.1590/1414-431x20198934

  87. 87.

    Ke Y., Al Aboody M.S., Alturaiki W., Alsagaby S.A., Alfaiz F.A., Veeraraghavan V.P., Mickymaray S. Photosynthesized gold nanoparticles from Catharanthus roseus induces caspase-mediated apoptosis in cervical cancer cells (HeLa). Artificial Cells Nanomed. Biotechnol. 2019;47:1938-1946.

    Not in our library10.1080/21691401.2019.1614017

  88. 88.

    Middleton E., Kandaswami C., Harborne J.B. The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. The Flavonoids: Advances in Research since 1986. 1993;619-652.

    Not in our library10.1007/978-1-4899-2911-2_15

  89. 89.

    Kumar G., Banu G.S., Kannan V., Pandian M.R. Antihepatotoxic effect of beta-carotene on paracetamol induced hepatic damage in rats. Indian J. Exp. Biol. 2005;43:351-355.

    Not in our library

  90. 90.

    Kumar G., Banu G.S., Pappa P.V., Sundararajan M., Pandian M.R. Hepatoprotective activity of Trianthema portulacastrum L. against paracetamol and thioacetamide intoxication in albino rats. J. Ethnopharmacol. 2004;92:37-40.

    Not in our library10.1016/j.jep.2003.12.009

  91. 91.

    Kumar G., Murugesan A.G. Hypolipidaemic activity of Helicteres isora L. bark extracts in streptozotocin induced diabetic rats. J. Ethnopharmacol. 2008;116:161-166.

    Not in our library10.1016/j.jep.2007.11.020

  92. 92.

    Kumar G., Sharmila Banu G., Ganesan Murugesan A. Effect of Helicteres isora bark extracts on heart antioxidant status and lipid peroxidation in streptozotocin diabetic rats. J. Appl. Biomed. 2008;6:89-95.

    Not in our library10.32725/jab.2008.012

  93. 93.

    Kumar G., Banu G.S., Pandian M.R. Biochemical activity of selenium and glutathione on country made liquor (CML) induced hepatic damage in rats. Indian J. Clin. Biochem. 2007;22:105-108.

    Not in our library10.1007/bf02912891

  94. 94.

    Ziberna L., Fornasaro S., Čvorović J., Tramer F., Passamonti S. Bioavailability of Flavonoids. Polyphenols in Human Health and Disease. 2014;489-511.

    Not in our library10.1016/b978-0-12-398456-2.00037-2

  95. 95.

    Kumar G., Sharmila Banu G., Murugesan A.G., Rajasekara Pandian M. Effect ofHelicteres isora. Bark Extracts on Brain Antioxidant Status and Lipid Peroxidation in Streptozotocin Diabetic Rats. Pharma. Biol. 2007;45:753-759.

    Not in our library10.1080/13880200701585782

  96. 96.

    Liu W., Li L.P., Zhang J.D., Li Q., Shen H., Chen S.M., He L.J., Yan L., Xu G.T., An M.M., et al. Synergistic Antifungal Effect of Glabridin and Fluconazole. PLoS ONE. 2014;9:e103442.

    Not in our library10.1371/journal.pone.0103442

  97. 97.

    Salazar-Aranda R., Granados-Guzmán G., Pérez-Meseguer J., González G., de Torres N. Activity of Polyphenolic Compounds against Candida glabrata. Molecules. 2015;20:17903-17912.

    Not in our library10.3390/molecules201017903

  98. 98.

    Oliveira M.R.d., Nabavi S.F., Daglia M., Rastrelli L., Nabavi S.M. Epigallocatechin gallate and mitochondria—A story of life and death. Pharmacol. Res. 2016;104:70-85.

    Not in our library10.1016/j.phrs.2015.12.027

  99. 99.

    Oliveira V.M., Carraro E., Auler M.E., Khalil N.M. Quercetin and rutin as potential agents antifungal against Cryptococcus spp. Braz. J. Biol. 2016;76:1029-1034.

    Not in our library10.1590/1519-6984.07415

  100. 100.

    Yang Y.-X., An M.-M., Jin Y.-S., Chen H.-S. Chemical constituents from the rhizome of Polygonum paleaceum and their antifungal activity. J. Asian Nat. Prod. Res. 2016;19:47-52.

    Not in our library10.1080/10286020.2016.1196672

  101. 101.

    da Silva C.R., de Andrade Neto J.B., de Sousa Campos R., Figueiredo N.S., Sampaio L.S., Magalhães H.I.F., Cavalcanti B.C., Gaspar D.M., de Andrade G.M., Lima I.S.P., et al. Synergistic Effect of the Flavonoid Catechin, Quercetin, or Epigallocatechin Gallate with Fluconazole Induces Apoptosis in Candida tropicalis Resistant to Fluconazole. Antimicrob. Agents Chemother. 2013;58:1468-1478.

    Not in our library10.1128/aac.00651-13

  102. 102.

    Andrade J.T., Santos F.R.S., Lima W.G., Sousa C.D.F., Oliveira L.S.F.M., Ribeiro R.I.M.A., Gomes A.J.P.S., Araújo M.G.F., Villar J.A.F.P., Ferreira J.M.S. Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents. J. Antibiotics. 2018;71:702-712.

    Not in our library10.1038/s41429-018-0048-9

  103. 103.

    Houlihan A.J., Conlin P., Chee-Sanford J.C. Water-soluble exudates from seeds of Kochia scoparia exhibit antifungal activity against Colletotrichum graminicola. PLoS ONE. 2019;14:e0218104.

    Not in our library10.1371/journal.pone.0218104

  104. 104.

    Mohotti S., Rajendran S., Muhammad T., Strömstedt A.A., Adhikari A., Burman R., de Silva E.D., Göransson U., Hettiarachchi C.M., Gunasekera S. Screening for bioactive secondary metabolites in Sri Lankan medicinal plants by microfractionation and targeted isolation of antimicrobial flavonoids from Derris scandens. J. Ethnopharmacol. 2020;246:112158.

    Not in our library10.1016/j.jep.2019.112158

  105. 105.

    Lee J.A., Chee H.Y. In VitroAntifungal Activity of Equol against Candida albicans. Mycobiology. 2010;38:328.

    Not in our library10.4489/myco.2010.38.4.328

  106. 106.

    Bitencourt T.A., Komoto T.T., Massaroto B.G., Miranda C.E.S., Beleboni R.O., Marins M., Fachin A.L. Trans-chalcone and quercetin down-regulate fatty acid synthase gene expression and reduce ergosterol content in the human pathogenic dermatophyte Trichophyton rubrum. BMC Compl. Altern. Med. 2013;13.

    Not in our library10.1186/1472-6882-13-229

  107. 107.

    Edziri H., Mastouri M., Mahjoub M.A., Mighri Z., Mahjoub A., Verschaeve L. Antibacterial, Antifungal and Cytotoxic Activities of Two Flavonoids from Retama raetam Flowers. Molecules. 2012;17:7284-7293.

    Not in our library10.3390/molecules17067284

  108. 108.

    Quiroga E.N., Sampietro D.A., Sgariglia M.A., Soberón J.R., Vattuone M.A. Antimycotic activity of 5′-prenylisoflavanones of the plant Geoffroea decorticans, against Aspergillus species. Int. J. Food Microbiol. 2009;132:42-46.

    Not in our library10.1016/j.ijfoodmicro.2009.03.013

  109. 109.

    Belofsky G., Kolaczkowski M., Adams E., Schreiber J., Eisenberg V., Coleman C.M., Zou Y., Ferreira D. Fungal ABC Transporter-Associated Activity of Isoflavonoids from the Root Extract of Dalea formosa. J. Nat. Prod. 2013;76:915-925.

    Not in our library10.1021/np4000763

  110. 110.

    Messier C., Epifano F., Genovese S., Grenier D. Inhibition of Candida albicans biofilm formation and yeast-hyphal transition by 4-hydroxycordoin. Phytomedicine. 2011;18:380-383.

    Not in our library10.1016/j.phymed.2011.01.013

  111. 111.

    Vieira M.L.A., Johann S., Hughes F.M., Rosa C.A., Rosa L.H. The diversity and antimicrobial activity of endophytic fungi associated with medicinal plant Baccharis trimera (Asteraceae) from the Brazilian savannah. Can. J. Microbiol. 2014;60:847-856.

    Not in our library10.1139/cjm-2014-0449

  112. 112.

    Mandalari G., Bennett R.N., Bisignano G., Trombetta D., Saija A., Faulds C.B., Gasson M.J., Narbad A. Antimicrobial activity of flavonoids extracted from bergamot (Citrus bergamia Risso) peel, a byproduct of the essential oil industry. J. Appl. Microbiol. 2007;103:2056-2064.

    Not in our library10.1111/j.1365-2672.2007.03456.x

  113. 113.

    Djouossi M.G., Tamokou J.-d.-D., Ngnokam D., Kuiate J.-R., Tapondjou L.A., Harakat D., Voutquenne-Nazabadioko L. Antimicrobial and antioxidant flavonoids from the leaves of Oncoba spinosa Forssk. (Salicaceae). BMC Compl. Altern. Med. 2015;15.

    Not in our library10.1186/s12906-015-0660-1

  114. 114.

    Gadetskaya A.V., Tarawneh A.H., Zhusupova G.E., Gemejiyeva N.G., Cantrell C.L., Cutler S.J., Ross S.A. Sulfated phenolic compounds from Limonium caspium: Isolation, structural elucidation, and biological evaluation. Fitoterapia. 2015;104:80-85.

    Not in our library10.1016/j.fitote.2015.05.017

  115. 115.

    Karalija E., Parić A., Dahija S., Bešta-Gajević R., Ćavar Zeljković S. Phenolic compounds and bioactive properties of Verbascum glabratum subsp. bosnense (K. Malý) Murb., an endemic plant species. Nat. Prod. Res. 2018;1-5.

    Not in our library10.1080/14786419.2018.1538221

  116. 116.
    Phytochemical Analysis and Antimicrobial Activity of Myrcia tomentosa (Aubl.) DC. Leaves · 2017
    Not checked
  117. 117.

    Toiu A., Vlase L., Vodnar D.C., Gheldiu A.-M., Oniga I. Solidago graminifolia L. Salisb. (Asteraceae) as a Valuable Source of Bioactive Polyphenols: HPLC Profile, In Vitro Antioxidant and Antimicrobial Potential. Molecules. 2019;24:2666.

    Not in our library10.3390/molecules24142666

  118. 118.

    da Costa M.P., Bozinis M.C.V., Andrade W.M., Costa C.R., da Silva A.L., Alves de Oliveira C.M., Kato L., Fernandes O.d.F.L., Souza L.K.H., Silva M.d.R.R. Antifungal and cytotoxicity activities of the fresh xylem sap of Hymenaea courbaril L. and its major constituent fisetin. BMC Compl. Altern. Med. 2014;14.

    Not in our library10.1186/1472-6882-14-245

  119. 119.

    Sohn H.-Y. Fungicidal Effect of Prenylated Flavonol, Papyriflavonol A, Isolated from Broussonetia papyrifera (L.) Vent. Against Candida albicans. J. Microbiol. Biotechnol. 2010;20:1397-1402.

    Not in our library10.4014/jmb.1007.07026

  120. 120.

    Boeck P., Leal P.C., Yunes R.A., Filho V.C., López S., Sortino M., Escalante A., Furlán R.L.E., Zacchino S. Antifungal Activity and Studies on Mode of Action of Novel Xanthoxyline-Derived Chalcones. Archiv. Pharmazie. 2005;338:87-95.

    Not in our library10.1002/ardp.200400929

  121. 121.

    Rajasekharan S.K., Ramesh S., Bakkiyaraj D. Synergy of flavonoids with HDAC inhibitor: new approach to targetCandida tropicalisbiofilms. J. Chemother. 2014;27:246-249.

    Not in our library10.1179/1973947814y.0000000186

  122. 122.

    Shao J., Zhang M., Wang T., Li Y., Wang C. The roles ofCDR1,CDR2,andMDR1in kaempferol-induced suppression with fluconazole-resistant Candida albicans. Pharma. Biol. 2015;54:984-992.

    Not in our library10.3109/13880209.2015.1091483

  123. 123.

    Da X., Nishiyama Y., Tie D., Hein K.Z., Yamamoto O., Morita E. Antifungal activity and mechanism of action of Ou-gon (Scutellaria root extract) components against pathogenic fungi. Sci. Rep. 2019;9.

    Not in our library10.1038/s41598-019-38916-w

  124. 124.

    Cantelli B.A.M., Bitencourt T.A., Komoto T.T., Beleboni R.O., Marins M., Fachin A.L. Caffeic acid and licochalcone A interfere with the glyoxylate cycle of Trichophyton rubrum. Biomed. Pharmacother. 2017;96:1389-1394.

    Not in our library10.1016/j.biopha.2017.11.051

  125. 125.

    Baptista R., Madureira A.M., Jorge R., Adão R., Duarte A., Duarte N., Lopes M.M., Teixeira G. Antioxidant and Antimycotic Activities of Two NativeLavandulaSpecies from Portugal. Evid. Based Compl. Altern. Med. 2015;2015:1-10.

    Not in our library10.1155/2015/570521

  126. 126.

    González-Alamilla E.N., Gonzalez-Cortazar M., Valladares-Carranza B., Rivas-Jacobo M.A., Herrera-Corredor C.A., Ojeda-Ramírez D., Zaragoza-Bastida A., Rivero-Perez N. Chemical Constituents of Salix babylonica L. and Their Antibacterial Activity Against Gram-Positive and Gram-Negative Animal Bacteria. Molecules. 2019;24:2992.

    Not in our library10.3390/molecules24162992

  127. 127.

    Huang S., Cao Y.Y., Dai B.D., Sun X.R., Zhu Z.Y., Cao Y.B., Wang Y., Gao P.H., Jiang Y.Y. In Vitro Synergism of Fluconazole and Baicalein against Clinical Isolates of Candida albicans Resistant to Fluconazole. Biol. Pharma. Bull. 2008;31:2234-2236.

    Not in our library10.1248/bpb.31.2234

  128. 128.

    Dai B.D., Cao Y.Y., Huang S., Xu Y.G., Gao P.H., Wang Y., Jiang Y.Y. Baicalein induces programmed cell death in Candida albicans. J. Microbiol. Biotechnol. 2009;19:803-809.

    Not in our library

  129. 129.

    Kang K., Fong W.-P., Tsang P.W.-K. Antifungal Activity of Baicalein Against Candida krusei Does Not Involve Apoptosis. Mycopathologia. 2010;170:391-396.

    Not in our library10.1007/s11046-010-9341-2

  130. 130.

    Serpa R., Franca E.J.G., Furlaneto-Maia L., Andrade C.G.T.J., Diniz A., Furlaneto M.C. In vitro antifungal activity of the flavonoid baicalein against Candida species. J. Med. Microbiol. 2012;61:1704-1708.

    Not in our library10.1099/jmm.0.047852-0

  131. 131.

    Tsang P.W.-K., Chau K.-Y., Yang H.-P. Baicalein exhibits inhibitory effect on the energy-dependent efflux pump activity in non-albicans Candidafungi. J. Chemother. 2014;27:61-62.

    Not in our library10.1179/1973947814y.0000000177

  132. 132.

    Lee H., Woo E.-R., Lee D.G. Apigenin induces cell shrinkage in Candida albicans by membrane perturbation. FEMS Yeast Res. 2018;18.

    Not in our library10.1093/femsyr/foy003

  133. 133.

    Mangoyi R., Midiwo J., Mukanganyama S. Isolation and characterization of an antifungal compound 5-hydroxy-7,4’-dimethoxyflavone from Combretum zeyheri. BMC Compl. Altern. Med. 2015;15.

    Not in our library10.1186/s12906-015-0934-7

  134. 134.

    Katerere D.R., Gray A.I., Nash R.J., Waigh R.D. Phytochemical and antimicrobial investigations of stilbenoids and flavonoids isolated from three species of Combretaceae. Fitoterapia. 2012;83:932-940.

    Not in our library10.1016/j.fitote.2012.04.011

  135. 135.

    Perez C., Tiraboschi I.N., Ortega M.G., Agnese A.M., Cabrera J.L. Further Antimicrobial Studies of 2’4’-dihidroxy-5’-(1?-dimethylallyl)-6-prenylpinocembrin from Dalea elegans. Pharma. Biol. 2003;41:171-174.

    Not in our library10.1076/phbi.41.3.171.15090

  136. 136.

    Peralta M.A., da Silva M.A., Ortega M.G., Cabrera J.L., Paraje M.G. Antifungal activity of a prenylated flavonoid from Dalea elegans against Candida albicans biofilms. Phytomedicine. 2015;22:975-980.

    Not in our library10.1016/j.phymed.2015.07.003

  137. 137.

    Sasaki H., Kashiwada Y., Shibatav H., Takaishi Y. Prenylated Flavonoids from the Roots of Desmodium caudatum and Evaluation of Their Antifungal Activity. Planta Med. 2012;78:1851-1856.

    Not in our library10.1055/s-0032-1315391

  138. 138.

    Lourenção Brighenti F., Salvador M.J., Vidal Lacerda Gontijo A., Botazzo Delbem A.C., Botazzo Delbem Á.C., Soares C.P., Carvalho de Oliveira M.A., Miorelli Girondi C., Koga-Ito C.Y. Plant extracts: initial screening, identification of bioactive compounds and effect against Candida albicansbiofilms. Future Microbiol. 2017;12:15-27.

    Not in our library10.2217/fmb-2016-0094

  139. 139.

    Seleem D., Benso B., Noguti J., Pardi V., Murata R.M. In vitro and in vivo Antifungal Activity of Lichochalcone-A against Candida albicans Biofilms. PLoS ONE. 2016;11:e0157188.

    Not in our library10.1371/journal.pone.0157188

  140. 140.

    Kulkarni R.R., Tupe S.G., Gample S.P., Chandgude M.G., Sarkar D., Deshpande M.V., Joshi S.P. Antifungal dimeric chalcone derivative kamalachalcone E fromMallotus philippinensis. Nat. Prod. Res. 2013;28:245-250.

    Not in our library10.1080/14786419.2013.843178

  141. 141.

    ElSohly H.N., Joshi A.S., Nimrod A.C., Walker L.A., Clark A.M. Antifungal Chalcones from Maclura tinctoria. Planta Med. 2001;67:87-89.

    Not in our library10.1055/s-2001-10621

  142. 142.

    Teodoro G.R., Brighenti F.L., Delbem A.C.B., Delbem Á.C.B., Khouri S., Gontijo A.V.L., Pascoal A.C.R.F., Salvador M.J., Koga-Ito C.Y. Antifungal activity of extracts and isolated compounds fromBuchenavia tomentosaon Candida albicans and non-albicans. Future Microbiol. 2015;10:917-927.

    Not in our library10.2217/fmb.15.20

  143. 143.

    Herrera C.L., Alvear M., Barrientos L., Montenegro G., Salazar L.A. The antifungal effect of six commercial extracts of Chilean propolis on Candida spp. Ciencia e Investigación Agraria. 2010;37.

    Not in our library10.4067/s0718-16202010000100007

  144. 144.

    Yoon T.M., Kim J.W., Kim J.G., Kim W.G., Suh J.W. Talosins A and B: New Isoflavonol Glycosides with Potent Antifungal Activity from Kitasatospora kifunensis MJM341. J. Antibiotics. 2006;59:633-639.

    Not in our library10.1038/ja.2006.84

  145. 145.

    Taveira M., Silva L.s.R., Vale-Silva L.s.A., Pinto E.n., Valentão P.c., Ferreres F., Guedes de Pinho P., Andrade P.B. Lycopersicon esculentumSeeds: An Industrial Byproduct as an Antimicrobial Agent. J. Agric. Food Chem. 2010;58:9529-9536.

    Not in our library10.1021/jf102215g

  146. 146.

    Yousefbeyk F., Gohari A.R., Hashemighahderijani Z., Ostad S.N., Sourmaghi M.H.S., Amini M., Golfakhrabadi F., Jamalifar H., Amin G., Amin M. Erratum to: Bioactive terpenoids and flavonoids from Daucus littoralis Smith subsp. hyrcanicus Rech.f, an endemic species of Iran. DARU J. Pharma. Sci. 2014;22.

    Not in our library10.1186/2008-2231-22-33

  147. 147.

    Agnihotri V.K., ElSohly H.N., Khan S.I., Jacob M.R., Joshi V.C., Smillie T., Khan I.A., Walker L.A. Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity. Phytochem. Lett. 2008;1:89-93.

    Not in our library10.1016/j.phytol.2008.03.003

  148. 148.

    Awouafack M.D., McGaw L.J., Gottfried S., Mbouangouere R., Tane P., Spiteller M., Eloff J.N. Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae). BMC Compl. Altern. Med. 2013;13.

    Not in our library10.1186/1472-6882-13-289

  149. 149.

    Shakirullah M., Ahmad H., Shah M.R., Ahmad I., Ishaq M., Khan N., Badshah A., Khan I. Antimicrobial activities of Conyzolide and Conyzoflavone fromConyza canadensis. J. Enzyme Inhibit. Med. Chem. 2010;26:468-471.

    Not in our library10.3109/14756366.2010.528413

  150. 150.

    Yenjai C., Prasanphen K., Daodee S., Wongpanich V., Kittakoop P. Bioactive flavonoids from Kaempferia parviflora. Fitoterapia. 2004;75:89-92.

    Not in our library10.1016/j.fitote.2003.08.017

  151. 151.

    Xu S., Shang M.-Y., Liu G.-X., Xu F., Wang X., Shou C.-C., Cai S.-Q. Chemical Constituents from the Rhizomes of Smilax glabra and Their Antimicrobial Activity. Molecules. 2013;18:5265-5287.

    Not in our library10.3390/molecules18055265

  152. 152.

    Moshi M., Joseph C., Innocent E., Nkunya M. In VitroAntibacterial and Antifungal Activities of Extracts and Compounds fromUvaria scheffleri. Pharma. Biol. 2004;42:269-273.

    Not in our library10.1080/13880200490511035

  153. 153.

    Qu J., Xie C., Guo H., Yu W., Lou H. Antifungal dibenzofuran bis(bibenzyl)s from the liverwort Asterella angusta. Phytochemistry. 2007;68:1767-1774.

    Not in our library10.1016/j.phytochem.2007.04.036

  154. 154.

    Picerno P., Mencherini T., Sansone F., Del Gaudio P., Granata I., Porta A., Aquino R.P. Screening of a polar extract of Paeonia rockii: Composition and antioxidant and antifungal activities. J. Ethnopharmacol. 2011;138:705-712.

    Not in our library10.1016/j.jep.2011.09.056

  155. 155.

    Mulaudzi R.B., Ndhlala A.R., Kulkarni M.G., Van Staden J. Pharmacological properties and protein binding capacity of phenolic extracts of some Venda medicinal plants used against cough and fever. J. Ethnopharmacol. 2012;143:185-193.

    Not in our library10.1016/j.jep.2012.06.022

  156. 156.

    De Leo M., Braca A., De Tommasi N., Norscia I., Morelli I., Battinelli L., Mazzanti G. Phenolic Compounds fromBaseonema acuminatum Leaves: Isolation and Antimicrobial Activity. Planta Med. 2004;70:841-846.

    Not in our library10.1055/s-2004-827233

  157. 157.

    Mbaveng A.T., Kuete V., Ngameni B., Beng V.P., Ngadjui B.T., Meyer J.J.M., Lall N. Antimicrobial activities of the methanol extract and compounds from the twigs of Dorstenia mannii (Moraceae). BMC Compl. Altern. Med. 2012;12.

    Not in our library10.1186/1472-6882-12-83

  158. 158.

    Gabriela N., Rosa A.M., Catiana Z.I., Soledad C., Mabel O.R., Esteban S.J., Veronica B., Daniel W., Ines I.M. The Effect of Zuccagnia punctata, an Argentine Medicinal Plant, on Virulence Factors from Candida Species. Nat. Prod. Comm. 2014;9:1934578X1400900.

    Not in our library10.1177/1934578x1400900712

  159. 159.

    Zuzarte M., Vale-Silva L., Gonçalves M.J., Cavaleiro C., Vaz S., Canhoto J., Pinto E., Salgueiro L. Antifungal activity of phenolic-rich Lavandula multifida L. essential oil. Eur. J. Clin. Microbiol. Infect. Dis. 2011;31:1359-1366.

    Not in our library10.1007/s10096-011-1450-4

  160. 160.

    Orhan D.D., Özçelik B., Özgen S., Ergun F. Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiol. Res. 2010;165:496-504.

    Not in our library10.1016/j.micres.2009.09.002

  161. 161.

    Wächter G.A., Hoffmann J.J., Furbacher T., Blake M.E., Timmermann B.N. Antibacterial and antifungal flavanones from Eysenhardtia texana. Phytochemistry. 1999;52:1469-1471.

    Not in our library10.1016/s0031-9422(99)00221-6

  162. 162.

    Lopes G., Pinto E., Salgueiro L. Natural Products: An Alternative to Conventional Therapy for Dermatophytosis? Mycopathologia. 2016;182:143-167.

    Not in our library10.1007/s11046-016-0081-9

  163. 163.

    Correia A.F., Silveira D., Fonseca-Bazzo Y.M., Magalhães P.O., Fagg C.W., da Silva E.C., Gomes S.M., Gandolfi L., Pratesi R., de Medeiros Nóbrega Y.K. Activity of crude extracts from Brazilian cerrado plants against clinically relevant Candida species. BMC Compl. Altern. Med. 2016;16.

    Not in our library10.1186/s12906-016-1164-3

  164. 164.

    Yamaguchi M.U., Garcia F.P., Cortez D.A.G., Ueda-Nakamura T., Filho B.P.D., Nakamura C.V. Antifungal effects of Ellagitannin isolated from leaves of Ocotea odorifera (Lauraceae). Antonie van Leeuwenhoek. 2010;99:507-514.

    Not in our library10.1007/s10482-010-9516-3

  165. 165.
    Ellagitannins from Raspberry (Rubus idaeus L.) Fruit as Natural Inhibitors of Geotrichum candidum · 2016
    Not checked
  166. 166.

    dos Santos C., Vargas Á., Fronza N., dos Santos J.H.Z. Structural, textural and morphological characteristics of tannins from Acacia mearnsii encapsulated using sol-gel methods: Applications as antimicrobial agents. Colloids Surfaces B Biointerfaces. 2017;151:26-33.

    Not in our library10.1016/j.colsurfb.2016.11.041

  167. 167.

    Cushnie T.P.T., Lamb A.J. Antimicrobial activity of flavonoids. Int. J.Antimicrob. Agents. 2005;26:343-356.

    Not in our library10.1016/j.ijantimicag.2005.09.002

  168. 168.

    Tapas A.R., Sakarkar D.M., Kakde R.B. Flavonoids as Nutraceuticals: A Review. Trop. J. Pharma. Res. 2008;7.

    Not in our library10.4314/tjpr.v7i3.14693

  169. 169.

    Taleb-Contini S.H., Salvador M.J., Watanabe E., Ito I.Y., Oliveira D.C.R.d. Antimicrobial activity of flavonoids and steroids isolated from two Chromolaena species. Revista Brasileira de Ciências Farmacêuticas. 2003;39:403-408.

    Not in our library10.1590/s1516-93322003000400007

  170. 170.

    Li K., Xing S., Wang M., Peng Y., Dong Y., Li X. Anticomplement and Antimicrobial Activities of Flavonoids from Entada phaseoloides. Nat. Prod. Comm. 2012;7:1934578X1200700.

    Not in our library10.1177/1934578x1200700715

  171. 171.

    Ahmadi F., Sadeghi S., Modarresi M., Abiri R., Mikaeli A. Chemical composition, in vitro anti-microbial, antifungal and antioxidant activities of the essential oil and methanolic extract of Hymenocrater longiflorus Benth., of Iran. Food Chem. Toxicol. 2010;48:1137-1144.

    Not in our library10.1016/j.fct.2010.01.028

  172. 172.

    Montagner C., de Souza S.M., Groposo C., Delle Monache F., Smânia E.F.A., Smânia Jr A. Antifungal Activity of Coumarins. Zeitschrift für Naturforschung C. 2008;63:21-28.

    Not in our library10.1515/znc-2008-1-205

  173. 173.

    Navarro-García V.M., Rojas G., Avilés M., Fuentes M., Zepeda G. In vitro antifungal activity of coumarin extracted from Loeselia mexicana Brand. Mycoses. 2011;54:e569-e571.

    Not in our library10.1111/j.1439-0507.2010.01993.x

  174. 174.

    Raut J.S., Shinde R.B., Chauhan N.M., Karuppayil S.M. Phenylpropanoids of Plant Origin as Inhibitors of Biofilm Formation by Candida albicans. J. Microbiol. Biotechnol. 2014;24:1216-1225.

    Not in our library10.4014/jmb.1402.02056

  175. 175.

    Salas M.P., Céliz G., Geronazzo H., Daz M., Resnik S.L. Antifungal activity of natural and enzymatically-modified flavonoids isolated from citrus species. Food Chem. 2011;124:1411-1415.

    Not in our library10.1016/j.foodchem.2010.07.100

  176. 176.

    Mendoza L., Yañez K., Vivanco M., Melo R., Cotoras M. Characterization of extracts from winery by-products with antifungal activity against Botrytis cinerea. Indust. Crops Prod. 2013;43:360-364.

    Not in our library10.1016/j.indcrop.2012.07.048

  177. 177.

    Han Y. Synergic Anticandidal Effect of Epigallocatechin-O-gallate Combined with Amphotericin B in a Murine Model of Disseminated Candidiasis and Its Anticandidal Mechanism. Biol. Pharma.Bull. 2007;30:1693-1696.

    Not in our library10.1248/bpb.30.1693

  178. 178.

    Han Y. Synergic effect of grape seed extract with amphotericin B against disseminated candidiasis due to Candida albicans. Phytomedicine. 2007;14:733-738.

    Not in our library10.1016/j.phymed.2007.08.004

  179. 179.

    Sagdic O., Ozturk I., Ozkan G., Yetim H., Ekici L., Yilmaz M.T. RP-HPLC–DAD analysis of phenolic compounds in pomace extracts from five grape cultivars: Evaluation of their antioxidant, antiradical and antifungal activities in orange and apple juices. Food Chem. 2011;126:1749-1758.

    Not in our library10.1016/j.foodchem.2010.12.075

  180. 180.
    Ethnomedicinal, Phytochemical and Ethnopharmacological Aspects of Four Medicinal Plants of Malvaceae Used in Indian Traditional Medicines: A Review · 2017
    Not checked
  181. 181.

    Bitencourt T.A., Macedo C., Franco M.E., Rocha M.C., Moreli I.S., Cantelli B.A.M., Sanches P.R., Beleboni R.O., Malavazi I., Passos G.A., et al. Trans-chalcone activity against Trichophyton rubrum relies on an interplay between signaling pathways related to cell wall integrity and fatty acid metabolism. BMC Genomics. 2019;20.

    Not in our library10.1186/s12864-019-5792-0

  182. 182.

    Terças A.G., Monteiro A.d.S., Moffa E.B., Santos J.R.A.d., Sousa E.M.d., Pinto A.R.B., Costa P.C.d.S., Borges A.C.R., Torres L.M.B., Barros Filho A.K.D., et al. Phytochemical Characterization of Terminalia catappa Linn. Extracts and Their antifungal Activities against Candida spp. Front. Microbiol. 2017;8.

    Not in our library10.3389/fmicb.2017.00595

  183. 183.

    Bottari N.B., Lopes L.Q.S., Pizzuti K., Filippi dos Santos Alves C., Corrêa M.S., Bolzan L.P., Zago A., de Almeida Vaucher R., Boligon A.A., Giongo J.L., et al. Antimicrobial activity and phytochemical characterization of Carya illinoensis. Microb. Pathogen. 2017;104:190-195.

    Not in our library10.1016/j.micpath.2017.01.037

  184. 184.

    Teodoro G.R., Gontijo A.V.L., Salvador M.J., Tanaka M.H., Brighenti F.L., Delbem A.C.B., Delbem Á.C.B., Koga-Ito C.Y. Effects of Acetone Fraction From Buchenavia tomentosa Aqueous Extract and Gallic Acid on Candida albicans Biofilms and Virulence Factors. Front. Microbiol. 2018;9.

    Not in our library10.3389/fmicb.2018.00647

  185. 185.

    Reddy M., Gupta S., Jacob M., Khan S., Ferreira D. Antioxidant, Antimalarial and Antimicrobial Activities of Tannin-Rich Fractions, Ellagitannins and Phenolic Acids from Punica granatum L. Planta Med. 2007;73:461-467.

    Not in our library10.1055/s-2007-967167

  186. 186.

    Shahzad M., Sherry L., Rajendran R., Edwards C.A., Combet E., Ramage G. Utilising polyphenols for the clinical management of Candida albicans biofilms. Int. J. Antimicrob. Agents. 2014;44:269-273.

    Not in our library10.1016/j.ijantimicag.2014.05.017

  187. 187.

    da Silva D.L., Magalhães T.F.F., dos Santos J.R.A., de Paula T.P., Modolo L.V., de Fátima A., Buzanello Martins C.V., Santos D.A., de Resende-Stoianoff M.A. Curcumin enhances the activity of fluconazole againstCryptococcus gattii-induced cryptococcosis infection in mice. J. Appl.Microbiol. 2015;120:41-48.

    Not in our library10.1111/jam.12966

  188. 188.
    The Anti-Adhesive Effect of Curcumin on Candida albicans Biofilms on Denture Materials · 2017
    Not checked
  189. 189.

    Paul S., Mohanram K., Kannan I. Antifungal activity of curcumin-silver nanoparticles against fluconazole-resistant clinical isolates of Candida species. AYU (Int. Q. J. Res. Ayurveda). 2018;39:182.

    Not in our library10.4103/ayu.ayu_24_18

  190. 190.

    Ghannoum M.A., Rice L.B. Antifungal Agents: Mode of Action, Mechanisms of Resistance, and Correlation of These Mechanisms with Bacterial Resistance. Clin. Microbiol. Rev. 1999;12:501-517.

    Not in our library10.1128/cmr.12.4.501

  191. 191.

    Walker G.M., White N.A. Introduction to Fungal Physiology. Fungi. 2005;1-34.

    Not in our library10.1002/0470015330.ch1

  192. 192.

    Pinto E., Vale-Silva L., Cavaleiro C., Salgueiro L. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. J. Med. Microbiol. 2009;58:1454-1462.

    Not in our library10.1099/jmm.0.010538-0

  193. 193.

    Evans M.D., Dizdaroglu M., Cooke M.S. Oxidative DNA damage and disease: induction, repair and significance. Mutat.Res.Rev. Mutat. Res. 2004;567:1-61.

    Not in our library10.1016/j.mrrev.2003.11.001

  194. 194.

    Wong-ekkabut J., Xu Z., Triampo W., Tang I.M., Peter Tieleman D., Monticelli L. Effect of Lipid Peroxidation on the Properties of Lipid Bilayers: A Molecular Dynamics Study. Biophys. J. 2007;93:4225-4236.

    Not in our library10.1529/biophysj.107.112565

  195. 195.

    Rautenbach M., Troskie A.M., Vosloo J.A. Antifungal peptides: To be or not to be membrane active. Biochimie. 2016;130:132-145.

    Not in our library10.1016/j.biochi.2016.05.013

  196. 196.

    Khan A., Ahmad A., Akhtar F., Yousuf S., Xess I., Khan L.A., Manzoor N. Induction of oxidative stress as a possible mechanism of the antifungal action of three phenylpropanoids. FEMS Yeast Res. 2010;11:114-122.

    Not in our library10.1111/j.1567-1364.2010.00697.x

  197. 197.

    Vargas-Sánchez R.D., Torrescano-Urrutia G.R., Acedo-Félix E., Carvajal-Millán E., González-Córdova A.F., Vallejo-Galland B., Torres-Llanez M.J., Sánchez-Escalante A. Antioxidant and Antimicrobial Activity of Commercial Propolis Extract in Beef Patties. J. Food Sci. 2014;79:C1499-C1504.

    Not in our library10.1111/1750-3841.12533

  198. 198.

    Reis M.P.C., Carvalho C.R.C., Andrade F.A., Fernandes O.F.L., Arruda W., Silva M.R.R. Fisetin as a promising antifungal agent againstCryptocococcus neoformansspecies complex. J. Appl. Microbiol. 2016;121:373-379.

    Not in our library10.1111/jam.13155

  199. 199.

    Li X.-C., Joshi A.S., ElSohly H.N., Khan S.I., Jacob M.R., Zhang Z., Khan I.A., Ferreira D., Walker L.A., Broedel S.E., et al. Fatty Acid Synthase Inhibitors from Plants: Isolation, Structure Elucidation, and SAR Studies. J. Nat. Prod. 2002;65:1909-1914.

    Not in our library10.1021/np020289t

  200. 200.

    Yun J., Lee H., Ko H.J., Woo E.-R., Lee D.G. Fungicidal effect of isoquercitrin via inducing membrane disturbance. Biochim. Biophys. Acta (BBA) Biomembr. 2015;1848:695-701.

    Not in our library10.1016/j.bbamem.2014.11.019

  201. 201.

    Moazeni M., Hedayati M.T., Nabili M., Mousavi S.J., Abdollahi Gohar A., Gholami S. Glabridin triggers over-expression of MCA1 and NUC1 genes in Candida glabrata: Is it an apoptosis inducer? J. Mycol. Méd. 2017;27:369-375.

    Not in our library10.1016/j.mycmed.2017.05.002

  202. 202.

    Sangalli-Leite F., Scorzoni L., Alves de Paula e Silva A.C., da Silva J.d.F., de Oliveira H.C., de Lacorte Singulani J., Gullo F.P., Moraes da Silva R., Regasini L.O., Siqueira da Silva D.H., et al. Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation. Int. J. Antimicrob. Agents. 2016;48:504-511.

    Not in our library10.1016/j.ijantimicag.2016.07.025

  203. 203.

    Yun D.G., Lee D.G. Silymarin exerts antifungal effects via membrane-targeted mode of action by increasing permeability and inducing oxidative stress. Biochim. Biophys. Acta (BBA) Biomembr. 2017;1859:467-474.

    Not in our library10.1016/j.bbamem.2017.01.009

  204. 204.

    Cao Y., Dai B., Wang Y., Huang S., Xu Y., Cao Y., Gao P., Zhu Z., Jiang Y. In vitro activity of baicalein against Candida albicans biofilms. Int. J. Antimicrob. Agents. 2008;32:73-77.

    Not in our library10.1016/j.ijantimicag.2008.01.026

  205. 205.

    Gibellini L., Bianchini E., De Biasi S., Nasi M., Cossarizza A., Pinti M. Natural Compounds Modulating Mitochondrial Functions. Evid. Based Complement. Alternat. Med. 2015;2015:1-13.

    Not in our library10.1155/2015/527209

  206. 206.

    Guntuku L., Naidu V.G.M., Ganesh Yerra V. Mitochondrial Dysfunction in Gliomas: Pharmacotherapeutic Potential of Natural Compounds. Curr. Neuropharmacol. 2016;14:567-583.

    Not in our library10.2174/1570159x14666160121115641

  207. 207.

    Canonico B., Candiracci M., Citterio B., Curci R., Squarzoni S., Mazzoni A., Papa S., Piatti E. Honey flavonoids inhibit Candida albicans morphogenesis by affecting DNA behavior and mitochondrial function. Future Microbiol. 2014;9:445-456.

    Not in our library10.2217/fmb.14.17

  208. 208.

    Ning Y., Ling J., Wu C.D. Synergistic effects of tea catechin epigallocatechin gallate and antimycotics against oral Candida species. Archiv. Oral Biol. 2015;60:1565-1570.

    Not in our library10.1016/j.archoralbio.2015.07.001

  209. 209.

    da Costa Cordeiro B.M.P., de Lima Santos N.D., Ferreira M.R.A., de Araújo L.C.C., Junior A.R.C., da Conceição Santos A.D., de Oliveira A.P., da Silva A.G., da Silva Falcão E.P., dos Santos Correia M.T., et al. Hexane extract from Spondias tuberosa (Anacardiaceae) leaves has antioxidant activity and is an anti-Candida agent by causing mitochondrial and lysosomal damages. BMC Compl. Altern. Med. 2018;18.

    Not in our library10.1186/s12906-018-2350-2

  210. 210.

    Reiners J.J. Suppression of cell cycle progression by flavonoids: dependence on the aryl hydrocarbon receptor. Carcinogenesis. 1999;20:1561-1566.

    Not in our library10.1093/carcin/20.8.1561

  211. 211.

    Manoharan R.K., Lee J.-H., Kim Y.-G., Lee J. Alizarin and Chrysazin Inhibit Biofilm and Hyphal Formation by Candida albicans. Front. Cell. Infect. Microbiol. 2017;7.

    Not in our library10.3389/fcimb.2017.00447

  212. 212.
    Effects of Magnolol and Honokiol on Adhesion, Yeast-Hyphal Transition, and Formation of Biofilm by Candida albicans · 2015
    No notice
  213. 213.

    Han B., Chen J., Yu Y.-q., Cao Y.-b., Jiang Y.-y. Antifungal activity ofRubus chingiiextract combined with fluconazole against fluconazole-resistant Candida albicans. Microbiol. Immunol. 2016;60:82-92.

    Not in our library10.1111/1348-0421.12357

  214. 214.
    A new Prenylated Flavonoid induces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells · 2017
    Not checked
  215. 215.

    Kang K., Fong W.-P., Tsang P.W.-K. Novel antifungal activity of purpurin against Candidaspeciesin vitro. Med. Mycol. 2010;48:904-911.

    Not in our library10.3109/13693781003739351

  216. 216.

    Li Y., Chang W., Zhang M., Li X., Jiao Y., Lou H. Synergistic and drug-resistant reversing effects of diorcinol D combined with fluconazole against Candida albicans. FEMS Yeast Res. 2015;15.

    Not in our library10.1093/femsyr/fov001

  217. 217.

    Sharma M., Manoharlal R., Shukla S., Puri N., Prasad T., Ambudkar S.V., Prasad R. Curcumin Modulates Efflux Mediated by Yeast ABC Multidrug Transporters and Is Synergistic with Antifungals. Antimicrob. Agents Chemother. 2009;53:3256-3265.

    Not in our library10.1128/aac.01497-08

  218. 218.

    Sharma M., Prasad R. The Quorum-Sensing Molecule Farnesol Is a Modulator of Drug Efflux Mediated by ABC Multidrug Transporters and Synergizes with Drugs in Candida albicans. Antimicrob. Agents Chemother. 2011;55:4834-4843.

    Not in our library10.1128/aac.00344-11

  219. 219.

    Yiğit D., Yiğit N., Mavi A. Antioxidant and antimicrobial activities of bitter and sweet apricot (Prunus armeniaca L.) kernels. Braz. J. Med. Biol. Res. 2009;42:346-352.

    Not in our library10.1590/s0100-879x2009000400006

  220. 220.

    Moudgal V., Sobel J. Antifungals to treat Candida albicans. Exp. Opin. Pharmacother. 2010;11:2037-2048.

    Not in our library10.1517/14656566.2010.493875

  221. 221.

    Saito H., Tamura M., Imai K., Ishigami T., Ochiai K. Catechin inhibits Candida albicans dimorphism by disrupting Cek1 phosphorylation and cAMP synthesis. Microb. Pathogen. 2013;56:16-20.

    Not in our library10.1016/j.micpath.2013.01.002

  222. 222.

    Cassetta A., Stojan J., Krastanova I., Kristan K., Brunskole Švegelj M., Lamba D., Lanišnik Rižner T. Structural basis for inhibition of 17β-hydroxysteroid dehydrogenases by phytoestrogens: The case of fungal 17β-HSDcl. J. Steroid Biochem. Mol. Biol. 2017;171:80-93.

    Not in our library10.1016/j.jsbmb.2017.02.020

  223. 223.

    Qian S., Fan W., Qian P., Zhang D., Wei Y., Chen H., Li X. Apigenin Restricts FMDV Infection and Inhibits Viral IRES Driven Translational Activity. Viruses. 2015;7:1613-1626.

    Not in our library10.3390/v7041613

  224. 224.

    Mukherjee P.K., Sheehan D.J., Hitchcock C.A., Ghannoum M.A. Combination Treatment of Invasive Fungal Infections. Clin.Microbiol. Rev. 2005;18:163-194.

    Not in our library10.1128/cmr.18.1.163-194.2005

  225. 225.

    Hemaiswarya S., Kruthiventi A.K., Doble M. Synergism between natural products and antibiotics against infectious diseases. Phytomedicine. 2008;15:639-652.

    Not in our library10.1016/j.phymed.2008.06.008

  226. 226.

    Wagner H., Ulrich-Merzenich G. Synergy research: Approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009;16:97-110.

    Not in our library10.1016/j.phymed.2008.12.018

  227. 227.

    Pippi B., Lana A.J.D., Moraes R.C., Güez C.M., Machado M., de Oliveira L.F.S., Lino von Poser G., Fuentefria A.M. In vitroevaluation of the acquisition of resistance, antifungal activity and synergism of Brazilian red propolis with antifungal drugs onCandidaspp. J. Appl. Microbiol. 2015;118:839-850.

    Not in our library10.1111/jam.12746

  228. 228.

    Moraes R.C., Carvalho A.R., Lana A.J.D., Kaiser S., Pippi B., Fuentefria A.M., Ortega G.G. In vitrosynergism of a water insoluble fraction ofUncaria tomentosacombined with fluconazole and terbinafine against resistant non-Candida albicans isolates. Pharma. Biol. 2016;55:406-415.

    Not in our library10.1080/13880209.2016.1242631

  229. 229.

    Danielli L.J., Pippi B., Soares K.D., Duarte J.A., Maciel A.J., Machado M.M., Oliveira L.F.S., Bordignon S.A.L., Fuentefria A.M., Apel M.A. Chemosensitization of filamentous fungi to antifungal agents using Nectandra Rol. ex Rottb. species essential oils. Ind. Crops Prod. 2017;102:7-15.

    Not in our library10.1016/j.indcrop.2017.03.013

  230. 230.

    Wang Y.-H., Dong H.-H., Zhao F., Wang J., Yan F., Jiang Y.-Y., Jin Y.-S. The synthesis and synergistic antifungal effects of chalcones against drug resistant Candida albicans. Bioorg. Med. Chem. Lett. 2016;26:3098-3102.

    Not in our library10.1016/j.bmcl.2016.05.013

  231. 231.

    Li D.-D., Chai D., Huang X.-W., Guan S.-X., Du J., Zhang H.-Y., Sun Y., Jiang Y.-Y. PotentIn VitroSynergism of Fluconazole and Osthole against Fluconazole-Resistant Candida albicans. Antimicrob. Agents Chemother. 2017;61.

    Not in our library10.1128/aac.00436-17

  232. 232.

    Ahmad A., Wani M.Y., Khan A., Manzoor N., Molepo J. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans. PLoS ONE. 2015;10:e0145053.

    Not in our library10.1371/journal.pone.0145053

  233. 233.

    Fatima A., Gupta V.K., Luqman S., Negi A.S., Kumar J.K., Shanker K., Saikia D., Srivastava S., Darokar M.P., Khanuja S.P.S. Antifungal activity ofGlycyrrhiza glabraextracts and its active constituent glabridin. Phytother. Res. 2009;23:1190-1193.

    Not in our library10.1002/ptr.2726

  234. 234.

    Gao M., Wang H., Zhu L. Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida albicans in In Vitro and In Vivo Antifungal Managements of Vulvovaginal Candidiasis. Cell. Physiol. Biochem. 2016;40:727-742.

    Not in our library10.1159/000453134

Cited by papers we hold 4

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.