Pub Date : 2026-01-20DOI: 10.1016/j.jep.2026.121186
Lingjing Lu , Xinyue Huang , Yu Zhou , Yun Zhao , Yongqing Zou , Wenen Huang , Hongxia Ma , Min Hu
Ethnopharmacological relevance
Yangjing Zhongyu decoction (YZD), a traditional Chinese herbal formula, shows promise for treating polycystic ovary syndrome (PCOS), but its mechanisms of action remain unclear. Ferroptosis has emerged as a potential contributor to PCOS.
Aim of the study
To determine YZD's effects on PCOS by regulating ferroptosis in multiple organs.
Materials and methods
Dihydrotestosterone (DHT)-induced PCOS mice received YZD treatment at low/medium/high doses. We assessed metabolic (body weight, glucose tolerance, hepatic steatosis) and reproductive (estrous cycles, hormones, histology) parameters. Ferroptosis markers and related genes were analyzed in the liver, ovary, and uterus.
Results
YZD significantly improved both metabolic dysfunction (reduced body weight, improved glucose tolerance) and reproductive abnormalities (restored estrous cyclicity, normalized ovarian morphology). Mechanistically, YZD demonstrated consistent upregulation of glutathione peroxidase 4 (GPX4) in all tissues and downregulation of 4-hydroxynonenal (4HNE) in liver and uterine tissues. The effects on iron metabolism and mitochondrial function showed tissue-specific patterns. In liver tissue, YZD downregulated pro-ferroptotic genes (Slc1a5, Gls2, Cs, Tfrc, and Ireb2) and Slc7a11, and upregulated protective factors (Fth1, Ftl1, Fpn1, and Ho1). Ovarian tissue exhibited downregulation of Slc1a5, Tfrc, Ireb2, and Fpn1 along with upregulation of Gclc, Gss, and Ftl1. In the uterus, YZD treatment decreased the expression of Slc1a5, Cs, and Ireb2 and increased the expression of Slc7a11 and Gss.
Conclusions
YZD ameliorates PCOS by inhibiting ferroptosis in multiple organs, primarily via GPX4 activation and iron homeostasis regulation, thus supporting its potential as a natural therapeutic for PCOS.
{"title":"Yangjing Zhongyu decoction ameliorates polycystic ovary syndrome via multi-organ ferroptosis inhibition: A mechanistic study","authors":"Lingjing Lu , Xinyue Huang , Yu Zhou , Yun Zhao , Yongqing Zou , Wenen Huang , Hongxia Ma , Min Hu","doi":"10.1016/j.jep.2026.121186","DOIUrl":"10.1016/j.jep.2026.121186","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Yangjing Zhongyu decoction (YZD), a traditional Chinese herbal formula, shows promise for treating polycystic ovary syndrome (PCOS), but its mechanisms of action remain unclear. Ferroptosis has emerged as a potential contributor to PCOS.</div></div><div><h3>Aim of the study</h3><div>To determine YZD's effects on PCOS by regulating ferroptosis in multiple organs.</div></div><div><h3>Materials and methods</h3><div>Dihydrotestosterone (DHT)-induced PCOS mice received YZD treatment at low/medium/high doses. We assessed metabolic (body weight, glucose tolerance, hepatic steatosis) and reproductive (estrous cycles, hormones, histology) parameters. Ferroptosis markers and related genes were analyzed in the liver, ovary, and uterus.</div></div><div><h3>Results</h3><div>YZD significantly improved both metabolic dysfunction (reduced body weight, improved glucose tolerance) and reproductive abnormalities (restored estrous cyclicity, normalized ovarian morphology). Mechanistically, YZD demonstrated consistent upregulation of glutathione peroxidase 4 (GPX4) in all tissues and downregulation of 4-hydroxynonenal (4HNE) in liver and uterine tissues. The effects on iron metabolism and mitochondrial function showed tissue-specific patterns. In liver tissue, YZD downregulated pro-ferroptotic genes (<em>Slc1a5</em>, <em>Gls2</em>, <em>Cs</em>, <em>Tfrc</em>, and <em>Ireb2</em>) and <em>Slc7a11,</em> and upregulated protective factors (<em>Fth1</em>, <em>Ftl1</em>, <em>Fpn1</em>, and <em>Ho1</em>). Ovarian tissue exhibited downregulation of <em>Slc1a5</em>, <em>Tfrc</em>, <em>Ireb2</em>, and <em>Fpn1</em> along with upregulation of <em>Gclc</em>, <em>Gss</em>, and <em>Ftl1</em>. In the uterus, YZD treatment decreased the expression of <em>Slc1a5</em>, <em>Cs</em>, and <em>Ireb2</em> and increased the expression of <em>Slc7a11</em> and <em>Gss</em>.</div></div><div><h3>Conclusions</h3><div>YZD ameliorates PCOS by inhibiting ferroptosis in multiple organs, primarily via GPX4 activation and iron homeostasis regulation, thus supporting its potential as a natural therapeutic for PCOS.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121186"},"PeriodicalIF":5.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025663","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}
Pub Date : 2026-01-19DOI: 10.1016/j.jep.2026.121244
Chunling Wang , Xiaotao Feng , Wentao Zhang , Lizhen Huang , Xiangdong Lu , Mengjie Sun , Mengyuan Gao , Xiaodong Wen
Ethnopharmacological relevance
Fructus Mume (FM) is derived from the nearly ripe fruit of Prunus mume Sieb. et Zucc., and widely used as a traditional medicine in Asian countries. FM has the effect of calming Liver to stop endogenous Wind, and has been used for thousands of years in the treatment of Parkinson's disease (PD), as recorded in ancient formulas such as Wumei Pills. However, the specific mechanism by which it treats PD remains larger unclear.
Purpose
The aim of this study was to investigate the effects and mechanisms by which the active ingredients of FM (Fructus Mume flavonoids, FMF) mitigate the progression of PD.
Methods
We isolated FMF from FM and explored its chemical composition and active compound content. In vivo and in vitro PD models were employed to investigate the alleviative effects of FMF on PD and its underlying mechanisms.
Results
We identified 193 compounds and quantified 154 flavonoid compounds in the FMF. Six compounds were present at concentrations exceeding 100 μg/g, namely Isorhamnetin (1287.0639 μg/g), Narcissin (764.9639 μg/g), Nicotiflorin (613.8568 μg/g), Quercetin (435.5215 μg/g), Nepitrin (295.4833 μg/g), and Kaempferol (241.9767 μg/g). Moreover, FMF alleviated behavioral deficits in PD rats. FMF also inhibited the loss of neurons and the formation of α-synuclein aggregates, and promoted the expression of tyrosine hydroxylase in the substantia nigra pars compacta in PD rats. In vivo and in vitro PD models demonstrated that autophagy inhibition significantly abolished the neuroprotective effects of FMF. Mechanically, FMF could enhance mitophagy to attenuate the mitochondrial dysfunction by activating the Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK) signaling pathway.
Conclusion
FMF promotes neuronal mitophagy to exert the neuroprotective effects by activating the CaMKKβ/AMPK signaling pathway. These findings provide a theoretical foundation for the application of FM in the treatment of PD and promote the clinical application of FM.
{"title":"Total flavonoids isolated from Fructus Mume (Prunus mume Sieb. et Zucc.) mitigate Parkinson's disease progression by promoting neuronal mitophagy via activation of the CaMKKβ/AMPK signaling pathway","authors":"Chunling Wang , Xiaotao Feng , Wentao Zhang , Lizhen Huang , Xiangdong Lu , Mengjie Sun , Mengyuan Gao , Xiaodong Wen","doi":"10.1016/j.jep.2026.121244","DOIUrl":"10.1016/j.jep.2026.121244","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Fructus Mume</em> (FM) is derived from the nearly ripe fruit of <em>Prunus mume Sieb. et Zucc.</em>, and widely used as a traditional medicine in Asian countries. FM has the effect of calming Liver to stop endogenous Wind, and has been used for thousands of years in the treatment of Parkinson's disease (PD), as recorded in ancient formulas such as Wumei Pills. However, the specific mechanism by which it treats PD remains larger unclear.</div></div><div><h3>Purpose</h3><div>The aim of this study was to investigate the effects and mechanisms by which the active ingredients of FM (<em>Fructus Mume</em> flavonoids, FMF) mitigate the progression of PD.</div></div><div><h3>Methods</h3><div>We isolated FMF from FM and explored its chemical composition and active compound content. <em>In vivo</em> and <em>in vitro</em> PD models were employed to investigate the alleviative effects of FMF on PD and its underlying mechanisms.</div></div><div><h3>Results</h3><div>We identified 193 compounds and quantified 154 flavonoid compounds in the FMF. Six compounds were present at concentrations exceeding 100 μg/g, namely Isorhamnetin (1287.0639 μg/g), Narcissin (764.9639 μg/g), Nicotiflorin (613.8568 μg/g), Quercetin (435.5215 μg/g), Nepitrin (295.4833 μg/g), and Kaempferol (241.9767 μg/g). Moreover, FMF alleviated behavioral deficits in PD rats. FMF also inhibited the loss of neurons and the formation of α-synuclein aggregates, and promoted the expression of tyrosine hydroxylase in the substantia nigra pars compacta in PD rats. <em>In vivo</em> and <em>in vitro</em> PD models demonstrated that autophagy inhibition significantly abolished the neuroprotective effects of FMF. Mechanically, FMF could enhance mitophagy to attenuate the mitochondrial dysfunction by activating the Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK) signaling pathway.</div></div><div><h3>Conclusion</h3><div>FMF promotes neuronal mitophagy to exert the neuroprotective effects by activating the CaMKKβ/AMPK signaling pathway. These findings provide a theoretical foundation for the application of FM in the treatment of PD and promote the clinical application of FM.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121244"},"PeriodicalIF":5.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018736","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}
Pub Date : 2026-01-19DOI: 10.1016/j.jep.2026.121245
QiWei Yang , Tao Huang , HaoQi Chen , Xi Cao , WenFeng Zhu , YiShan Peng , Lin Yu , QiYi Zhao , Li Wang , XiaoWen Wang , GenShu Wang
Ethnopharmacological relevance
Cistanche deserticola Y.C. Ma (Orobanchaceae), traditionally prescribed in Chinese medicine to “tonify the kidneys, nourish the essence, and moisten the intestines,” has long been used to treat disorders related to kidney deficiency, such as fatigue, impotence, infertility, and senile constipation. Modern pharmacological studies have further documented its hepatoprotective potential. Total glycosides extracted from C. deserticola (GCs) represent the major bioactive constituents and may provide novel therapeutic strategies for hepatic ischemia–reperfusion injury (HIRI), a severe complication of hepatic surgery and transplantation.
Aim of the study
This study aimed to evaluate the protective effects of GCs against HIRI and to elucidate the molecular mechanisms underlying their hepatoprotective activity, with a focus on the cyclic adenosine monophosphate (cAMP)–exchange protein directly activated by cAMP 2 (EPAC2)–RAS-related protein 1 (Rap1)–Hippo–Yes-associated protein (YAP)–c-Jun N-terminal kinase (JNK) signaling axis.
Materials and methods
A murine model of segmental HIRI and mouse liver organoid models subjected to hypoxia/reoxygenation (H/R) were used to assess the protective effects of GCs. Hepatocyte apoptosis, autophagy, oxidative stress markers, and signaling pathway activation were evaluated in vivo and in vitro. Genetic knockdown experiments targeting EPAC2, Rap1, YAP, and JNK were performed to validate the mechanistic involvement of these signaling molecules.
Results
GCs significantly attenuated HIRI-induced hepatic damage, as indicated by reduced apoptosis and enhanced autophagy in hepatocytes. Mechanistically, GCs increased cAMP levels, upregulated EPAC2, and activated Rap1, which in turn inhibited Hippo kinases mammalian sterile 20-like kinase 1 (MST1) and large tumor suppressor kinase 1 (LATS1), promoted YAP nuclear translocation, and facilitated YAP–JNK interaction. These events enhanced autophagy and conferred cytoprotection. Knockdown of EPAC2, Rap1, YAP, or JNK abolished the hepatoprotective effects of GCs. Liver organoid experiments further confirmed improved structural integrity and survival under H/R stress following GCs treatment.
Conclusions
GCs protect against HIRI by activating the EPAC2–Rap1–Hippo–YAP–JNK axis to promote autophagy and suppress apoptosis. These findings provide mechanistic insight into the hepatoprotective actions of GCs and support their evidence-based ethnopharmacological use as a promising therapeutic approach for ischemic liver injury.
民族药理学相关性：肉苁蓉（Orobanchaceae），传统中药处方“补肾、养精、润肠”，长期以来被用于治疗与肾虚相关的疾病，如疲劳、阳痿、不孕症和老年性便秘。现代药理学研究进一步证实了其保护肝脏的潜力。从荒漠草中提取的总苷（GCs）是主要的生物活性成分，可能为肝缺血再灌注损伤（HIRI）的治疗提供新的策略，这是肝脏手术和移植的严重并发症。研究目的：本研究旨在评估GCs对HIRI的保护作用，并阐明其肝保护作用的分子机制，重点研究cAMP 2 (EPAC2)- ras相关蛋白1 (Rap1)-希波-叶相关蛋白(YAP)-c-Jun n -末端激酶（JNK）信号轴直接激活的环腺苷单磷酸（cAMP）交换蛋白。材料和方法：采用小鼠节段性HIRI模型和缺氧/再氧化（H/R）小鼠肝类器官模型来评估gc的保护作用。在体内和体外评估肝细胞凋亡、自噬、氧化应激标志物和信号通路激活。我们进行了针对EPAC2、Rap1、YAP和JNK的基因敲低实验，以验证这些信号分子的机制参与。结果：GCs可显著减轻hiri诱导的肝损伤，肝细胞凋亡减少，自噬增强。在机制上，GCs增加cAMP水平，上调EPAC2，激活Rap1，进而抑制Hippo激酶，哺乳动物不育20样激酶1 （MST1）和大肿瘤抑制激酶1 (LATS1)，促进YAP核易位，促进YAP- jnk相互作用。这些事件增强了自噬并赋予细胞保护。EPAC2、Rap1、YAP或JNK的敲低可消除GCs的肝保护作用。肝类器官实验进一步证实，GCs治疗可改善H/R应激下的肝脏结构完整性和存活。结论：GCs通过激活EPAC2-Rap1-Hippo-YAP-JNK轴促进细胞自噬，抑制细胞凋亡，对HIRI具有保护作用。这些发现为GCs的肝保护作用提供了机制见解，并支持其作为缺血性肝损伤治疗方法的循证民族药理学应用。
{"title":"Natural glycosides from Cistanche deserticola alleviate hepatic ischemia–reperfusion injury via a cAMP-mediated signaling pathway","authors":"QiWei Yang , Tao Huang , HaoQi Chen , Xi Cao , WenFeng Zhu , YiShan Peng , Lin Yu , QiYi Zhao , Li Wang , XiaoWen Wang , GenShu Wang","doi":"10.1016/j.jep.2026.121245","DOIUrl":"10.1016/j.jep.2026.121245","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cistanche deserticola</em> Y.C. Ma (Orobanchaceae), traditionally prescribed in Chinese medicine to “tonify the kidneys, nourish the essence, and moisten the intestines,” has long been used to treat disorders related to kidney deficiency, such as fatigue, impotence, infertility, and senile constipation. Modern pharmacological studies have further documented its hepatoprotective potential. Total glycosides extracted from <em>C. deserticola</em> (GCs) represent the major bioactive constituents and may provide novel therapeutic strategies for hepatic ischemia–reperfusion injury (HIRI), a severe complication of hepatic surgery and transplantation.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the protective effects of GCs against HIRI and to elucidate the molecular mechanisms underlying their hepatoprotective activity, with a focus on the cyclic adenosine monophosphate (cAMP)–exchange protein directly activated by cAMP 2 (EPAC2)–RAS-related protein 1 (Rap1)–Hippo–Yes-associated protein (YAP)–c-Jun N-terminal kinase (JNK) signaling axis.</div></div><div><h3>Materials and methods</h3><div>A murine model of segmental HIRI and mouse liver organoid models subjected to hypoxia/reoxygenation (H/R) were used to assess the protective effects of GCs. Hepatocyte apoptosis, autophagy, oxidative stress markers, and signaling pathway activation were evaluated in vivo and in vitro. Genetic knockdown experiments targeting EPAC2, Rap1, YAP, and JNK were performed to validate the mechanistic involvement of these signaling molecules.</div></div><div><h3>Results</h3><div>GCs significantly attenuated HIRI-induced hepatic damage, as indicated by reduced apoptosis and enhanced autophagy in hepatocytes. Mechanistically, GCs increased cAMP levels, upregulated EPAC2, and activated Rap1, which in turn inhibited Hippo kinases mammalian sterile 20-like kinase 1 (MST1) and large tumor suppressor kinase 1 (LATS1), promoted YAP nuclear translocation, and facilitated YAP–JNK interaction. These events enhanced autophagy and conferred cytoprotection. Knockdown of EPAC2, Rap1, YAP, or JNK abolished the hepatoprotective effects of GCs. Liver organoid experiments further confirmed improved structural integrity and survival under H/R stress following GCs treatment.</div></div><div><h3>Conclusions</h3><div>GCs protect against HIRI by activating the EPAC2–Rap1–Hippo–YAP–JNK axis to promote autophagy and suppress apoptosis. These findings provide mechanistic insight into the hepatoprotective actions of GCs and support their evidence-based ethnopharmacological use as a promising therapeutic approach for ischemic liver injury.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121245"},"PeriodicalIF":5.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018770","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}
Pub Date : 2026-01-19DOI: 10.1016/j.jep.2026.121247
Xize Wu , Changbin Yuan , Haotian Wang , Xue Pan , Ruiying Wang , Qicheng Cai , Yuxi Huang , Jiaqi Ren , Jian Kang , Meijia Cheng , Xiaoyu Gao , Yue Li , Kaifeng Yu , Jiaxiang Pan
Ethnopharmacological relevance
ShenLingBaiZhu Powder (SLBZP) is a renowned traditional Chinese medicinal formula that has been historically and clinically applied for managing obesity (OB) and atherosclerosis (AS). Nevertheless, its precise molecular mechanisms remain to be fully elucidated.
Aim of the study
To systematically clarify the material basis and multi-target mechanisms of SLBZP against OB-AS comorbidity by integrating network pharmacology and experimental validation.
Material and methods
Bioinformatics analysis of public transcriptomic datasets was performed to identify common differentially expressed genes and Hub genes between OB and AS, which were validated in a cellular co-culture model of free fatty acid-induced differentiated 3T3-L1 adipocytes and oxidized low-density lipoprotein-induced RAW 264.7 macrophage foam cells. Bioactive compounds in SLBZP-containing serum were characterized by HPLC-Q-TOF-MS/MS. Network pharmacology predicted potential targets and pathways. Finally, in vitro experiments were conducted to assess the effects of SLBZP on lipid accumulation, cell activity, inflammatory cytokine secretion, apoptosis, and key signaling pathways.
Results
Bioinformatics analysis identified 115 common crosstalk genes related to inflammation, immune responses, chemotaxis, and apoptosis in OB and AS comorbidity. Machine learning pinpointed three Hub genes, MNDA, PTPRC, and MMP9, which were upregulated in the comorbidity model. Mass spectrometry identified 62 specific compounds in the drug-containing serum. Network pharmacology predictions suggested that SLBZP might alleviate inflammation and apoptosis by regulating pathways such as NF-κB. In vitro experiments demonstrated that adipocytes under pathological conditions promoted macrophage foam cell formation, whereas SLBZP significantly inhibited lipid accumulation, reduced levels of pro-inflammatory cytokines (IL6, IL1β, TNF), and decreased apoptosis. These protective effects were antagonized by a TLR4 agonist, indicating the involvement of the TLR4/NF-κB pathway. Molecular docking indicated high binding affinity of chenodeoxycholic acid, genistein, and 18β-glycyrrhetinic acid to key targets of pathways and apoptosis.
Conclusions
MNDA, PTPRC, and MMP9 may serve as potential biomarkers for OB and AS comorbidity. SLBZP alleviates the comorbid process by improving lipid metabolism, suppressing inflammation, and inhibiting apoptosis, mechanisms likely associated with modulation of the TLR4/NF-κB signaling pathway.
{"title":"ShenLingBaiZhu powder ameliorates obesity and atherosclerosis by inhibiting inflammation and apoptosis through the suppression of the TLR4/NF-κB pathway","authors":"Xize Wu , Changbin Yuan , Haotian Wang , Xue Pan , Ruiying Wang , Qicheng Cai , Yuxi Huang , Jiaqi Ren , Jian Kang , Meijia Cheng , Xiaoyu Gao , Yue Li , Kaifeng Yu , Jiaxiang Pan","doi":"10.1016/j.jep.2026.121247","DOIUrl":"10.1016/j.jep.2026.121247","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>ShenLingBaiZhu Powder (SLBZP) is a renowned traditional Chinese medicinal formula that has been historically and clinically applied for managing obesity (OB) and atherosclerosis (AS). Nevertheless, its precise molecular mechanisms remain to be fully elucidated.</div></div><div><h3>Aim of the study</h3><div>To systematically clarify the material basis and multi-target mechanisms of SLBZP against OB-AS comorbidity by integrating network pharmacology and experimental validation.</div></div><div><h3>Material and methods</h3><div>Bioinformatics analysis of public transcriptomic datasets was performed to identify common differentially expressed genes and Hub genes between OB and AS, which were validated in a cellular co-culture model of free fatty acid-induced differentiated 3T3-L1 adipocytes and oxidized low-density lipoprotein-induced RAW 264.7 macrophage foam cells. Bioactive compounds in SLBZP-containing serum were characterized by HPLC-Q-TOF-MS/MS. Network pharmacology predicted potential targets and pathways. Finally, in vitro experiments were conducted to assess the effects of SLBZP on lipid accumulation, cell activity, inflammatory cytokine secretion, apoptosis, and key signaling pathways.</div></div><div><h3>Results</h3><div>Bioinformatics analysis identified 115 common crosstalk genes related to inflammation, immune responses, chemotaxis, and apoptosis in OB and AS comorbidity. Machine learning pinpointed three Hub genes, MNDA, PTPRC, and MMP9, which were upregulated in the comorbidity model. Mass spectrometry identified 62 specific compounds in the drug-containing serum. Network pharmacology predictions suggested that SLBZP might alleviate inflammation and apoptosis by regulating pathways such as NF-κB. In vitro experiments demonstrated that adipocytes under pathological conditions promoted macrophage foam cell formation, whereas SLBZP significantly inhibited lipid accumulation, reduced levels of pro-inflammatory cytokines (IL6, IL1β, TNF), and decreased apoptosis. These protective effects were antagonized by a TLR4 agonist, indicating the involvement of the TLR4/NF-κB pathway. Molecular docking indicated high binding affinity of chenodeoxycholic acid, genistein, and 18β-glycyrrhetinic acid to key targets of pathways and apoptosis.</div></div><div><h3>Conclusions</h3><div>MNDA, PTPRC, and MMP9 may serve as potential biomarkers for OB and AS comorbidity. SLBZP alleviates the comorbid process by improving lipid metabolism, suppressing inflammation, and inhibiting apoptosis, mechanisms likely associated with modulation of the TLR4/NF-κB signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121247"},"PeriodicalIF":5.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018707","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}
Pub Date : 2026-01-18DOI: 10.1016/j.jep.2026.121240
Linyuan Xue , Jiyixuan Li , Li Sun , Ting Liu , Ben Lam , Kunyue Xing , Bing Liang , Jiayi Hu , Zihan Zheng , Ying Yang , Yanghui Huo , Yutao Xiu , Jiazhen Xu , Dongming Xing
<div><h3>Ethnopharmacological relevance</h3><div>Mulberry (<em>Morus alba</em> L.) has a longstanding history of use in Traditional Chinese Medicine (TCM). It is recorded in the classic <em>Compendium of Materia Medica</em> (Ben Cao Gang Mu) that mulberry possesses the efficacy to “strengthen muscles and bones”. This traditional indication suggests a potential role in skeletal health, yet its scientific and pharmacological basis has not been fully elucidated. The present study provides the first experimental evidence that a standardized polyphenol extract from mulberry (ABRU) bidirectionally regulates bone metabolism, simultaneously promoting bone formation and inhibiting bone loss. This work not only validates a centuries-old ethnopharmacological claim with modern molecular and functional evidence but also identifies mulberry polyphenols as a promising candidate for developing natural product-based therapies for bone metabolic disorders like osteoporosis.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the dual regulatory effects and mechanisms of mulberry polyphenols (ABRU) on bone metabolism.</div></div><div><h3>Methods</h3><div>MC3T3 cells and Bone marrow-derived macrophages (BMDMs) were used to evaluate the effects of various mulberry extracts on osteoblastic mineralization and osteoclastogenesis. Active extracts were analyzed for their chemical composition using liquid chromatography-mass spectrometry (LC-MS). Network pharmacology, molecular docking, ROC analysis, and thermal shift assays were employed to identify the molecular targets of ABRU. The dual regulation of bone metabolism by ABRU was further assessed <em>in vivo</em> using subcutaneous bone formation assays and a D-galactose-induced mouse model of bone loss.</div></div><div><h3>Results</h3><div><em>In vitro</em> experiments demonstrated that mulberry polyphenol (ABRU) significantly enhanced osteoblast proliferation and differentiation. After 24 h, osteoblast proliferation doubled, after 14 days, mineralization (measured by Alizarin Red staining) and alkaline phosphatase activity both increased two-fold. ABRU also inhibited osteoclast function, achieving 50 % suppression within 6 days, indicating a dual regulatory effect on bone metabolism—promoting bone formation while inhibiting resorption. Further investigation using Pparg knockdown revealed that silencing <em>Pparg</em> reduced SOST expression and upregulated osteogenic markers ALP, OCN, RUNX2. Crucially, <em>Pparg</em> suppression activated the Wnt signaling pathway, evidenced by increased LRP5/TCF expression and enhanced nuclear accumulation of β-catenin.<em>In vivo</em>, oral administration of ABRU dose-dependently increased subcutaneous bone formation in nude mice by 2–4 fold. In the D-galactose-induced aging bone loss model, ABRU supplementation improved bone mineral density by ∼20 %, increased trabecular bone area by 24.5 %, and reduced osteoclast number by 58.4 %.</div><div>Mechanistically,
民族药理学相关性：桑树（Morus alba L.）在中药（TCM）中具有悠久的使用历史。据《本草纲目》记载，桑具有“壮筋骨”的功效。这一传统适应症提示其在骨骼健康方面的潜在作用，但其科学和药理学基础尚未完全阐明。本研究首次提供了桑多酚提取物（ABRU）双向调节骨代谢，同时促进骨形成和抑制骨丢失的实验证据。这项工作不仅用现代分子和功能证据验证了数百年前的民族药理学主张，而且还确定了桑葚多酚作为开发基于天然产物的骨代谢紊乱（如骨质疏松症）疗法的有希望的候选者。研究目的：探讨桑多酚（mulberry polyphenols， ABRU）对骨代谢的双重调控作用及其机制。方法：采用MC3T3细胞和原代骨髓基质细胞（BMSCs）观察桑树提取物对成骨细胞矿化和破骨细胞生成的影响。采用液相色谱-质谱法（LC-MS）分析活性提取物的化学成分。采用网络药理学、分子对接、ROC分析和热移分析来确定ABRU的分子靶点。通过皮下骨形成实验和d -半乳糖诱导的骨丢失小鼠模型，进一步评估ABRU对骨代谢的双重调节。结果：体外实验表明桑多酚（ABRU）能显著促进成骨细胞的增殖和分化。24小时后，成骨细胞增殖增加一倍，14天后，矿化（茜素红染色测定）和碱性磷酸酶活性均增加两倍。ABRU还能抑制破骨细胞的功能，在6天内达到50%的抑制，表明它对骨代谢具有双重调节作用，既促进骨形成，又抑制骨吸收。对Pparg基因敲除的进一步研究发现，沉默Pparg基因可降低SOST的表达，上调成骨标志物ALP、OCN、RUNX2。至关重要的是，Pparg抑制激活了Wnt信号通路，LRP5/TCF表达增加，β-catenin核积累增强。在体内，口服ABRU剂量依赖性地使裸鼠皮下骨形成增加2-4倍。在d -半乳糖诱导的衰老骨质流失模型中，补充ABRU可使骨密度提高约20%，使骨小梁面积增加24.5%，并使破骨细胞数量减少58.4%。从机制上讲，ABRU的核心多酚成分抑制PPARG的表达，导致硬化蛋白（SOST）活性下调。该分子通路支持ABRU对骨代谢的双重调控。结论：本研究首次通过体外和体内实验证明桑多酚（mulberry polyphenols， ABRU）促进骨形成，减轻老年性骨质流失。它还揭示了ABRU通过PPARG/SOST信号轴介导对成骨细胞分化和破骨细胞功能的双重调节作用。
{"title":"Mulberry polyphenols (ABRU) promote bone formation and alleviate bone loss via dual regulation of bone metabolism","authors":"Linyuan Xue , Jiyixuan Li , Li Sun , Ting Liu , Ben Lam , Kunyue Xing , Bing Liang , Jiayi Hu , Zihan Zheng , Ying Yang , Yanghui Huo , Yutao Xiu , Jiazhen Xu , Dongming Xing","doi":"10.1016/j.jep.2026.121240","DOIUrl":"10.1016/j.jep.2026.121240","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Mulberry (<em>Morus alba</em> L.) has a longstanding history of use in Traditional Chinese Medicine (TCM). It is recorded in the classic <em>Compendium of Materia Medica</em> (Ben Cao Gang Mu) that mulberry possesses the efficacy to “strengthen muscles and bones”. This traditional indication suggests a potential role in skeletal health, yet its scientific and pharmacological basis has not been fully elucidated. The present study provides the first experimental evidence that a standardized polyphenol extract from mulberry (ABRU) bidirectionally regulates bone metabolism, simultaneously promoting bone formation and inhibiting bone loss. This work not only validates a centuries-old ethnopharmacological claim with modern molecular and functional evidence but also identifies mulberry polyphenols as a promising candidate for developing natural product-based therapies for bone metabolic disorders like osteoporosis.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the dual regulatory effects and mechanisms of mulberry polyphenols (ABRU) on bone metabolism.</div></div><div><h3>Methods</h3><div>MC3T3 cells and Bone marrow-derived macrophages (BMDMs) were used to evaluate the effects of various mulberry extracts on osteoblastic mineralization and osteoclastogenesis. Active extracts were analyzed for their chemical composition using liquid chromatography-mass spectrometry (LC-MS). Network pharmacology, molecular docking, ROC analysis, and thermal shift assays were employed to identify the molecular targets of ABRU. The dual regulation of bone metabolism by ABRU was further assessed <em>in vivo</em> using subcutaneous bone formation assays and a D-galactose-induced mouse model of bone loss.</div></div><div><h3>Results</h3><div><em>In vitro</em> experiments demonstrated that mulberry polyphenol (ABRU) significantly enhanced osteoblast proliferation and differentiation. After 24 h, osteoblast proliferation doubled, after 14 days, mineralization (measured by Alizarin Red staining) and alkaline phosphatase activity both increased two-fold. ABRU also inhibited osteoclast function, achieving 50 % suppression within 6 days, indicating a dual regulatory effect on bone metabolism—promoting bone formation while inhibiting resorption. Further investigation using Pparg knockdown revealed that silencing <em>Pparg</em> reduced SOST expression and upregulated osteogenic markers ALP, OCN, RUNX2. Crucially, <em>Pparg</em> suppression activated the Wnt signaling pathway, evidenced by increased LRP5/TCF expression and enhanced nuclear accumulation of β-catenin.<em>In vivo</em>, oral administration of ABRU dose-dependently increased subcutaneous bone formation in nude mice by 2–4 fold. In the D-galactose-induced aging bone loss model, ABRU supplementation improved bone mineral density by ∼20 %, increased trabecular bone area by 24.5 %, and reduced osteoclast number by 58.4 %.</div><div>Mechanistically, ","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121240"},"PeriodicalIF":5.4,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010356","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}
Pub Date : 2026-01-18DOI: 10.1016/j.jep.2026.121243
Guang Chen , Shichen Zhou , Yuanyuan Chen , Jiayan Zhou , Ning Wang , Yibin Feng
Ethnopharmacological relevance
Despite the fact that herbal medicine has been used for a long time, their clinical application is challenged by unclear active ingredients and poorly understood mechanisms of action, resulting in considerable heterogeneity in therapeutic outcomes among patients.
Aim of the study
To explore the use of OLink-based biomarkers to predict the efficacy of Macaranga sinensis Müll.Arg in individuals with long COVID-related fatigue.
Materials and methods
This nested case-control study recruited long COVID participants who had routinely taken Macaranga sinensis Müll.Arg for more than three months. Case (response) and control (non-response) group were defined based on the change in Brief Fatigue Inventory (BFI) score. Plasma samples were analyzed using OLink. Mann–Whitney U test, Lasso and Ridge regression model, Random Forest, and Support Vector Machine (SVM) were used for differential expression analysis, feature selection, and biomarker identification, respectively.
Results
A total of 55 long COVID fatigue patients was included in this study (27 in case group and 28 in control group). Differential expression analysis filtered in a total of 13 potential biomarkers (log2 fold change >0.5; p < 0.05). Feature selection further selected 11 biomarkers, including uPA, TRAIL, IL-10, IL-18R1, CX3CL1, EPHB4, COL1A1, Flt3L, EGFR, IL-1RT2, and IFN-γ (all p < 1e-6). Random Forest and SVM identified the key biomarker of CX3CL1 (F1-score of 0.72).
Conclusions
Our exploratory analysis suggests that CX3CL1 is the candidate biomarker for predicting the efficacy of Macaranga sinensis Müll.Arg, warranting further investigation in larger studies. Our work highlights the translational potential of integrating statistical modeling and machine learning approaches with proteomic data to identify predictive biomarkers for herbal medicine efficacy in clinical settings.
尽管草药已经使用了很长时间，但其临床应用受到活性成分不明确和作用机制不清楚的挑战，导致患者治疗结果存在相当大的异质性。目的探讨基于olink的生物标志物对黄芩疗效的预测。在与covid - 19相关的长期疲劳的个体中。材料和方法本巢式病例对照研究招募了长期服用马卡兰加（Macaranga sinensis m ll）的患者。3个月以上。病例组（反应组）和对照组（无反应组）根据简短疲劳量表（BFI）评分的变化来定义。血浆样品使用OLink进行分析。分别使用Mann-Whitney U检验、Lasso和Ridge回归模型、随机森林和支持向量机（SVM）进行差异表达分析、特征选择和生物标志物鉴定。结果共纳入55例长时间COVID疲劳患者，其中病例组27例，对照组28例。差异表达分析共筛选出13个潜在的生物标志物（log2倍变化>；0.5; p < 0.05）。特征选择进一步选择了11个生物标志物，包括uPA、TRAIL、IL-10、IL-18R1、CX3CL1、EPHB4、COL1A1、Flt3L、EGFR、IL-1RT2和IFN-γ（均为p <； 1e-6）。随机森林和支持向量机识别出CX3CL1的关键生物标志物（f1得分为0.72）。结论探索性分析表明CX3CL1是预测黄芪疗效的候选生物标志物。这需要在更大的研究中进行进一步的调查。我们的工作强调了将统计建模和机器学习方法与蛋白质组学数据相结合的转化潜力，以确定临床环境中草药疗效的预测性生物标志物。
{"title":"OLink proteomic biomarker to predict clinical efficacy of Macaranga sinensis Müll.Arg: A nested case-control study","authors":"Guang Chen , Shichen Zhou , Yuanyuan Chen , Jiayan Zhou , Ning Wang , Yibin Feng","doi":"10.1016/j.jep.2026.121243","DOIUrl":"10.1016/j.jep.2026.121243","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Despite the fact that herbal medicine has been used for a long time, their clinical application is challenged by unclear active ingredients and poorly understood mechanisms of action, resulting in considerable heterogeneity in therapeutic outcomes among patients.</div></div><div><h3>Aim of the study</h3><div>To explore the use of OLink-based biomarkers to predict the efficacy of <em>Macaranga sinensis</em> Müll.Arg in individuals with long COVID-related fatigue.</div></div><div><h3>Materials and methods</h3><div>This nested case-control study recruited long COVID participants who had routinely taken <em>Macaranga sinensis</em> Müll.Arg for more than three months. Case (response) and control (non-response) group were defined based on the change in Brief Fatigue Inventory (BFI) score. Plasma samples were analyzed using OLink. Mann–Whitney <em>U</em> test, Lasso and Ridge regression model, Random Forest, and Support Vector Machine (SVM) were used for differential expression analysis, feature selection, and biomarker identification, respectively.</div></div><div><h3>Results</h3><div>A total of 55 long COVID fatigue patients was included in this study (27 in case group and 28 in control group). Differential expression analysis filtered in a total of 13 potential biomarkers (log<sub>2</sub> fold change >0.5; p < 0.05). Feature selection further selected 11 biomarkers, including uPA, TRAIL, IL-10, IL-18R1, CX3CL1, EPHB4, COL1A1, Flt3L, EGFR, IL-1RT2, and IFN-γ (all p < 1e-6). Random Forest and SVM identified the key biomarker of CX3CL1 (F1-score of 0.72).</div></div><div><h3>Conclusions</h3><div>Our exploratory analysis suggests that CX3CL1 is the candidate biomarker for predicting the efficacy of <em>Macaranga sinensis</em> Müll.Arg, warranting further investigation in larger studies. Our work highlights the translational potential of integrating statistical modeling and machine learning approaches with proteomic data to identify predictive biomarkers for herbal medicine efficacy in clinical settings.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121243"},"PeriodicalIF":5.4,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001848","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}
Pub Date : 2026-01-18DOI: 10.1016/j.jep.2026.121236
XianPing Zheng , JingLu Hu , ZiLiang Chen , MingDe Liao , ShuLin Luo , SiDing Lu , BoJie Lin
Background
Alopecia, especially androgenetic alopecia (AGA), is a common condition affecting many individuals globally, impacting both men and women. Current treatments, such as minoxidil and finasteride, have limitations regarding efficacy and side effects. Traditional Chinese Medicine (TCM) offers alternative treatments, with naringin—a flavonoid found in Citrus species—emerging as a potential candidate due to its influence on the Wnt/β-catenin signaling pathway, a key regulator of hair follicle growth.
Materials and methods
This study assessed the effects of naringin on hair regeneration in C57BL/6J mice through a dose-dependent approach. Mice were divided into five groups (1 %, 2 %, 4 % naringin, saline, and 5 % minoxidil). Hair regrowth was evaluated via macroscopic and histological examinations, immunohistochemistry, and molecular biology assays. Expression levels of key proteins in the Wnt/β-catenin pathway were measured, and molecular docking was performed to investigate interactions between naringin and β-catenin.
Results
The 4 % naringin group exhibited superior hair growth, with significantly higher hair follicle density and greater cell proliferation compared to other groups, including the 5 % minoxidil group. Molecular analysis confirmed enhanced expression of Wnt10b, β-catenin, and VEGF-A, along with a reduction in Wnt5a. Molecular docking revealed stable binding between naringin and β-catenin, suggesting a specific interaction that may mediate its effects.
Conclusions
Naringin promotes hair regeneration through activation of the Wnt/β-catenin signaling pathway, with the 4 % concentration showing the best results. This natural compound, particularly at 4 % concentration, demonstrates hair growth-promoting efficacy comparable to 5 % minoxidil by activating the Wnt/β-catenin pathway, offering a promising alternative for alopecia treatment.
{"title":"Naringin promotes hair regeneration via wnt/β-catenin pathway: A dose-dependent study in C57BL/6J mice","authors":"XianPing Zheng , JingLu Hu , ZiLiang Chen , MingDe Liao , ShuLin Luo , SiDing Lu , BoJie Lin","doi":"10.1016/j.jep.2026.121236","DOIUrl":"10.1016/j.jep.2026.121236","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia, especially androgenetic alopecia (AGA), is a common condition affecting many individuals globally, impacting both men and women. Current treatments, such as minoxidil and finasteride, have limitations regarding efficacy and side effects. Traditional Chinese Medicine (TCM) offers alternative treatments, with naringin—a flavonoid found in Citrus species—emerging as a potential candidate due to its influence on the Wnt/β-catenin signaling pathway, a key regulator of hair follicle growth.</div></div><div><h3>Materials and methods</h3><div>This study assessed the effects of naringin on hair regeneration in C57BL/6J mice through a dose-dependent approach. Mice were divided into five groups (1 %, 2 %, 4 % naringin, saline, and 5 % minoxidil). Hair regrowth was evaluated via macroscopic and histological examinations, immunohistochemistry, and molecular biology assays. Expression levels of key proteins in the Wnt/β-catenin pathway were measured, and molecular docking was performed to investigate interactions between naringin and β-catenin.</div></div><div><h3>Results</h3><div>The 4 % naringin group exhibited superior hair growth, with significantly higher hair follicle density and greater cell proliferation compared to other groups, including the 5 % minoxidil group. Molecular analysis confirmed enhanced expression of Wnt10b, β-catenin, and VEGF-A, along with a reduction in Wnt5a. Molecular docking revealed stable binding between naringin and β-catenin, suggesting a specific interaction that may mediate its effects.</div></div><div><h3>Conclusions</h3><div>Naringin promotes hair regeneration through activation of the Wnt/β-catenin signaling pathway, with the 4 % concentration showing the best results. This natural compound, particularly at 4 % concentration, demonstrates hair growth-promoting efficacy comparable to 5 % minoxidil by activating the Wnt/β-catenin pathway, offering a promising alternative for alopecia treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121236"},"PeriodicalIF":5.4,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001829","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}
Pub Date : 2026-01-17DOI: 10.1016/j.jep.2026.121225
Jacinta Katunge Kawenze, Emmanuel Nyongesa Waswa, Felix Wambua Muema, Clintone Onyango Ochieng, Elijah Mbandi Mkala, Elizabeth Syowai Mutinda, Victoire Izabayo, Victor Omondi Onjolo, Harriet Melany Nyamvula, Paul Musili, Yerong Hu, Guang-Wan Hu
Ethnopharmacological relevance: Coccinia species have long been utilized for their cultural significance, ecological balance, and managing diverse ailments since ancient times. These plants are indispensable sources of traditional medicines for ailments such as diabetes, skin diseases, asthma, constipation, stomachache, malaria, snakebites, jaundice, cough, and leishmaniasis among others.
Aim of the study: This review provides an overview of existing knowledge related to ethnobotany, phytochemistry, pharmacological properties, and toxicology of Coccinia species.
Materials and methods: Informationwas obtained through surveying electronic databases, including Google Scholar, Web of Science, PubMed, SCI-Finder, Springer, Elsevier, and other related bibliographic sources such as theses and books published between 1973 and 2024.
Results: Six (6) Coccinia species have been reported as significant sources of traditional medicines that remedy diverse ailments, prominently, diabetes, asthma, constipation, jaundice, and sexually transmitted infections. A total of 204 phytochemicals including terpenes and terpenoids (24), phenolic compounds (53), esters (21), and hydrocarbons (21) among others were reported. The crude extracts and screened bioactive constituents exhibited outstanding pharmacological activities such as antidiabetic, anticancer, antimalarial, antimicrobial, antileishmanial, anti-inflammatory, antioxidative, antitussive, hepatoprotective, antinociceptive, anti-dyslipidemic, and anti-ulcers.
Conclusion: This review scrutinized the data on traditional medicinal uses, phytochemistry, pharmacology, and toxicology of Coccinia species. Several pharmacological properties of Coccinia species are consistent with their ethnomedicinal uses. Coccinia species displayed some variations in their phytochemical profile indicating a diverse range of potentially beneficial properties across different species. Few studies have focused on the toxicology of Coccinia species, and thus, the need for further research on this area, for pharmaceutical standardization.
民族药理学相关性：自古以来，球虫物种就因其文化意义、生态平衡和管理各种疾病而长期被利用。这些植物是治疗糖尿病、皮肤病、哮喘、便秘、胃痛、疟疾、蛇咬伤、黄疸、咳嗽和利什曼病等疾病的传统药物不可缺少的来源。研究目的：综述了球虫属植物在民族植物学、植物化学、药理和毒理学等方面的研究进展。资料与方法：通过调查谷歌Scholar、Web of Science、PubMed、SCI-Finder、施普林格、Elsevier等电子数据库以及1973 - 2024年间发表的论文和书籍等相关书目来源获得信息。结果：据报道，六(6)种球菌是治疗各种疾病的传统药物的重要来源，特别是糖尿病，哮喘，便秘，黄疸和性传播感染。共报道了204种植物化学物质，包括萜烯和萜类化合物（24种）、酚类化合物（53种）、酯类（21种）和碳氢化合物（21种）等。粗提物和筛选出的生物活性成分具有抗糖尿病、抗癌、抗疟疾、抗菌、抗利什曼原虫、抗炎、抗氧化、止咳、保肝、抗伤、抗血脂异常、抗溃疡等药理活性。结论：本文综述了球虫属植物的传统药用、植物化学、药理和毒理学等方面的资料。球虫属植物的一些药理特性与其民族医学用途一致。球虫种类在其植物化学特征上显示出一些差异，这表明不同种类的球虫具有不同的潜在有益特性。目前关于球虫毒理学的研究较少，需要进一步开展这方面的研究，以促进药物标准化。
{"title":"Ethnobotany, phytochemistry, pharmacology, and toxicology of the genus Coccinia Wight & Arn: A comprehensive review.","authors":"Jacinta Katunge Kawenze, Emmanuel Nyongesa Waswa, Felix Wambua Muema, Clintone Onyango Ochieng, Elijah Mbandi Mkala, Elizabeth Syowai Mutinda, Victoire Izabayo, Victor Omondi Onjolo, Harriet Melany Nyamvula, Paul Musili, Yerong Hu, Guang-Wan Hu","doi":"10.1016/j.jep.2026.121225","DOIUrl":"https://doi.org/10.1016/j.jep.2026.121225","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Coccinia species have long been utilized for their cultural significance, ecological balance, and managing diverse ailments since ancient times. These plants are indispensable sources of traditional medicines for ailments such as diabetes, skin diseases, asthma, constipation, stomachache, malaria, snakebites, jaundice, cough, and leishmaniasis among others.</p><p><strong>Aim of the study: </strong>This review provides an overview of existing knowledge related to ethnobotany, phytochemistry, pharmacological properties, and toxicology of Coccinia species.</p><p><strong>Materials and methods: </strong>Informationwas obtained through surveying electronic databases, including Google Scholar, Web of Science, PubMed, SCI-Finder, Springer, Elsevier, and other related bibliographic sources such as theses and books published between 1973 and 2024.</p><p><strong>Results: </strong>Six (6) Coccinia species have been reported as significant sources of traditional medicines that remedy diverse ailments, prominently, diabetes, asthma, constipation, jaundice, and sexually transmitted infections. A total of 204 phytochemicals including terpenes and terpenoids (24), phenolic compounds (53), esters (21), and hydrocarbons (21) among others were reported. The crude extracts and screened bioactive constituents exhibited outstanding pharmacological activities such as antidiabetic, anticancer, antimalarial, antimicrobial, antileishmanial, anti-inflammatory, antioxidative, antitussive, hepatoprotective, antinociceptive, anti-dyslipidemic, and anti-ulcers.</p><p><strong>Conclusion: </strong>This review scrutinized the data on traditional medicinal uses, phytochemistry, pharmacology, and toxicology of Coccinia species. Several pharmacological properties of Coccinia species are consistent with their ethnomedicinal uses. Coccinia species displayed some variations in their phytochemical profile indicating a diverse range of potentially beneficial properties across different species. Few studies have focused on the toxicology of Coccinia species, and thus, the need for further research on this area, for pharmaceutical standardization.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121225"},"PeriodicalIF":5.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003482","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}
Pub Date : 2026-01-17DOI: 10.1016/j.jep.2025.121146
Jinni Meng , Ping Wei , Heping Yang , Lin Chen , Cheng Peng , Ou Dai , Qinmei Zhou , Liang Xiong
<div><h3>Ethnopharmacological relevance</h3><div><em>Ligusticum</em> <em>chuanxiong</em> Hort. (Chuanxiong) is a traditional Chinese medicinal herb whose rhizome has been historically and clinically used to treat conditions such as headache, dizziness, and depression. These traditional application broadly correlate with modern diagnoses of cerebrovascular dysfunction, impaired cerebral blood flow, and neuroinflammation. As a characteristic phthalide dimer and major bioactive constituent of Chuanxiong, levistilide A (LA) has shown significant therapeutic potential. However, its specific antidepressant and anxiolytic properties require further clarification.</div></div><div><h3>Aim of the study</h3><div>This study aimed to assess the efficacy of LA against depression and anxiety, with the further goal of elucidating its underlying molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>A depression- and anxiety-like state was induced in C57BL/6 mice by LPS challenge after which they received therapeutic intervention with different doses of LA. The therapeutic efficacy was assessed by behavioral tests, histopathological analyses, and enzyme-linked immunosorbent assays (ELISA). Concurrently, we assessed microglial activation via immunofluorescence, along with mitochondrial status by measuring reactive oxygen species (ROS) levels with flow cytometry and examining ultrastructure with transmission electron microscopy (TEM). To investigate the cellular mechanisms, LPS-stimulated BV2 cells was established<em>.</em> In this model, autophagic flux was quantitatively measured using Bafilomycin A1 (Baf A1) inhibition assays combined with Western blot analysis of LC3B-II. And mitophagy was evaluated by co-immunofluorescence LC3B with the mitochondrial marker Tomm40 in both BV2 cells and mouse hippocampal CA3. Building on this, computational approaches, along with experimental methodologies including immunofluorescence and western blotting, were utilized to elucidate the underlying molecular mechanisms. Furthermore, SIRT3-specific <em>siRNA</em> (<em>siRNA</em>-SIRT3) was used for further validation.</div></div><div><h3>Results</h3><div>The LA treatment demonstrated a notable protective role against LPS-induced depression and anxiety through ameliorating behaviors accompanied by depression- and anxiety-like behaviors, attenuating neuronal damage, downregulating pro-inflammatory cytokine expression levels, and suppressing microglial overactivation. Mechanistically, LA alleviated oxidative stress and mitochondrial dysfunction by reducing ROS accumulation and mitigating mitochondrial damage. In the LPS-induced BV2 cells, LA treatment significantly enhanced autophagic flux, as evidenced by the further accumulation of LC3B-II upon Baf A1 inhibition, which confirmed the promotion of functional autophagy. Concurrently, the increased co-localization of Tomm40 with LC3B upon LA treatment provided direct evidence for mitophagy activation. Molecular docki
{"title":"Levistilide A from Ligusticum chuanxiong alleviates LPS-induced depression- and anxiety-like behaviors by promoting mitophagy through the SIRT3/PINK1/Parkin pathway","authors":"Jinni Meng , Ping Wei , Heping Yang , Lin Chen , Cheng Peng , Ou Dai , Qinmei Zhou , Liang Xiong","doi":"10.1016/j.jep.2025.121146","DOIUrl":"10.1016/j.jep.2025.121146","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ligusticum</em> <em>chuanxiong</em> Hort. (Chuanxiong) is a traditional Chinese medicinal herb whose rhizome has been historically and clinically used to treat conditions such as headache, dizziness, and depression. These traditional application broadly correlate with modern diagnoses of cerebrovascular dysfunction, impaired cerebral blood flow, and neuroinflammation. As a characteristic phthalide dimer and major bioactive constituent of Chuanxiong, levistilide A (LA) has shown significant therapeutic potential. However, its specific antidepressant and anxiolytic properties require further clarification.</div></div><div><h3>Aim of the study</h3><div>This study aimed to assess the efficacy of LA against depression and anxiety, with the further goal of elucidating its underlying molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>A depression- and anxiety-like state was induced in C57BL/6 mice by LPS challenge after which they received therapeutic intervention with different doses of LA. The therapeutic efficacy was assessed by behavioral tests, histopathological analyses, and enzyme-linked immunosorbent assays (ELISA). Concurrently, we assessed microglial activation via immunofluorescence, along with mitochondrial status by measuring reactive oxygen species (ROS) levels with flow cytometry and examining ultrastructure with transmission electron microscopy (TEM). To investigate the cellular mechanisms, LPS-stimulated BV2 cells was established<em>.</em> In this model, autophagic flux was quantitatively measured using Bafilomycin A1 (Baf A1) inhibition assays combined with Western blot analysis of LC3B-II. And mitophagy was evaluated by co-immunofluorescence LC3B with the mitochondrial marker Tomm40 in both BV2 cells and mouse hippocampal CA3. Building on this, computational approaches, along with experimental methodologies including immunofluorescence and western blotting, were utilized to elucidate the underlying molecular mechanisms. Furthermore, SIRT3-specific <em>siRNA</em> (<em>siRNA</em>-SIRT3) was used for further validation.</div></div><div><h3>Results</h3><div>The LA treatment demonstrated a notable protective role against LPS-induced depression and anxiety through ameliorating behaviors accompanied by depression- and anxiety-like behaviors, attenuating neuronal damage, downregulating pro-inflammatory cytokine expression levels, and suppressing microglial overactivation. Mechanistically, LA alleviated oxidative stress and mitochondrial dysfunction by reducing ROS accumulation and mitigating mitochondrial damage. In the LPS-induced BV2 cells, LA treatment significantly enhanced autophagic flux, as evidenced by the further accumulation of LC3B-II upon Baf A1 inhibition, which confirmed the promotion of functional autophagy. Concurrently, the increased co-localization of Tomm40 with LC3B upon LA treatment provided direct evidence for mitophagy activation. Molecular docki","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121146"},"PeriodicalIF":5.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001828","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}
Pub Date : 2026-01-17DOI: 10.1016/j.jep.2026.121227
Huanrong Wang, Di Hu, Nianzhu Liu, Jie Qiu, Xi Zhang, Wei Jiang
Ethnopharmacological relevance
Salvia plebeia R.Br. (Lamiaceae), the dried aerial parts, has been traditionally used across China and East/South Asia to treat sore throat, bronchitis, nephritis edema, abscesses, mastitis, hemorrhoids, and bleeding disorders, consistent with traditional indications of heat-clearing, detoxifying, cooling blood, and promoting diuresis.
Aim of the review
This study provides a systematic overview of the ethnopharmacology, phytochemistry, pharmacological activities, quality control, and current applications of S. plebeia, while highlighting current research gaps and future perspectives.
Materials and methods
A comprehensive literature search was conducted using multiple scientific databases, including Web of Science, PubMed, Elsevier, ACS, CNKI, and Google Scholar, covering publications from database inception to October 2025. Relevant information on the ethnopharmacology, phytochemistry, pharmacological activities, quality control, and applications of S. plebeia was systematically collected, screened, and synthesized according to predefined inclusion/exclusion criteria.
Results
To date, 325 constituents have been identified, dominated by flavonoids, phenolic acids, terpenoids, volatile oils, sterols, lignans, and others. Extracts and purified compounds show tradition-relevant anti-inflammatory, antiviral, immunoregulatory, and antioxidant activities, while other reported effects (hepatoprotective, hypolipidemic, cardiovascular-protective, sedative/anticonvulsant, anticancer, and anti-photoaging) are presented as exploratory findings. Quality evaluation evolved from UV and HPLC to UPLC-MS fingerprinting using flavonoids and sesquiterpenes as markers. In practical applications, S. plebeia has been used in medicinal preparations for the management of pharyngitis, bronchitis, nephritis, dermatitis, and anorectal inflammation. In food sector, it has been developed into functional products, including health teas, chewable or effervescent tablets, composite beverages, and co-fermented vinegars.
Conclusion
Although S. plebeia shows broad pharmacological potential, current investigations remain constrained by incomplete chemical space coverage, limited pharmacokinetic and toxicological characterization, and insufficient well-designed clinical evidence. Future research should focus on comprehensive constituent profiling, mechanism-oriented validation aligned with traditional indications, standardized quality markers/fingerprints, and rigorous PK–toxicology–clinical translation, to promote safe, effective, and evidence-based utilization of S. plebeia in medicine and functional food development.
鼠尾草的民族药理学意义。（Lamiaceae），干燥的空气部分，传统上在中国和东亚/南亚用于治疗喉咙痛，支气管炎，肾炎水肿，脓肿，乳腺炎，痔疮和出血性疾病，符合传统的清热，解毒，凉血，利尿的适应症。本文从民族药理学、植物化学、药理活性、质量控制、应用现状等方面进行了综述，并对其研究现状和前景进行了展望。材料与方法对Web of Science、PubMed、Elsevier、ACS、CNKI、b谷歌Scholar等多个科学数据库进行了全面的文献检索，涵盖了从建库到2025年10月的出版物。系统地收集、筛选、合成了白羊草的民族药理学、植物化学、药理活性、质量控制和应用等方面的相关资料。结果目前已鉴定出325种成分，主要为黄酮类、酚酸类、萜类、挥发油类、甾醇类、木脂素类等。提取物和纯化的化合物显示出传统的抗炎、抗病毒、免疫调节和抗氧化活性，而其他已报道的作用（保护肝脏、降血脂、保护心血管、镇静/抗惊厥、抗癌和抗光老化）则是探索性的发现。以黄酮类化合物和倍半萜类化合物为标记物，从紫外和高效液相色谱技术发展到UPLC-MS指纹图谱技术。在实际应用中，葡萄球菌已被用于治疗咽炎、支气管炎、肾炎、皮炎和肛肠炎症的药物制剂中。在食品领域，它已发展成为功能性产品，包括保健茶，咀嚼或泡腾片，复合饮料，共发酵醋。结论尽管葡萄球菌具有广泛的药理潜力，但目前的研究仍受到化学空间覆盖不完整、药代动力学和毒理学表征有限以及缺乏精心设计的临床证据的限制。未来的研究应集中在全面的成分分析、符合传统适应症的机制验证、标准化的质量标记/指纹图谱、严格的pk毒理学-临床翻译等方面，以促进其在医学和功能食品开发中的安全、有效和循证利用。
{"title":"Salvia plebeia R.Br.: A comprehensive review of its ethnopharmacology, phytochemistry, pharmacological activities, quality control, and current applications","authors":"Huanrong Wang, Di Hu, Nianzhu Liu, Jie Qiu, Xi Zhang, Wei Jiang","doi":"10.1016/j.jep.2026.121227","DOIUrl":"10.1016/j.jep.2026.121227","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Salvia plebeia</em> R.Br. (Lamiaceae), the dried aerial parts, has been traditionally used across China and East/South Asia to treat sore throat, bronchitis, nephritis edema, abscesses, mastitis, hemorrhoids, and bleeding disorders, consistent with traditional indications of heat-clearing, detoxifying, cooling blood, and promoting diuresis.</div></div><div><h3>Aim of the review</h3><div>This study provides a systematic overview of the ethnopharmacology, phytochemistry, pharmacological activities, quality control, and current applications of <em>S. plebeia</em>, while highlighting current research gaps and future perspectives.</div></div><div><h3>Materials and methods</h3><div>A comprehensive literature search was conducted using multiple scientific databases, including Web of Science, PubMed, Elsevier, ACS, CNKI, and Google Scholar, covering publications from database inception to October 2025. Relevant information on the ethnopharmacology, phytochemistry, pharmacological activities, quality control, and applications of <em>S</em>. <em>plebeia</em> was systematically collected, screened, and synthesized according to predefined inclusion/exclusion criteria.</div></div><div><h3>Results</h3><div>To date, 325 constituents have been identified, dominated by flavonoids, phenolic acids, terpenoids, volatile oils, sterols, lignans, and others. Extracts and purified compounds show tradition-relevant anti-inflammatory, antiviral, immunoregulatory, and antioxidant activities, while other reported effects (hepatoprotective, hypolipidemic, cardiovascular-protective, sedative/anticonvulsant, anticancer, and anti-photoaging) are presented as exploratory findings. Quality evaluation evolved from UV and HPLC to UPLC-MS fingerprinting using flavonoids and sesquiterpenes as markers. In practical applications, <em>S. plebeia</em> has been used in medicinal preparations for the management of pharyngitis, bronchitis, nephritis, dermatitis, and anorectal inflammation. In food sector, it has been developed into functional products, including health teas, chewable or effervescent tablets, composite beverages, and co-fermented vinegars.</div></div><div><h3>Conclusion</h3><div>Although <em>S. plebeia</em> shows broad pharmacological potential, current investigations remain constrained by incomplete chemical space coverage, limited pharmacokinetic and toxicological characterization, and insufficient well-designed clinical evidence. Future research should focus on comprehensive constituent profiling, mechanism-oriented validation aligned with traditional indications, standardized quality markers/fingerprints, and rigorous PK–toxicology–clinical translation, to promote safe, effective, and evidence-based utilization of <em>S. plebeia</em> in medicine and functional food development.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"361 ","pages":"Article 121227"},"PeriodicalIF":5.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001849","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号