Pub Date : 2026-02-07DOI: 10.1016/j.jep.2026.121331
Yunxuan Zhang , Jingnan Miao , Dan Zhou , Dan Xu , Pingcong Fu , Yingqi Ou , Dingyao Pan , Chunfeng Li , Danning Zheng , Junqiang Qiu
<div><h3>Ethnopharmacological relevance</h3><div><em>Dioscorea bulbifera</em> L., the dried tuber of which is known as “Huangyaozi (黄药子)” in Traditional Chinese medicine (TCM), has a history of medicinal use spanning centuries within TCM and other traditional medical systems. It is traditionally utilized to dispel nodules and reduce goiter, clear heat and resolve toxins, and cool the blood to stop bleeding. Its primary applications include the treatment of conditions such as goiter, throat obstruction, carbuncles, and inflammatory swellings. In clinical TCM practice, <em>D. bulbifera</em> is frequently incorporated as a key component in compound formulations aimed at managing thyroid disorders and specific inflammatory conditions.</div></div><div><h3>Aim of the review</h3><div>This review aimed to systematically delineate the dual character of <em>D. bulbifera</em> by synthesizing research from January 2010 to December 2025 on its phytochemistry, pharmacology, and mechanisms of liver toxicity, with a focus on evaluating detoxification strategies to reconcile its efficacy with safety.</div></div><div><h3>Methods</h3><div>This comprehensive narrative review was conducted using targeted keywords related to <em>D. bulbifera</em> (e.g., "Huangyaozi," "Air potato") and its toxic component, Diosbulbin B (DB), across major databases including Elsevier, Web of Science, PubMed and Google Scholar.</div></div><div><h3>Results</h3><div>Documented in both classical and modern texts, <em>D. bulbifera</em> possesses a well-established ethnopharmacological history. Phytochemical studies from January 2010 to December 2025 have identified 99 newly reported compounds in <em>D. bulbifera</em>, primarily terpenoids, steroids, and phenolics. These constituents confer a broad spectrum of pharmacological activities, including antitumor, antioxidant, antimicrobial, antidiabetic, and immunomodulatory effects, mediated through key signaling pathways such as mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2). Hepatotoxicity, the most extensively researched adverse effect, is intrinsically linked to the diterpenoid lactone DB. Its mechanism involves CYP450-mediated metabolic activation, generating reactive intermediates that trigger oxidative stress, mitochondrial dysfunction, and inhibition of hepatobiliary transporters. Guided by TCM theory, strategies such as herbal compatibility (e.g., with <em>Angelica sinensis</em> Radix, <em>Glycyrrhizae</em> Radix et Rhizoma) and processing, alongside modern approaches like co-administration with protective agents (e.g., ferulic acid), show preclinical promise in reducing toxicity while preserving efficacy.</div></div><div><h3>Conclusion</h3><div>This review clarifies the efficacy-toxicity paradox of <em>D. bulbifera</em> and synthesizes key detoxification strategies centered on DB. To ensure its safe modernization, future research must prioritize holistic pharmacokinetic studies, systemati
民族药理学相关性：黄薯蓣（Dioscorea bulbifera L.），其干块茎在中医中被称为“黄药子”，在中医和其他传统医学体系中具有数百年的药用历史。传统上用于祛除结节，减少甲状腺肿，清热解毒，凉血止血。它的主要应用包括治疗甲状腺肿、咽喉阻塞、痈和炎症性肿胀等病症。在临床中医实践中，黄顶菊经常作为关键成分纳入旨在管理甲状腺疾病和特定炎症条件的复方制剂。综述目的：本文综合2010年1月至2025年12月在黄顶菊植物化学、药理学和肝毒性机制方面的研究，系统地描述了黄顶菊的双重特性，重点评价了其解毒策略，以协调其有效性和安全性。方法：通过Elsevier、Web of Science、PubMed和谷歌Scholar等主要数据库，以黄药子、空气土豆等黄药子相关的目标关键词及其毒性成分黄黄素B （Diosbulbin B， DB）进行综合综述。结果：在古典和现代文献中都有文献记载，黄刺菊具有完善的民族药理学历史。从2010年1月到2025年12月的植物化学研究中，发现了99种新报道的化合物，主要是萜类、类固醇和酚类物质。这些成分具有广泛的药理活性，包括抗肿瘤、抗氧化、抗菌、抗糖尿病和免疫调节作用，通过关键信号通路介导，如丝裂原活化蛋白激酶（MAPK）和核因子红细胞2相关因子2 （Nrf2）。肝毒性是研究最广泛的不良反应，与二萜内酯DB有内在联系。其机制涉及cyp450介导的代谢激活，产生触发氧化应激、线粒体功能障碍和抑制肝胆转运蛋白的活性中间体。在中医理论的指导下，诸如草药配伍（如与当归、甘草等）和加工等策略，以及与保护剂（如阿魏酸）共同给药等现代方法，在降低毒性的同时保持疗效方面显示出临床前的希望。结论：本文阐明了黄僵菌的药效-毒性悖论，并综合了以黄僵菌为中心的关键解毒策略。为了确保其安全现代化，未来的研究必须优先考虑整体药代动力学研究，使用Roussel Uclaf因果关系评估方法（RUCAM）等工具进行系统的临床安全性评估，并采用创新方法。这些包括应用跨学科的方法（如超分子化学）来阐明煎剂的解毒机制，进行DB药效团的结构修饰，以及开发肝毒性的预测性生物标志物。
{"title":"The double-edged sword of Dioscorea bulbifera L.: Recent advances in its pharmacological benefits and hepatotoxicity, and the quest for detoxification strategies","authors":"Yunxuan Zhang , Jingnan Miao , Dan Zhou , Dan Xu , Pingcong Fu , Yingqi Ou , Dingyao Pan , Chunfeng Li , Danning Zheng , Junqiang Qiu","doi":"10.1016/j.jep.2026.121331","DOIUrl":"10.1016/j.jep.2026.121331","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Dioscorea bulbifera</em> L., the dried tuber of which is known as “Huangyaozi (黄药子)” in Traditional Chinese medicine (TCM), has a history of medicinal use spanning centuries within TCM and other traditional medical systems. It is traditionally utilized to dispel nodules and reduce goiter, clear heat and resolve toxins, and cool the blood to stop bleeding. Its primary applications include the treatment of conditions such as goiter, throat obstruction, carbuncles, and inflammatory swellings. In clinical TCM practice, <em>D. bulbifera</em> is frequently incorporated as a key component in compound formulations aimed at managing thyroid disorders and specific inflammatory conditions.</div></div><div><h3>Aim of the review</h3><div>This review aimed to systematically delineate the dual character of <em>D. bulbifera</em> by synthesizing research from January 2010 to December 2025 on its phytochemistry, pharmacology, and mechanisms of liver toxicity, with a focus on evaluating detoxification strategies to reconcile its efficacy with safety.</div></div><div><h3>Methods</h3><div>This comprehensive narrative review was conducted using targeted keywords related to <em>D. bulbifera</em> (e.g., \"Huangyaozi,\" \"Air potato\") and its toxic component, Diosbulbin B (DB), across major databases including Elsevier, Web of Science, PubMed and Google Scholar.</div></div><div><h3>Results</h3><div>Documented in both classical and modern texts, <em>D. bulbifera</em> possesses a well-established ethnopharmacological history. Phytochemical studies from January 2010 to December 2025 have identified 99 newly reported compounds in <em>D. bulbifera</em>, primarily terpenoids, steroids, and phenolics. These constituents confer a broad spectrum of pharmacological activities, including antitumor, antioxidant, antimicrobial, antidiabetic, and immunomodulatory effects, mediated through key signaling pathways such as mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2). Hepatotoxicity, the most extensively researched adverse effect, is intrinsically linked to the diterpenoid lactone DB. Its mechanism involves CYP450-mediated metabolic activation, generating reactive intermediates that trigger oxidative stress, mitochondrial dysfunction, and inhibition of hepatobiliary transporters. Guided by TCM theory, strategies such as herbal compatibility (e.g., with <em>Angelica sinensis</em> Radix, <em>Glycyrrhizae</em> Radix et Rhizoma) and processing, alongside modern approaches like co-administration with protective agents (e.g., ferulic acid), show preclinical promise in reducing toxicity while preserving efficacy.</div></div><div><h3>Conclusion</h3><div>This review clarifies the efficacy-toxicity paradox of <em>D. bulbifera</em> and synthesizes key detoxification strategies centered on DB. To ensure its safe modernization, future research must prioritize holistic pharmacokinetic studies, systemati","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121331"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142554","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 : 2026-02-06DOI: 10.1016/j.jep.2026.121329
Zhiren Yao , Can Hu , Siyang Fang , Yaping Huang , Yanhua Qin , Lei Wang , Jian Zhang , Zhiqi Yin , Ke Pan
Ethnopharmacological relevance
Cyclocarya paliurus (Batal.) Iljinsk, a millennia-old traditional Chinese herb, is prized for its ability to clear the lungs and nourish the liver. Additionally, it is employed in traditional Chinese medicine practice for heat clearance and detoxification, addressing conditions such as lung diseases.
Aim of the study
This study aimed to evaluate beneficial effects of polysaccharides (CPP) from C. paliurus on chronic obstructive pulmonary disease (COPD) and its potential mechanisms.
Materials and methods
The chemical characterization of the isolated and purified CPP was conducted using fourier-transform infrared spectroscopy, ultraviolet spectroscopy and scanning electron microscopy. COPD was induced in male BALB/c mice by intranasal infusion of LPS and exposure to cigarette smoke for 28 days. Lung tissues were then collected for subsequent histopathological and molecular analyses. The mechanism of CPP against COPD was investigated through transcriptomic data mining and Western blot analysis. Additionally, acute toxicity of CPP was assessed in mice following a single oral dose of 15 g/kg.
Results
Experimental evidence established that CPP consists of six monosaccharides: fucose, arabinose, rhamnose, galactose, glucose, and xylose. CPP treatment significantly reduced the levels of PCO2 and HCO3− in the blood of COPD mice, concurrently alleviating pulmonary inflammation. Mechanistic investigations have revealed that CPP exerts its anti-inflammatory effect by modulating the AhR/NF-κB pathway. In addition, CPP demonstrated safety at doses exceeding 100 times the effective level.
Conclusion
The results suggest that CPP holds promise as a potential therapeutic agent for the intervention of COPD. These findings provide a theoretical basis for the development of the ethnic medicinal herb Cyclocarya paliurus.
{"title":"Polysaccharide from Cyclocarya paliurus ameliorates chronic obstructive pulmonary disease through the inflammatory pathway regulated by the AhR/NF-κB pathway","authors":"Zhiren Yao , Can Hu , Siyang Fang , Yaping Huang , Yanhua Qin , Lei Wang , Jian Zhang , Zhiqi Yin , Ke Pan","doi":"10.1016/j.jep.2026.121329","DOIUrl":"10.1016/j.jep.2026.121329","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cyclocarya paliurus (Batal.)</em> Iljinsk, a millennia-old traditional Chinese herb, is prized for its ability to clear the lungs and nourish the liver. Additionally, it is employed in traditional Chinese medicine practice for heat clearance and detoxification, addressing conditions such as lung diseases.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate beneficial effects of polysaccharides (CPP) from <em>C. paliurus</em> on chronic obstructive pulmonary disease (COPD) and its potential mechanisms.</div></div><div><h3>Materials and methods</h3><div>The chemical characterization of the isolated and purified CPP was conducted using fourier-transform infrared spectroscopy, ultraviolet spectroscopy and scanning electron microscopy. COPD was induced in male BALB/c mice by intranasal infusion of LPS and exposure to cigarette smoke for 28 days. Lung tissues were then collected for subsequent histopathological and molecular analyses. The mechanism of CPP against COPD was investigated through transcriptomic data mining and Western blot analysis. Additionally, acute toxicity of CPP was assessed in mice following a single oral dose of 15 g/kg.</div></div><div><h3>Results</h3><div>Experimental evidence established that CPP consists of six monosaccharides: fucose, arabinose, rhamnose, galactose, glucose, and xylose. CPP treatment significantly reduced the levels of PCO<sub>2</sub> and HCO<sub>3</sub><sup>−</sup> in the blood of COPD mice, concurrently alleviating pulmonary inflammation. Mechanistic investigations have revealed that CPP exerts its anti-inflammatory effect by modulating the AhR/NF-κB pathway. In addition, CPP demonstrated safety at doses exceeding 100 times the effective level.</div></div><div><h3>Conclusion</h3><div>The results suggest that CPP holds promise as a potential therapeutic agent for the intervention of COPD. These findings provide a theoretical basis for the development of the ethnic medicinal herb <em>Cyclocarya paliurus.</em></div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121329"},"PeriodicalIF":5.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142543","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 : 2026-02-06DOI: 10.1016/j.jep.2026.121333
Kumarla Kaluva Ruhinaz , Hari Prakash Kalla , Lokesh V. Thimmana , Somasekhar Reddy Kanala , Parasuraman Aiya Subramani , Rajeswara Reddy Saddala , Kalpana Panati , Venkata Ramireddy Narala
<div><h3>Ethnopharmacological relevance</h3><div><em>Bauhinia purpurea</em> Linn.<em>,</em> traditionally used in Southeast Asian medicine for respiratory and inflammatory conditions, exhibits potent antioxidant and anti-inflammatory properties that support its continued exploration in modern phytomedicine. However, its therapeutic potential in hyperoxia-induced acute lung injury (HALI) remains unexplored. HALI remains a significant clinical challenge, particularly in patients requiring high inspired oxygen concentrations, such as those with acute respiratory distress syndrome. The oxidative stress and inflammation associated with HALI currently lack targeted pharmacological interventions, prompting the exploration of natural products with antioxidant and anti-inflammatory properties.</div></div><div><h3>Objective</h3><div>This study investigates the protective effects of the ethyl acetate extract of <em>B. purpurea</em> L., leaves (BPE) against HALI in a murine model.</div></div><div><h3>Methods</h3><div>Mice were exposed to >95% O<sub>2</sub> to induce HALI and treated with varying doses of BPE. Inflammatory cell infiltration, lung histopathology, alveolar-capillary barrier integrity, cytokine expression, oxidative stress markers, and antioxidant enzyme levels were assessed. LC-MS analysis, network pharmacology, and <em>in silico</em> docking were conducted to explore the phytochemical profile and predicted molecular interactions of BPE.</div></div><div><h3>Results</h3><div>BPE treatment significantly reduced hyperoxia-induced leukocyte infiltration, particularly neutrophils and macrophages, into bronchoalveolar lavage (BAL) fluid. Histological analysis revealed attenuated lung injury and decreased alveolar wall thickening in BPE-treated groups. BPE also markedly lowered BAL fluid protein content and Evans blue dye extravasation, indicating reduced alveolar-capillary leakage. Gene expression analysis showed that BPE suppressed the expression of proinflammatory cytokines (<em>IL-1β, TNFα, IL-6,</em> and <em>COX-2</em>) and upregulated antioxidant genes (<em>SOD-1, NRF-2 and NQO1</em>). Biochemically, BPE restored catalase and superoxide dismutase levels, reduced malondialdehyde, and decreased serum nitrite concentrations. Notably, BPE restored the expression of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of anti-inflammatory responses. LC-MS profiling suggested the presence of several phytochemicals previously reported to possess antioxidant or anti-inflammatory properties, including gerberinol, pheophorbide A, rhamnetin-3-sophoroside, quercuslactone A, vernolepin, flavidulol C, and cimifugin. Network-based analyses predicted that these compounds may be associated with antioxidant and inflammatory signaling pathways relevant to HALI.</div></div><div><h3>Conclusion</h3><div>BPE confers significant protection against HALI by modulating oxidative stress, suppressing inflammatory responses, prese
{"title":"Phytotherapeutic potential of Bauhinia purpurea Linn. in hyperoxic lung injury: Insights from in vivo, network pharmacology and in silico analyses","authors":"Kumarla Kaluva Ruhinaz , Hari Prakash Kalla , Lokesh V. Thimmana , Somasekhar Reddy Kanala , Parasuraman Aiya Subramani , Rajeswara Reddy Saddala , Kalpana Panati , Venkata Ramireddy Narala","doi":"10.1016/j.jep.2026.121333","DOIUrl":"10.1016/j.jep.2026.121333","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Bauhinia purpurea</em> Linn.<em>,</em> traditionally used in Southeast Asian medicine for respiratory and inflammatory conditions, exhibits potent antioxidant and anti-inflammatory properties that support its continued exploration in modern phytomedicine. However, its therapeutic potential in hyperoxia-induced acute lung injury (HALI) remains unexplored. HALI remains a significant clinical challenge, particularly in patients requiring high inspired oxygen concentrations, such as those with acute respiratory distress syndrome. The oxidative stress and inflammation associated with HALI currently lack targeted pharmacological interventions, prompting the exploration of natural products with antioxidant and anti-inflammatory properties.</div></div><div><h3>Objective</h3><div>This study investigates the protective effects of the ethyl acetate extract of <em>B. purpurea</em> L., leaves (BPE) against HALI in a murine model.</div></div><div><h3>Methods</h3><div>Mice were exposed to >95% O<sub>2</sub> to induce HALI and treated with varying doses of BPE. Inflammatory cell infiltration, lung histopathology, alveolar-capillary barrier integrity, cytokine expression, oxidative stress markers, and antioxidant enzyme levels were assessed. LC-MS analysis, network pharmacology, and <em>in silico</em> docking were conducted to explore the phytochemical profile and predicted molecular interactions of BPE.</div></div><div><h3>Results</h3><div>BPE treatment significantly reduced hyperoxia-induced leukocyte infiltration, particularly neutrophils and macrophages, into bronchoalveolar lavage (BAL) fluid. Histological analysis revealed attenuated lung injury and decreased alveolar wall thickening in BPE-treated groups. BPE also markedly lowered BAL fluid protein content and Evans blue dye extravasation, indicating reduced alveolar-capillary leakage. Gene expression analysis showed that BPE suppressed the expression of proinflammatory cytokines (<em>IL-1β, TNFα, IL-6,</em> and <em>COX-2</em>) and upregulated antioxidant genes (<em>SOD-1, NRF-2 and NQO1</em>). Biochemically, BPE restored catalase and superoxide dismutase levels, reduced malondialdehyde, and decreased serum nitrite concentrations. Notably, BPE restored the expression of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of anti-inflammatory responses. LC-MS profiling suggested the presence of several phytochemicals previously reported to possess antioxidant or anti-inflammatory properties, including gerberinol, pheophorbide A, rhamnetin-3-sophoroside, quercuslactone A, vernolepin, flavidulol C, and cimifugin. Network-based analyses predicted that these compounds may be associated with antioxidant and inflammatory signaling pathways relevant to HALI.</div></div><div><h3>Conclusion</h3><div>BPE confers significant protection against HALI by modulating oxidative stress, suppressing inflammatory responses, prese","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121333"},"PeriodicalIF":5.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142560","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 : 2026-02-06DOI: 10.1016/j.jep.2026.121305
Seung-Yub Song , Duc Dat Le , Mina Lee , Seung-Sik Cho , Dae-Hun Park
Ethnopharmacological relevance
Camellia japonica is recognized for its edible and therapeutic value in East Asia, and has anti-inflammatory, antioxidative, and antiasthmatic properties. However, the active compound and the modes of action are unclear.
Aim of the study: To evaluate the anti-AMD effect of hyperoside isolated from the leaves and twigs of Camellia japonica and to explore the underlying mechanisms using an ARPE-19 AMD cell model.
Material and methods
The hyperoside content in the extracts was evaluated using feature-based molecular network and UHPLC-MS/MS system. Network pharmacology was used to predict the interactions of hyperoside with AMD-related signaling pathways and the underlying mechanisms. For in vitro evaluation of the anti-AMD effects, ARPE-19 cells were divided into six treatment groups: CON, no treatment; A2E, AMD induction using 30 μM A2E and 20 mW/cm2 blue light treatment; Lutein, treatment with 25 μM lutein as a positive control; and three Hyperoside groups, treated with 37.5, 75, or 150 μM hyperoside. The antiapoptotic effect of hyperoside was evaluated using flow cytometry and TUNEL assays, and the intrinsic apoptotic pathway proteins (Bcl-xL, Bad, and Bim) were analyzed via western blotting. The interactions of hyperoside with JNK and p38 MAPKs were determined using western blotting, and molecular docking. The antioxidative effect of hyperoside was measured via DPPH and ABTS radical scavenging assays; Nrf2/HO-1 activation and SOD-1 stimulation were analyzed using western blotting and immunofluorescence assay. The anticarbonyl effect (4-HNE and MDA) was measured using western blotting.
Results
Hyperoside was nontoxic to ARPE-19 cells up to 150 μM. It dose-dependently decreased A2E and blue light-induced AMD in ARPE-19 cells by upregulating the antiapoptotic Bcl-2 protein (Bcl-xL) and downregulating the proapoptotic Bcl-2 proteins (Bad and Bim). Hyperoside dephosphorylated JNK and p38 MAPKs in a dose-dependent manner, eradicated DPPH and ABTS radicals, and activated Nrf2/HO-1 and SOD-1. It also decreased the levels of 4-HNE and MDA.
Conclusion
We conclude that C. japonica hyperoside could be a promising anti-AMD drug.
{"title":"Camellia japonica hyperoside exhibits anti-age-related macular degeneration effects in an ARPE-19 cell model by inhibiting apoptosis via JNK-Nrf2/HO-1 activation","authors":"Seung-Yub Song , Duc Dat Le , Mina Lee , Seung-Sik Cho , Dae-Hun Park","doi":"10.1016/j.jep.2026.121305","DOIUrl":"10.1016/j.jep.2026.121305","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Camellia japonica</em> is recognized for its edible and therapeutic value in East Asia, and has anti-inflammatory, antioxidative, and antiasthmatic properties. However, the active compound and the modes of action are unclear.</div><div><em>Aim of the study</em>: To evaluate the anti-AMD effect of hyperoside isolated from the leaves and twigs of <em>Camellia japonica</em> and to explore the underlying mechanisms using an ARPE-19 AMD cell model.</div></div><div><h3>Material and methods</h3><div>The hyperoside content in the extracts was evaluated using feature-based molecular network and UHPLC-MS/MS system. Network pharmacology was used to predict the interactions of hyperoside with AMD-related signaling pathways and the underlying mechanisms. For <em>in vitro</em> evaluation of the anti-AMD effects, ARPE-19 cells were divided into six treatment groups: CON, no treatment; A2E, AMD induction using 30 μM A2E and 20 mW/cm<sup>2</sup> blue light treatment; Lutein, treatment with 25 μM lutein as a positive control; and three Hyperoside groups, treated with 37.5, 75, or 150 μM hyperoside. The antiapoptotic effect of hyperoside was evaluated using flow cytometry and TUNEL assays, and the intrinsic apoptotic pathway proteins (Bcl-xL, Bad, and Bim) were analyzed via western blotting. The interactions of hyperoside with JNK and p38 MAPKs were determined using western blotting, and molecular docking. The antioxidative effect of hyperoside was measured via DPPH and ABTS radical scavenging assays; Nrf2/HO-1 activation and SOD-1 stimulation were analyzed using western blotting and immunofluorescence assay. The anticarbonyl effect (4-HNE and MDA) was measured using western blotting.</div></div><div><h3>Results</h3><div>Hyperoside was nontoxic to ARPE-19 cells up to 150 μM. It dose-dependently decreased A2E and blue light-induced AMD in ARPE-19 cells by upregulating the antiapoptotic Bcl-2 protein (Bcl-xL) and downregulating the proapoptotic Bcl-2 proteins (Bad and Bim). Hyperoside dephosphorylated JNK and p38 MAPKs in a dose-dependent manner, eradicated DPPH and ABTS radicals, and activated Nrf2/HO-1 and SOD-1. It also decreased the levels of 4-HNE and MDA.</div></div><div><h3>Conclusion</h3><div>We conclude that <em>C. japonica</em> hyperoside could be a promising anti-AMD drug.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121305"},"PeriodicalIF":5.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142557","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 : 2026-02-06DOI: 10.1016/j.jep.2026.121315
Nan Xiao , Jinsong Gao , Yutong Yang , Chenghui Li , Xuejuan Shen , Xiangyu Chen , Xiaodie Chen , Yanbin Pan , Huiqun Huang , Simin Yang , Shuting Zeng , Xiaodong Duan , Yongan Deng , Chengkai Chen , Yixuan Huang , Danping Huang , Zunpeng Shu , Li Zhang
Ethnopharmacological relevance
Vascular aging is a significant driver of age-related cardiovascular diseases, in which the immune-inflammatory response driven by excessive formation of neutrophil extracellular traps (NETs) is a core process accelerating this progression. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine (TCM) formula widely used for treating cardio-cerebrovascular diseases, but whether it acts through modulating NET-driven vascular aging is unknown.
Aim of the study
This study aims to investigate the mechanism by which BHD delays vascular aging, focusing on the NETs formation pathway.
Materials and methods
Based on a D-galactose-induced aging mouse model, this study focused on neutrophils and combined transcriptomics, network pharmacology and molecular biology methods to explore the mechanism of BHD in delaying vascular aging.
Results
The present study identified 23 major chemical constituents in BHD and demonstrated its efficacy in ameliorating aging phenotypes in a D-galactose-induced aging mouse model. BHD treatment significantly alleviated aortic structural degeneration, reduced oxidative stress and inflammatory cytokine levels, and downregulated key senescence markers including p16 and p21. Integrated multi-omics analysis implicated NET suppression as a primary mechanism underlying the anti-aging benefits of BHD. Both in vivo and in vitro experiments confirmed that BHD inhibits NETosis by modulating the HMGB1/TLR4/p38 signaling pathway, leading to reduced expression of critical NET components. Notably, HMGB1 overexpression partially reversed the inhibitory effects of BHD on NETosis, establishing HMGB1 as a key effector molecule.
Conclusion
For the first time, our findings unveil a novel mechanism whereby BHD alleviates vascular aging by modulating the immune microenvironment through inhibition of the HMGB1–TLR4–p38–NETs cascade. These findings provide a novel immunomodulatory perspective on BHD and highlight its potential as a holistic therapeutic strategy against vascular aging.
{"title":"Buyang Huanwu Decoction attenuates vascular aging by suppressing the pathway of neutrophil extracellular trap formation via modulation of the HMGB1/TLR4/p38 signaling pathway","authors":"Nan Xiao , Jinsong Gao , Yutong Yang , Chenghui Li , Xuejuan Shen , Xiangyu Chen , Xiaodie Chen , Yanbin Pan , Huiqun Huang , Simin Yang , Shuting Zeng , Xiaodong Duan , Yongan Deng , Chengkai Chen , Yixuan Huang , Danping Huang , Zunpeng Shu , Li Zhang","doi":"10.1016/j.jep.2026.121315","DOIUrl":"10.1016/j.jep.2026.121315","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Vascular aging is a significant driver of age-related cardiovascular diseases, in which the immune-inflammatory response driven by excessive formation of neutrophil extracellular traps (NETs) is a core process accelerating this progression. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine (TCM) formula widely used for treating cardio-cerebrovascular diseases, but whether it acts through modulating NET-driven vascular aging is unknown.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the mechanism by which BHD delays vascular aging, focusing on the NETs formation pathway.</div></div><div><h3>Materials and methods</h3><div>Based on a D-galactose-induced aging mouse model, this study focused on neutrophils and combined transcriptomics, network pharmacology and molecular biology methods to explore the mechanism of BHD in delaying vascular aging.</div></div><div><h3>Results</h3><div>The present study identified 23 major chemical constituents in BHD and demonstrated its efficacy in ameliorating aging phenotypes in a D-galactose-induced aging mouse model. BHD treatment significantly alleviated aortic structural degeneration, reduced oxidative stress and inflammatory cytokine levels, and downregulated key senescence markers including p16 and p21. Integrated multi-omics analysis implicated NET suppression as a primary mechanism underlying the anti-aging benefits of BHD. Both in vivo and in vitro experiments confirmed that BHD inhibits NETosis by modulating the HMGB1/TLR4/p38 signaling pathway, leading to reduced expression of critical NET components. Notably, HMGB1 overexpression partially reversed the inhibitory effects of BHD on NETosis, establishing HMGB1 as a key effector molecule.</div></div><div><h3>Conclusion</h3><div>For the first time, our findings unveil a novel mechanism whereby BHD alleviates vascular aging by modulating the immune microenvironment through inhibition of the HMGB1–TLR4–p38–NETs cascade. These findings provide a novel immunomodulatory perspective on BHD and highlight its potential as a holistic therapeutic strategy against vascular aging.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121315"},"PeriodicalIF":5.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142575","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 : 2026-02-05DOI: 10.1016/j.jep.2026.121308
Shaoliang Li , Pengning Wu , Yue Wang, Dehao Wang, Haihua Qian, Dan Zhang
Ethnopharmacological relevance
Tianwang Buxin Dan (TWBXD) is a classical Chinese formula traditionally prescribed to “nourish Yin, calm the mind and relieve bowel stagnation” in disorders characterized by heart-kidney disharmony, insomnia, anxiety, and constipation. However, the mechanistic basis associating its gut-regulating and emotion-modulating effects along the gut-brain axis remains unclear.
Aim of the study
To investigate whether TWBXD ameliorates functional constipation comorbid with emotional disturbances by modulating mitogen-activated protein kinase/Extracellular Signal-Regulated Kinase/c-Jun N-terminal Kinase (MAPK/ERK/JNK) signaling, hypothalamic-pituitary-adrenal (HPA)-axis activity, and autophagy-related mitochondrial integrity in the colon and hippocampus.
Materials and methods
A diphenoxylate-induced rat model of functional constipation with anxiety/depression-like behavior was treated with low, medium, or high doses of TWBXD. Intestinal transit, fecal parameters, and distal colonic transit were also assessed. Emotional behaviors were evaluated using open-field and elevated plus-maze tests. Colonic and hippocampal histopathology and ultrastructure were examined using hematoxylin and eosin staining, Nissl staining, and transmission electron microscopy. Serum corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels were measured using enzyme-linked immunosorbent assay. MAPK/ERK/JNK-related proteins and brain-derived neurotrophic factor (BDNF) were analyzed by Western blotting. The major chemical constituents of TWBXD were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry(UHPLC–MS/MS).
Results
TWBXD dose-dependently improved intestinal transit, fecal moisture, and body weight gain, and alleviated anxiety-/depression-like behaviors. TWBXD preserved colonic mucosal architecture and hippocampal neuronal integrity, mitigated mitochondrial swelling and excessive autophagic vacuole formation, downregulated colonic phosphorylated ERK (p-ERK), phosphorylated JNK, and phosphorylated p38, restored hippocampal BDNF expression while normalizing p-ERK levels, and reduced serum CRF, ACTH, and CORT levels.
Conclusion
TWBXD exerts multi-target therapeutic effects on functional constipation with emotional disturbances by suppressing MAPK/ERK/JNK overactivation, normalizing HPA-axis hyperactivity, and protecting mitochondrial structure and autophagy along the gut-brain axis, providing mechanistic support for its traditional use in gut-brain-related disorders.
{"title":"Tianwangbuxiandan decoction alleviates constipation and associated emotional disorders via regulating the brain-gut axis: Involving MAPK/ERK/JNK signaling pathways","authors":"Shaoliang Li , Pengning Wu , Yue Wang, Dehao Wang, Haihua Qian, Dan Zhang","doi":"10.1016/j.jep.2026.121308","DOIUrl":"10.1016/j.jep.2026.121308","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Tianwang Buxin Dan (TWBXD) is a classical Chinese formula traditionally prescribed to “nourish Yin, calm the mind and relieve bowel stagnation” in disorders characterized by heart-kidney disharmony, insomnia, anxiety, and constipation. However, the mechanistic basis associating its gut-regulating and emotion-modulating effects along the gut-brain axis remains unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate whether TWBXD ameliorates functional constipation comorbid with emotional disturbances by modulating mitogen-activated protein kinase/Extracellular Signal-Regulated Kinase/c-Jun N-terminal Kinase (MAPK/ERK/JNK) signaling, hypothalamic-pituitary-adrenal (HPA)-axis activity, and autophagy-related mitochondrial integrity in the colon and hippocampus.</div></div><div><h3>Materials and methods</h3><div>A diphenoxylate-induced rat model of functional constipation with anxiety/depression-like behavior was treated with low, medium, or high doses of TWBXD. Intestinal transit, fecal parameters, and distal colonic transit were also assessed. Emotional behaviors were evaluated using open-field and elevated plus-maze tests. Colonic and hippocampal histopathology and ultrastructure were examined using hematoxylin and eosin staining, Nissl staining, and transmission electron microscopy. Serum corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels were measured using enzyme-linked immunosorbent assay. MAPK/ERK/JNK-related proteins and brain-derived neurotrophic factor (BDNF) were analyzed by Western blotting. The major chemical constituents of TWBXD were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry(UHPLC–MS/MS).</div></div><div><h3>Results</h3><div>TWBXD dose-dependently improved intestinal transit, fecal moisture, and body weight gain, and alleviated anxiety-/depression-like behaviors. TWBXD preserved colonic mucosal architecture and hippocampal neuronal integrity, mitigated mitochondrial swelling and excessive autophagic vacuole formation, downregulated colonic phosphorylated ERK (p-ERK), phosphorylated JNK, and phosphorylated p38, restored hippocampal BDNF expression while normalizing p-ERK levels, and reduced serum CRF, ACTH, and CORT levels.</div></div><div><h3>Conclusion</h3><div>TWBXD exerts multi-target therapeutic effects on functional constipation with emotional disturbances by suppressing MAPK/ERK/JNK overactivation, normalizing HPA-axis hyperactivity, and protecting mitochondrial structure and autophagy along the gut-brain axis, providing mechanistic support for its traditional use in gut-brain-related disorders.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121308"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137199","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 : 2026-02-05DOI: 10.1016/j.jep.2026.121276
Ye-Lim You , Ha-Jun Byun , Jin-Young Jeon , Bo-Ra Kim , Ji Eun Hwang , Jun Hee Lee , Hyeon-Son Choi
Ethnopharmacological relevance
Euglena gracilis has a history of traditional use in East Asia as a functional food with reported antioxidant and immunomodulatory benefits. This study investigates the pharmacological potential of its bioactive component, standardized alkali-treated β-glucan (AEGB), in mitigating systemic toxicity induced by environmental pollutants, providing a rationale to investigate its protective effects in the context of particulate matter (PM2.5)-induced injury.
Aim of the study
To evaluate the protective effects of standardized alkali-treated E. gracilis β-glucan (AEGB) against PM2.5-induced pulmonary and cerebral toxicity in BALB/c mice via the lung–brain axis.
Materials and methods
AEGB was prepared and standardized to contain 93% (w/w) β-glucan. BALB/c mice were intranasally exposed to PM2.5 and orally administered AEGB (200/400 mg/kg). Efficacy was evaluated via BALF analysis, histopathology, and immunoblotting, focusing on MAPK, NF-κB, NRF2–HO-1, and CREB–BDNF–TrkB pathways.
Results
AEGB exhibited higher antioxidant activity than untreated β-glucan. In PM2.5-exposed mice, AEGB (400 mg/kg) reduced inflammatory cells in BALF by 69.5% and suppressed lung pro-inflammatory cytokines (IL-1β, IL-6). Histologically, it attenuated bronchial thickening and mucin production. In the brain, AEGB downregulated NF-κB by 72.1% and restored hippocampal neuronal area (+41.1%) and tight junction marker expression associated with blood–brain barrier integrity. At the molecular level, AEGB inhibited pulmonary MAPK/NF-κB and activated NRF2–HO-1, while enhancing the cerebral CREB–BDNF–TrkB neurotrophic pathway.
Conclusions
AEGB mitigates PM2.5-induced damage in both lung and brain tissues, accompanied by anti-inflammatory and neuroprotective responses consistent with inter-organ inflammatory/oxidative pathways relevant to the lung–brain axis. These findings validate the potential of E. gracilis-derived β-glucan as a functional agent for preserving respiratory and neural health.
{"title":"Standardized alkali-treated Euglena gracilis β-glucan mitigates PM2.5-induced pulmonary and cerebral injury through NF-κB, NRF2, and CREB–BDNF–TrkB pathways","authors":"Ye-Lim You , Ha-Jun Byun , Jin-Young Jeon , Bo-Ra Kim , Ji Eun Hwang , Jun Hee Lee , Hyeon-Son Choi","doi":"10.1016/j.jep.2026.121276","DOIUrl":"10.1016/j.jep.2026.121276","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Euglena gracilis</em> has a history of traditional use in East Asia as a functional food with reported antioxidant and immunomodulatory benefits. This study investigates the pharmacological potential of its bioactive component, standardized alkali-treated β-glucan (AEGB), in mitigating systemic toxicity induced by environmental pollutants, providing a rationale to investigate its protective effects in the context of particulate matter (PM2.5)-induced injury.</div></div><div><h3>Aim of the study</h3><div>To evaluate the protective effects of standardized alkali-treated <em>E. gracilis</em> β-glucan (AEGB) against PM2.5-induced pulmonary and cerebral toxicity in BALB/c mice via the lung–brain axis.</div></div><div><h3>Materials and methods</h3><div>AEGB was prepared and standardized to contain 93% (w/w) β-glucan. BALB/c mice were intranasally exposed to PM2.5 and orally administered AEGB (200/400 mg/kg). Efficacy was evaluated via BALF analysis, histopathology, and immunoblotting, focusing on MAPK, NF-κB, NRF2–HO-1, and CREB–BDNF–TrkB pathways.</div></div><div><h3>Results</h3><div>AEGB exhibited higher antioxidant activity than untreated β-glucan. In PM2.5-exposed mice, AEGB (400 mg/kg) reduced inflammatory cells in BALF by 69.5% and suppressed lung pro-inflammatory cytokines (IL-1β, IL-6). Histologically, it attenuated bronchial thickening and mucin production. In the brain, AEGB downregulated NF-κB by 72.1% and restored hippocampal neuronal area (+41.1%) and tight junction marker expression associated with blood–brain barrier integrity. At the molecular level, AEGB inhibited pulmonary MAPK/NF-κB and activated NRF2–HO-1, while enhancing the cerebral CREB–BDNF–TrkB neurotrophic pathway.</div></div><div><h3>Conclusions</h3><div>AEGB mitigates PM2.5-induced damage in both lung and brain tissues, accompanied by anti-inflammatory and neuroprotective responses consistent with inter-organ inflammatory/oxidative pathways relevant to the lung–brain axis. These findings validate the potential of <em>E. gracilis</em>-derived β-glucan as a functional agent for preserving respiratory and neural health.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121276"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137590","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}
Myrothamnus flabellifolius, the “resurrection plant,” traditionally used in southern Africa, shows strong potential for anti-virulence chemotherapy and for mitigating toxin-linked pathogenesis, reinforcing its enduring ethnomedicinal value.
Aim of the study
to investigate the phytochemical composition, antibiofilm, cytoprotective and anti-haemolytic effects, and potential antibacterial mechanisms of the extracts.
Materials and methods
Simultaneous extraction of plant material was done using hexane and aqueous acetone, followed by liquid-extraction of acetone extract. LC-MS was used for chemical profiling. Antioxidant activity was assessed. Haemolytic and cytoprotective activities were investigated against hydrogen peroxide and β-haemolytic pathogens. Antibacterial activity was assessed using broth micro-dilution, dehydrogenase and cell membrane disruption assays. Antibiofilm activity was investigated using the crystal violet, tetrazolium assays and evaluation of bacterial growth.
Results
Taxifolin, eriodyctiol, quercetin were identified in the ethyl acetate subfractions of the leaves (LEA) and stems (SEA) and phytosterols in the hexane fractions of the leaves (LH) and stem (SH). LEA and SEA exhibited strong antioxidant activity and provided significant protection of erythrocytes against oxidative and pathogen-induced haemolysis. LEA and SEA were active against Pseudomonas aeruginosa (MIC = 160 μg/mL), LH showed similar activity against Staphylococcus aureus (MIC = 160 μg/mL). The extracts disrupted the bacterial cell envelopes and inhibited dehydrogenase-linked metabolisms. Sub-MIC of LH, SH, and SEA significantly reduced biofilm formation in P. aeruginosa and Streptococcus pyogenes, despite exerting minimal effects on planktonic growth.
Conclusion
M. flabellifolius shows strong multi-target antibacterial and sub-MIC antibiofilm activity, alongside notable antioxidant, cryoprotection and potential for addressing oxidative stress-linked ailments.
{"title":"Phytochemical profiling, anti-virulence effects, and antibacterial mechanisms of Myrothamnus flabellifolius (Welw.) extracts","authors":"Mashilo Mash Matotoka, Talita Jessica Mnisi, Potsiso Letau Koma, Matsilane Lethabo Mashilo, Peter Masoko","doi":"10.1016/j.jep.2026.121342","DOIUrl":"10.1016/j.jep.2026.121342","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Myrothamnus flabellifolius,</em> the “resurrection plant,” traditionally used in southern Africa, shows strong potential for anti-virulence chemotherapy and for mitigating toxin-linked pathogenesis, reinforcing its enduring ethnomedicinal value.</div></div><div><h3>Aim of the study</h3><div>to investigate the phytochemical composition, antibiofilm, cytoprotective and anti-haemolytic effects, and potential antibacterial mechanisms of the extracts.</div></div><div><h3>Materials and methods</h3><div>Simultaneous extraction of plant material was done using hexane and aqueous acetone, followed by liquid-extraction of acetone extract. LC-MS was used for chemical profiling. Antioxidant activity was assessed. Haemolytic and cytoprotective activities were investigated against hydrogen peroxide and <em>β</em>-haemolytic pathogens. Antibacterial activity was assessed using broth micro-dilution, dehydrogenase and cell membrane disruption assays. Antibiofilm activity was investigated using the crystal violet, tetrazolium assays and evaluation of bacterial growth.</div></div><div><h3>Results</h3><div>Taxifolin, eriodyctiol, quercetin were identified in the ethyl acetate subfractions of the leaves (LEA) and stems (SEA) and phytosterols in the hexane fractions of the leaves (LH) and stem (SH). LEA and SEA exhibited strong antioxidant activity and provided significant protection of erythrocytes against oxidative and pathogen-induced haemolysis. LEA and SEA were active against <em>Pseudomonas aeruginosa</em> (MIC = 160 μg/mL), LH showed similar activity against <em>Staphylococcus aureus</em> (MIC = 160 μg/mL). The extracts disrupted the bacterial cell envelopes and inhibited dehydrogenase-linked metabolisms. Sub-MIC of LH, SH, and SEA significantly reduced biofilm formation in <em>P. aeruginosa</em> and <em>Streptococcus pyogenes</em>, despite exerting minimal effects on planktonic growth.</div></div><div><h3>Conclusion</h3><div><em>M. flabellifolius</em> shows strong multi-target antibacterial and sub-MIC antibiofilm activity, alongside notable antioxidant, cryoprotection and potential for addressing oxidative stress-linked ailments.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121342"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137597","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 : 2026-02-05DOI: 10.1016/j.jep.2026.121332
Xin-Ye Du , Lei Xu , Dan Liu , Zhi-Jun Zhang , Rong-Tao Li
Ethnopharmacological relevance
Shegan Mahuang Decoction (SMD), a traditional Chinese medicinal prescription outlined in “Jin Gui Yao Lue”. For approximately two thousand years, it has been widely used to treat asthma and flu-like symptoms in China and Japan for around twenty centuries. While the efficacy is confirmed, its pharmacological mechanism remains unclear.
Aim of the study
This study aimed to systematically evaluate the protective effects of SMD against influenza A virus (IAV)-induced pneumonia and explore its action mechanism.
Materials and methods
Material basis and absorbed components of SMD were analyzed using UHPLC-HRMS. Integrating absorbed components and network pharmacology to predict its potential for treating influenza and its mechanism of action. By using the IAV pneumonia model, the abilities of SMD to suppress pathogenic-evil and pneumonia were confirmed using MDCK cells and BALB/c mice.
Results
UHPLC-HRMS identified 497 components in SMD, of which 125 were absorbed into the bloodstream of mice. Network pharmacology analysis based on absorbed components indicates SMD's anti-influenza effects through multiple biological processes associated with infection and immunity. SMD can inhibit viral proliferation in vitro and protect MDCK cells. It increased survival in infected mice from 8 to over 12 days. In the mice with IAV pneumonia, SMD significantly alleviated pathological damage, reduced viral proteins and mucins in lung tissue. It also regulates cytokines including TNF-α, IL-1β, and IL-6, and inhibited the activation of TLR/TAK/NF-κB and MEK/ERK signaling pathways.
Conclusion
This study has confirmed that SMD can alleviate the hyper-inflammatory response in the host induced by IAV. It suggests that SMD can treat pneumonia by inhibiting pathogenic-evil factors.
{"title":"Elucidating the material basis and mechanism of Shegan Mahuang decoction in inhibiting influenza virus pneumonia based on UHPLC-HRMS, network pharmacology and experimental verification","authors":"Xin-Ye Du , Lei Xu , Dan Liu , Zhi-Jun Zhang , Rong-Tao Li","doi":"10.1016/j.jep.2026.121332","DOIUrl":"10.1016/j.jep.2026.121332","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shegan Mahuang Decoction (SMD), a traditional Chinese medicinal prescription outlined in “<em>Jin Gui Yao Lue</em>”. For approximately two thousand years, it has been widely used to treat asthma and flu-like symptoms in China and Japan for around twenty centuries. While the efficacy is confirmed, its pharmacological mechanism remains unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to systematically evaluate the protective effects of SMD against influenza A virus (IAV)-induced pneumonia and explore its action mechanism.</div></div><div><h3>Materials and methods</h3><div>Material basis and absorbed components of SMD were analyzed using UHPLC-HRMS. Integrating absorbed components and network pharmacology to predict its potential for treating influenza and its mechanism of action. By using the IAV pneumonia model, the abilities of SMD to suppress pathogenic-evil and pneumonia were confirmed using MDCK cells and BALB/c mice.</div></div><div><h3>Results</h3><div>UHPLC-HRMS identified 497 components in SMD, of which 125 were absorbed into the bloodstream of mice. Network pharmacology analysis based on absorbed components indicates SMD's anti-influenza effects through multiple biological processes associated with infection and immunity. SMD can inhibit viral proliferation <em>in vitro</em> and protect MDCK cells. It increased survival in infected mice from 8 to over 12 days. In the mice with IAV pneumonia, SMD significantly alleviated pathological damage, reduced viral proteins and mucins in lung tissue. It also regulates cytokines including TNF-α, IL-1β, and IL-6, and inhibited the activation of TLR/TAK/NF-κB and MEK/ERK signaling pathways.</div></div><div><h3>Conclusion</h3><div>This study has confirmed that SMD can alleviate the hyper-inflammatory response in the host induced by IAV. It suggests that SMD can treat pneumonia by inhibiting pathogenic-evil factors.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121332"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131903","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 : 2026-02-05DOI: 10.1016/j.jep.2026.121334
Nancy E. Rodríguez-Garza , Ramiro Quintanilla-Licea , Diana E. Caballero-Hernández , Ana L. Delgado-Miranda , César I. Romo-Sáenz , Ricardo Gomez-Flores
Ethnopharmacological relevance
Ruta chalepensis L. (rue) is a medicinal plant commonly used in folk medicine and is known to contain bioactive secondary metabolites with pharmacological potential. Among these, chalepensin has been previously described to exhibit antitumor activity in vitro; however, its in vivo efficacy and safety profile remain poorly characterized.
Aim of the study
To evaluate the in vitro and in vivo antitumor activity of chalepensin against L5178Y-R murine lymphoma and to assess its acute toxicity profile.
Materials and methods
Chalepensin was isolated from the leaves and stems of R. chalepensis. Cytotoxic activity was determined in vitro with the MTT assay against tumor and normal cell lines. In silico analyses were performed to predict pharmacokinetic properties and explore potential molecular interactions. Acute toxicity was assessed in BALB/c mice following intraperitoneal administration of chalepensin (100 and 1000 mg/kg). Antitumor efficacy was evaluated in BALB/c mice bearing L5178Y-R lymphoma by monitoring tumor volume and survival.
Results
Chalepensin exhibited potent cytotoxic activity against L5178Y-R cells (IC50 = 8.1 μg/mL; SI = 66.5). In silico analyses predicted favorable pharmacokinetic properties. Acute toxicity studies revealed no mortality, clinical signs of toxicity, or significant alterations in biochemical and hematological parameters. In vivo, chalepensin induced a significant reduction in tumor volume between days 10 and 20 (p < 0.05) and significantly prolonged mean survival time, showing comparable or superior efficacy to vincristine under the tested conditions. Molecular docking suggested a preferential interaction with the Cyclin A2–CDK2 complex, supporting a potential cytostatic mechanism consistent with the observed in vivo effects.
Conclusion
Chalepensin demonstrates promising antitumor activity against L5178Y-R murine lymphoma, along with a favorable acute toxicity profile. These findings support its potential for further preclinical development and warrant additional studies to elucidate its molecular mechanisms and long-term safety.
{"title":"Pharmacological potential of chalepensin from Ruta chalepensis L.: Acute toxicity and in vivo antitumor activity in the L5178Y-R murine model","authors":"Nancy E. Rodríguez-Garza , Ramiro Quintanilla-Licea , Diana E. Caballero-Hernández , Ana L. Delgado-Miranda , César I. Romo-Sáenz , Ricardo Gomez-Flores","doi":"10.1016/j.jep.2026.121334","DOIUrl":"10.1016/j.jep.2026.121334","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ruta chalepensis</em> L. (rue) is a medicinal plant commonly used in folk medicine and is known to contain bioactive secondary metabolites with pharmacological potential. Among these, chalepensin has been previously described to exhibit antitumor activity <em>in vitro</em>; however, its <em>in vivo</em> efficacy and safety profile remain poorly characterized.</div></div><div><h3>Aim of the study</h3><div>To evaluate the <em>in vitro</em> and <em>in vivo</em> antitumor activity of chalepensin against L5178Y-R murine lymphoma and to assess its acute toxicity profile.</div></div><div><h3>Materials and methods</h3><div>Chalepensin was isolated from the leaves and stems of <em>R. chalepensis</em>. Cytotoxic activity was determined <em>in vitro</em> with the MTT assay against tumor and normal cell lines. <em>In silico</em> analyses were performed to predict pharmacokinetic properties and explore potential molecular interactions. Acute toxicity was assessed in BALB/c mice following intraperitoneal administration of chalepensin (100 and 1000 mg/kg). Antitumor efficacy was evaluated in BALB/c mice bearing L5178Y-R lymphoma by monitoring tumor volume and survival.</div></div><div><h3>Results</h3><div>Chalepensin exhibited potent cytotoxic activity against L5178Y-R cells (IC<sub>50</sub> = 8.1 μg/mL; SI = 66.5). <em>In silico</em> analyses predicted favorable pharmacokinetic properties. Acute toxicity studies revealed no mortality, clinical signs of toxicity, or significant alterations in biochemical and hematological parameters. <em>In vivo</em>, chalepensin induced a significant reduction in tumor volume between days 10 and 20 (p < 0.05) and significantly prolonged mean survival time, showing comparable or superior efficacy to vincristine under the tested conditions. Molecular docking suggested a preferential interaction with the Cyclin A2–CDK2 complex, supporting a potential cytostatic mechanism consistent with the observed <em>in vivo</em> effects.</div></div><div><h3>Conclusion</h3><div>Chalepensin demonstrates promising antitumor activity against L5178Y-R murine lymphoma, along with a favorable acute toxicity profile. These findings support its potential for further preclinical development and warrant additional studies to elucidate its molecular mechanisms and long-term safety.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121334"},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137524","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}
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