Yong Lin , Yuanqi Du , Minggang Wang , Jiongfen Li , Haixian Li , De Wang , Di Pang , Na Wang , Dewen Mao , Fuli Long
{"title":"Jiedu Huayu suppress ferroptosis induced by 5-lipoxygenase-dependent peroxidation in acute liver failure","authors":"Yong Lin , Yuanqi Du , Minggang Wang , Jiongfen Li , Haixian Li , De Wang , Di Pang , Na Wang , Dewen Mao , Fuli Long","doi":"10.1016/j.jep.2025.120343","DOIUrl":"10.1016/j.jep.2025.120343","url":null,"abstract":"<div><h3>Ethnopharmacology relevance</h3><div>Jiedu Huayu Granules (JDHY), a compound formula of six traditional Chinese herbal medicines, has been used for nearly twenty years to treat acute liver failure (ALF) with good clinical efficacy. Its underlying drug mechanisms warrant in-depth exploration.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the inhibitory effects and mechanisms of JDHY on D-Galactosamine + Lipopolysaccharides (D-GalN + LPS)-induced ALF cell and animal models in mice.</div></div><div><h3>Materials and methods</h3><div>The 10 mg/mL D-GalN+1 μg/mL LPS-induced ALF cell model in mice was established according to previous methods, and 15 % JDHY-containing serum was used for intervention. Transcriptomics and proteomics analyses were employed to explore the effective mechanism of JDHY in treating ALF, and verification was carried out at the cell and animal levels based on the omics results.</div></div><div><h3>Results</h3><div>Transcriptomics revealed JDHY anti-ALF mechanism involves ferroptosis. Proteomics suggested 5-lipoxygenase (5-LOX) mediates JDHY anti-ferroptotic effects. Crucially, 5-LOX subcellular localization influences its activity: cytoplasmic retention exacerbates ALF oxidative stress and ferroptosis, which ferroptosis inhibitor Fer-1 significantly attenuated. Mechanistically, cAMP-PKA pathway activation promotes 5-LOX nuclear-to-cytoplasmic translocation. Conversely, JDHY inhibited cAMP-PKA expression, facilitated 5-LOX nuclear reflux, and alleviated ferroptosis—mimicking PKA siRNA effects. In addition, JDHY inhibition of ALF ferroptosis might be multifaceted, as we also found that it promoted the expression levels of Slc7a11, GSH, and GPX4, indirectly improving the antioxidant capacity of cells.</div></div><div><h3>Conclusion</h3><div>JDHY suppresses 5-LOX-catalyzed lipid peroxidation via negative feedback regulation of the cAMP-PKA pathway, mitigating ALF-associated ferroptosis. Moreover, the data provided in this paper suggest that 5-LOX can serve as a potential target for inhibiting ALF ferroptosis, providing a scientific basis for the clinical prevention and treatment of ALF.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120343"},"PeriodicalIF":5.4,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lihua Cui , Meihua Lu , Wen Li , Yao Yin , Caixia Li , Ming Chen
{"title":"Hu Gan Tang ameliorates metabolic-associated fatty liver disease by inhibiting ferroptosis through the Nrf2/GPX4 pathway","authors":"Lihua Cui , Meihua Lu , Wen Li , Yao Yin , Caixia Li , Ming Chen","doi":"10.1016/j.jep.2025.120342","DOIUrl":"10.1016/j.jep.2025.120342","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Hu Gan Tang (HGT), a modified formulation of the traditional Chinese medicine “Si jun zi”, is based on the principle of “strengthening the spleen, resolving dampness, and purging turbidity” for the treatment of metabolic-associated fatty liver disease (MAFLD). HGT has shown efficacy in alleviating liver damage in MAFLD patients. Nevertheless, its underlying molecular mechanisms remain unexplored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the hepatoprotective effects of HGT against MAFLD by regulating hepatic ferroptosis in both <em>in vivo</em> and <em>in vitro</em> models.</div></div><div><h3>Materials and methods</h3><div>The MAFLD rat model was established through exposure to a high-fat diet (HFD). HGT was administered intragastrically for eight consecutive weeks. Histological and biochemical tests were conducted to assess liver damage. In an <em>in vitro</em> study, HepG2 cells were incubated with free fatty acids (FFAs) in the presence or absence of HGT drug-containing serum. Ferroptosis-related parameters, including intracellular Fe<sup>2+</sup> levels, MDA and SOD levels, ROS levels, and the expression levels of ferroptosis-related proteins and modulators, were quantified both <em>in vivo</em> and <em>in vitro</em>. Additionally, Nrf2 inhibitor (ML385) and GPX4 inhibitor (RSL3) were utilized to validate the underlying mechanisms of HGT's hepatoprotective effects.</div></div><div><h3>Results</h3><div>The results demonstrated that HGT alleviated liver injury and reduced lipid accumulation. Furthermore, HGT suppressed oxidative stress by decreasing MDA and ROS levels while increasing SOD levels in both <em>in vivo</em> and <em>in vitro</em> settings. Additionally, HGT inhibited ferroptosis by reducing Fe<sup>2+</sup> accumulation, upregulating xCT, GPX4, and FTH1 expression, and enhancing nuclear Nrf2 expression in liver tissue and steatotic HepG2 cells. Further research revealed that HGT reduced lipid accumulation, suppressed oxidative stress, and alleviated ferroptosis in hepatocytes by activating the Nrf2/GPX4 signaling pathway. These findings provide a novel therapeutic mechanism for HGT in ameliorating MAFLD.</div></div><div><h3>Conclusion</h3><div>HGT significantly suppresses hepatic ferroptosis, reduces oxidative stress, diminishes lipid accumulation, and ameliorates liver damage by activating the Nrf2/GPX4 pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120342"},"PeriodicalIF":5.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongfei Zheng , Shuang Liu , Jiale Mao , Tao Li , Songquan Wu , Hongliang Zhang , Xin Fu , Houxing Lei , Qiaoyong Ye , Shaochang Wu , Xiaoqin Zhang
{"title":"Huoxiang-Shihu herbal formula attenuates alcoholic-induced gastric injury by regulating the HIF-1α/VEGF pathway and inhibiting oxidative stress","authors":"Yongfei Zheng , Shuang Liu , Jiale Mao , Tao Li , Songquan Wu , Hongliang Zhang , Xin Fu , Houxing Lei , Qiaoyong Ye , Shaochang Wu , Xiaoqin Zhang","doi":"10.1016/j.jep.2025.120334","DOIUrl":"10.1016/j.jep.2025.120334","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The main ingredient of the Huoxiang Shihu Chinese Medicine Formula (HS) is <em>Chimonanthus salicifolius</em> H. It is the first medicine of the She ethnic group. HS is a classical prescription for treating alcoholic gastritis, although its therapeutic mechanism remains uncertain.</div></div><div><h3>Aim of the study</h3><div>The study aimed to elucidate the therapeutic mechanism of HS in alcoholic gastritis through network pharmacology and experimental validation.</div></div><div><h3>Methods</h3><div>A mouse model of alcohol-induced gastritis was established and treated with oral HS decoction at doses of 1 g/kg, 2.5 g/kg, and 5 g/kg for two consecutive weeks. Gastric mucosal protection was evaluated by hematoxylin and eosin (H&E) staining, quantification of inflammatory markers, ELISA assays, and immunohistochemistry to assess oxidative stress levels. Liquid chromatography–mass spectrometry (LC-MS/MS) analysis identified chemical constituents in the HS formula. Potential targets were identified via network pharmacology and subsequently confirmed using immunohistochemistry and Western blot analysis. The binding energy of key active substances and core proteins in HS was initially determined through molecular docking.</div></div><div><h3>Results</h3><div>HS administration significantly alleviated mucosal pathology by reducing inflammatory cytokine levels, enhancing superoxide dismutase (SOD) and catalase (CAT) activities, and decreasing malondialdehyde (MDA) and nitric oxide (NO) concentrations. In vitro, serum containing HS reduced intracellular ROS levels and promoted cell migration and proliferation while modulating oxidative stress-related markers. A total of 51 compounds were identified from HS, with the HIF-1α/VEGF axis emerging as the core mechanism. Experimental validation confirmed that HS inhibited the HIF-1α, VEGF, and VEGFR2 expression, regulated oxidative stress indicators (NO, MDA, SOD, CAT), and reduced inflammatory cytokines including TNF-α, IL-6, and IL-1β. The molecular docking results indicated that diosmin in HS had the highest binding energy with VEGFR2 protein, which was −10.6 kcal/mol, and it might be the drug substance for HS to exert anti-alcoholic gastritis.</div></div><div><h3>Conclusion</h3><div>HS protects against alcohol-induced gastric mucosal injury by inhibiting oxidative stress and inflammatory responses through modulation of the HIF-1α/VEGF axis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120334"},"PeriodicalIF":5.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Achyrocline satureioides: in silico and in vivo evaluation of the potential neuroprotective effect of the aqueous extract","authors":"Peterson Alves Santos , Pricila Pflüger , Marilise Brittes Rott , Hipólito Gómez-Couso , Ionara Rodrigues , Patricia Pereira , José Ángel Fontenla","doi":"10.1016/j.jep.2025.120335","DOIUrl":"10.1016/j.jep.2025.120335","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Achyrocline satureioides</em> (Lam.) DC is traditionally used as an infusion in several South American countries to treat various health conditions, including those affecting the central nervous system. Recent studies indicate its potential neuroprotective effects and suggest possible benefits in alleviating neurological symptoms in COVID-19 patients. However, its direct impact on the central nervous system remains underexplored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to assess the <em>Achyrocline satureioides</em> effects infusion on dopaminergic and cholinergic neurodegeneration patterns induced by reserpine or manganese in <em>Caenorhabditis elegans</em> (<em>C. elegans</em>), and to perform <em>in silico</em> analysis of the primary bioactive compounds in the <em>Achyrocline satureioides</em> aqueous extract (ASAE).</div></div><div><h3>Materials and methods</h3><div>Using <em>C. elegans</em> as an experimental model, we evaluated the neuroprotective effects of the aqueous extract of <em>Achyrocline satureioides</em> on dopaminergic and/or cholinergic neurodegeneration induced by reserpine or manganese. Behavioral assays evaluated the preservation of motor function and pharyngeal pumping in nematodes. In addition, <em>in silico</em> studies were performed with the bioactive compounds identified in the extract and compared with drugs currently used for Parkinson's and Alzheimer's diseases.</div></div><div><h3>Results</h3><div>In the studies with <em>C. elegans</em>, neurodegeneration induced by reserpine (60 μM) was attenuated at the highest extract concentration (25 mg/ml) tested. Additionally, animals previously exposed to the extract exhibited improved behavior at both concentrations (10 and 25 mg/ml). When neurodegeneration was induced by manganese (50 mM), both concentrations of the ASAE reduced neurodegeneration and improved behavior. <em>In silico</em> studies evaluated the absorption, distribution, metabolism, and elimination (ADME) properties and molecular docking of identified compounds against established targets associated with neurodegenerative diseases.</div></div><div><h3>Conclusions</h3><div>The <em>Achyrocline satureioides</em> bioactive compounds appear to influence pathways targeted by current therapies for Parkinson's and Alzheimer's diseases. The aqueous extract demonstrated promising neuroprotective potential and modulation of the dopaminergic and cholinergic systems, reducing neurodegenerative damage and enhancing behavior.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120335"},"PeriodicalIF":5.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minping Wei , Yanwei Zhou , Xiaosu Hu , Huaimao Tie , Qingmin Chen , Weirong Yao
{"title":"In vivo bacterial infection acne treatment of Sapindus saponins: Skin microbiota, network pharmacology, and transcriptomic analysis","authors":"Minping Wei , Yanwei Zhou , Xiaosu Hu , Huaimao Tie , Qingmin Chen , Weirong Yao","doi":"10.1016/j.jep.2025.120345","DOIUrl":"10.1016/j.jep.2025.120345","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Sapindus <em>mukorossi</em> has been traditionally used in China for skin whitening and acne treatment. Previous studies have confirmed the antibacterial activity of Sapindus saponins against <em>Cutibacterium acnes</em>, which is reportedly the primary factor causing inflamed lesions in acne vulgaris. However, the anti-acne activity <em>in vivo</em> and related cellular targets of Sapindus saponins are still unknown.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the anti-acne effects <em>in vivo</em> and the action mechanism of <em>Sapindus mukorossi</em> saponins fraction (SMSF) by the strategy of network pharmacology, transcriptomic analysis, and microbiome integration.</div></div><div><h3>Materials and methods</h3><div>The network pharmacology analysis was used to evaluate the cellular targets of SMSF treatment on acne. The transcriptome analysis was utilized to identify the differentially expressed genes (DEGs), and the 16S rDNA sequencing was employed to analyze the composition of skin microbiota.</div></div><div><h3>Results</h3><div>SMSF was proven to have no acute, continuous skin or eye irritation in New Zealand rabbits when the concentration was below 50 mg/mL. SMSF could greatly reduce the lesion degree of rabbit ear acne and significantly decrease the content of pro-inflammatory factors in the rabbit ear tissue and serum after treatment for 14 days. The contents of dihydrotestosterone and leukotriene were significantly decreased, and the structure of bacterial microbiota was regulated. The network pharmacology analysis showed that the main 79 anti-acne targets of SMSF such as tumor necrosis factor (TNF) and interleukin 10. The transcriptomic analysis confirmed that there were 2084 DEGs between the SMSF-treated group and the model group, of which 870 were up-regulated and 1214 were down-regulated. Correlation analysis between the DEGs and the anti-acne targets predicted by network pharmacology showed that there were 6 overlapping targets, including TNF, vitamin D receptor, androgen receptor, prostaglandin endoperoxide synthase 2, peroxisome proliferator activated receptor gamma, and nuclear receptor subfamily 3, group C, member 1. Moreover, SMSF achieved anti-acne activities by maintaining normal cellular protein synthesis, regulating cytokine production as well as regulating cancer-related genes and the mitogen-activated protein kinase signaling pathway.</div></div><div><h3>Conclusion</h3><div>SMSF exerted anti-acne activities via multiple targets and signaling pathways. This study provided a theoretical basis for the utilization of Sapindus saponins in the fields of medicine and cosmetics, and supplied a guiding significance for the development of natural anti-acne drugs.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120345"},"PeriodicalIF":5.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Long Wu, Tao Lin, Zhe Zhang, Dong Peng, Shanying Xiao, Jinghao Liang, Heng Yu, Yi Wang, Furong Huang, Hede Yan
{"title":"Ginsenoside Rg1 improves chronic neuropathic pain by inhibiting NLRP3 inflammasome activation and cell pyroptosis in microglia.","authors":"Long Wu, Tao Lin, Zhe Zhang, Dong Peng, Shanying Xiao, Jinghao Liang, Heng Yu, Yi Wang, Furong Huang, Hede Yan","doi":"10.1016/j.jep.2025.120346","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120346","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Panax notoginseng, documented in Sheng Nong's Herbal Classic, has long been used to relieve pain. Its major bioactive component, ginsenoside Rg1, exhibits diverse pharmacological activities, but its role in chronic neuropathic pain(CNP) remains poorly understood.</p><p><strong>Aim of the study: </strong>This study endeavors to decipher the analgesic functions of Ginsenoside Rg1 and explore the molecular mechanisms that underlie them.</p><p><strong>Materials and methods: </strong>Sciatic nerve ligation - induced CCI was employed to create a neuropathic pain mouse model for evaluating Rg1's impact. The standard Von Frey filament test measured limb withdrawal thresholds to quantify Rg1's impact on neuropathic pain. Immunofluorescence and immunohistochemical staining determined Iba - 1, NLRP3, and ROS cellular distribution and expression. Western blot analysis detected protein expressions of NLRP3 - signaling, mitophagy, and pyroptosis - related factors.</p><p><strong>Results: </strong>To evaluate the effect of Rg1, a mouse model of neuropathic pain was established via CCI induced by sciatic nerve ligation. Mechanistically, Rg1 promoted microglial mitophagy through TFEB nuclear translocation. Suppressed NLRP3 expression and reduced caspase - 1 p10 and IL - 1β p17 secretion confirmed NLRP3 inhibition, which 3 - methyladenine reversed. Additionally, Rg1 enhanced mitophagy by scavenging ROS, restoring mitochondrial potential, and improving abnormal mitochondria.</p><p><strong>Conclusion: </strong>Our findings suggest that Ginsenoside Rg1 has potential as a therapeutic agent for CNP, as it effectively alleviates CNP in rats via promoting microglial mitophagy, inhibiting NLRP3 inflammasome activation, and suppressing microglial pyroptosis.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120346"},"PeriodicalIF":5.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antimalarial Activity of Hydroalcoholic Extract and Fractions from Gnidia stenophylla Roots: In-Vitro Effects on P. falciparum and In-Vivo Suppression in P. berghei-Infected Mice.","authors":"Samson Sahile Salile, Alfoalem Araba Abiye, Asayebirehan Getachew, Asfaw Debela, Eyasu Makonnen, Vetri Selvan Subramaniyan, Negussu Mekonnen","doi":"10.1016/j.jep.2025.120341","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120341","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>The roots of Gnidia stenophylla Gilg (Thymelaeaceae) are used in Ethiopian traditional medicine to treat malaria. This plant has not been fully evaluated scientifically for antimalarial efficacy against Plasmodium species.</p><p><strong>Aim of the study: </strong>To assess the antimalarial potential of Gnidia stenophylla root extracts and fractions through in vitro and in vivo assays.</p><p><strong>Materials and methods: </strong>A hydroalcoholic extract was prepared from dried G. stenophylla roots and fractionated into dichloromethane, n-butanol, and aqueous fractions. In vitro antiplasmodial activity was tested against P. falciparum using a standard lactate dehydrogenase assay to determine IC<sub>50</sub> values. For in vivo evaluation, mice were infected with P. berghei and treated with various doses of the extract/fractions. Endpoints included parasitemia suppression, survival time, packed cell volume (PCV), body weight, and temperature.</p><p><strong>Results: </strong>The crude extract showed moderate in vitro activity (IC<sub>50</sub> = 29.96 ± 1.53 μg/mL), while the aqueous fraction was highly active (IC<sub>50</sub> = 7.65 ± 1.00 μg/mL). Dichloromethane and n-butanol fractions were weakly active. In P. berghei-infected mice, the aqueous fraction at 400 mg/kg produced the highest parasitemia suppression (62.9%) and significantly improved survival compared to controls. This fraction also minimized PCV reduction, weight loss, and temperature drop.</p><p><strong>Conclusions: </strong>Gnidia stenophylla root contains bioactive compounds with antimalarial efficacy. The aqueous fraction, in particular, showed strong activity both in vitro and in vivo, supporting the traditional use of this plant for malaria. These findings justify further isolation of the active constituents and development of standardized extracts.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120341"},"PeriodicalIF":5.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Licochalcone A promotes autophagy to ameliorate NAFLD by inhibiting the mTOR and regulating ULK1/Beclin1/VPS34 pathway.","authors":"Jingjing Li, Dongna Zhang, Pan Liu, Ruikang Fang, Yiquan Li, Yilong Zhu, Meiwen Dong, Shimin Xie, Yunyun Liu, Jiali Wu, Guangze Zhu, Jicheng Han","doi":"10.1016/j.jep.2025.120333","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120333","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Licorice is one of the most commonly used Chinese medicines. Licochalcone A (Lico A) is a flavonoid,which is one of the main components extracted from licorice. It has a variety of pharmacological activities such as improving glucose and lipid metabolism. However, the therapeutic efficacy of Lico A against non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism of this action remains unclear.</p><p><strong>Aim of the study: </strong>The aim of this study was to investigate the interventional effect and mechanism of action of Licochalcone A in NAFLD by combining in vivo and in vitro experiments.</p><p><strong>Materials and methods: </strong>NAFLD mouse model was established with MCD feed, and an in vitro cell model was established with free fatty acid (FFA) formulated with palmitic acid (PA) and oleic acid (OA). After stimulation with Licochalcone A, the changes in the in vivo and in vitro models were observed to clarify whether Licochalcone A has an ameliorative effect on NAFLD. The mechanism of action of Licochalcone A in ameliorating NAFLD was further verified by transcriptomics, mTOR-related protein detection, agonist and inhibitor experiments.</p><p><strong>Results: </strong>Compared with the model group, the number of intracellular lipid vacuoles and red fat droplets was reduced in the Lico A group, and the size of adipocytes was reduced. Meanwhile, the liver function and lipid indexes such as AST, ALT, TG, CHO, HDL-C and LDL-C were reduced. mTOR expression level was reduced, and the expression levels of ULK1, Beclin-1, VPS34, Atg5 and Atg12 were increased.</p><p><strong>Conclusion: </strong>Licochalcone A alleviates NAFLD, reduces hepatic lipid deposition and enhances liver function. Its mechanism of action is related to the inhibition of mTOR expression and regulation of ULK1/Beclin-1/VPS34 pathway thereby promoting autophagy.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120333"},"PeriodicalIF":5.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}