Antimicrobial Dihydroflavonols and Isoflavans Isolated from the Root Bark of Dalbergia gloveri.

Three new dihydroflavonols, gloverinols A-C (1-3), a new flavon-3-ol, gloverinol D (4), two new isoflavans, gloveriflavan A (5) and B (6), and seven known compounds were isolated from the root bark of Dalbergia gloveri. The structures of the isolates were elucidated by using NMR, ECD, and HRESIMS data analyses. Among the isolated compounds, gloverinol B (2), gloveriflavan B (6), and 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4-hydroxyphenyl)-1-propanone (10) were the most active against Staphylococcus aureus, with MIC values of 9.2, 18.4, and 14.2 µM, respectively.

Alpinumisoflavone ameliorates H2O2-induced intracellular damages through SIRT1 activation in pre-eclampsia cell models.

Pre-eclampsia (PE) is classified as pregnancy-specific hypertensive disease and responsible for severe fetal and maternal morbidity and mortality, which influenced an approximate 3 âˆ¼ 8 % of all pregnancies in both developed and developing countries. However, the exact pathological mechanism underlying PE has not been elucidated and it is urgent to find innovate pharmacotherapeutic agents for PE. Recent studies have reported that a crucial part of the etiology of PE is played by placental oxidative stress. Therefore, to treat PE, a possible treatment approach is to mitigate the placental oxidative stress. Alpinumisoflavone (AIF) is a prenylated isoflavonoid originated in mandarin melon berry called Cudrania tricuspidate, and is well known for its versatile pharmacotherapeutic properties, including anti-fibrotic, anti-inflammatory, anti-tumor, and antioxidant activity. However, protective property of AIF on extravillous trophoblast (EVT) under placental oxidative stress has not been elucidated yet. Therefore, we assessed stimulatory effects of AIF on the viability, invasion, migration, mitochondria function in the representative EVT cell line, HTR-8/SVneo cell. Moreover, protective activities of AIF from H2O2 were confirmed, in terms of reduction in apoptosis, ROS production, and depolarization of mitochondrial membrane. Furthermore, we confirmed the direct interaction of AIF with sirtuin1 (SIRT1) using molecular docking analysis and SIRT1-mediated signaling pathways associated with the protective effects of AIF on HTR-8/SVneo cells under oxidative stress. Finally, beneficial efficacy of AIF against oxidative stress was further confirmed using BeWo cells, syncytiotrophoblast cell lines. These results suggest that AIF may ameliorate H2O2-induced intracellular damages through SIRT1 activation in human trophoblast cells.

The flavonoids from the fruits of Psoralea corylifolia and their potential in inhibiting metastasis of human non-small cell lung cancers.

Nineteen flavonoids were isolated from the fruits of Psoralea corylifolia L., including a novel flavanol (3) and three novel isoflavones (12-14). Their chemical structures were unequivocally determined through comprehensive spectral data analysis. The anti-proliferative effect of the isolated flavonoids was assessed in vitro using the MTT assay. Molecular docking and ELISA were employed to determine the inhibitory effects of the active compounds on ALK5. Isobavachalcone was found to inhibit TGF-ß1 induced EMT in A549 cells by Wound healing assay and Transwell chamber assay. Immunofluorescence assay and Western blot assay showed that IBC could inhibit cytoskeleton rearrangement, reduce the phosphorylation of ALK5, ERK, and Smad, down-regulate Snail expression, and up-regulate E-cadherin expression in TGF-ß1 induced A549 cells, thereby exerting the potential inhibitory effects on epithelial-mesenchymal transition (EMT) process in A549 cells. The findings presented herein establish a fundamental basis for investigating the anti-proliferative and anti-metastatic properties of psoralen flavonoids in human non-small cell lung cancer.

Pharmacological properties of extracts and prenylated isoflavonoids from the fruits of Osage orange (Maclura pomifera (Raf.) C.K.Schneid.).

Osage orange trees (Maclura pomifera (Raf.) C.K.Schneid.) are distributed worldwide, particularly in south-east states of the USA. They produce large quantities of strong yellow fruits, bigger than oranges, but these fruits are inedible, with an acid milky juice which is little consumed by birds and insects. Extracts prepared from Osage orange fruits (hedge apple) have revealed a range of pharmacological properties of interest in human and veterinary medicine. In addition, Osage orange extracts can be used in agriculture and aquaculture, and as dyeing agent for the textile industry. Extracts contain potent antioxidant compounds, notably the isoflavonoids pomiferin and auriculasin, together with other terpenoids and flavonoids. The structural characteristics and pharmacological properties of the major prenylated isoflavones isolated from M. pomifera are discussed here, with a focus on the two phenolic compounds osajin and warangalone, and the two catechol analogues pomiferin and auriculasin. The mechanisms at the origin of their potent antioxidant and anti-inflammatory effects are presented, notably inhibition of xanthine oxidase, phosphodiesterase 5A and kinases such as RKS2 and kRAS. Osajin and auriculasin display marked anticancer properties, owing to their ability to inhibit tumor cell proliferation, migration and tumor angiogenesis. Different molecular mechanisms are discussed, including osajin­copper complexation and binding to quadruplex DNA. An overview of the mechanism of action of the prenylated isoflavones from Osage orange is presented, with the objective to promote their knowledge and to raise opportunities to better exploit the fruits of Osage orange, abundant but largely neglected at present.

Antimicrobial isoflavans and other metabolites of Dalea nana.

The phytochemical investigation of extracts from Dalea nana roots and aerial parts led to the isolation of thirteen phenolic compounds. Three previously undescribed isoflavans, named verdeans A-C (1, 3, and 7), were characterized. Two additional isoflavans (2 and 5) were previously undescribed enantiomers of known compounds. A previously undescribed isoflavone (verdean D, 10) was found, and the known specialized metabolites, isoflavans 4, 6, 8, and 9, isoflavone 11, flavone 12, and a 2-arylbenzofuran 13, were also isolated. All but one (7) of the isoflavans were prenylated. The structures of the previously undescribed compounds were deduced by NMR spectroscopy, supported by HRESI mass spectrometry. The absolute configurations of 1-3, 5, and 7-9 were determined by ECD. Compounds 1, 3, 4, 6, and 8 exhibited in vitro antimicrobial activities, causing complete growth inhibition (MIC) at concentrations between 6.7 and 37.0 µM against Cryptococcus neoformans and between 8.9 and 25.0 µM against methicillin resistant Staphylococcus aureus (MRSA). The most broadly active previously undescribed compound was verdean A (1), with MIC values of 6.7 and 12.9 µM toward C. neoformans and MRSA, respectively, and an MIC of 10.0 µM against the often-intractable C. albicans.

A new method based on dispersive solid phase microextraction with commercial MOFs coupled to LC-MS/MS for the determination of isoflavones in soy drinks.

For the first time, a method based on dispersive solid phase microextraction (D-µSPE) using commercial metal-organic frameworks coupled to liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) has been proposed for the determination of isoflavones in soy drinks. The use of commercial sorbents simplifies the sample treatment procedure and allows their application to routine analysis. Optimization of the parameters involved in the microextraction process was carried out using a Box-Behnken experimental design. Under the optimized conditions, the limits of detection ranged between 2 and 7 µg L-1; the intra-day and inter-day precision were <10 and 20%, respectively, and the recoveries were in the range of 61-120%. No significant matrix effect was found, which allowed the use of external standard calibration method. The method was successfully applied to the determination of isoflavones in commercial soy milk samples.

Puerarin-A Promising Flavonoid: Biosynthesis, Extraction Methods, Analytical Techniques, and Biological Effects.

Flavonoids, a variety of plant secondary metabolites, are known for their diverse biological activities. Isoflavones are a subgroup of flavonoids that have gained attention for their potential health benefits. Puerarin is one of the bioactive isoflavones found in the Kudzu root and Pueraria genus, which is widely used in alternative Chinese medicine, and has been found to be effective in treating chronic conditions like cardiovascular diseases, liver diseases, gastric diseases, respiratory diseases, diabetes, Alzheimer's disease, and cancer. Puerarin has been extensively researched and used in both scientific and clinical studies over the past few years. The purpose of this review is to provide an up-to-date exploration of puerarin biosynthesis, the most common extraction methods, analytical techniques, and biological effects, which have the potential to provide a new perspective for medical and pharmaceutical research and development.

Five new flavonoids and their pharmacological activities from Iris tenuifolia Pall.

Five new components including two new isoflavones, 5, 7, 2', 3'-tetrahydroxy-6-methoxyisoflavone (1), 5, 7, 2', 3'-tetrahydroxy-8-methoxyisoflavone (2), one flavonol 3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavonol (3), one flavanone (2S)-5, 7, 3'-trihydroxy-2'-methoxyflavanone (4), and one flavanonol (2R, 3R)-3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavanonol (5), along with nine known flavonoids (6-14) were isolated from under ground parts of Iris tenuifolia Pall. Their structures were elucidated by NMR and HRESIMS data and by comparison of CD spectra with compounds having similar structure. The separated compounds were evaluated for in vitro antioxidant activities by DPPH and ABTS. The α-glucosidase inhibitory activity of the compounds were evaluated with the pNPG method, the results indicated flavonoids were potential inhibitors of α-glucosidase. Moreover, in vitro anti-oxidative assay using flow cytometry indicated that compounds 1-5 showed strong oxidation resistance ability on C8D1A cells without affecting the cell viability.

New flavonoid and their anti-A549 cell activity from the bi-directional solid fermentation products of Astragalus membranaceus and Cordyceps kyushuensis.

Astragalus membranaceus and Cordyceps kyushuensis were used to obtain Astragalus membranaceus-Cordyceps kyushuensis bi-directional solid fermentation products using the bi-directional solid fermentation technique. The fermentation products were isolated and purified to obtain 20 individual compounds, of which compound 1 was a novel isoflavane, and compounds 2, 3, and 4 were novel isoflavones, along with 16 known compounds. In vitro experiments demonstrated that compounds 4, 5, 8, 10, and 20 exhibited significant inhibitory activity against A549 lung cancer cells. Specifically, the IC50 value of the novel compound 4 was 53.4 µM, while the IC50 value of cordycepin was 9.0 µM.

Estrogenic Activity of Derris scandens Stem Extract and its Major Compounds Using MCF-7 Cell Proliferation Assay and Estrogen-Related Gene Expression.

Derris scandens, which contains isoflavones and prenylated derivatives, has analgesic and anti-inflammatory properties and is an ingredient in traditional Thai medicine for perimenopause and menopause. However, the estrogenic activity of D. scandens has not yet been explored. Therefore, this study aimed to examine the estrogenic activity of the stem extract of D. scandens and its isoflavone derivatives. In this study, we conducted a proliferation assay in MCF-7 cells, and used quantitative reverse transcription polymerase chain reaction to assess gene expression. We found that the relative cell proliferation of the compounds (1 µM) was ranked in the following order as compared to 0.1 nM 17ß-estradiol (100%): genistein (97.84%) > derrisisoflavone A (83.17%) > genistein-7-O-[α-rhamnopyranosyl-(1 → 6)-glucopyranoside] (69.55%) > 6,8-diprenylgenistein (51.91%) > lupalbigenin (18.72%). Furthermore, cotreatment with 1 µM lupalbigenin and 0.1 nM 17ß-estradiol was performed, which decreased cell proliferation to 80.38%. In vitro results suggest that lupalbigenin has an estrogen-antagonistic effect. At a dose of 1 µM, genistein had the strongest efficacy in increasing the expression of human estrogen receptor ß by 4.0-fold compared to the control. Furthermore, genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-ß-glucopyranoside augmented the gene expression of human estrogen receptor α and human estrogen receptor ß by 1.5- and 3.4-fold, respectively. Prenylated derivatives of genistein (derrisisoflavone A, 6,8-diprenylgenistein, and lupalbigenin) significantly suppressed the gene expression of the human androgen receptor. The administration of the crude extract at 10 µg/mL significantly suppressed human androgen receptor (0.6-fold) and transmembrane protease serine 2 (0.1-fold) expression but did not significantly affect human estrogen receptor α and human estrogen receptor ß gene expression. This herbal medicine may be safe for estrogen-exposed breast cancer patients.

Isoflavones isolated from the fruits of Ficus altissima and their anti-proliferative activities.

Ficus altissima, also known as lofty fig, is a monoecious plant from the Moraceae family commonly found in southern China. In this study, we isolated and identified one new isoflavone (1), three new hydroxycoumaronochromones (2a, 2b and 3a) and 12 known compounds from the fruits of F. altissima. Their chemical structures were determined using spectroscopic analysis methods. We also tested all the isolated compounds for their anti-proliferative activities against eight human tumour cell lines (A-549, AGS, K562, K562/ADR, HepG2, HeLa, SPC-A-1 and CNE2) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Our experiments showed that compound 6 exhibited obvious anti-proliferative activity against the K562 cell line with an IC50 value of 1.55 µM. Additionally, compounds 8 and 9 showed significant anti-proliferative activities against the AGS and K562 cell lines, respectively. Moreover, compound 6 induced apoptosis in K562 cells through the caspase family signalling pathway.

Antiviral Rotenoids and Isoflavones Isolated from Millettia oblata ssp. teitensis.

Three new (1-3) and six known rotenoids (5-10), along with three known isoflavones (11-13), were isolated from the leaves of Millettia oblata ssp. teitensis. A new glycosylated isoflavone (4), four known isoflavones (14-18), and one known chalcone (19) were isolated from the root wood extract of the same plant. The structures were elucidated by NMR and mass spectrometric analyses. The absolute configuration of the chiral compounds was established by a comparison of experimental ECD and VCD data with those calculated for the possible stereoisomers. This is the first report on the use of VCD to assign the absolute configuration of rotenoids. The crude leaves and root wood extracts displayed anti-RSV (human respiratory syncytial virus) activity with IC50 values of 0.7 and 3.4 µg/mL, respectively. Compounds 6, 8, 10, 11, and 14 showed anti-RSV activity with IC50 values of 0.4-10 µM, while compound 3 exhibited anti-HRV-2 (human rhinovirus 2) activity with an IC50 of 4.2 µM. Most of the compounds showed low cytotoxicity for laryngeal carcinoma (HEp-2) cells; however compounds 3, 11, and 14 exhibited low cytotoxicity also in primary lung fibroblasts. This is the first report on rotenoids showing antiviral activity against RSV and HRV viruses.

Identification of Dalbergiae Odoriferae Lignum active ingredients and potential mechanisms in the treatment of adriamycin-induced cardiotoxicity based on network pharmacology and experimental verification.

The purpose of this study is to investigate the ingredients and mechanisms through which Dalbergiae Odoriferae Lignum (DOL) reduces adriamycin-induced cardiotoxicity. DOL's ingredients and drug targets were acquired from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and adriamycin-induced cardiotoxicity disease targets were gathered from GeneCards and National Center for Biotechnology Information (NCBI). The therapeutic targets of DOL against adriamycin-induced cardiotoxicity were identified by intersecting drug and disease targets. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted using R. Subsequently, core targets were determined and used for molecular docking with DOL ingredients. In vitro and in vivo experiments validated DOL's primary ingredients against adriamycin-induced cardiotoxicity efficacy. Western blot and immunohistochemistry verified its impact on target protein. After intersecting 530 drug targets and 51 disease targets, 19 therapeutic targets for DOL alleviated adriamycin-induced cardiotoxicity were received. Molecular docking demonstrated that DOL primary ingredient formononetin had a robust binding affinity for nitric oxide synthase 3 (NOS3). Experimental results showed that formononetin effectively mitigated adriamycin-induced cardiotoxicity. Additionally, western blot and immunohistochemistry showed that formononetin improved NOS3 expression. The network pharmacology and experimentation suggest that the primary ingredient of DOL, formononetin, may target NOS3 to act as a therapeutic agent for adriamycin-induced cardiotoxicity.

Auriculasin enhances ROS generation to regulate colorectal cancer cell apoptosis, ferroptosis, oxeiptosis, invasion and colony formation.

Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive system, and Chinese herbal medicine plays an important role in tumor treatment. The in-depth study of auriculasin isolated from Flemingia philippinensis showed that auriculasin promoted reactive oxygen species (ROS) generation in a concentration-dependent manner; when ROS scavenger NAC was added, the effects of auriculasin in promoting ROS generation and inhibiting cell viability were blocked. Auriculasin induced CRC cell apoptosis, led to mitochondrial shrinkage, and increased the intracellular accumulation of Fe2+ and MDA. When auriculasin and NAC were added simultaneously, the levels of apoptosis, Fe2+ and MDA returned to the control group levels, indicating that auriculasin activated apoptosis and ferroptosis by inducing ROS generation. In addition, auriculasin promoted the expression of Keap1 and AIFM1, but significantly reduced the phosphorylation level of AIFM1, while NAC significantly blocked the regulation of Keap1 and AIFM1 by auriculasin, which indicates that auriculasin can also induce oxeiptosis through ROS. When Z-VAD-FMK, Ferrostatin-1, Keap1 siRNA, PGAM5 siRNA and AIFM1 siRNA were added respectively, the inhibitory effect of auriculasin on cell viability was significantly weakened, indicating that auriculasin inhibits cell viability by inducing apoptosis, ferroptosis and oxeiptosis. Auriculasin also inhibited the invasion and clone forming ability of CRC cells, while NAC blocked the above effects of auriculasin. Therefore, auriculasin can promote CRC cell apoptosis, ferroptosis and oxeiptosis by inducing ROS generation, thereby inhibiting cell viability, invasion and clone formation, indicating that auriculasin has a significant antitumor effect.

Antioxidant Potential and Cytotoxic Effect of Isoflavones Extract from Thai Fermented Soybean (Thua-Nao).

Thua-nao, or Thai fermented soybeans, is a traditional Lanna fermented food in Northern Thailand. It is produced by using a specific bacterial species called Bacillus subtilis var. Thua-nao. We investigated the antioxidant activity and cytotoxic effect of isoflavones from Thua-nao. The phenolic compound contents and total flavonoid contents were determined by spectrophotometry. The antioxidant activity was examined using the ABTS, FRAP, and DPPH assays. The isoflavone contents and phenolic compositions were examined by the high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) techniques. The ability of isoflavones to inhibit human cancer cell growth was assessed by the MTT assay. The total phenolic content, total flavonoid content, and antioxidant activities of the isoflavones were 49.00 ± 0.51 mg GAE/g of dry extract (DE), 10.76 ± 0.82 mg QE/g of DE, 61.03 ± 0.97 µmol Trolox/g of DE, 66.54 ± 3.97 µM FeSO4/g of DE, and 22.47 ± 1.92% of DPPH inhibition, respectively. Additionally, the isoflavone extracts from Thua-nao had high isoflavone contents and polyphenolic compound compositions, especially daidzein and genistein. The isoflavone demonstrated a weak inhibition of MCF-7 and HEK293 cancer cell growth. It has a high antioxidant component, which is beneficial and can be developed for new therapeutic uses. However, further studies on the benefits of Thua-nao should be performed for realizing better and more effective uses soon.

Antibacterial Activities of Prenylated Isoflavones from Maclura tricuspidata against Fish Pathogenic Streptococcus: Their Structure-Activity Relationships and Extraction Optimization.

Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an important key for their antibacterial activities (minimum inhibitory concentrations: 1.95-500 µg/mL). Through principal component analysis, characteristic prenylated isoflavones such as 6,8-diprenlygenistein (4) were identified as pivotal compounds that largely determine each part's antibacterial activities. M. tiricuspidata ripe fruits (MTF), which showed the highest antibacterial activity among the parts tested, were optimized for high antibacterial activity and low cytotoxicity on fathead minnow cells using Box-Behnken design. Optimized extraction conditions were deduced to be 50%/80 °C/7.5 h for ethanol concentration/extraction temperature/time, and OE-MTF showed contents of 6,8-diprenlygenistein (4), 2.09% with a MIC of 40 µg/mL. These results suggest that OE-MTF and its active isoflavones have promising potential as eco-friendly antibacterial agents against streptococcosis in aquaculture.

Calycosin-7-O-ß-Glucoside Isolated from Astragalus membranaceus Promotes Osteogenesis and Mineralization in Human Mesenchymal Stem Cells.

Stem cells have received attention in various diseases, such as inflammatory, cancer, and bone diseases. Mesenchymal stem cells (MSCs) are multipotent stem cells that are critical for forming and repairing bone tissues. Herein, we isolated calycosin-7-O-ß-glucoside (Caly) from the roots of Astragalus membranaceus, which is one of the most famous medicinal herbs, and investigated the osteogenic activities of Caly in MSCs. Caly did not affect cytotoxicity against MSCs, whereas Caly enhanced cell migration during the osteogenesis of MSCs. Caly increased the expression and enzymatic activities of ALP and the formation of mineralized nodules during the osteogenesis of MSCs. The osteogenesis and bone-forming activities of Caly are mediated by bone morphogenetic protein 2 (BMP2), phospho-Smad1/5/8, Wnt3a, phospho-GSK3ß, and phospho-AKT, inducing the expression of runt-related transcription factor 2 (RUNX2). In addition, Caly-mediated osteogenesis and RUNX2 expression were attenuated by noggin and wortmannin. Moreover, the effects were validated in pre-osteoblasts committed to the osteoblast lineages from MSCs. Overall, our results provide novel evidence that Caly stimulates osteoblast lineage commitment of MSCs by triggering RUNX2 expression, suggesting Caly as a potential anabolic drug to prevent bone diseases.

Potential therapeutic interventions of plant-derived isoflavones against acute lung injury.

Acute lung injury (ALI) is a life-threatening syndrome that possibly leads to high morbidity and mortality as no therapy exists. Several natural ingredients with negligible adverse effects have recently been investigated to possibly inhibit the inflammatory pathways associated with ALI at the molecular level. Isoflavones, as phytoestrogenic compounds, are naturally occurring bioactive compounds that represent the most abundant category of plant polyphenols (Leguminosae family). A broad range of therapeutic activities of isoflavones, including antioxidants, chemopreventive, anti-inflammatory, antiallergic and antibacterial potentials, have been extensively documented in the literature. Our review exclusively focuses on the possible anti-inflammatory, antioxidant role of botanicals'-derived isoflavones against ALI and their immunomodulatory effect in experimentally induced ALI. Despite the limited scope covering their molecular mechanisms, isoflavones substantially contributed to protecting from ALI via inhibiting toll-like receptor 4 (TLR4)/Myd88/NF-κB pathway and subsequent cytokines, chemokines, and adherent proteins. Nonetheless, future research is suggested to fill the gap in elucidating the protective roles of isoflavones to alleviate ALI concerning antioxidant potentials, inhibition of the inflammatory pathways, and associated molecular mechanisms.

Prenylated isoflavones from the roots of Flemingia philippinensis as potential inhibitors of ß-amyloid aggregation.

In our efforts to find potential agents for the treatment of Alzheimer's disease in naturally occurring compounds, a systematic investigation for the active constituents of Flemingia philippinensis was carried out. Four new prenylated isoflavones, philippinone A-D (1-4), together with six known analogues (5-10), were obtained from the roots of Flemingia philippinensis. Their structures were established through extensive physical and spectroscopic data analysis. All the isolates were evaluated for their inhibitory effect of self-induced Aß aggregation among which compound 5 showed significant Aß aggregation inhibitory ability with the inhibitory rate of 70.56%. The results of molecular docking experiment for compounds 1 and 6 corresponded to that of the thioflavin-T assay. Moreover, the results further clarified the effects of different substituent group of tested compounds on the Aß aggregation inhibition. A preliminary structure-activity relationship is further discussed. Our results suggested that the isoflavonoids may mitigate the progression of AD and compounds 2 and 5 may be a candidate in the treatment of AD.

Fungicidal Activity and Mechanism of Action of Glabridin from Glycyrrhiza glabra L.

Glycyrrhiza glabra (Licorice) belongs to the Fabaceae family and its extracts have exhibited significant fungicidal activity against phytopathogenic fungi, which has mainly been attributed to the presence of phenolic compounds such as flavonoids, isoflavonoids and chalcones. In this study, a series of licorice flavonoids, isoflavonoids and chalcones were evaluated for their fungicidal activity against phytopathogenic fungi. Among them, glabridin exhibited significant fungicidal activity against ten kinds of phytopathogenic fungi. Notably, glabridin displayed the most active against Sclerotinia sclerotiorum with an EC50 value of 6.78 µg/mL and was 8-fold more potent than azoxystrobin (EC50, 57.39 µg/mL). Moreover, the in vivo bioassay also demonstrated that glabridin could effectively control S. sclerotiorum. The mechanism studies revealed that glabridin could induce reactive oxygen species accumulation, the loss of mitochondrial membrane potential and cell membrane destruction through effecting the expression levels of phosphatidylserine decarboxylase that exerted its fungicidal activity. These findings indicated that glabridin exhibited pronounced fungicidal activities against S. sclerotiorum and could be served as a potential fungicidal candidate.