Jingxuan Zhu , Nan Song , Jiaxin Wang, Qun Wang, Yuan Cao, Meiling Zhang, Xiaofei Sun, Lianqun Jia
{"title":"Mechanism of action of Danlou tablets affecting MAFLD via KEAP1-mediated oxeiptosis","authors":"Jingxuan Zhu , Nan Song , Jiaxin Wang, Qun Wang, Yuan Cao, Meiling Zhang, Xiaofei Sun, Lianqun Jia","doi":"10.1016/j.jep.2025.119521","DOIUrl":"10.1016/j.jep.2025.119521","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Metabolic fatty liver disease (MAFLD) is a significant risk factor for atherosclerotic cardiovascular disease. Several preliminary studies on MAFLD animal models have indicated the therapeutic potential of Danlou tablets (DLT), a primary Chinese medicine used for managing coronary artery disease. However, the underlying mechanism of DLT in the treatment of MAFLD remains elusive.</div></div><div><h3>Aim of the study</h3><div>Clarify the potential effective components of DLT in the treatment of MAFLD, and preliminarily verify the molecular mechanism against MAFLD <em>in vivo</em> and <em>in vitro</em> experiments.</div></div><div><h3>Materials and methods</h3><div>The composition of DLT and their content in DLT-treated rat serum were analyzed using UPLC/ESI- Q TRAP-MS/MS. Mice were given a high-fat diet to establish the MAFLD model. Then, the MAFLD mice were treated with DLT. Liver sections were taken for histopathological assessment. Furthermore, <em>in vivo</em> and <em>in vitro</em> alterations in the oxeiptosis pathway, <em>de novo</em> fatty acid synthesis, and Triglyceride catabolism were verified by qRT-PCR, Western Blot, and Immunofluorescence experiments. Moreover, how DLT modulated the oxeiptosis pathway was further investigated by rescue experimental strategies.</div></div><div><h3>Results</h3><div>We isolated and detected a total of 1003 compounds from DLT, 109 of which were found in rat plasma, and hypothesized that 11 active ingredients represented by Tanshinone IIA might play a major role in anti-MAFLD. Furthermore, we found that DLT increased Triglyceride catabolism and suppressed <em>de novo</em> fatty acid synthesis <em>in vivo</em> and <em>in vitro</em>, thereby significantly attenuating hepatic lipid deposition. Mechanistically, DLT restored the phosphorylation of Protein Kinase B, promoted Triglyceride catabolism and inhibited the <em>de novo</em> fatty acid synthesis through the oxeiptosis pathway (KEAP1/PGAM5/AIFM1).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that DLT promotes Triglyceride catabolism and inhibit <em>de novo</em> fatty acid synthesis by affecting the activation of the oxeiptosis pathway, suggesting a potential therapeutic strategy for ameliorating NAFLD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119521"},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468020","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}
Yujun Luo , Wanfu Lin , Shuang Xiang , Yuanrong Shi , Meihuan Fu , Xiaofeng Zhai , Changquan Ling , Binbin Cheng
{"title":"Paeoniflorin inhibits chronic restraint stress-induced progression of hepatocellular carcinoma through suppressing norepinephrine-induced activation of hepatic stellate cells via SRC/AKT/ERK pathways","authors":"Yujun Luo , Wanfu Lin , Shuang Xiang , Yuanrong Shi , Meihuan Fu , Xiaofeng Zhai , Changquan Ling , Binbin Cheng","doi":"10.1016/j.jep.2025.119517","DOIUrl":"10.1016/j.jep.2025.119517","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Paeoniae Radix Alba (the root of Paeonia lactiflora Pall.) is a well-known Chinese herb medicine used for alleviating depression and anxiety. Paeoniflorin (PF), an active ingredient of Paeoniae Radix Alba, is usually used in emotion and inflammation-related diseases. In recent years, some studies showed that PF may also possess anti-tumor potential.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the effects of PF on chronic restraint stress (CRS)-induced hepatocellular carcinoma (HCC) progression and elucidate the potential molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>ICR male mice bearing H22-Luc orthotopic transplant tumors were subjected to CRS and administrated with PF. To identify the direct target of PF, network pharmacology, RNA sequencing, and molecular docking analyses were employed. CCK8, Western blotting and qRT-PCR assays were performed to explore the molecular mechanisms of PF.</div></div><div><h3>Results</h3><div>PF mitigated CRS-induced depression-like behaviors in tumor-bearing mice and suppressed the growth of orthotopically transplanted tumors. PF also decreased the number of c-fos positive neurons in the paraventricular nucleus of hypothalamus in CRS-exposed mice and lowered the serum norepinephrine (NE) level. NE treatment promoted the proliferation and αSMA production of hepatic stellate cells (HSCs), but did not alter the viability and migration of HCC cells. Furthermore, the conditional medium (CM) from NE-treated HSCs enhanced the proliferation and migration of HCC cells. PF not only inhibited NE-induced activation of HSCs, also reduced HSCs-CM induced viability and migration of HCC cells. Network pharmacology and RNA sequencing showed SRC was a potential target of PF in HSCs, which was further validated by molecular docking and cellular thermal shift assay. NE treatment upregulated the phosphorylation of SRC, AKT and ERK1/2 in HSCs, which was inhibited by PF.</div></div><div><h3>Conclusion</h3><div>The findings of this study support that PF could ameliorate CRS-induced HCC progression by inhibiting CRS-induced HSCs activation through SRC/AKT/ERK signaling pathway. Our work may provide a new prospect for PF in the treatment of HCC with comorbid psychological stress.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119517"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458103","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}
Pan Taowen , Fan Shuyuan , ShiXiaoli , WangAnnan , Qiu Feng , Zhang Yizhong , Liu Jing , Li Bin , Li Kun , Diao Yunpeng
{"title":"Corrigendum to “Study on the action mechanism of the peptide compounds of Wuguchong on diabetic ulcers, based on UHPLC-Q-TOF-MS, network pharmacology and experimental validation” [J. Ethnopharmacol. 288 (2022) 114974]","authors":"Pan Taowen , Fan Shuyuan , ShiXiaoli , WangAnnan , Qiu Feng , Zhang Yizhong , Liu Jing , Li Bin , Li Kun , Diao Yunpeng","doi":"10.1016/j.jep.2025.119356","DOIUrl":"10.1016/j.jep.2025.119356","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119356"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A systematic pharmacological strategy-based to decode the synergistic mechanism of 7,4′-dihydroxyflavone in combination with vitamin D3 against asthma","authors":"Ziyi Chen , Xiaoyu Liu , Xiaoyang Feng , Aiping Lyu , Wei Zhou","doi":"10.1016/j.jep.2025.119513","DOIUrl":"10.1016/j.jep.2025.119513","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>7,4′-dihydroxyflavone (74DHF), extracted from Gancao (<em>Rhizoma Glycyrrhizae</em>), has demonstrated to mediate the asthma pathology, while Vitamin D3 (VD3) plays a role in asthma treatment due to its immunomodulatory effects. However, the potential molecular or systems mechanism of 74DHF in combination with VD3 against asthma has not yet been elucidated.</div><div>Aim of the study: The current study not only deepens our understanding of the complex synergistic mechanism of 74DHF andVD3 against asthma but also proposes a promising strategy to promote the development of combination therapy.</div></div><div><h3>Materials and methods</h3><div>This study employed a systems pharmacology-based approach integrating target fishing, data integration, bioinformatics analysis, network analysis, Gene Ontology (GO) enrichment analysis, pathway analysis, and <em>in vitro</em> experiment validation to elucidate the pharmacological mechanisms of the combination of 74DHF and VD3 for asthma treatment.</div></div><div><h3>Results</h3><div>Our investigation revealed 47 overlapping targets, 20 core targets, 10 optimal common GO processes, and 10 key pathways closely associated with asthma in the combination of 74DHF and VD3. The combined treatment of 74DHF and VD3 inhibited the inflammatory response (TNF-α and IL-6) induced by LPS in macrophages and epithelial to mesenchymal transition (EMT) related genes expression (CDH1 and ACTA2) in bronchial epithelial cells under the stimulation of TGF-β1.</div></div><div><h3>Conclusion</h3><div>The present study deciphered the molecular mechanism of combined therapeutic effect of 74DHF and VD3 on asthma on systemic and cellular level.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119513"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457757","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}
Yuewei Lin , Qi He , Baihao Chen , Zuang Li , Chuyi Chen , Wei Deng , Haishan Li , Jiamin Yang , Bin Mai , Zhen Zhang , Dongping Wang , Huizhi Guo , Yongchao Tang , Kai Yuan , Guoye Mo , Liangliang Xu , Yongxian Li , Haibin Wang , Shuncong Zhang
{"title":"Zuogui Pills alleviate iron overload-induced osteoporosis by attenuating ROS-mediated osteoblast apoptosis via the PI3K-AKT pathway and mitigating mitochondrial damage","authors":"Yuewei Lin , Qi He , Baihao Chen , Zuang Li , Chuyi Chen , Wei Deng , Haishan Li , Jiamin Yang , Bin Mai , Zhen Zhang , Dongping Wang , Huizhi Guo , Yongchao Tang , Kai Yuan , Guoye Mo , Liangliang Xu , Yongxian Li , Haibin Wang , Shuncong Zhang","doi":"10.1016/j.jep.2025.119455","DOIUrl":"10.1016/j.jep.2025.119455","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Zuogui Pill (ZGP) is a classic herbal formula in Traditional Chinese Medicine, primarily used to tonify the kidney and replenish essence, and is widely applied in treating various kidney deficiency-related conditions. Over time, ZGP has demonstrated significant efficacy in addressing symptoms such as fatigue, weakness, and soreness of the lower back and knees, which are often caused by kidney deficiency. According to Traditional Chinese Medicine theory, the kidneys govern the bones, meaning that sufficient kidney essence is closely related to bone strength. By nourishing the kidneys and replenishing essence, ZGP helps to increase bone density and improve bone microstructure, making it an important therapeutic option for osteoporosis.</div></div><div><h3>Aim of the study</h3><div>To investigate the protective effects of ZGP in iron overload-induced osteoporosis and elucidate its molecular mechanisms through the activation of the Phosphoinositide 3-Kinase (PI3K)/Protein Kinase B (AKT) and Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathways, which reduce oxidative stress, inhibit osteoblast apoptosis, and promote osteoblast differentiation and mineralization.</div></div><div><h3>Materials and methods</h3><div>An in <em>vivo</em> mouse model of iron overload-induced osteoporosis and an in <em>vitro</em> MC3T3-E1 osteoblast model were used. In <em>vitro</em> experiments involved the use of ZGP containing-serum, along with transcriptomic analysis, Western blot, flow cytometry, TUNEL staining, and immunofluorescence, to assess the effects on oxidative stress, mitochondrial function, and apoptosis. In <em>vivo</em> experiments evaluated the effects of ZGP on bone mass, oxidative stress, and apoptosis using Micro-computed tomography (micro-CT), Hematoxylin and eosin staining (H&E), TUNEL staining, and immunohistochemistry.</div></div><div><h3>Results</h3><div>The study found that ZGP containing-serum significantly enhanced the viability of osteoblasts induced by iron overload and reduced apoptosis through the reactive oxygen species (ROS)-mediated Phosphoinositide 3-Kinase (PI3K)/Protein Kinase B (AKT) pathway while mitigating mitochondrial damage. In <em>vivo</em>, micro-computed tomography results showed that ZGP improved bone mass, and decreased ROS and apoptosis, consistent with the in <em>vitro</em> findings.</div></div><div><h3>Conclusion</h3><div>ZGP demonstrates significant antioxidant and anti-apoptotic effects in iron overload-induced osteoporosis, primarily through the ROS-mediated PI3K/AKT pathway and by reducing mitochondrial damage. These findings suggest that ZGP may be a promising therapeutic agent for treating osteoporosis associated with iron overload.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119455"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458171","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}
Yan Chen , Yan Zhu , Zihu Tan , Xueyi Zhang , Jiafeng Hu , Ruichi Zhu , Minjie Xie , Jing Wang , Lizhu Chen , Zhenli Guo
{"title":"Jiajian Shuyu pills effectively ameliorate cognitive impairment via regulating the inflammation of microglia in an Alzheimer's disease mouse model","authors":"Yan Chen , Yan Zhu , Zihu Tan , Xueyi Zhang , Jiafeng Hu , Ruichi Zhu , Minjie Xie , Jing Wang , Lizhu Chen , Zhenli Guo","doi":"10.1016/j.jep.2025.119508","DOIUrl":"10.1016/j.jep.2025.119508","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline and behavioral impairments in the elderly. Microglia, the resident immune cells of the central nervous system, play a crucial role in modulating the pathological processes associated with AD. Jiajian Shuyu Pills (JJSYP) are frequently employed in the treatment of AD, purportedly by enhancing the physiological functions of human tissues and organs to modulate the immune response. Nevertheless, the underlying mechanisms by which JJSYP exert their therapeutic effects in the context of AD remain inadequately elucidated.</div></div><div><h3>Aim of the study</h3><div>This study aimed to assess the effects of JJSYP on cognitive enhancement and the alleviation of neuroinflammation in the treatment of AD, as well as to explore the underlying mechanisms using mouse models.</div></div><div><h3>Materials and methods</h3><div>The components of JJSYP in serum were analyzed using HPLC-Q/TOF-MS. APP/PS1 transgenic mice served as AD models in this investigation. Cognitive function in the AD mice was assessed through the Mirror Water Maze Test and the Novel Object Recognition Test. The quantification of apoptotic hippocampal cells was conducted using Nissl staining and TUNEL staining. Immunofluorescence (IF) and Western blot (WB) analyses were employed to examine microglial activation and the expression of relevant proteins. Transcriptomic sequencing analysis and network pharmacology were administrated to explore the potential mechanisms of JJSYP in AD treatment. Inflammatory cytokine levels in the brain were measured using RT-PCR.</div></div><div><h3>Results</h3><div>A total of 74 absorbed prototype components from JJSYP were identified. JJSYP effectively improved cognitive function and neuroapoptosis in AD model mice by modulating the activation of microglia. The JJSYP intervention alleviated neuroinflammation by suppressing microglial activation and reducing the accumulation of amyloid β-protein. Through transcriptome sequencing and WB verification, 34 differentially expressed genes (DEGs) were identified, including ACKR3, NR1H3 and Adra1a. Following treatment with a high dose of JJSYP, both ACKR3 and NR1H3 showed a significant decrease compared to the model group. Conversely, ADRA1A expression was reduced in model group compared to the control group, but increased following high dose JJSYP treatment. Research involving RNA sequencing and network pharmacology indicated that JJSYP altered the activation of CXCL12/ACKR3 signaling pathways in the hippocampus.</div></div><div><h3>Conclusions</h3><div>JJSYP exhibits potential anti-Alzheimer's Disease effects and warrants further investigation and development as a prosper treatment for AD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119508"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438118","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}
Liang Wei , Wenjun Ma , Shangwei Liu , Shengcheng Mi , Qiong Shen , Qi Lu , Zhangguo Liu ([email protected])
{"title":"Mahonia bealei (Fort.) Carr. Leaf extract modulates the TLR2/MyD88/NF-κB signaling pathway to inhibit PGN-induced inflammation in RAW264.7 cells","authors":"Liang Wei , Wenjun Ma , Shangwei Liu , Shengcheng Mi , Qiong Shen , Qi Lu , Zhangguo Liu ([email protected])","doi":"10.1016/j.jep.2025.119510","DOIUrl":"10.1016/j.jep.2025.119510","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Mahonia bealei</em> (Fort.) Carr. (<em>M. bealei</em>) is a traditional Chinese medicinal plant and one of the herbs used by the Hmong people. It has been recorded in the most recent editions of the Chinese Pharmacopoeia as well as in Hmong medicinal works such as Hmong Pharmacopoeia, for its ability to clear away heat, dry up dampness, and to remove fire and toxins. Currently, the plant is widely cultivated in China, Japan, Mexico, the United States, and Europe, and it appears to be naturalized in the eastern United States. Our earlier research demonstrated that <em>M. bealei</em> leaf extract (MBE) effectively reduced inflammation in xylene-induced ear swelling in mice and cotton ball granuloma in rats. The unclear specific anti-inflammatory mechanism necessitated further investigation in this study.</div></div><div><h3>Aim of the study</h3><div>The aim of this study was to investigate the mechanism of anti-inflammatory effects of MBE on PGN-stimulated RAW264.7 macrophages through the TLR2/MyD88/NF-κB signaling pathway.</div></div><div><h3>Methods</h3><div>Firstly, <em>M. bealei</em> leaf extract (MBE) was obtained by ultrasonic synergistic high-speed homogenization extraction. The main active components in MBE were determined by UPLC-Q-TOF-MS/MS and the interaction of the main components with TLR2 was verified by molecular docking technique. Then, PGN-induced RAW264.7 cells were used to establish an inflammation model, and then the administration concentration of MBE and the modeling concentration of PGN were determined by the CCK-8 method, and the protective effect of MBE on PGN-induced cellular inflammation was evaluated. Meanwhile, the effect of MBE on the morphology of RAW264.7 cells was observed by scanning electron microscopy. The effect of MBE on the focal death of RAW264.7 cells was determined by flow cytometry. Subsequently, NO levels were measured using the Griess method, while PGE2, TNF-α, IL-1β, IL-6, and IL-10 concentrations were assessed via ELISA. ROS levels were determined by fluorescent staining in each group of cells. The expression levels of TLR2, MyD88, IκB, IKK, and NF-κB in the TLR2/MyD88/NF-κB pathway were analyzed using RT-qPCR for mRNA and Western blot for protein.</div></div><div><h3>Results</h3><div>Nineteen major components were detected from MBE by UPLC-Q-TOF-MS/MS, and 10 of them with higher relative abundance were selected for molecular docking with TLR2, respectively, and all of them showed low binding energies and good stability. MBE was shown to be effective in ameliorating the PGN-induced inflammatory condition of RAW264.7 cells, as demonstrated by the CCK-8 method, scanning electron microscopy, and flow cytometry. MBE effectively suppressed the release of inflammatory cytokines NO, PGE2, TNF-α, IL-1β, and IL-6, while enhancing IL-10 production. The RT-qPCR and Western Blot analyses demonstrated that MBE could decreased the mRNA and protein levels of TLR2 a","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119510"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458100","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}
Yulin Qi , Siqi Du , Wenwen Li , Xianzhe Qiu , Fengjie Zhou , Liding Bai , Boli Zhang , Zhuoxin Mi , Weiqiang Qian , Lin Li , Xin Zhao , Yuhong Li
{"title":"Sanye tablet regulates gut microbiota and bile acid metabolism to attenuate hepatic steatosis","authors":"Yulin Qi , Siqi Du , Wenwen Li , Xianzhe Qiu , Fengjie Zhou , Liding Bai , Boli Zhang , Zhuoxin Mi , Weiqiang Qian , Lin Li , Xin Zhao , Yuhong Li","doi":"10.1016/j.jep.2025.119514","DOIUrl":"10.1016/j.jep.2025.119514","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Sanye Tablet (SYT), a patent traditional Chinese prescription, is commonly used in treating type 2 diabetes mellitus and hyperlipidemia. Both clinical and animal studies suggest that SYT effectively regulates lipid metabolism. However, its mode of action on hepatic steatosis has yet to be fully elucidated.</div></div><div><h3>Aim of study</h3><div>This study investigates the lipid-regulating effects and underlying mechanism of SYT in high-fat diet (HFD)-induced hepatic steatosis mice.</div></div><div><h3>Material and methods</h3><div>The inhibitory effects of SYT on developing hepatic steatosis were investigated in HFD-fed C57BL/6N mice. Biochemical markers, including total cholesterol (TC) and triglycerides (TG), were measured using specific kits. Hepatic histological alterations were determined by Hematoxylin and Eosin (H&E) and Oil Red O staining. Hepatic, fecal, and systemic bile acids (BAs) profiles were detected by UPLC-MS. mRNA and protein levels of BAs synthesis-related enzymes and critical nodes of farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15)/fibroblast growth factor receptor 4 (FGFR4) signaling were detected. Fecal microbial composition was analyzed by 16S rRNA gene sequencing and the antimicrobial activity of SYT was further evaluated <em>in vitro</em>.</div></div><div><h3>Results</h3><div>SYT alleviated HFD-induced hepatic steatosis by decreasing TG and TC levels, relieving hepatocyte ballooning, and promoting hepatic BAs synthesis. Moreover, SYT significantly increased the levels of taurine-conjugated BAs in the liver and feces, which in turn inhibited the FXR/FGF15/FGFR4 signaling. Consequently, the hepatic BAs synthesis-related enzyme expression was promoted to reduce lipid accumulation. Notably, SYT remodeled the gut microbiota composition of HFD-fed mice, especially inhibiting the growth of bile salt hydrolase (BSH)-producing bacteria, such as <em>Lactobacillus murinus</em>, <em>Lactobacillus johnsonii</em>, and <em>Enterococcus faecalis</em>.</div></div><div><h3>Conclusion</h3><div>The findings illustrated that SYT prevented hepatic steatosis by improving hepatic lipid accumulation, which is reflected in modulating the gut-liver axis. SYT corrects BAs profile, restores perturbed FXR/FGF15/FGFR4 signaling and promotes hepatic BAs synthesis, which is associated with modulation on certain BSH-producing bacteria.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119514"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458160","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}
Sheng Hu , Fang Shen , Ning Jia , Caiyun Zhang , Xinxin Wu , Wencheng Jiang , Bin Li , Qilong Chen
{"title":"Novel monomers recipe derived from Shengji-Huayu formula targeting PI3K/Akt signaling pathway for diabetic wound healing based on accurate network pharmacology","authors":"Sheng Hu , Fang Shen , Ning Jia , Caiyun Zhang , Xinxin Wu , Wencheng Jiang , Bin Li , Qilong Chen","doi":"10.1016/j.jep.2025.119509","DOIUrl":"10.1016/j.jep.2025.119509","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shengji-Huayu (SJHY) formula has been used clinically for diabetic ulcer (DU) treatment. The transcriptional profiles analysis revealed the PI3K/Akt signaling pathway plays a critical role for diabetic wound healing. However, the effects and underlying mechanisms of SJHY are often challenging in diabetic wound treatment.</div></div><div><h3>Aim of the study</h3><div>To explore the novel monomers recipe and mechanism of SJHY treated diabetic wound via the <em>in vivo</em> and <em>in vitro</em> experiments.</div></div><div><h3>Materials and methods</h3><div>The diabetic wound mice model was established to evaluate the therapeutic efficacy of SJHY treated diabetic ulcer. The transcriptional profile was implemented to identify the differentially expressed genes (DEGs) of SJHY treated diabetic wound mice. The constructed PPI network and KEGG-target network were used to identify the core pathway and related targets. The HPLC-MS method was used to identify the ingredients of SJHY formula. The molecular docking and <em>in vitro</em> experiment was used to screen which monomers regulated core pathway in diabetic wound. Finally, a novel monomers recipe was performed for diabetic wound healing.</div></div><div><h3>Results</h3><div>The <em>in vivo</em> experiment demonstrated SJHY formula significantly promoted diabetic wound healing. Transcriptomic and network analysis revealed the existence of PI3K/Akt signaling pathway was high correlated with SJHY treated diabetic wound. The HPLC-MS and molecular docking revealed that Calycosin (Cal) and Dehydromiltirone (DHT) were strongly targeting Itga6 and Thbs1. The mRNA and protein levels suggested that Itga6 and Thbs1 acted as important upstream regulators of PI3K/Akt signaling pathway in diabetic wound, and the <em>in vitro</em> experiments revealed Cal, DHT and their recipe were significantly increased the levels of Itga6, Thbs1, PI3K and Akt in MGO induced <em>HaCaT</em> cells.</div></div><div><h3>Conclusions</h3><div>SJHY formula has therapeutic efficiency for diabetic wound healing, and Cal and DHT may be a part of the important monomers that alleviate inflammation via activating the PI3K/Akt signaling pathway by regulated Itga6 and Thbs1. Our study demonstrated Cal and DHT formed a novel monomers recipe, which may be one of the critical strategies of SJHY formula promote diabetic wound healing.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119509"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458102","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}
Zhiying Bian , Yong Li , Anhui Zhao , Jing Bai , Ting Li , Shuqi Niu , Sijing Liu , Jinlin Guo
{"title":"Progress in research on the formation mechanism, chemical composition, pharmacological effects, and clinical applications of Musk: A Review","authors":"Zhiying Bian , Yong Li , Anhui Zhao , Jing Bai , Ting Li , Shuqi Niu , Sijing Liu , Jinlin Guo","doi":"10.1016/j.jep.2025.119512","DOIUrl":"10.1016/j.jep.2025.119512","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Moschus</em> (Musk), a precious zoogenous medicinal material in traditional Chinese medicine (TCM), has been extensively utilized for centuries with well-documented therapeutic efficacy. It has important medicinal and economic value and is derived from the secretions of the scent gland sacs of male musk deer, which are dried and solidified under specific physiological conditions. Contemporary pharmacological investigations have validated its multifaceted pharmacological activities, including but not limited to anti-inflammatory, antioxidant, antitumor, and neuroregulatory effects, thereby substantiating its unique therapeutic status in the TCM pharmacopoeia.</div></div><div><h3>Aim of the study</h3><div>This review aims to provide a comprehensive summation of the advancements in research concerning the formation mechanism, chemical composition, pharmacological effects, and clinical applications of Musk, emphasizing its distinctive appeal and vast potential in traditional Chinese medicine.</div></div><div><h3>Materials and methods</h3><div>Use Google Scholar, Scifinder, PubMed, Springer, Elsevier, Wiley, Web of Science and other online database search to collect the literature on mechanisms of formation, chemical composition, pharmacological effect and clinical applications of Moschus published before February 2025. The key words are “Moschus”, “Musk”, “Formation of mechanisms”, “Chemical composition” and “Pharmacological effect” and “Clinical applications”.</div></div><div><h3>Results</h3><div>In modern clinical practice, Niu Musk San has demonstrated efficacy in treating hepatic encephalopathy. Preparations such as She Xiang Bao Xin Wan and Artificial Musk Tablets have demonstrated promising results in the management of coronary heart disease and angina pectoris. Proprietary preparations containing Musk, including Liushen Pills and She Xiang Bao Xin Wan, are acknowledged for their anti-inflammatory properties. Furthermore, studies have indicate that Musk may exert an influence on stem cell proliferation, differentiation, and migration by modulating crucial signaling pathways such as Wnt/β-catenin and PI3K/Akt.</div></div><div><h3>Conclusion</h3><div>The pharmacological effects of Musk present a novel perspective and stimulate innovative approaches and methodologies within pioneering fields such as stem cell therapy and tissue engineering. This comprehensive summary of research progress, encompassing the formation mechanism, chemical composition, pharmacological effects, and clinical applications of musk, underscores its distinctive allure and extensive potential within the realm of TCM.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119512"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458158","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}