Journal of ethnopharmacology最新文献

{"title":"LianZhiXiaoYan Formula alleviates LPS-induced chronic pneumonia via regulating metabolic reprogramming through SIRT3-SDH-SUCNR1 signaling pathway.","authors":"Siyuan Liu, Jincheng Lv, Peng Peng, Xianshu Song, Pengyu Dai, Fangle Liu, Yufeng Yao, Chenchen Zhu, Chaozhan Lin","doi":"10.1016/j.jep.2025.120646","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120646","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Recurrent or persistent respiratory tract infection may progress to chronic pneumonia or other debilitating sequelae in the absence of appropriate therapeutic interventions, seriously compromising the patients' quality of life. LianZhiXiaoYan Formula (LZXYF), a Chinese prescription composed of Chinese medical herbs Andrographis herba (ChuanXinLian) and Radix helicteris (ShanZhiMa), possesses efficiency of clearing heat and detoxifying, and shown a good therapeutic effect on respiratory infectious diseases, but its mechanism of action is not clear.</p><p><strong>Aim of the study: </strong>Aim to evaluate the therapeutic efficacy of LZXYF in treatment of CP and investigate its molecular and physiological mechanisms.</p><p><strong>Materials and methods: </strong>The therapeutic effects of LZXYF on CP was evaluated in an LPS-induced murine model by assessing the pulmonary function, lung histopathology, and biochemical indicators. To explore the mechanism of LZXYF, the lung metabolomics and the components of LZXYF distributed in lung were analyzed by UHPLC-Q-TOF-MS/MS. The impact of LZXYF on SIRT3-SDH-SCUNR1 pathway was investigated using RT-qPCR and Western blot, and the interaction between LZXYF and SIRT3 was verified via CETSA. LPS-induced LLC cell and succinate-induced RAW264.7 cell were employed to investigate the effect and mechanism of LZXYF on metabolic reprogramming and inflammation regulation, with selective inhibition of SIRT3 and SUCNR1, respectively.</p><p><strong>Results: </strong>LZXYF treatment improved pulmonary function as demonstrated by increased Tidal volume, enhanced Minute ventilation, elevated Peak expiratory flow rate, and reduced Timed inspiration (P < 0.05). Moreover, histopathological analysis revealed that LZXYF treatment attenuated emphysema and airway remodeling, concomitant with reduced the levels of TGF-β and HYP (P < 0.01). Metabolomics demonstrated that LZXYF treatment restored 38 dysregulated metabolites in CP mice, primarily involving tryptophan, histidine, lysine and arginine metabolic pathways. Correlation analysis of 16 lung-distributed components and the 38 differential metabolites further indicated that LZXYF alleviated CP through SIRT3 signaling pathway mediated metabolic reprogramming. We further demonstrated that LZXYF could up-regulate SIRT3 to enhance the activities of SDH (P < 0.01), a metabolic enzyme in TCA cycle, thereby regulating metabolic reprogramming and inhibiting the activation of SUCNR1 to prevent succinate-induced inflammation responses (P < 0.01). Furthermore, we elucidated that the active components of LZXYF exerted ameliorated effects by up-regulating SIRT3 expression in LPS or 3-TYP induced LLC cell metabolic reprogramming, which revealed SIRT3 as a critical molecular target for LZXYF to improve metabolic reprogramming and suppress inflammatory responses induced by succinate.</p><p><strong>Conclusion: </strong>LXZYF could ameliorate CP t","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120646"},"PeriodicalIF":5.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175516","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":"Wumei Wan ameliorates ulcerative colitis in rats by modulating the inflammation-pyroptosis-intestinal stem cell axis.","authors":"Yao Zhang, Fei Ge, Haonan Qu, Caihong Zhao, Jingzhe Gu, Qianwei Xu, Huiling Lei, Jian Liu, Xiaojing Wang, Yuanyuan Chu, Xue Yu, Di Zhang, Dongmei Zhang, Shujing Zhang, Ke Han, Meng Chen","doi":"10.1016/j.jep.2025.120645","DOIUrl":"10.1016/j.jep.2025.120645","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease primarily characterised by persistent disruption of the colonic epithelial barrier. Despite the proven clinical efficacy of the traditional Chinese medicine formulation Wumei Wan (WMW), its pharmacological mechanisms remain inadequately understood.</p><p><strong>Aim of the study: </strong>This study aims to elucidate the therapeutic mechanisms through which WMW promotes the repair of colonic epithelial barrier damage in UC.</p><p><strong>Methods: </strong>UC was induced in rats via dextran sulfate sodium (DSS), followed by treatment with low- and high-dose WMW or the positive control 5-ASA. Therapeutic effects of WMW on colonic barrier damage were assessed using conventional indices and serum biomarkers. Mechanistic insights were derived through network pharmacology analysis and transcriptome sequencing (RNA-seq), with experimental validation performed using reverse transcription quantitative PCR, Western blot analysis, and immunofluorescence (IF).</p><p><strong>Results: </strong>Both high- and low-dose WMW improved serum biomarkers associated with intestinal barrier function (endotoxin, diamine oxidase, and D-lactate), alongside conventional metrics such as disease activity index, ZO-1, and MUC2 expression. Network pharmacology and RNA-seq analyses identified key therapeutic mechanisms, including modulation of pyroptosis, regeneration of LGR5⁺ intestinal stem cells (ISCs), and regulation of inflammatory signalling pathways. Experimental validation confirmed that WMW inhibited pyroptosis-associated proteins (NAIP5, NAIP6, NLRC4, GSDMD-N, caspase-1 p20, IL1β, and IL18) while promoting ISC regeneration via upregulation of LGR5, ASCL2, and IL11RA1, with co-localisation of LGR5 and IL11RA1-a novel finding. Additionally, WMW suppressed phosphorylation of JAK2/STAT3 pathway components (p-JAK2 and p-STAT3) and elements of the STING1/IRF3 pathway (p-STING1, p-IRF3, and p-NF-κB p65), offering moderate complementary regulation of inflammatory pathways in UC.</p><p><strong>Conclusions: </strong>WMW mitigates UC-associated epithelial barrier dysfunction through a multifaceted mechanism involving inhibition of NAIP5/6-NLRC4 pathway-mediated epithelial pyroptosis, enhancement of ASCL2/IL11RA1-dependent LGR5⁺ ISC regeneration, and suppression of JAK-STAT and STING1/IRF3 inflammatory signalling. This polypharmacological action, driven by WMW's complex phytochemical composition, underscores therapeutic potential of multi-target herbal medicines in addressing the multifactorial pathogenesis of UC.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120645"},"PeriodicalIF":5.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175598","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":"Traditional uses, chemical constituents, pharmacological activities and toxicology of Chinese medicinal leech (Shuizhi): A comprehensive review","authors":"Jingbo Liu,&nbsp;Lingna Wang,&nbsp;Wenna Duan,&nbsp;Yongqing Zhang,&nbsp;Qiu Jiang","doi":"10.1016/j.jep.2025.120634","DOIUrl":"10.1016/j.jep.2025.120634","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Chinese medicinal leech (<em>Shuizhi</em> in Chinese) has been widely used in traditional Asian medicine, particularly in China, to treat blood stasis-related disorders, including hematological diseases, gynecological diseases, trauma, arthritis, and edema.</div></div><div><h3>Aim of the study</h3><div>This review systematically evaluates leech's traditional uses, chemical constituents, pharmacological activities, and toxicology, aiming to provide insights for its further development and utilization.</div></div><div><h3>Material and methods</h3><div>The relevant information of leech was obtained from several databases. Moreover, the medical books, PhD and MSc dissertations in Chinese were also used to perform this work.</div></div><div><h3>Results</h3><div>Traditional uses of leech have lasted for millennia in China. Within the past decades, approximately 100 chemical constituents, including proteins, peptides, amino acid, lipids, sterols, fatty acid esters, and trace elements, have been identified from leech. Modern pharmacological studies have confirmed numerous bioactivities of leech, such as anticoagulant activity, antithrombotic activity, antiatherosclerotic activity, anti-fibrotic activity, anti-inflammatory activity. Additionally, toxicity studies confirm its safety.</div></div><div><h3>Conclusion</h3><div>Based on the summary of the research work of leech, we systematically show the traditional uses, chemical constituents, pharmacological activities and toxicology studies. Leech is a renowned traditional ethnic medicine with numerous pharmacological activities attributed to its bioactive components, and are being actively developed for uses other than traditional uses. Modern pharmacological research primarily focuses on its cardiovascular and cerebrovascular system effect. Therefore, it is important to further explore its pharmacological activities and fill the research gaps related to other traditional uses and chemical constituents. In addition, its safety studies should be expanded to prepare for clinical use.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120634"},"PeriodicalIF":5.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149372","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":"Multiomics analysis reveals early administration of the Medhya rasayana formulation of Bacopa monnieri (L.) Wettst. and Centella asiatica (L.) Urb. prevents neuroinflammation and cognitive deficits in an AβO-injected AD mouse model.","authors":"Swathi Maruthiyodan, Gagan Munegowda, Manju Thomas, Gireesh Gangadharan, Manjunath Bandu Joshi, Kamalesh Dattaram Mumbrekar, Aditi Goyal, Anita Mahadevan, Anandan Erayur Mana, Muraleedharan Thrikovil Sankaran, Valiathan Marthanda Varma Sankaran, Guruprasad Kanive Parashiva","doi":"10.1016/j.jep.2025.120633","DOIUrl":"10.1016/j.jep.2025.120633","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Medhya rasayana is a classical Ayurvedic formulation comprising of neuroactive herbs such as Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., whose nomenclature corresponds to the latest revision in World Flora Online (accessed on July 31, 2025). It is traditionally used to enhance memory, cognition, and overall brain health, as well as to manage mental illness and neurological disorders across different age groups. However, the underlying molecular mechanism remains largely undefined.</p><p><strong>Aim of the study: </strong>In this study, we aimed to investigate whether a rasayana preparation of B. monnieri (Bm) and C. asiatica (Ca) delays the onset or progression of Alzheimer's disease (AD) in an amyloid beta oligomer (AβO)-injected mouse model by preventing key hallmarks, including cognitive impairment and neuroinflammation.</p><p><strong>Materials and methods: </strong>Bm and Ca rasayana formulations were orally administered to healthy 16-week-old mice for two months, followed by the induction of AD via stereotaxic injection of AβO into the hippocampus. Seven days post-AβO injection, a battery of behavioural tests were conducted to evaluate the impact of rasayanas on cognitive outcomes. Furthermore, transcriptomic (RNA-seq) and metabolomic (LC‒MS) profiling of hippocampal tissue was performed to investigate the molecular and biochemical effects of rasayana intervention.</p><p><strong>Results: </strong>The results of the behavioral data revealed that AβO injection impaired spatial and social memory, whereas rasayana pretreatment preserved cognitive function and prevented AβO-induced deficits in the AD mouse model. Furthermore, transcriptomic analysis of the hippocampus with or without rasayana pretreatment revealed that the rasayana formulation beneficially modulated key biological processes, including the inflammatory response, cytokine and TNF regulation, positive regulation of the MAPK cascade, and antigen processing and presentation. Metabolomic analysis further revealed that rasayana pretreatment conferred neuroprotection via glutathione and pyrimidine metabolism.</p><p><strong>Conclusion: </strong>Our findings indicate that pretreatment with Bm and Ca rasayana prevents AβO-induced neuroinflammation and cognitive deficits in an AD mouse model by suppressing proinflammatory pathways and restoring redox balance, suggesting its potential for delaying the onset of disease progression.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120633"},"PeriodicalIF":5.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149403","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":"Xiaoyao San reverses the pro-breast cancer effect of depression by inhibiting glutamate levels in intestinal flora","authors":"Yingchao Wu ,&nbsp;Yuqi Liang ,&nbsp;Jiaqi Cui ,&nbsp;Jieting Chen ,&nbsp;Junfeng Huang ,&nbsp;Congwen Yang ,&nbsp;Qian Zuo ,&nbsp;Qianjun Chen","doi":"10.1016/j.jep.2025.120636","DOIUrl":"10.1016/j.jep.2025.120636","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Xiaoyao San (XYS), a traditional Chinese herbal remedy used to soothe the liver and resolve depression, has long been employed in the treatment of depression and has recently demonstrated promising effects against breast cancer. However, the exact mechanism of its action against depressive breast cancer remains unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to identify the molecular targets of XYS responsible for reversing depressive breast cancer and to elucidate its underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>Behavioral and histopathological analyses will be used to validate the efficacy of XYS in ameliorating depressive breast cancer in chronic unpredictable mild stress (CUMS) models. The differentially expressed genes associated with depressive breast cancer were identified by transcriptomic technology, and network pharmacology was used to predict the target genes of XYS. Furthermore, a pseudogerm-free mouse model was established to explore the mechanistic basis of XYS intervention, and intestinal metabolomics was integrated with 16S rDNA gene sequencing to assess microbiota-related pathways.</div></div><div><h3>Results</h3><div>XYS significantly reversed depression-like behaviors and tumor growth-promoting effects in a CUMS model. Taken together, the results of the transcriptomic data and network pharmacology predictions indicate that XYS may alleviate depression-related breast cancer through modulation of the glutamate receptor signaling pathway. Additional metabolomics and 16S rDNA sequencing studies demonstrated that XYS altered glutamate metabolism in depressive breast cancer mice. Furthermore, the elimination of intestinal flora by antibiotics weakened the efficacy of XYS in the treatment of depressive breast cancer.</div></div><div><h3>Conclusion</h3><div>These findings suggest that XYS has potential therapeutic value for treating depressive breast cancer through inhibition of glutamate level within gut microbiota.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120636"},"PeriodicalIF":5.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149409","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":"Anti-tumor effect of flavonoids isolated from Bidens Pilosa L. by regulating the activity of myeloid-derived suppressor cells within the tumor microenvironment in mice.","authors":"Yang Tao, Maoxin Du, Meihua Zhu, Weiqing Sun, Guiyuan Zeng, Jiayan Xiong, Jinmin Li, Ziyi Yang, Baomin Fan, Ruyi Zhang, Guangzhi Zeng","doi":"10.1016/j.jep.2025.120635","DOIUrl":"10.1016/j.jep.2025.120635","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Colon cancer is one of the most common malignant tumors worldwide. Bidens pilosa L., an annual herb of the Asteraceae, has long been used to treat inflammatory-related illnesses, including cancer. As a population of immunosuppressive cells in the TME, MDSCs play a pivotal role in tumorigenesis and progression, and the effect of B. pilosa on MDSCs has rarely been reported.</p><p><strong>Aim of study: </strong>To investigate the anti-tumor effect of a mixture of two flavonoids, MTF, isolated from B. pilosa, which showed immunotherapeutic activity in regulating the function of MDSCs in colon cancer.</p><p><strong>Materials and methods: </strong>The regulatory effects of the flavonoid MTF on MDSCs differentiation and immune function were tested by qRT-PCR and flow cytometry. Its underlying immunotherapeutic mechanism, cytotoxicity, and anti-angiogenic activity were investigated using SIE luciferase/Western blot, CCK-8/apoptosis, and MDSC-HUVEC co-culture assays, respectively. The in vivo anti-tumor activity of MTF was subsequently investigated in both CT26. WT and CT26. WT/MDSCs syngeneic models.</p><p><strong>Results: </strong>MTF and its components effectively depleted MDSCs by inhibiting their differentiation and inducing apoptosis, thereby restoring suppressed CD4⁺ T cell function. In vivo, MTF not only reduced intratumoral MDSCs but also counteracted MDSC-driven angiogenesis, leading to inhibited tumor growth and enhanced sensitivity to 5-FU treatment.</p><p><strong>Conclusion: </strong>Flavonoid MTF showed a good anti-tumor effect in mice by regulating MDSCs activity within the TME, which contributes to the clinical use of this traditional herb.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120635"},"PeriodicalIF":5.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149395","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":"EuroKhat: A pilot study on Khat consumption among Yemeni migrants in Germany","authors":"Abdullah Shabalah ,&nbsp;Nils Opel ,&nbsp;Alexander Refisch","doi":"10.1016/j.jep.2025.120639","DOIUrl":"10.1016/j.jep.2025.120639","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Khat (<em>Catha edulis</em>), an amphetamine-like stimulant, is deeply rooted in the sociocultural traditions of the Arabian Peninsula and the Horn of Africa, with regular consumption reported by 90 % of men and 50 % of women in Yemen. Beyond its sociocultural role, khat use has been associated with adverse mental health outcomes, including anxiety, insomnia, stress, dysphoric mood, and, in cases of frequent high-dose use, psychosis. Migration to non-khat-producing countries in Europe may alter consumption patterns, yet data on its use among Yemeni migrants in Germany remains limited.</div></div><div><h3>Material and methods</h3><div>This study examined khat consumption patterns among Yemeni migrants in Germany compared to a non-Yemeni control group. A total of 278 participants (159 Yemeni migrants and 119 non-Yemeni residents) completed an anonymous online survey assessing sociodemographic factors, substance use, and mental health, using validated scales (DASS-21, UCLA Loneliness Scale, SCL-90).</div></div><div><h3>Results</h3><div>Reported Khat use was prevalent among Yemeni migrants (63.5 % lifetime use), however retrospective assessments indicate a significant decline in frequent use post-migration. The fraction of participants reporting rare or no use increased from 30 % in Yemen to 75 % in Germany, while occasional use remained stable. No significant associations were found between khat use and psychological distress (depression, anxiety, stress, or psychotic symptoms). However, a significant negative correlation between khat use and loneliness (ρ = −0.29, p = 0.003). None of the control group had ever used khat, yet they reported significantly higher alcohol and cannabis consumption.</div></div><div><h3>Conclusion</h3><div>While khat remains a key cultural practice in Yemeni migrants, none of the non-Yemeni residents ever consumed Khat. In contrast, non-Yemeni reported higher alcohol and cannabis use, underscoring sociocultural influences on substance use. As a pilot study with limited sample size and descriptive analyses, the findings are preliminary and should be interpreted with caution. Future research should explore the role of cultural adaptation and social integration in shaping substance use behaviors among migrant populations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120639"},"PeriodicalIF":5.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149365","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":"Astragalus membranaceus Fisch. ex Bunge-derived astragaloside IV recovers bilateral cavernous nerve injury-induced erectile dysfunction and corporal fibrosis by inhibiting the TGF-β1/Smad2 pathway in rats.","authors":"Serhat Sevgi, Irem Cavusoglu Nalbantoglu, Gokcen Kerimoglu, Sabri Murat Kesim, Arthur L Burnett, Sena F Sezen","doi":"10.1016/j.jep.2025.120640","DOIUrl":"10.1016/j.jep.2025.120640","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Astragalus membranaceus Fisch. ex Bunge, a medicinal herb widely used in Traditional Chinese Medicine, contains Astragaloside IV (AS-IV) as its active component which has shown diverse pharmacological activities like antifibrotic effect in a number of preclinical studies. Given the lack of effective therapies for erectile dysfunction (ED) associated with nerve injury-induced cavernous fibrosis, AS-IV has emerged as a promising candidate for targeting fibrosis-related pathologies.</p><p><strong>Aim of the study: </strong>This study aimed to investigate the potential protective effect of AS-IV mediated by TGF-β1/Smad2 signal inhibition, on ED in a rat model of bilateral cavernous nerve injury (BCNI).</p><p><strong>Materials and methods: </strong>Seventy-two male Sprague-Dawley rats were divided equally into six experimental groups (n = 6) in each of the 7 and 14 days post-injury: Sham + vehicle, Sham+1 mg/kg/day AS-IV, Sham+5 mg/kg/day AS-IV, BCNI + vehicle, BCNI+1 mg/kg/day AS-IV and BCNI+5 mg/kg/day AS-IV. Erectile function was evaluated by intracavernous pressure (ICP)/mean arterial pressure (MAP) ratios. Furthermore, penile tissues were analyzed by western blotting (TGF-β1, p-Smad2, Smad2, fibronectin protein expressions) and Masson's trichrome staining (smooth muscle content and collagen deposition).</p><p><strong>Results: </strong>Erectile function (maximum ICP/MAP and total ICP/MAP) was significantly reduced in BCNI groups at both post-injury (p < 0.001). 7 days treatment of AS-IV showed no effect, whereas both low and high doses for 14 days significantly preserved erectile function (p < 0.01). In the BCNI groups at both 7 and 14 days post-injury, TGF-β1 and fibronectin expression, as well as the p-Smad2/Smad2 ratio, were significantly increased (p < 0.05). AS-IV dose-dependently suppressed the elevations in p-Smad2/Smad2 ratio, TGF-β1 and fibronectin expressions at both post-injuries. Fibrotic changes were markedly aggravated in BCNI group at 14 days post-injury (p < 0.05). Corporal fibrosis was histologically prevented after only 14 days of high-dose AS-IV treatment. (p < 0.01).</p><p><strong>Conclusions: </strong>AS-IV ameliorated BCNI-induced ED in rats by reducing corporal fibrosis via the inhibition of the TGF-β1/Smad2 pathway. These preliminary findings suggest the need for further investigation into its therapeutic potential for nerve injury-induced ED.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120640"},"PeriodicalIF":5.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149406","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":"Zhichi Suanzaoren Decoction alleviates perimenopausal insomnia via restoring astrocytic primary cilia and modulating Wnt/GSK-3β/GR signaling axis","authors":"Zeyu Zhang ,&nbsp;Yufei Liu ,&nbsp;Boyang Zhao ,&nbsp;Hanxin Fu ,&nbsp;Jiaxin Wang ,&nbsp;MingJia Zhang ,&nbsp;Yonghua Zhang ,&nbsp;Linlin Hu ,&nbsp;Xin Zhang","doi":"10.1016/j.jep.2025.120631","DOIUrl":"10.1016/j.jep.2025.120631","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Traditional Chinese medicine has historically used Zhichi Suanzaoren Decoction (ZSD) to alleviate perimenopausal insomnia (PMI). ZSD has demonstrated clinical efficacy in treating PMI-related symptoms; however, its active constituents and mechanisms of action remain unclear.</div></div><div><h3>Aim of the study</h3><div>The aim of this study was to explore the bioactive components of ZSD using UPLC-Q-TOF/MS, evaluate its efficacy in vivo experiments, and elucidate its potential mechanisms of action—particularly the role of primary hippocampal astrocyte cilia in PMI.</div></div><div><h3>Materials and methods</h3><div>The main components of ZSD were analyzed by UPLC-Q-TOF/MS. A PMI model was established using bilateral ovariectomy, followed by ZSD treatment. Behavioral tests and pentobarbital sodium-induced sleep synergy experiments were used to assess anti-insomnia and anxiolytic effects. Mechanistic studies included ELISA, Nissl staining, immunohistochemistry, transcriptome sequencing, immunofluorescence staining, qRT-PCR, Western blotting, and adeno-associated virus (AAV)-mediated Foxj1 knockdown.</div></div><div><h3>Results</h3><div>A total of 97 chemical components in the aqueous extract of ZSD were identified using UPLC-Q-TOF/MS in positive- and negative-ion modes. ZSD significantly improved sleep and reduced anxiety in PMI mice; increased hippocampal GABA levels; and reduced serum ACTH, CORT, IL-6, TNF-α, and IL-1β levels. ZSD exerts a protective effect on hippocampal neurons and reduces neuroinflammation. Transcriptomic and protein-level analyses demonstrated that ZSD inhibited Wnt signaling by promoting Foxj1 expression and restoring primary cilia in astrocytes. This led to dual effects: (1) activation of the GSK-3β/GR signaling pathway, restoring HPA axis function and reversing glucocorticoid resistance; and (2) suppression of β-catenin nuclear translocation and astrocyte-driven neuroinflammation.</div></div><div><h3>Conclusions</h3><div>ZSD can alleviate insomnia, anxiety, and neuroinflammation in a PMI model. The therapeutic effects are mediated through the restoration of primary astrocyte cilia via Foxj1 upregulation. These findings highlight a previously unrecognized role of primary cilia in the pathogenesis of PMI and provide a scientific rationale for the clinical application of ZSD and traditional Chinese medicine in mood-related disorders.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120631"},"PeriodicalIF":5.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137702","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":"Chrysophanein of Rhubarb rescues ILC3-Derived IL-22 by blocking CCDC25/ILK/HIF-1α for mucosal healing in ulcerative colitis mice","authors":"Bo Xu ,&nbsp;Shuiling Cao ,&nbsp;Chunjing Li ,&nbsp;Meng Zhao ,&nbsp;Qing Wang ,&nbsp;Xueqian Xie ,&nbsp;Hongxu Chen ,&nbsp;Rui Xu ,&nbsp;Qi Yi ,&nbsp;Xuezhou Ke ,&nbsp;Ying Zhu ,&nbsp;Lian Zhou ,&nbsp;Xia Luo","doi":"10.1016/j.jep.2025.120628","DOIUrl":"10.1016/j.jep.2025.120628","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>In traditional Chinese medicine, <em>rhei radix et rhizoma</em>, is derived from the dried roots and rhizomes of <em>Rheum palmatum</em> L., <em>Rheum tanguticum Maxim. ex Balf</em>. or <em>medicinal Rheum officinale Baill</em>, are used to treat intestinal carbuncle and abdominal pain, as well as damp-heat dysentery. Chrysophanein is a natural compound extracted from <em>rhei radix et rhizoma</em> with significant anti-inflammatory properties.</div></div><div><h3>Aim</h3><div>Ulcerative colitis (UC) is characterized by chronic mucosal inflammation. Current therapies alleviate symptoms via anti-inflammatory effects but fail to prevent relapse. Restoring the intestinal mucosal barrier represents a novel therapeutic strategy beyond conventional approaches. This study aims to show that chrysophanein ameliorates UC symptoms by targeting the coiled-coil domain containing protein 25/integrin-linked kinase/hypoxia-inducible factor-1α(CCDC25/ILK/HIF-α) pathway to repair mucosal barrier integrity.</div></div><div><h3>Methods</h3><div>We established a CCDC25-overexpressing UC mouse model through the intraperitoneal injection of adeno-associated virus (AAV)-CCDC25, alongside providing the mice with free access to dextran sulfate sodium(DSS). Disease progression was evaluated through body weight, survival status, colon length, endoscopy, and histopathology. chrysophanein-treated UC mice were assessed via Alcian blue staining (mucin quantification), WB (Occludin/ZO-1/claudin-1), in vivo imaging (FITC-dextran 4000 distribution), limulus amebocyte lysate assay (serum LPS), bacterial translocation assays, WB (CCDC25/ILK/HIF-1α pathway), and flow cytometry (IL-22⁺ILC3s). Transmission electron microscopy (TEM) evaluated epithelial morphology, and co-culture experiments examined chrysophanein's protective effects on enterocytes.</div></div><div><h3>Results</h3><div>Compared to control AAV-UC mice, CCDC25-overexpressing mice exhibited exacerbated symptoms. chrysophanein significantly attenuated weight loss, hematochezia, and colon damage, enhanced mucosal barrier function (mucin, ZO-1/Occludin/Claudin-1), reduced bacterial translocation and serum LPS, suppressed CCDC25/ILK/HIF-1α, and elevated IL-22⁺ILC3 proportions in UC mice. However, CCDC25 overexpression diminished chrysophanein's efficacy, correlating with reduced IL-22⁺ILC3s. chrysophanein-MNK3-conditioned media increased TEER, lowered FD4 permeability, and upregulated ZO-1 (mimicking IL-22 recombinant protein), whereas OECCDC25-MNK3 media reversed these effects, confirming CCDC25's overexpression interferes with chrysophanein-mediated intestinal epithelial barrier repair via the IL-22 pathway.</div></div><div><h3>Conclusion</h3><div>Chrysophanein rescues ILC3-derived IL-22 by blocking CCDC25/ILK/HIF-1α for mucosal healing in UC.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120628"},"PeriodicalIF":5.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137753","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}