A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata. var. villosa resulted in the isolation of 23 withanolide derivatives, including one novel 13,20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2-4). Architecturally, physalinin A (1) represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety. The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), infrared (IR) spectroscopy, and quantum chemical calculations to confirm structural assignments. The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines (HEL, HCT-116, Colo320DM, and MDA-MB-231). Among them, eight derivatives (2, 5-8, 14, 15, and 23) exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values of 0.18 ± 0.03 to 17.02 ± 0.21 μmol·L^-1. Structure-activity relationship (SAR) analysis suggested that the presence of an epoxide ring enhances anticancer activity, potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression. These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.
Withanolides/isolation & purification* ; Physalis/chemistry* ; Humans ; Molecular Structure ; Cell Line, Tumor ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Cell Proliferation/drug effects* ; Plant Leaves/chemistry* ; Plant Extracts/pharmacology*

Saccharomyces cerevisiae/genetics* ; Ergosterol ; Fermentation

Sterols, a class of cyclopentane poly-hydrophenanthrene derivatives, are the predominant membrane constituent of eukaryotes. These substances have a variety of biological activities and have been widely used in food and pharmaceutical industries. The presence of endogenous ergosterol biosynthetic pathway in Saccharomyces cerevisiae cells make it an ideal chassis for the de novo synthesis of sterol and its derivatives. Most recently, the rational modification of organelles provides a novel strategy for the directed transportation and storage of target products and the ultimate enhanced product synthesis. This review summarizes the phenotypic responses of S. cerevisiae cells upon different physiological stimulations and the underlying molecular mechanisms. Reinforcement of sterol production through directed storage, transportation, and excretion of sterols offers a novel strategy for breaking the limitation of de novo biosynthesis of sterols in yeast.
Ergosterol ; Phytosterols ; Saccharomyces cerevisiae ; Sterols

Withania somnifera, also known as Indian ginseng, is an important traditional medicine in the Ayurvedic medical system of India, which has a significant effect of adaptation. Modern studies have shown that the main chemical components of W. somnifera are withanolides, which have antioxidant, anti-tumor, enhancing immunity, cardiovascular protection, neuroprotection, anti-stress, anti-stress reaction and hypoglycemic activities. Studies on human, animal, mutagenesis, genotoxicity, reproductive toxicity and drug interaction showed that W. somnifera had good safety. Clinical trials have proved that W. somnifera is effective in treating a variety of human diseases. As a famous traditional medicine and modern dietary supplement, it has a high reputation and market in the international health product market, but in China, there is little scientific research, market development, product introduction and application. In this paper, the traditional application, chemical composition, pharmacological activity, safety evaluation and clinical study of the plant were introduced, so as to increase the understanding of the dual use of the plant, and to provide reference for the future introduction of the product, the service to the health of the Chinese people and the promotion of the "double cycle" of the trade of health products between China and the international community.
Animals ; China ; Humans ; Neoplasms ; Plant Extracts ; Withania ; Withanolides

Online gradient extraction-high performance liquid chromatography( HPLC) method was developed for simultaneous determination of high and low polar components in Cordyceps. The sample powder of Cordyceps was uniformly mixed with diatomaceous earth,packed into extraction tank,and installed into the HPLC system. Online gradient extraction was conducted with mobile phase at 70 ℃. The separation was performed on Zorbax SB-AQ( 4. 6 mm×150 mm,5 μm) column with 0. 1% formic acid solution-methanol as the mobile phase for gradient elution at 1. 0 mL·min~(-1). The column temperature was 30 ℃,and detection wavelength was set at 260 nm. The results showed that the high and low polar components in Cordyceps could be simultaneously extracted and separated by the developed method. Meanwhile,six high polar compounds( uracil,uridine,thymine,inosine,guanosine and adenosine) and one low polar compound( ergosterol) were identified by comparison with the reference peaks. The established method is rapid,stable and environment friendly,which is helpful to improve the quality evaluation level for Cordyceps.
Chromatography, High Pressure Liquid ; Cordyceps ; chemistry ; Ergosterol ; analysis ; Nucleosides ; analysis

Withaminimas A-F (1-6), six new withaphysalin-type withanolides were isolated from the aerial parts of Physalis minima L.. The structures of these compounds were elucidated through a variety of spectroscopic techniques including HR-MS, NMR, and ECD. Compound 1 belongs to rare 18-norwithanolides, and 2-3 were 13/14-secowithanolides. According to the traditional usage of P. minima, inhibitory effects on nitric oxide (NO) production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated, and compounds 1-4 exhibited significant inhibitory effects with IC values among 3.91-18.46 μmol·L.
Animals ; Anti-Inflammatory Agents ; chemistry ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Lipopolysaccharides ; pharmacology ; Macrophages ; drug effects ; immunology ; Mice ; Molecular Structure ; Physalis ; chemistry ; RAW 264.7 Cells ; Structure-Activity Relationship ; Withanolides ; chemistry ; pharmacology

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.
ATP-Binding Cassette Transporters ; genetics ; metabolism ; Antifungal Agents ; chemistry ; metabolism ; pharmacology ; Azoles ; pharmacology ; Biosynthetic Pathways ; drug effects ; genetics ; Candida albicans ; chemistry ; drug effects ; metabolism ; Cell Membrane ; chemistry ; metabolism ; Coculture Techniques ; Drug Resistance, Fungal ; drug effects ; Ergosterol ; metabolism ; Fungal Proteins ; genetics ; metabolism ; Lipids ; chemistry ; Molecular Structure ; Permeability ; Phenyl Ethers ; chemistry ; metabolism ; pharmacology ; Sterols ; chemistry ; metabolism ; Stilbenes ; chemistry ; metabolism ; pharmacology ; Triterpenes ; chemistry ; metabolism ; pharmacology

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.
Anti-Infective Agents ; Betaine ; Cell Membrane ; Cryptococcus ; Cryptococcus neoformans ; Dandruff ; Ergosterol ; Fungi ; Gene Deletion ; Genetic Testing ; Genomics ; Humans ; Malassezia ; Methods ; Skin ; Transcriptome

BACKGROUND: In our preliminary study, we screened for their potential to inhibit 5α-reductase, and Melandrium firmum (MF) extract showed the most potent activity as confirmed by high-performance liquid chromatography (HPLC). OBJECTIVE: This study aimed to investigate the effects of MF extract on 5α-reductase activity and its mechanisms of action in the prevention or treatment of androgenetic alopecia. METHODS: HPLC was used to measure 5α-reductase activity. The hair growth-promoting effect of MF extract in the shaved dorsal skin of C57BL/6J mice was studied for 30 days. Hair follicles were examined by histological examination. Protein and mRNA levels of growth factors involved in hair growth were determined by western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) and qPCR, respectively. Cell proliferation was measured by (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. RESULTS: MF extract at 0.5 mg/ml showed 43.5% inhibition of 5α-reductase. MF extract promoted hair growth by inducing anagen phase reflected by skin color, hair density, and the number and size of hair follicles. It not only reduces the expression of transforming growth factor-beta 1 (TGF-β1) and Dickkopf-1 (DKK-1), but also markedly upregulated insulin-like growth factor 1 and keratinocyte growth factor in the dorsal dermal tissue. Ursolic acid, ecdcysteron, and ergosterol peroxide were identified as active constituents by activity-guided fractionation to inhibit 5α-reductase. They decreased the gene expression of TGF-β1 and DKK-1 in human hair dermal papilla cells. CONCLUSION: In summary, these finding indicate that MF extract might be a good drug candidate for hair growth promotion.
Alopecia ; Animals ; Blotting, Western ; Cell Proliferation ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Ergosterol ; Fibroblast Growth Factor 7 ; Gene Expression ; Hair Follicle ; Hair ; Humans ; Intercellular Signaling Peptides and Proteins ; Mice ; RNA, Messenger ; Skin ; Skin Pigmentation

Chemical investigation of the ethyl acetate extract of Gibberella moniliformis JS1055 endophytic fungus derived from a halophyte, Vitex rotundifolia, led to the isolation of nine compounds including 7-butyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (1), 7-butyl-6,8-dihydroxy-3(R)-pentylisochroman-1-one (2), 7-butyl-6,8-dihydroxy-3(R)-pentylisochroman-1-one (3), 5α,8α-epidioxyergosta-6,9(11),22-trien-3-ol (4), ergosterol peroxide (5), tetradecanoic acid (6), 8-O-methylfusarubin (7), nicotinic acid (8) and adenosine (9). They were identified by extensive spectroscopic data analysis including 1D, 2D (¹H-¹H COSY, HSQC, HMBC) NMR, and ESIMS. All the isolates (1
Adenosine ; Ergosterol ; Fungi ; Gibberella ; Moniliformis ; Myristic Acid ; Niacin ; Salt-Tolerant Plants ; Statistics as Topic ; Vitex