Antifungal Activity of Ellagic Acid In Vitro and In Vivo

Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti‐inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38‐A and M27‐A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33 µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0 µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC = 18.75 µg/ml). Studies on the mechanism of action using an HPLC‐based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14α‐demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0 mg/cm²) significantly enhanced the cure rate in a guinea‐pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent. Copyright © 2015 John Wiley & Sons, Ltd.     

Composition and antimicrobial activity of Achillea clavennae L. essential oil

The volatile constituents of Achillea clavennae L. (Asteraceae), rare plant of Europe, have been analysed using GC/MS. Twenty- five components making up 81.6% of the oil were characterized with camphor (29.5%), myrcene (5.5%), 1,8-cineole (5.3%), beta-caryophyllene (5.1%) and linalool (4.9%) being the major constituents. The essential oil was evaluated for antibacterial and antifungal activities. The screening of the antimicrobial activity of essential oil was conducted by a disc diffusion test against Gram-positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis), Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis) and fungal organisms (Aspergillus niger, Aspergillus fumigatus, Candida albicans). The activity was more pronounced against Gram-negative and fungal organisms than against Gram-positive bacteria. A. clavennae oil was found to possess antimicrobial activity against Klebsiella pneumoniae, Pseudomonas aeruginosa and all fungal organisms.     

植物挥发油成分分析及抗假丝酵母菌活性的研究进展

侵袭性真菌感染是造成目前临床真菌感染的发病率和死亡率逐年上升的重要原因,其中以假丝酵母菌感染尤为严重。近年来主要的抗真菌药物均发现一定程度的毒副作用,由于临床上抗真菌药物的广泛使用造成耐药性日趋严重,因此迫切需要寻找安全有效的新型抗真菌药物。天然植物成分尤其是植物挥发油多具有抗菌消炎、解热镇痛、抗病毒等多种生物活性,其凭借来源广、低毒、广谱、作用途径多样化等优点成为了抗真菌药物研究开发的热点。植物挥发油的抗假丝酵母菌活性与其中成分及含量紧密相关。该文综述了近年来不同科属的植物挥发油的成分分析及抗假丝酵母菌活性研究,系统归纳总结了唇形科、樟科、桃金娘科等植物挥发油的提取、分析及抗假丝酵母菌活性的研究方法和结果,并对目前的研究方向进行了展望,以期为今后植物挥发油的成分分析和活性研究提供方向,为植物挥发油开发成为新的抗假丝酵母菌药物奠定理论基础,为真菌耐药问题造成的临床难题提供新的解决方案。     

黄芩及其有效成分抗菌作用新进展

近年来,随着免疫功能下降人群的不断增多,细菌/真菌感染率大幅上升,伴随耐药现象的出现,临床可供选择的抗菌药物越来越有限。黄芩Scutellaria baicalensis Georgi为唇形科黄芩属多年生草本,黄芩及其有效成分具有抗炎、抗氧化、抗肿瘤和抗菌等多重药理作用,尤其显著的抗细菌抗真菌活性对于治疗日渐增多的耐药性细菌/真菌感染有重要意义。该文结合国内外对黄芩及其有效成分的研究,对近年来其抗菌作用及机制研究进展作一综述。     

Antifungal activity of medicinal plant extracts; preliminary screening studies

ETHNOPHARMACOLOGICAL RELEVANCE: In the setting of HIV and organ transplantation, opportunistic fungal infections have become a common cause of morbidity and mortality. Thus antifungal therapy is playing a greater role in health care. Traditional plants are a valuable source of novel antifungals. AIM OF THE STUDY: To assess in vitro antifungal activity of aqueous plant extracts. The minimum inhibitory concentrations were determined for each extract in the setting of human pathogenic fungal isolates. MATERIALS AND METHODS: Plants were harvested and identification verified. Aqueous extracts were obtained and antifungal susceptibilities determined using serial dilutional extracts with a standardized microdilution broth methodology. Twenty-three fungal isolates were cultured and exposed to the plant extracts. Five known antifungals were used as positive controls. Results were read at 48 and 72 h. RESULTS: Of the 14 plants analyzed, Fragaria virginiana Duchesne, Epilobium angustifolium L. and Potentilla simplex Michx. demonstrated strong antifungal potential overall. Fragaria virginiana had some degree of activity against all of the fungal pathogens. Alnus viridis DC., Betula alleghaniensis Britt. and Solidago gigantea Ait. also demonstrated a significant degree of activity against many of the yeast isolates. CONCLUSION: Fragaria virginiana, Epilobium angustifolium and Potentilla simplex demonstrate promising antifungal potential.     

乌蕨的研究进展

乌蕨为鳞始蕨科植物乌蕨的全草和根茎,是一种民间中草药,素有“万能解毒药”之美称,其具有抗菌、抗炎、保肝、抗肿瘤等生物活性作用。从品种鉴别、化学成分、含量测定、药理作用等方面就乌蕨近年来的研究进展进行综述,以期为其深入研究与开发提供参考。     

Antifungal Activity of Gallic Acid In Vitro and In Vivo

Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38‐A and M27‐A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC‐based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α‐demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.     

Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria

Ginger (Zingiber officinale Roscoe) has been used widely as a food spice and an herbal medicine. In particular, its gingerol-related components have been reported to possess antimicrobial and antifungal properties, as well as several pharmaceutical properties. However, the effective ginger constituents that inhibit the growth of oral bacteria associated with periodontitis in the human oral cavity have not been elucidated. This study revealed that the ethanol and n-hexane extracts of ginger exhibited antibacterial activities against three anaerobic Gram-negative bacteria, Porphyromonas gingivalis ATCC 53978, Porphyromonas endodontalis ATCC 35406 and Prevotella intermedia ATCC 25611, causing periodontal diseases. Thereafter, five ginger constituents were isolated by a preparative high-performance liquid chromatographic method from the active silica-gel column chromatography fractions, elucidated their structures by nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry and their antibacterial activity evaluated. In conclusion, two highly alkylated gingerols, [10]-gingerol and [12]-gingerol effectively inhibited the growth of these oral pathogens at a minimum inhibitory concentration (MIC) range of 6-30 microg/mL. These ginger compounds also killed the oral pathogens at a minimum bactericidal concentration (MBC) range of 4-20 microg/mL, but not the other ginger compounds 5-acetoxy-[6]-gingerol, 3,5-diacetoxy-[6]-gingerdiol and galanolactone.     

Accelerating the discovery of biologically active small molecules using a high-throughput yeast halo assay

The budding yeast Saccharomyces cerevisiae, a powerful model system for the study of basic eukaryotic cell biology, has been used increasingly as a screening tool for the identification of bioactive small molecules. We have developed a novel yeast toxicity screen that is easily automated and compatible with high-throughput screening robotics. The new screen is quantitative and allows inhibitory potencies to be determined, since the diffusion of the sample provides a concentration gradient and a corresponding toxicity halo. The efficacy of this new screen was illustrated by testing materials including 3104 compounds from the NCI libraries, 167 marine sponge crude extracts, and 149 crude marine-derived fungal extracts. There were 46 active compounds among the NCI set. One very active extract was selected for bioactivity-guided fractionation, resulting in the identification of crambescidin 800 as a potent antifungal agent.     

土荆皮抗真菌化学成分研究

目的对土荆皮Pseudolaricis Cortex抗真菌活性部位进行化学成分研究。方法土荆皮粗粉以95%乙醇回流提取,所得浸膏采用溶剂法分为不同提取部位,体外抗真菌活性测试显示其醋酸乙酯部位对白色念珠菌具有显著的抑制作用。采用硅胶、Sephadex LH-20、制备高效液相色谱对土荆皮醋酸乙酯部位进行分离纯化,并通过波谱数据分析对化合物进行结构鉴定。结果从土荆皮醋酸乙酯部位分离得到5个化合物,分别鉴定为土荆皮酸B(1)、土荆皮酸C(2)、香草酸(3)、香草酸-4-O-β-D-阿洛糖苷(4)、17-羟基土荆皮酸B(5)。结论化合物5为一新化合物,命名为土荆皮酸I;化合物4为首次从该植物中分离得到。体外抗真菌活性测试显示,化合物1对白色念珠菌生长具有显著的抑制作用,化合物2和5仅显示微弱的抑菌活性。     

Capisterones A and B, which enhance fluconazole activity in Saccharomyces cerevisiae, from the marine green alga Penicillus capitatus

A whole-cell-based assay using Saccharomyces cerevisiae strains that overexpress Candida albicans CDR1 and MDR1 efflux pumps has been employed to screen natural product extracts for reversal of fluconazole resistance. The tropical green alga Penicillus capitatus was selected for bioassay-guided isolation, leading to the identification of capisterones A and B (1 and 2), which were recently isolated from this alga and shown to possess antifungal activity against the marine pathogen Lindra thallasiae. Current work has assigned their absolute configurations using electronic circular dichroism and determined their preferred conformations in solution based on detailed NOE analysis. Compounds 1 and 2 significantly enhanced fluconazole activity in S. cerevisiae, but did not show inherent antifungal activity when tested against several opportunistic pathogens or cytotoxicity to several human cancer and noncancerous cell lines (up to 35 microM). These compounds may have a potential for combination therapy of fungal infections caused by clinically relevant azole-resistant strains.     

Artocarpus: A review of its traditional uses,phytochemistry and pharmacology

The genus Artocarpus (Moraceae) comprises about 50 species of evergreen and deciduous trees. Economically, the genus is of appreciable importance as a source of edible fruit, yield fairly good timber and is widely used in folk medicines. The aim of the present review is to present comprehensive information of the chemical constituents, biological and pharmacological research on Artocarpus which will be presented and critically evaluated. The close connection between traditional and modern sources for ethnopharmacological uses of Artocarpus species, especially for treatment against inflammation, malarial fever, diarrhoea, diabetes and tapeworm infection. Artocarpus species are rich in phenolic compounds including flavonoids, stilbenoids, arylbenzofurons and Jacalin, a lectin. The extracts and metabolites of Artocarpus particularly those from leaves, bark, stem and fruit possess several useful bioactive compounds and recently additional data are available on exploitation of these compounds in the various biological activities including antibacterial, antitubercular, antiviral, antifungal, antiplatelet, antiarthritic, tyrosinase inhibitory and cytotoxicity. Several pharmacological studies of the natural products from Artocarpus have conclusively established their mode of action in treatment of various diseases and other health benefits. Jacalin, a lectin present in seeds of this plant has a wide range of activities. Strong interdisciplinary programmes that incorporate conventional and new technologies will be critical for the future development of Artocarpus as a promising source of medicinal products. In the present review, attempts on the important findings have been made on identification; synthesis and bioactivity of metabolites present in Artocarpus which have been highlighted along with the current trends in research on Artocarpus.     

Anti‐Dermatophyte and Anti‐Malassezia Activity of Extracts Rich in Polymeric Flavan‐3‐ols Obtained from Vitis vinifera Seeds

Several human skin diseases are associated with fungi as dermatophytes and Malassezia. Skin mycoses are increasing and new alternatives to conventional treatments with improved efficacy and/or safety profiles are desirable. For the first time, the anti‐dermatophytes and the anti‐Malassezia activities of Vitis vinifera seed extracts obtained from different table and wine cultivars have been evaluated. Geometric minimal inhibitory concentration ranged from 20 to 97 µg/mL for dermatophytes and from 32 to 161 µg/mL for Malassezia furfur . Dried grape seed extracts analyzed by HPLC/DAD/ESI/MS showed different quali–quantitative compositions in terms of monomeric and polymeric flavan‐3‐ols. The minimal inhibitory concentrations for Trichophyton mentagrophytes and for M. furfur were inversely correlated with the amount of the polymeric fraction (r = ?0.7639 and r = ?0.7228, respectively). Differently, the antifungal activity against T. mentagrophytes was not correlated to the content of flavan‐3‐ol monomers (r = 0.2920) and only weakly correlated for M. furfur (r = ?0.53604). These results suggest that extracts rich in polymeric flavan‐3‐ols, recovered from V. vinifera seeds, could be used for the treatment of skin fungal infections. Copyright © 2016 John Wiley & Sons, Ltd.     

千里光属植物的化学成分研究进展

查阅国内外文献33篇,综述近年来有关千里光属植物在化学成分及其特征成分吡咯里西啶类生物碱的提取、分离和鉴定方法等方面的研究进展。千里光属植物由于所含的吡咯里西啶类生物碱具有肝毒作用,故在对该属植物进行开发研究新药时,安全性评价应放在首位。今后在化学成分、构效关系、药理、临床和质量控制等方面均需进一步深入研究并加以充分开发和利用。     

Traditional medical uses of Drimia species in terms of phytochemistry,pharmacology and toxicology

Drimia genus includes plants that used from ancient time for various ailments such as dropsy, respiratory ailment, bone and joint complications,skin disorders, epilepsy and cancer. Toxic properties of some Drimia species also were noted by ancient scientists and these plants have been traditionally used for rat control. Bufadienolides have been identified as the main constituents in the genus of Drimia. Phenolics, sterols, protein and some of other phytochemicals have been also isolated from these plants. Pharmacological and clinical studies have strongly approved their effect on cardiovascular system. Extracts and compounds isolated from Drimia species showed biological activities such as antibacterial, antifungal, antiviral, antioxidant, anti-inflammatory and insecticidal effects throughseveral in vivo and in vitro studies. Moreover, cytotoxic and antitumor activities which may be related to bufadienolide content of these plants have been considered by many researchers. Traditional therapeutic values of these plants for treating respiratory and rheumatic ailments as well as skin disorders are needed to be validated through more researches. Toxic effects of these plants and isolated compounds have been investigated through several in vivo studies. Drimia plants and their isolated compounds have narrow therapeutic index, so patients should be prohibited from applying these plants without medical supervision and should be informed about the main intoxication symptoms before starting treatment. Moreover, interaction of Drimia plants with other constituents of traditional herbal mixtures as well as chemical and biological modalities for reducing toxicity of bufadienolide compounds can be subjected for future studies.     

New bioactive peroxides from marine sponges of the family plakiniidae

In our continuing program to identify compounds with antifungal properties, the ethanol extracts of two sponges of the family Plakinidae were found to inhibit the growth of the fungal pathogens Candida albicans and Aspergillus fumigatus. From these organisms three new compounds and five known compounds have been identified. A new 1,2-dioxane ring peroxide acid, 1, has been isolated from the sponge Plakortis halichondrioides along with five known compounds. Two new 1,2-dioxolane peroxide acids, 3 and 4, have been isolated from the sponge Plakinastrella onkodes. The structures were established by interpretation of spectral data. The three new compounds exhibit moderate activity against the fungal pathogen C. albicans with MICs of 5, 1.6, and 1.6 microg/mL respectively, for 1, 3, and 4. Compound 1 also showed in vitro inhibition of the fungal pathogen A. fumigatus with an IC(90) value of 5.6 microg/mL.     

Oxygenated analogues of gorgosterol and ergosterol from the soft coral Capnella lacertiliensis

From the dichloromethane solubles of Capnella lacertiliensis five new sterols were isolated that are highly functionalized with oxygen-containing substituents: 12beta-acetoxy-7alpha-hydroxygorgosterol (1), 12beta-acetoxy-7alpha,19-dihydroxygorgosterol (2), 12beta-acetoxyergost-5-ene-3beta,23-diol (4), 12beta-acetoxyergost-5-ene-3beta,11beta,16-triol (5), and 11beta-acetoxyergost-5-ene-3beta,12beta,16-triol (6). The structures of all compounds were deduced from interpretation of their spectroscopic data, mainly 1D and 2D NMR spectra and HREIMS. Biological activities of the isolates were assessed, and all were found to be weakly antifungal. Compounds 5 and 6 were also found to have weak tyrosine kinase p56(lck)() (TK) inhibitory activity at the 200 microgram/mL level.     

植物精油抑制真菌及真菌毒素的研究进展

真菌及真菌毒素极易污染食品、果蔬、中药材、农产品等基质使其霉败变质,这不仅造成巨大的资源浪费和经济损失,还会带来潜在的安全隐患,严重威胁人们的身体健康和生命安全,这一问题已引起全球性的广泛关注。研究者们竭力探索科学有效的策略和措施抑制或防止诸多基质的真菌和真菌毒素污染。化学合成抑菌剂备受欢迎,但是同时存在残毒、公害、抗性等问题,已被禁止使用。植物精油因具有抑菌活性强、抑菌谱广、高挥发性、生物降解性良好、在基质中低残留、无毒或低毒对人体相对安全、对环境友好等优点,可作为潜在的新型绿色防霉抑菌剂。针对植物精油的分布、抑制真菌生长及真菌毒素合成的作用、抑菌广谱性、安全性评价、抑菌机制进行综述,以期为研发天然、绿色抗真菌剂提供科学参考。     

Known and novel terpenes from Buddleja globosa displaying selective antifungal activity against dermatophytes

Lipophilic extracts of the stembark of Buddleja globosa were found to have antifungal activity at 125 microg/mL against three dermatophytic fungal species but had no activity at 1000 microg/mL against four other fungal species or two yeast species. Bioassay-guided fractionation of Si gel column eluates using the sensitive fungal species resulted in active fractions from which were isolated five compounds that were characterized by spectroscopic methods as one novel and four known compounds. The known compounds were the diterpene buddlejone (1), the bisditerpene maytenone, and the two sesquiterpenes buddledin A and buddledin B, while the novel compound was characterized as the diterpene deoxybuddlejone (2). The minimum inhibitory concentration of all the compounds was determined against all the microorganisms under test, and buddledins A and B were shown to exhibit the greatest antifungal activity, with values of 43 microM and 51 microM, respectively, against the sensitive fungi Trichophyton rubrum, Tricophyton interdigitale, and Epidermophyton floccosum.     

Morphological changes of the filamentous fungus Mucor mucedo and inhibition of chitin synthase activity induced by anethole

trans‐Anethole (anethole), a major component of anise oil, has a broad antimicrobial spectrum with antimicrobial activity relatively weaker than those of well‐known antibiotics, and significantly enhances the antifungal activity of polygodial and dodecanol against the baker's yeast Saccharomyces cerevisiae and human pathogenic yeast Candida albicans. However, the antifungal mechanism of anethole is unresolved. Anethole demonstrated antifungal activity against the filamentous fungus, Mucor mucedo IFO 7684, accompanied by hyphal morphological changes such as swollen hyphae at the tips. Its minimum growth inhibitory concentration was 0.625 mm . A hyperosmotic condition (1.2 m sorbitol) restricted the induction of morphological changes, while hypoosmotic treatment (distilled water) induced bursting of hyphal tips and leakage of cytoplasmic constituents. Furthermore, anethole dose‐dependently inhibited chitin synthase (CHS) activity in permeabilized hyphae in an uncompetitive manner. These results suggest that the morphological changes of M. mucedo could be explained by the fragility of cell walls caused by CHS inhibition. Copyright © 2011 John Wiley & Sons, Ltd.