Journal of ethnopharmacology最新文献

{"title":"Astragali radix - Curcumae rhizoma herb pair suppresses hepatocellular carcinoma through EGFR/AKT/mTOR pathway and induces lipid peroxidation-related ferroptosis via HIF-1α/HO-1/GPX4 axis","authors":"Chen Wang ,&nbsp;Chen-Hao Shi ,&nbsp;Hao-Yang Bai ,&nbsp;Jun Lu ,&nbsp;Hong-Tao Hu ,&nbsp;Yu-Mei Sun ,&nbsp;Hang Gao ,&nbsp;Hai An ,&nbsp;Jia-Hui Lu ,&nbsp;Hua-Jun Zhao ,&nbsp;Zhi-Hui Zhu","doi":"10.1016/j.jep.2025.119912","DOIUrl":"10.1016/j.jep.2025.119912","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Astragali Radix - Curcumae Rhizoma herb pair (ACHP) originated from the famous traditional Chinese medicine text “<em>YiXueZhongZhongCanXiLu</em>”, in which the two herbs were paired to form Chinese herbal compounds commonly used clinically for digestive system tumors, such as hepatocellular carcinoma (HCC). Although ACHP has been inherited for thousands of years in China, its mechanism against HCC remains unclear.</div></div><div><h3>Aim of the study</h3><div>The study aims to evaluate the effect and explore the mechanism of ACHP against HCC.</div></div><div><h3>Methods</h3><div>The efficacy and safety of ACHP against HCC <em>in vivo</em> were evaluated by tumor volume, organ index, H&amp;E staining, hepatic and renal factors. The serum metabolites of ACHP were identified by UPLC-Q-TOF-MS/MS. The key targets and potential mechanisms of ACHP against HCC were screened by transcriptomics, network pharmacology and molecular docking. The effect and induction of ferroptosis of ACHP-containing serum on HCC <em>in vitro</em> was evaluated by MTT, colony formation assay and specific detection kits. The expression of ferroptosis-related proteins and pathways <em>in vivo</em> was detected by immunohistochemistry.</div></div><div><h3>Results</h3><div>ACHP significantly inhibited tumor proliferation compared to the two herbs used separately, and showed a favorable safety profile. A total of 75 serum metabolites were identified in both positive and negative ion modes. Transcriptomics results revealed that ferroptosis played a key role in the anti-HCC process of ACHP. Network pharmacology and molecular docking results suggested that the anti-HCC effect of ACHP may be related to EGFR/AKT/mTOR pathway and HIF-1α/HO-1/GPX4 axis. <em>In vitro</em> and <em>in vivo</em> experiments further demonstrated that ACHP suppressed oncogenic signaling via the EGFR/AKT/mTOR pathway while inducing lipid peroxidation-related ferroptosis through HIF-1α/HO-1/GPX4 axis, thereby inhibiting HepG2 cells proliferation and HCC mice tumor growth.</div></div><div><h3>Conclusion</h3><div>ACHP exerts its effects by suppressing oncogenic signaling through the EGFR/AKT/mTOR pathway and inducing lipid peroxidation-related ferroptosis in HCC via the HIF-1α/HO-1/GPX4 axis. This systematic investigation establishes a coherent pharmacological chain from compound identification to mechanism verification, highlighting ACHP's therapeutic potential as a ferroptosis inducer targeting oncogenic signaling networks in HCC.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119912"},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894401","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":"The evaluation of the anti-inflammatory effects of Acorus calamus L. ethanolic extract on ovalbumin-induced allergic asthma in mice","authors":"Zeinab Zaheri Abdevand ,&nbsp;Yaghoob Vafamand ,&nbsp;Alireza Malayeri ,&nbsp;Mohammad Amin Behmanesh","doi":"10.1016/j.jep.2025.119903","DOIUrl":"10.1016/j.jep.2025.119903","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Asthma is a protracted respiratory condition typified by inflammation of the airways, increased bronchial reactivity, and recurrent episodes of wheezing and breathlessness. Stimulation of immune cells in the airways releases inflammatory mediators such as histamine, leukotrienes, and cytokines, leading to bronchoconstriction, increased mucus production, and airway inflammation.</div></div><div><h3>Aim of the study</h3><div>Traditional medicine manuscripts mention that the rhizome extract of the <em>Acorus calamus</em> is beneficial for shortness of breath and cough. Recent studies have confirmed its antimicrobial, anti-inflammatory, and antioxidant properties. The research assessed the potential anti-inflammatory properties of the <em>Acorus calamus</em> in mice models of allergic asthma triggered by ovalbumin.</div></div><div><h3>Materials and methods</h3><div>The mice were sensitized on days 1, 14, and 21 to 23 with Ovalbumin (OVA). Dexamethasone (3 mg/kg) or <em>Acorus calamus</em> (50, 100, or 200 mg/kg) was administered by oral gavage on days 15–23. On day 25, Bronchoalveolar Lavage Fluid (BALF) and blood, and Lung tissue were collected.</div></div><div><h3>Results</h3><div>Treatment with <em>Acorus calamus</em> extract significantly decreased inflammatory cells (neutrophil, eosinophil, macrophage, lymphocyte) numbers and Interleukin-4 (IL-4) and levels in BALF and reduced total Immunoglobulin E (IgE) levels in serum and Nitric Oxide (NO) in lung tissue—also, significantly enhanced Interferon-γ (INF-γ) levels in BALF. Histological examination of the lung with Hematoxylin and Eosin, Periodic Acid-Schiff, and Trichrome Masson staining demonstrated that <em>Acorus calamus</em> significantly attenuated inflammatory cell infiltration and mucus-producing goblet cells in the lung.</div></div><div><h3>Conclusion</h3><div>The results indicate that <em>Acorus calamus</em> exerts anti-inflammatory effects in allergic asthma and may hold potential as an innovative treatment option for allergic bronchial asthma.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119903"},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899157","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":"Biyuantong decoction improves chronic rhinosinusitis by inhibiting inflammatory cell adhesion via NF-кB pathway modulation","authors":"Yuying Ye ,&nbsp;Yinyin Yao ,&nbsp;Shanshan He ,&nbsp;Xinyi Zhao ,&nbsp;Weiyu Wang ,&nbsp;Mengting Lin ,&nbsp;Yafei Su ,&nbsp;Guoqing Wu ,&nbsp;Feng Zhou ,&nbsp;Li Wang ,&nbsp;Chunlian Zhong ,&nbsp;Mingqing Huang ,&nbsp;Hui Wu ,&nbsp;Yusheng Lu","doi":"10.1016/j.jep.2025.119907","DOIUrl":"10.1016/j.jep.2025.119907","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Biyuantong decoction (BYT), a traditional Chinese medicinal formulation, has been used for years to treat chronic rhinosinusitis (CRS) with good clinical results. However, the underlying mechanisms of its treatment for CRS remain to be fully elucidated.</div></div><div><h3>Study aim</h3><div>This research investigates the molecular mechanism by which BYT ameliorates CRS and provide new perspectives for CRS treatment research.</div></div><div><h3>Materials and methods</h3><div>Clinical research is conducted on CRS patients who underwent surgery, and post-operative treatments and observations were performed. The pathological alterations of CRS were inspected by H&amp;E staining and nasal endoscopy. Flow cytometry and ELISA were employed to measure the levels of inflammatory cells and cytokines in the peripheral blood of CRS patients. The cytotoxic impacts of BYT were assessed by cell viability, cell cycle and apoptosis assays. The effects of BYT on the adhesion and invasion of inflammatory cells to endothelial cells were evaluated by hetero-adhesion and transwell assay. Flow cytometry was employed to analyze the expression of cell adhesion molecules (CAMs) on HUVECs. The effects of BYT on NF-κB signaling pathway was analyzed by Western blot and immunofluorescence staining. The chemical components of BYT was determined by UPLC-HRMS, and network pharmacology analysis was adopted to predict potential targets in the NF-κB pathway.</div></div><div><h3>Results</h3><div>Clinical samples demonstrated that BYT treatment could effectively alleviate sinus mucosal edema and significantly decreased the recurrence rate after surgery. H&amp;E staining disclosed obvious inflammatory cell infiltration in the sinus mucosa of CRS patients. Flow cytometry and ELISA results indicated that BYT treatment reduced the levels of eosinophils (median decrease 16.21 %) and cytokines in peripheral blood. Cell adhesion and transwell assays manifested that BYT inhibited the adhesion and invasion of U937 cells to TNF-α-induced HUVECs. Moreover, BYT counteracted the TNF-α-induced upregulation of CAMs on endothelial cells. Western blot and immunofluorescence analyses confirmed that BYT reduced the expression of NF-κB-related proteins and hindered the nuclear translocation of NF-κB. <span>Network</span> pharmacology analysis and component identification of BYT further supported the function of its compounds in synergistically modulating NF-κB signaling.</div></div><div><h3>Conclusion</h3><div>BYT enhances the clinical efficacy of CRS by suppressing inflammatory cell adhesion and infiltration into the nasal mucosa via NF-кB pathway regulation. These findings provide a robust foundation for the clinical application of BYT in CRS treatment and suggest interrupting inflammatory cell adhesion as a potential new approach.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119907"},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898441","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":"Ginsenoside Rg1 attenuates T2DM-induced renal damage and fibrosis by inhibiting TRPC6-ChREBP-TXNIP signaling","authors":"Hui Zhang ,&nbsp;Haoyu Liang ,&nbsp;Lei Fan ,&nbsp;Xing Zhu ,&nbsp;Pengmin Ji ,&nbsp;Yong Su ,&nbsp;Weiping Li ,&nbsp;Weizu Li","doi":"10.1016/j.jep.2025.119863","DOIUrl":"10.1016/j.jep.2025.119863","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>As a traditional Chinese medicine, ginseng has many benefits, including regulating blood sugar, blood pressure and so on. Ginsenoside Rg1 is the main active component of ginseng and has been found to significantly improve renal pathological injury in type 2 diabetes mellitus (T2DM) mice. However, the effects and mechanisms of Rg1 in attenuating T2DM are not fully understood.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the role of Rg1 in the treatment of renal damage and fibrosis induced by T2DM and its molecular mechanism.</div></div><div><h3>Materials and methods</h3><div>T2DM models were constructed on mice and cells respectively and were administered with corresponding drugs. SA-β-Gal and Oil Red O were used to observe cell senescence and lipid droplet deposition; H&amp;E and PAS were used to observe pathological changes in the kidney; masson and sirius red were used to evaluate the level of renal fibrosis. Immunohistochemistry, immunofluorescence and Western blotting were performed to analyze the relevant indexes which resulted in the detection of ROS levels <em>in vitro</em> and <em>in vivo</em>. Calcium imaging was used to test the level of [Ca²⁺]_i.</div></div><div><h3>Results</h3><div>Rg1 and <em>Trpc6</em> knockout could significantly improve kidney dysfunction, attenuate renal injury and fibrosis and also decrease the expression levels of TRPC6, CaN, TXNIP, ChREBP, p-ASK1 and NLRP3 inflammasome. Meanwhile, Rg1 and <em>Trpc6</em> knockout significantly inhibited mitochondrial damage and apoptosis protein release. Additionally, Rg1 treatment has been shown to markedly reduce lipid deposition and ROS accumulation in T2DM, while <em>Trpc6</em> knockout exhibited no effect on these parameters.</div></div><div><h3>Conclusion</h3><div>Rg1 treatment can inhibit the TRPC6-ChREBP-TXNIP pathway, thereby improving chronic T2DM-induced renal injury and fibrosis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119863"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895256","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":"Vaccarin treats lactation insufficiency through the ALKBH5-SFRP2-Wnt/β-catenin signaling pathway","authors":"Qiuyun Xue ,&nbsp;Hui Li ,&nbsp;Guosheng Liu ,&nbsp;Youyi Xiong ,&nbsp;Guoliang Zhou ,&nbsp;Pengfei Xu ,&nbsp;Juan He ,&nbsp;Xiaomei Wang ,&nbsp;Chenggui Miao","doi":"10.1016/j.jep.2025.119898","DOIUrl":"10.1016/j.jep.2025.119898","url":null,"abstract":"<div><h3>Ethnopharmacologic significance</h3><div>Vaccarin, a natural small molecule extracted from <em>Gypsophila vaccaria</em> (L.) Sm., is an active flavonoid glycoside.</div></div><div><h3>Background</h3><div>Lactation insufficiency refers to insufficient milk secretion in women after childbirth, which affects the feeding of infants and even their development. Our preliminary experiments showed that alkylation repair homolog protein 5 (ALKBH5) was abnormally overexpressed in mammary tissue of lactation deficiency model rats, which played an important role in regulating milk secretion, but the mechanism was not clear, and no research reports were reported in this aspect.</div></div><div><h3>Purpose</h3><div>The aim of this study was to investigate whether Vaccarin (Vac) treated lactation insufficiency through the ALKBH5-SFRP2-Wnt/β-catenin signaling pathway.</div></div><div><h3>Methods</h3><div>The lactation insufficiency model rats and primary cultured rat mammary epithelial cells (RMECs) were used as experimental subjects. RT-qPCR, Western blot, RNA Immunoprecipitation, immunofluorescence and related methods were used to study the mechanism of Vac treatment for lactation insufficiency.</div></div><div><h3>Results</h3><div>Vac effectively increased the milk production, significantly improved the thickness and density of mammary ducts and follicles, and promoted the prolactin (PRL) secretion and the prolactin receptor (PRLR) expression in lactation insufficiency model rats. Vac significantly promoted the expression of FASN, CSN2, and GLUT1. ALKBH5 was upregulated in the mammary gland of model mice, promoting SFRP2 expression and inhibiting the Wnt/β-catenin signaling pathway and the expression of FASN, CSN2 and GLUT1. Furthermore, Vac inhibited the expression of SFRP2 by targeting the ALKBH5, and subsequently activated the Wnt/β-catenin signaling pathway to promote milk secretion in the lactation insufficiency model rats.</div></div><div><h3>Conclusion</h3><div>Vac promoted milk secretion and improved lactation insufficiency through the ALKBH5-SFRP2-Wnt/β-catenin signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119898"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899284","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":"Lactiplantibacillus plantarum fermentation enhances the antidepressant effects of Hemerocallis citrina Baroni in chronic restraint stress mice","authors":"Pengru Chen ,&nbsp;Yang Lin ,&nbsp;Xiaofeng Li ,&nbsp;Junxiang Li ,&nbsp;Peng Liu ,&nbsp;Xiangyun Zhang ,&nbsp;Xiaohu Ma ,&nbsp;Yonghong Zhu ,&nbsp;Zhiming Zhang ,&nbsp;Pingrong Yang ,&nbsp;Chunjiang Zhang","doi":"10.1016/j.jep.2025.119897","DOIUrl":"10.1016/j.jep.2025.119897","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Hemerocallis citrina Baroni</em> (<em>H. citrina</em>), referred to as ‘Forgetting Sadness Grass,’ is a traditional Chinese medicine (TCM) known for its antidepressant effects. Fermentation is an ancient processing method for TCM. Whether fermentation affects the antidepressant effect of <em>H. citrina</em> is unknown.</div></div><div><h3>Aim</h3><div>In this study, we aim to evaluate the effect of fermented and unfermented <em>H. citrina</em> on chronic restraint stress-induced depression and the underlying mechanism.</div></div><div><h3>Materials and methods</h3><div><em>H. citrina</em> was co-fermented with <em>Lactiplantibacillus plantarum</em> strains LZU-J-TSL-6 and LZU-J-LZ1-1 to produce fermented <em>H. citrina</em> (FH). Both <em>H. citrina</em> and FH were evaluated for effects on depression and anxiety in chronic restraint stress (CRS) mice.</div></div><div><h3>Results</h3><div>Fermentation increased flavonoids and phenols while reducing terpenoids. Both <em>H. citrina</em> and FH exhibited antidepressant effects, with FH showing superior efficacy in alleviating depressive symptoms. Specifically, FH effectively alleviated weight loss, behavioral abnormalities, and hippocampal pathological damage caused by CRS, while significantly reducing serum levels of cortisol and inflammatory factors, and increasing hippocampal serotonin (5-HT) level. Moreover, FH can restore CRS-induced gut microbiota dysbiosis by promoting the colonization of beneficial microbes, such as <em>Lactobacillus</em>, and inhibiting the growth of harmful microbes, like <em>Bacteroides_H</em>. Importantly, we discovered that the antidepressant effects of FH are closely associated with substances such as L-theanine and myo-inositol, as well as with the metabolic pathways of alanine, aspartic acid, and glutamic acid.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that fermentation alters the composition of active ingredients in <em>H. citrina</em> and enhance its role in depression. It highlights the potential therapeutic application of FH in treating depression.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119897"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898376","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 activities and lipid profile of ethanolic extract of Ficus sur Forssk (described by Peter Forsskål) in Plasmodium berghei infected albino rats","authors":"Odangowei Inetiminebi Ogidi ,&nbsp;Timipa Richard Ogoun ,&nbsp;Pere-Ere Sarah Tobia","doi":"10.1016/j.jep.2025.119901","DOIUrl":"10.1016/j.jep.2025.119901","url":null,"abstract":"<div><h3>Aim of the study</h3><div>Drug-resistant malaria is a significant issue in sub-Saharan Africa due to the limited availability of healthcare. This study examined the curative and antimalarial properties of <em>Ficus sur</em> leaf extract using a mouse model.</div></div><div><h3>Materials and methods</h3><div>Thirty (30) male albino rats of the wistar strain, with weights spanning from 150 to 200 g, were divided into fifteen groups, each consisting of six rats. Group 1, which served as the control, administered 0.2 ml of 1 × 10¹ <em>Plasmodium berghei</em> (NK 65 strain) infected erythrocytes intraperitoneally to Groups 2 to 5. Parasite control group 2 did not receive any treatment. From day 4 to day 8, the extract was administered to groups 3, 4, and 5 at varying doses: 400 mg/kg b.w. for the high dosage, 200 mg/kg b.w. for the moderate dose, and 10 mg/kg b.w. for chloroquine, respectively. Blood samples were collected from the submandibular region of the animals on days 0, 4, and 8 to evaluate parasitemia and lipid profile.</div></div><div><h3>Results</h3><div>The findings from this study indicate that by day 4, all treated groups showed similar parasitemia levels to the positive control (PC), with a significant increase (p &lt; 0.001). By day 8, parasitemia was highest in the P.C. group (48.74 ± 0.42 %), while high dose extract (HDE), low dose extract (LDE), and standard control (SC) significantly reduced parasitemia (p &lt; 0.001). The SC group demonstrated the highest inhibition (83.17 ± 0.65 %), proving the most effective in reducing parasitemia. While in lipid profile result, HDE and LDE effectively restored low density lipoprotein (LDL) and total cholesterol (T. Chol) levels, with HDE being more effective, while the SC group maintained near-normal values. High density lipoprotein (HDL) levels were significantly improved by HDE and LDE, though not reaching negative control (NC) values, while SC showed near-normal levels. Triglyceride (Trig.) levels remained consistent across all groups with no significant differences.</div></div><div><h3>Conclusion</h3><div>The findings indicate that <em>Ficus sur</em> fractions possess promising antimalarial properties and could be explored as a potential alternative therapy for malaria treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119901"},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895255","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":"p-Synephrine ameliorates non-alcoholic fatty liver disease by regulating liver-adipose axis via AMPK/NF-kappa B pathway","authors":"Wei-Feng Cai ,&nbsp;Qi-Cong Chen ,&nbsp;Qian Ni ,&nbsp;Li Liu ,&nbsp;Qiang Liu ,&nbsp;Yan-Kui Yi ,&nbsp;Cui-Ping Jiang ,&nbsp;Chun-Yan Shen","doi":"10.1016/j.jep.2025.119890","DOIUrl":"10.1016/j.jep.2025.119890","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Citrus aurantium&lt;/em&gt; L. var. &lt;em&gt;amara&lt;/em&gt; Engl. is a folk medicine and dietary supplement popularly used in alleviating indigestion due to food retention and obesity. &lt;em&gt;p&lt;/em&gt;-Synephrine, a principal proto-alkaloid in &lt;em&gt;Citrus aurantium&lt;/em&gt; L. var. &lt;em&gt;amara&lt;/em&gt; Engl., is extensively utilized due to its numerous benefits, particularly its potential to ameliorate obesity. Previous studies of our research demonstrated that &lt;em&gt;p&lt;/em&gt;-synephrine had the potential to alleviate insulin resistance (IR) and liver lipid accumulation caused by high-fat diet (HFD), as well as enlargement of cells in adipose tissue. However, the effects of &lt;em&gt;p&lt;/em&gt;-synephrine in ameliorating non-alcoholic fatty liver disease (NAFLD) were still unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of study&lt;/h3&gt;&lt;div&gt;To explore the effects of &lt;em&gt;p&lt;/em&gt;-synephrine on HFD-induced NAFLD and its mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;NAFLD mice were developed by HFD feeding and treated with &lt;em&gt;p&lt;/em&gt;-synephrine once a day for 21 weeks. The protective effects of &lt;em&gt;p&lt;/em&gt;-synephrine against NAFLD and its mechanisms were evaluated by OGTT, ITT, biochemical index measurements, H&amp;E, immunofluorescence, Sirius red staining, oil red O staining, immunohistochemistry, RT-qPCR, Western blot, network pharmacology, and molecular docking assays.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results of network pharmacology suggested that AMPK-α1 might be the core target, and AMPK and insulin signaling pathways might be the key regulatory pathways of &lt;em&gt;p&lt;/em&gt;-synephrine to alleviate NAFLD. Molecular docking confirmed AMPK-α1 as a probable direct molecular target. &lt;em&gt;p&lt;/em&gt;-Synephrine significantly reduced HFD-induced weight gain of the body, liver, and iWAT. It improved glucose tolerance, insulin tolerance and lipid metabolism disorders caused by HFD. Serum levels of NO, TNF-α, and IL-6 in NAFLD mice were suppressed. AST, ALT, and HYP levels in serum and liver were inhibited. Morphological observation showed &lt;em&gt;p&lt;/em&gt;-synephrine alleviated hepatic steatosis and fibrosis. &lt;em&gt;p&lt;/em&gt;-Synephrine administration also significantly inhibited hepatic de novo lipogenesis (DNL), as evidenced by its regulation of non-esterified fatty acid (NEFA) and TG contents, as well as SREBP-1c, FASN, and ACC1 mRNA expression levels. &lt;em&gt;p-&lt;/em&gt;Synephrine also reversed HFD-induced histopathological changes in iWAT, promoted iWAT browning by increasing UCP1 and PGC-1α expression. Simultaneously, &lt;em&gt;p&lt;/em&gt;-synephrine intervention markedly increased phosphorylation levels of IRS-1, PI3K, and Akt, and protein expression of GLUT-4 in iWAT and liver. Expression of TNF-α, IL-6, and IL-1β and NF-κB activation in iWAT and liver were attenuated through the treatment of &lt;em&gt;p&lt;/em&gt;-synephrine. Further assays showed that &lt;em&gt;p&lt;/em&gt;-synephrine intervention potently regulated AMPK pathway in iWAT and liver of mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This investigation","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119890"},"PeriodicalIF":4.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888074","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":"Xihuang pill suppressed primary liver cancer growth by downregulation of AFP and YAP signaling","authors":"Sha Luo ,&nbsp;Zhen Huang ,&nbsp;Yuewen Dai ,&nbsp;Shuyang Wang ,&nbsp;Wantao Yu ,&nbsp;Zhihan Li ,&nbsp;Qing Pu ,&nbsp;Lihui Yang ,&nbsp;Tianyi Yang ,&nbsp;Yu Tang ,&nbsp;Zhang Wang ,&nbsp;Jiabo Wang ,&nbsp;Jingxiao Wang","doi":"10.1016/j.jep.2025.119891","DOIUrl":"10.1016/j.jep.2025.119891","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Xihuang Pill (XHP) is a traditional Chinese medicine formula that was originally used to treat malignant ulcers. Recent studies revealed its therapeutic effects on various malignant tumors. However, its potential efficacy and mechanisms in primary liver cancer (PLC) were not thoroughly investigated.</div></div><div><h3>Aim of the study</h3><div>This study aimed to elucidate the efficacy and potential mechanisms of XHP in the treatment of PLC.</div></div><div><h3>Methods</h3><div>An orthotopic PLC mice model was established adopting hydrodynamic tail vein injection method. Human liver cancer cell lines and organoids were utilized to assess the effect of XHP <em>in vitro</em>. The expressions of alpha-fetoprotein (AFP) and Yes-associated protein (YAP) were evaluated with western blotting. The mRNA expressions of YAP downstream targets were detected with qRT-PCR. Data from Liver Hepatocellular Carcinoma Collection of the Cancer Genome Atlas (TCGA-LIHC) were extracted to identify the potential targets of HCC. The major active components of XHP methanol extract and XHP medicated serum were detected by UHPLC-MS/MS. Human liver cancer cell lines were used to assess the efficacy and potential mechanisms of these active components in XHP <em>in vitro</em>. Finally, molecular docking was conducted to predict the binding affinities of XHP's active components with AFP and YAP.</div></div><div><h3>Results</h3><div>XHP inhibited PLC tumor growth in the mice model with decreased AFP and Ki-67 index. <em>In vitro</em>, XHP suppressed the proliferation and migration of liver cancer cell lines in a time- and dose-dependent manner. Furthermore, even with a low concentration (5 mg/mL), XHP paralyzed the growth of PLC organoids derived from patients. Mechanistically, XHP downregulated the expression of AFP and YAP signaling <em>in vitro</em> and <em>in vivo</em>. UHPLC-MS/MS analysis identified 25 active components in XHP medicated serum. Among them, certain active compounds suppressed PLC cell proliferation and downregulated AFP and YAP signaling, suggesting their therapeutic potentials in PLC. Molecular docking indicated that several components in XHP exhibited strong binding affinities with both AFP and YAP.</div></div><div><h3>Conclusion</h3><div>XHP inhibited PLC growth by suppressing AFP and YAP signaling. This study provides an experimental basis for XHP application in PLC treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119891"},"PeriodicalIF":4.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894402","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":"S100A9/RAGE pathway regulation of mitophagy and the effect of JianPi LiShi YangGan formula in acute-on-chronic liver failure","authors":"Jing Li ,&nbsp;Rui Hu ,&nbsp;Xingning Liu ,&nbsp;Lanfen Peng ,&nbsp;Jinyu Yi ,&nbsp;Xin Zhong ,&nbsp;Qi Huang ,&nbsp;Jialing Sun ,&nbsp;Wenxing Feng ,&nbsp;Wenfeng Ma ,&nbsp;Xiaozhou Zhou","doi":"10.1016/j.jep.2025.119887","DOIUrl":"10.1016/j.jep.2025.119887","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Mitophagy regulates cellular homeostasis and liver inflammation; however, it is inhibited in acute-on-chronic liver failure (ACLF), which drives disease progression. The <em>JianPi LiShi YangGan</em> formula (YGF) has the potential to improve inflammatory responses and reduce mortality in patients with ACLF. However, the precise mechanisms underlying these effects remain unknown.</div></div><div><h3>Aim of the study</h3><div>We investigated the role of S100A9/RAGE signaling in mitophagy and the protective effects of traditional Chinese medicinal compounds on ACLF.</div></div><div><h3>Materials and methods</h3><div>An ACLF mouse model was established using carbon tetrachloride, lipopolysaccharide, and d-galactose. Hematoxylin and eosin staining and enzyme-linked immunosorbent assay were employed to evaluate the hepatoprotective effect of YGF in ACLF mice. Mitochondrial damage was assessed using transmission electron microscopy. Protein levels of mitophagy-related indicators were assessed through immunohistochemistry and western blotting, and immunofluorescence staining was performed to observe Lamp2 and COX-IV co-localization.</div></div><div><h3>Results</h3><div>The hepatocytes of ACLF mice contained damaged mitochondria, decreased mitophagy-related protein (Pink1, Parkin, and LC3B) expression and activated S100A9/RAGE signaling. Inhibiting S100A9 or RAGE improved liver injury in ACLF mice and enhanced Lamp2-COX-IV co-localization. In alpha mouse liver 12 (AML12) cells overexpressing RAGE, recombinant S100A9 protein inhibited mitophagy induced by 3-chlorocarbonyl benzoyl chloride. YGF reduced mitochondrial damage, increased Pink1, Parkin, and LC3B levels, and enhanced mitophagy while inhibiting S100A9/RAGE activation in the hepatocytes of ACLF mice.</div></div><div><h3>Conclusions</h3><div>This study found that S100A9/RAGE pathway activation impairs mitophagy, and YGF alleviates liver injury by downregulating S100A9 and RAGE signaling, which may be a novel therapeutic strategy for ACLF.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"348 ","pages":"Article 119887"},"PeriodicalIF":4.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895257","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}