首页 > 最新文献

Journal of ethnopharmacology最新文献

英文 中文
Qingluo Tongbi Formula attenuates Tripterygium wilfordii Hook. f.-induced hepatic metabolic dysfunction and oxidative stress via the SIRT1/HIF-1α pathway 清络通痹方对雷公藤有减毒作用。f.通过SIRT1/HIF-1α途径诱导肝脏代谢功能障碍和氧化应激。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-10 DOI: 10.1016/j.jep.2026.121352
Weijue Nie , Minghao Lu , Xin Sun , Hong Zhu , Baoping Jiang , Lingling Zhou , Xueping Zhou

Ethnopharmacological relevance

Tripterygium wilfordii Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases, but its clinical utility is limited by hepatotoxicity. Qingluo Tongbi Formula (QTF), a classic multi-herb prescription for rheumatoid arthritis containing TW, has shown good efficacy with fewer liver adverse effects in clinical practice.

Aim of the study

To evaluate whether QTF alleviates TW-induced hepatotoxicity and to elucidate the underlying metabolic and molecular mechanisms.

Materials and methods

A TW-induced hepatotoxicity model was established in C57BL/6J mice treated with TW alone, QTF, or TW combined with individual constituent herbs. Liver injury, oxidative stress, and lipid peroxidation were evaluated by serum biochemistry and histopathology. Untargeted metabolomics was performed to profile hepatic energy metabolism. In vitro, triptolide-injured AML12 hepatocytes were used to evaluate the protective effects of catalpol (CAT) and Panax notoginseng saponins (PNS) on cellular bioenergetics and the sirtuin 1 (SIRT1)/hypoxia-inducible factor-1α (HIF-1α) axis.

Results

In vivo, QTF significantly attenuated TW-induced hepatotoxicity, hypoglycaemia, oxidative stress, and lipid peroxidation, and partially normalized amino acid and glucose metabolism. In vitro, combined CAT and PNS restored mitochondrial respiration, rebalanced glycolysis and oxidative phosphorylation, improved glycogen utilization, and upregulated SIRT1 while suppressing HIF-1α in AML12 hepatocytes.

Conclusions

QTF protects against TW-induced hepatotoxicity, at least in part by modulating the SIRT1/HIF-1α axis, thereby alleviating oxidative stress and restoring hepatic energy and glucose metabolism. These findings provide a mechanistic basis for the detoxifying compatibility of QTF and support safer clinical application of TW-containing formulations.
民族药理学相关性:雷公藤钩。f. (TW)广泛用于治疗自身免疫性疾病和炎症性疾病,但其临床应用受到肝毒性的限制。清络通痹方是治疗类风湿关节炎的经典多药方剂,临床证明其疗效好,肝脏不良反应少。研究目的:评价芪黄酮是否能减轻tw诱导的肝毒性,并阐明其潜在的代谢和分子机制。材料与方法:分别用黄芪单用、中药复方、黄芪联合单药治疗C57BL/6J小鼠,建立黄芪所致肝毒性模型。通过血清生化和组织病理学评估肝损伤、氧化应激和脂质过氧化。采用非靶向代谢组学分析肝脏能量代谢。在体外,采用雷公藤甲素损伤的AML12肝细胞,研究了梓醇(CAT)和三七皂苷(PNS)对细胞生物能量学和sirtuin 1 (SIRT1)/缺氧诱导因子1α (HIF-1α)轴的保护作用。结果:在体内,QTF显著减轻了tw诱导的肝毒性、低血糖、氧化应激和脂质过氧化,并部分正常化了氨基酸和葡萄糖代谢。在体外,CAT和PNS联合治疗可恢复线粒体呼吸,重新平衡糖酵解和氧化磷酸化,改善糖原利用,上调SIRT1,同时抑制AML12肝细胞中的HIF-1α。结论:QTF至少在一定程度上通过调节SIRT1/HIF-1α轴来保护tw诱导的肝毒性,从而减轻氧化应激,恢复肝脏能量和葡萄糖代谢。这些发现为中药复方解毒配伍提供了机制基础,并为含中药复方的临床应用提供了支持。
{"title":"Qingluo Tongbi Formula attenuates Tripterygium wilfordii Hook. f.-induced hepatic metabolic dysfunction and oxidative stress via the SIRT1/HIF-1α pathway","authors":"Weijue Nie ,&nbsp;Minghao Lu ,&nbsp;Xin Sun ,&nbsp;Hong Zhu ,&nbsp;Baoping Jiang ,&nbsp;Lingling Zhou ,&nbsp;Xueping Zhou","doi":"10.1016/j.jep.2026.121352","DOIUrl":"10.1016/j.jep.2026.121352","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Tripterygium wilfordii</em> Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases, but its clinical utility is limited by hepatotoxicity. Qingluo Tongbi Formula (QTF), a classic multi-herb prescription for rheumatoid arthritis containing TW, has shown good efficacy with fewer liver adverse effects in clinical practice.</div></div><div><h3>Aim of the study</h3><div>To evaluate whether QTF alleviates TW-induced hepatotoxicity and to elucidate the underlying metabolic and molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>A TW-induced hepatotoxicity model was established in C57BL/6J mice treated with TW alone, QTF, or TW combined with individual constituent herbs. Liver injury, oxidative stress, and lipid peroxidation were evaluated by serum biochemistry and histopathology. Untargeted metabolomics was performed to profile hepatic energy metabolism. <em>In vitro</em>, triptolide-injured AML12 hepatocytes were used to evaluate the protective effects of catalpol (CAT) and <em>Panax notoginseng</em> saponins (PNS) on cellular bioenergetics and the sirtuin 1 (SIRT1)/hypoxia-inducible factor-1α (HIF-1α) axis.</div></div><div><h3>Results</h3><div><em>In vivo</em>, QTF significantly attenuated TW-induced hepatotoxicity, hypoglycaemia, oxidative stress, and lipid peroxidation, and partially normalized amino acid and glucose metabolism. <em>In vitro</em>, combined CAT and PNS restored mitochondrial respiration, rebalanced glycolysis and oxidative phosphorylation, improved glycogen utilization, and upregulated SIRT1 while suppressing HIF-1α in AML12 hepatocytes.</div></div><div><h3>Conclusions</h3><div>QTF protects against TW-induced hepatotoxicity, at least in part by modulating the SIRT1/HIF-1α axis, thereby alleviating oxidative stress and restoring hepatic energy and glucose metabolism. These findings provide a mechanistic basis for the detoxifying compatibility of QTF and support safer clinical application of TW-containing formulations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121352"},"PeriodicalIF":5.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180476","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}
引用次数: 0
Sangbaipi Decoction mitigates influenza pneumonia in mice by inhibiting ZBP1-mediated PANoptosis 桑白皮汤通过抑制zbp1介导的PANoptosis减轻小鼠流行性肺炎。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-10 DOI: 10.1016/j.jep.2026.121348
Chengcheng Zhang , Guofeng Yu , Miaomiao Liu , Ruikun Du , Jing Ma , Xuran Gu , Lijun Rong , Xuxiao Lv , Qinghua Cui

Ethnopharmacological relevance

Viral pneumonia remains a major global health concern. Sangbaipi Decoction (SBPD), a traditional Chinese medicine formula, which is used clinically to treat pneumonia, exhibits antiviral and anti-inflammatory effects. However, its pharmacological basis and mechanism of action (MOA) in vivo remain unclear.

Aim of the study

This study aimed to evaluate the therapeutic efficacy of SBPD on viral pneumonia and to elucidate its underlying MOA.

Materials and methods

The protective effects of SBPD were assessed in H1N1 (A/Puerto Rico/8/1934)-infected mice using histopathology, Western blot, and RT-qPCR. RNA sequencing was performed to identify key pathways modulated by SBPD. PANoptosis-related markers were examined both in vivo and in vitro, and Z-DNA-binding protein 1 (ZBP1) overexpression assays were conducted to verify its role in SBPD-mediated regulation of PANoptosis. A Poly(I:C)-induced acute lung injury model was used for further validation. Blood-absorbed constituents of SBPD were screened to identify bioactive components.

Results

SBPD treatment greatly reduced pulmonary viral load, lung index, and pro-inflammatory cytokine levels in H1N1-infected mice, alleviating lung injury. Transcriptomic analysis identified the ZBP1-mediated PANoptosis as a major regulatory target of SBPD. In vivo and in vitro studies demonstrated that SBPD downregulated the expression of ZBP1 and its downstream effectors, suppressing excessive inflammatory cell death. SBPD also attenuated Poly(I:C)-induced acute lung injury through the same pathway. Screening of blood-absorbed constituents of SBPD identified peimine, peiminine, chrysin, wogonin, and apigenin as active constituents that inhibit ZBP1-mediated PANoptosis.

Conclusion

SBPD mitigates influenza-induced pneumonia by suppressing ZBP1-mediated PANoptosis and excessive inflammation, highlighting its host-directed therapeutic potential for viral pneumonia.
民族药理学相关性:病毒性肺炎仍然是一个主要的全球健康问题。桑白皮汤(SBPD)是一种中药方剂,临床上用于治疗肺炎,具有抗病毒和抗炎作用。然而,其体内药理基础和作用机制(MOA)尚不清楚。研究目的:本研究旨在评价SBPD对病毒性肺炎的治疗效果,并阐明其潜在的MOA。材料与方法:采用组织病理学、western blot、RT-qPCR等方法评价SBPD对H1N1 (A/Puerto Rico/8/1934)感染小鼠的保护作用。RNA测序鉴定SBPD调控的关键通路。在体内和体外检测PANoptosis相关标志物,并通过z - dna结合蛋白1 (ZBP1)过表达实验验证其在sbpd介导的PANoptosis调节中的作用。Poly(I:C)诱导的急性肺损伤模型进一步验证。筛选SBPD血吸收成分,鉴定其生物活性成分。结果:SBPD治疗可显著降低h1n1感染小鼠肺病毒载量、肺指数及促炎细胞因子水平,减轻肺损伤。转录组学分析发现zbp1介导的PANoptosis是SBPD的主要调控靶点。体内和体外研究表明,SBPD下调ZBP1及其下游效应物的表达,抑制炎症细胞过度死亡。SBPD也通过相同的途径减轻Poly(I:C)诱导的急性肺损伤。对SBPD血吸收成分的筛选,鉴定出了能抑制zbp1介导的PANoptosis的活性成分为沛亚胺、沛亚胺、黄菊花素、枸杞素和芹菜素。结论:SBPD通过抑制zbp1介导的PANoptosis和过度炎症来减轻流感诱导的肺炎,突出了其对病毒性肺炎的宿主定向治疗潜力。
{"title":"Sangbaipi Decoction mitigates influenza pneumonia in mice by inhibiting ZBP1-mediated PANoptosis","authors":"Chengcheng Zhang ,&nbsp;Guofeng Yu ,&nbsp;Miaomiao Liu ,&nbsp;Ruikun Du ,&nbsp;Jing Ma ,&nbsp;Xuran Gu ,&nbsp;Lijun Rong ,&nbsp;Xuxiao Lv ,&nbsp;Qinghua Cui","doi":"10.1016/j.jep.2026.121348","DOIUrl":"10.1016/j.jep.2026.121348","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Viral pneumonia remains a major global health concern. Sangbaipi Decoction (SBPD), a traditional Chinese medicine formula, which is used clinically to treat pneumonia, exhibits antiviral and anti-inflammatory effects. However, its pharmacological basis and mechanism of action (MOA) <em>in vivo</em> remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the therapeutic efficacy of SBPD on viral pneumonia and to elucidate its underlying MOA.</div></div><div><h3>Materials and methods</h3><div>The protective effects of SBPD were assessed in H1N1 (A/Puerto Rico/8/1934)-infected mice using histopathology, Western blot, and RT-qPCR. RNA sequencing was performed to identify key pathways modulated by SBPD. PANoptosis-related markers were examined both <em>in vivo</em> and <em>in vitro</em>, and Z-DNA-binding protein 1 (ZBP1) overexpression assays were conducted to verify its role in SBPD-mediated regulation of PANoptosis. A Poly(I:C)-induced acute lung injury model was used for further validation. Blood-absorbed constituents of SBPD were screened to identify bioactive components.</div></div><div><h3>Results</h3><div>SBPD treatment greatly reduced pulmonary viral load, lung index, and pro-inflammatory cytokine levels in H1N1-infected mice, alleviating lung injury. Transcriptomic analysis identified the ZBP1-mediated PANoptosis as a major regulatory target of SBPD. <em>In vivo</em> and <em>in vitro</em> studies demonstrated that SBPD downregulated the expression of ZBP1 and its downstream effectors, suppressing excessive inflammatory cell death. SBPD also attenuated Poly(I:C)-induced acute lung injury through the same pathway. Screening of blood-absorbed constituents of SBPD identified peimine, peiminine, chrysin, wogonin, and apigenin as active constituents that inhibit ZBP1-mediated PANoptosis.</div></div><div><h3>Conclusion</h3><div>SBPD mitigates influenza-induced pneumonia by suppressing ZBP1-mediated PANoptosis and excessive inflammation, highlighting its host-directed therapeutic potential for viral pneumonia.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121348"},"PeriodicalIF":5.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180484","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}
引用次数: 0
Xuefu Zhuyu Decoction Attenuates Thoracic Aortic Dissection by Regulating VSMC Phenotypic Switching and Oxidative Stress via the JAK2/STAT3/HIF-1α Pathway. 血扶瘀汤通过调控VSMC表型转换和JAK2/STAT3/HIF-1α通路减轻胸主动脉夹层
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-10 DOI: 10.1016/j.jep.2026.121324
Li Cheng-Wen, Gao Rong, Jiang Yi-Fan, Wang Shou-Jia, Li Si-Yi, Li Chun-Yan, Liang Fan, Li Xiao-Qiang, Duan Wei-Xun, Song Fan

Ethnopharmacological relevance: Xuefu Zhuyu Decoction (XFZY), a classic formula for "blood stasis syndrome", has insufficient evidence for its thoracic aortic dissection (TAD) therapeutic efficacy and its underlying mechanism remains unclear.

Aim of study: This study aimed to elucidate the efficacy, mechanism, and key components of XFZY against TAD.

Material and method: Using a β-Aminopropionitrile (BAPN)-induced TAD mouse model, efficacy was assessed via survival, ultrasonography, and histology. Mechanisms were explored via integrated UPLC-Q-TOF-MS, clinical proteomics, bioinformatics, and molecular docking, with validation by western blotting and immunofluorescence.

Results: In TAD mice, XFZY exerted significant therapeutic effects, as evidenced by reduced mortality (mortality: 40.0% in TAD vs. 13.3% in high-dose group), attenuated aortic dilation (maximum diameter: 1.49 ± 0.08 mm in TAD vs. 1.10 ± 0.04 mm in high-dose group), ameliorated histopathological changes, restored VSMC contractile phenotype, and mitigated oxidative stress. Proteomic analyses identified 339 dysregulated proteins, and pinpointed JAK2/STAT3/HIF-1α axis as core regulatory axis. XFZY dose-dependently inhibited JAK2/STAT3 activation and HIF-1α expression. Molecular docking identified Naringin, Kaempferol, Glycyrrhizic acid, and Saikosaponins A/D as key components, with anti-TAD efficacy confirmed in vivo.

Conclusion: XFZY attenuated aortic tissue remodeling and improved the survival rate in TAD mice. This therapeutic effect was achieved by rescuing the VSMC contractile phenotype (inhibition of the JAK2/STAT3 pathway) and alleviating oxidative stress (downregulation of HIF-1α expression). Naringin, Kaempferol, Glycyrrhizic acid, and Saikosaponins A/D were identified as key components and exhibit effects similar to those of the XFZY extract. These findings establish a solid experimental basis for its clinical application.

民族药理学相关性:血瘀祛瘀汤作为治疗血瘀证的经典方剂,其治疗胸主动脉夹层(TAD)的疗效证据不足,其作用机制尚不清楚。研究目的:本研究旨在阐明XFZY抗TAD的疗效、作用机制及关键成分。材料和方法:采用β-氨基丙腈(BAPN)诱导的TAD小鼠模型,通过生存、超声和组织学评估疗效。通过整合UPLC-Q-TOF-MS、临床蛋白质组学、生物信息学和分子对接等方法探索其机制,并通过western blotting和免疫荧光验证。结果:在TAD小鼠中,XFZY具有显著的治疗作用,表现为降低死亡率(TAD组死亡率40.0%,高剂量组死亡率13.3%),减缓主动脉扩张(TAD组最大直径1.49±0.08 mm,高剂量组最大直径1.10±0.04 mm),改善组织病理学改变,恢复VSMC收缩表型,减轻氧化应激。蛋白质组学分析鉴定出339个异常蛋白,并确定JAK2/STAT3/HIF-1α轴为核心调控轴。XFZY剂量依赖性地抑制JAK2/STAT3激活和HIF-1α表达。分子对接鉴定出柚皮苷、山奈酚、甘草酸和柴草皂苷A/D为关键成分,体内抗tad作用得到证实。结论:XFZY能减轻TAD小鼠主动脉组织重构,提高生存率。这种治疗效果是通过挽救VSMC收缩表型(抑制JAK2/STAT3通路)和减轻氧化应激(下调HIF-1α表达)实现的。柚皮苷、山奈酚、甘草酸和柴草皂苷A/D被确定为关键成分,其作用与XFZY提取物相似。这些结果为其临床应用奠定了坚实的实验基础。
{"title":"Xuefu Zhuyu Decoction Attenuates Thoracic Aortic Dissection by Regulating VSMC Phenotypic Switching and Oxidative Stress via the JAK2/STAT3/HIF-1α Pathway.","authors":"Li Cheng-Wen, Gao Rong, Jiang Yi-Fan, Wang Shou-Jia, Li Si-Yi, Li Chun-Yan, Liang Fan, Li Xiao-Qiang, Duan Wei-Xun, Song Fan","doi":"10.1016/j.jep.2026.121324","DOIUrl":"https://doi.org/10.1016/j.jep.2026.121324","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Xuefu Zhuyu Decoction (XFZY), a classic formula for \"blood stasis syndrome\", has insufficient evidence for its thoracic aortic dissection (TAD) therapeutic efficacy and its underlying mechanism remains unclear.</p><p><strong>Aim of study: </strong>This study aimed to elucidate the efficacy, mechanism, and key components of XFZY against TAD.</p><p><strong>Material and method: </strong>Using a β-Aminopropionitrile (BAPN)-induced TAD mouse model, efficacy was assessed via survival, ultrasonography, and histology. Mechanisms were explored via integrated UPLC-Q-TOF-MS, clinical proteomics, bioinformatics, and molecular docking, with validation by western blotting and immunofluorescence.</p><p><strong>Results: </strong>In TAD mice, XFZY exerted significant therapeutic effects, as evidenced by reduced mortality (mortality: 40.0% in TAD vs. 13.3% in high-dose group), attenuated aortic dilation (maximum diameter: 1.49 ± 0.08 mm in TAD vs. 1.10 ± 0.04 mm in high-dose group), ameliorated histopathological changes, restored VSMC contractile phenotype, and mitigated oxidative stress. Proteomic analyses identified 339 dysregulated proteins, and pinpointed JAK2/STAT3/HIF-1α axis as core regulatory axis. XFZY dose-dependently inhibited JAK2/STAT3 activation and HIF-1α expression. Molecular docking identified Naringin, Kaempferol, Glycyrrhizic acid, and Saikosaponins A/D as key components, with anti-TAD efficacy confirmed in vivo.</p><p><strong>Conclusion: </strong>XFZY attenuated aortic tissue remodeling and improved the survival rate in TAD mice. This therapeutic effect was achieved by rescuing the VSMC contractile phenotype (inhibition of the JAK2/STAT3 pathway) and alleviating oxidative stress (downregulation of HIF-1α expression). Naringin, Kaempferol, Glycyrrhizic acid, and Saikosaponins A/D were identified as key components and exhibit effects similar to those of the XFZY extract. These findings establish a solid experimental basis for its clinical application.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121324"},"PeriodicalIF":5.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180511","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}
引用次数: 0
Gancao decoction ameliorated senecionine-induced Hepatic Sinusoidal Obstruction Syndrome in mice by inhibiting NET formation and senecionine bioactivation in liver 甘草汤通过抑制净网的形成和绿皮碱在肝脏的生物活性,改善绿皮碱诱导的小鼠肝窦梗阻综合征。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-09 DOI: 10.1016/j.jep.2026.121356
Shuang Zhang , Dongming Yan , Si Cheng , Jingyi Jin , Jiamin Cui , Chenghai Liu , Yue Li , Furong Qiu

Ethnopharmacological relevance

In China, pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS) accounts for approximately 50.0-88.6% of all HSOS cases, primarily resulting from inadvertent ingestion of Gynura japonica (Thunb.) Juel. (Tǔ sān qī). Glycyrrhiza uralensis Fisch. (Gān cǎo), a classical hepatoprotective herb in Traditional Chinese Medicine (TCM), has recently demonstrated significant protective effects against PA-induced HSOS in murine models. However, its underlying mechanisms remain poorly understood.

Aim of study

This study aimed to assess the therapeutic efficacy of Gancao decoction (GCD) and elucidate its underlying mechanisms in PA-induced HSOS.

Materials and methods

HSOS was induced in mice by senecionine (SEN), followed by treatment with GCD or enoxaparin (ENO, positive control). Histopathological and therapeutic efficacy was assessed by histopathological examination and serum biochemical analyses. Neutrophil depletion was employed to investigate the contribution of neutrophil extracellular traps (NETs) to the protective effects of GCD. Transcriptomic analysis was performed to identify potential targets of GCD. Mechanistic studies were investigated using quantitative real-time PCR (qPCR), Western blotting (WB), and immunofluorescence (IF). In addition, the inhibitory effect of GCD on SEN bioactivation was evaluated using human liver microsomes (HLMs).

Results

GCD improved serum biochemistry and hepatic histopathology in SEN-induced HSOS mice. Mechanistically, GCD suppressed intrahepatic neutrophil chemotaxis, thereby reducing NET formation and alleviating immunothrombosis. Furthermore, GCD inhibited the hepatic formation of dehydropyrrolizidine (DHP), the reactive metabolite responsible for SEN-induced HSOS.

Conclusion

GCD attenuated SEN-induced HSOS through dual mechanisms: (1) suppression of chemokine-driven neutrophil chemotaxis, leading to reduced NET formation and immunothrombosis; (2) inhibiting of SEN bioactivation. These findings provide mechanistic support for the ethnopharmacological use of Gancao in PA-HSOS and highlight its potential for clinical translation.
民族药理学相关性:在中国,吡咯利西啶生物碱(PA)引起的肝窦梗阻综合征(HSOS)约占所有HSOS病例的50.0% -88.6%,主要是由于误食黄花菊(Thunb)引起的。Juel。(t ā sān q ā)。乌拉尔甘草(Gān cǎo)是一种经典的中药保肝草药,最近在小鼠模型中显示出对pa诱导的HSOS有显著的保护作用。然而,其潜在机制仍然知之甚少。研究目的:观察甘草汤对pa诱导的HSOS的治疗作用,探讨其作用机制。材料和方法:用senecionine (SEN)诱导小鼠HSOS,然后用GCD或依诺肝素(ENO,阳性对照)治疗。通过组织病理学检查和血清生化分析评估组织病理学和治疗效果。中性粒细胞耗竭研究了中性粒细胞胞外陷阱(NETs)对GCD保护作用的贡献。转录组学分析用于鉴定GCD的潜在靶点。采用实时荧光定量PCR (qPCR)、Western blotting (WB)和免疫荧光(IF)进行机制研究。此外,利用人肝微粒体(HLMs)评价了GCD对SEN生物活化的抑制作用。结果:GCD改善了sen诱导的HSOS小鼠的血清生化和肝脏组织病理学。从机制上讲,GCD抑制肝内中性粒细胞趋化性,从而减少NET的形成,减轻免疫血栓形成。此外,GCD还能抑制肝生成脱氢吡咯利西定(DHP), DHP是sen诱导的HSOS的活性代谢物。结论:GCD通过双重机制减轻sen诱导的HSOS:(1)抑制趋化因子驱动的中性粒细胞趋化性,导致NET形成和免疫血栓形成减少;(2)抑制SEN生物活化。这些发现为甘草在PA-HSOS中的民族药理学应用提供了机制支持,并突出了其临床转化的潜力。
{"title":"Gancao decoction ameliorated senecionine-induced Hepatic Sinusoidal Obstruction Syndrome in mice by inhibiting NET formation and senecionine bioactivation in liver","authors":"Shuang Zhang ,&nbsp;Dongming Yan ,&nbsp;Si Cheng ,&nbsp;Jingyi Jin ,&nbsp;Jiamin Cui ,&nbsp;Chenghai Liu ,&nbsp;Yue Li ,&nbsp;Furong Qiu","doi":"10.1016/j.jep.2026.121356","DOIUrl":"10.1016/j.jep.2026.121356","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>In China, pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS) accounts for approximately 50.0-88.6% of all HSOS cases, primarily resulting from inadvertent ingestion of <em>Gynura japonica</em> (Thunb.) Juel. (Tǔ sān qī). <em>Glycyrrhiza uralensis</em> Fisch. (Gān cǎo), a classical hepatoprotective herb in Traditional Chinese Medicine (TCM), has recently demonstrated significant protective effects against PA-induced HSOS in murine models. However, its underlying mechanisms remain poorly understood.</div></div><div><h3>Aim of study</h3><div>This study aimed to assess the therapeutic efficacy of Gancao decoction (GCD) and elucidate its underlying mechanisms in PA-induced HSOS.</div></div><div><h3>Materials and methods</h3><div>HSOS was induced in mice by senecionine (SEN), followed by treatment with GCD or enoxaparin (ENO, positive control). Histopathological and therapeutic efficacy was assessed by histopathological examination and serum biochemical analyses. Neutrophil depletion was employed to investigate the contribution of neutrophil extracellular traps (NETs) to the protective effects of GCD. Transcriptomic analysis was performed to identify potential targets of GCD. Mechanistic studies were investigated using quantitative real-time PCR (qPCR), Western blotting (WB), and immunofluorescence (IF). In addition, the inhibitory effect of GCD on SEN bioactivation was evaluated using human liver microsomes (HLMs).</div></div><div><h3>Results</h3><div>GCD improved serum biochemistry and hepatic histopathology in SEN-induced HSOS mice. Mechanistically, GCD suppressed intrahepatic neutrophil chemotaxis, thereby reducing NET formation and alleviating immunothrombosis. Furthermore, GCD inhibited the hepatic formation of dehydropyrrolizidine (DHP), the reactive metabolite responsible for SEN-induced HSOS.</div></div><div><h3>Conclusion</h3><div>GCD attenuated SEN-induced HSOS through dual mechanisms: (1) suppression of chemokine-driven neutrophil chemotaxis, leading to reduced NET formation and immunothrombosis; (2) inhibiting of SEN bioactivation. These findings provide mechanistic support for the ethnopharmacological use of Gancao in PA-HSOS and highlight its potential for clinical translation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121356"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165541","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}
引用次数: 0
Inhibition of the p38/JNK MAPK pathway mediated by circadian rhythm genes: Study of the mechanism of Linggan Wuwei Jiangxin decoction in the treatment of COPD 抑制昼夜节律基因介导的p38/JNK MAPK通路:灵肝五味降心汤治疗COPD的机制研究
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-09 DOI: 10.1016/j.jep.2026.121349
Shihao Li , Ping Huang , Jingjing Li , Zhuang Huang , Kairui Zhang , Kai Chang , Huangen Kou , Benjiang Xiao , Meng Chen , Kaojiang Zhu , Rui Qian , Xing Hong , Yuxin Wen , Pengyu Chen , Qiong Wang , Fang Huang
<div><h3>Ethnopharmacological relevance</h3><div>Chronic obstructive pulmonary disease (COPD) is a frequently encountered respiratory disease. Its clinical symptoms are characterized by long-term coughing, expectoration, and other airway symptoms, resulting in significant harm. Linggan Wuwei Jiangxin Decoction (LGWWJXD) has the effects of warming the lungs, transforming fluid retention, and relieving cough and asthma, and is a classic prescription for treating COPD.</div></div><div><h3>Aim of the study</h3><div>This study aims to determine the mechanism of action of LGWWJXD in preventing and treating COPD.</div></div><div><h3>Materials and methods</h3><div>COPD rat models were established using a combination of exposure to cigarette smoke (CS), hypothermia, and lipopolysaccharide (LPS). Model rats were administered LGWWJXD. Histological changes in lung tissues were detected via hematoxylin-eosin (H&E) staining combined with transmission electron microscopy. Quantification of inflammatory factors in the bronchoalveolar lavage fluid, serum and cell culture medium were determined using enzyme-linked immunosorbent assays. The active ingredients of LGWWJXD and its components that could enter the systemic circulation were identified using UPLC-MS/MS. Metabolomic analysis characterized distinctive metabolites and associated pathways, and transcriptomics was used to identify differential genes and determine differential enrichment pathways. Core genes were identified through WGCNA combined with three machine learning algorithms. The interactions between cell subtypes was investigated through immune cell infiltration analysis and single-cell RNA sequencing. Molecular docking and molecular dynamics simulations were performed to screen key genes and core compounds. Subsequently, BEAS-2B cells were stimulated with CS and LPS to establish a COPD cell model, aiming to elucidate the mechanisms underlying the therapeutic effects of the key compounds. Finally, the aforementioned results were integrated to systematically explore the potential mechanism of LGWWJXD in the treatment of COPD. Finally, it was verified through western blotting and RT-PCR.</div></div><div><h3>Results</h3><div>LGWWJXD alleviated lung inflammation in rats, reduced pathological lung damage to help improve lung function, and reduced cigarette smoke-LPS-low temperature COPD. Metabolomics results showed that the levels of most differential metabolites were normal after LGWWJXD intervention, with arginine biosynthesis and purine metabolism being the main pathways. Transcriptomic analysis revealed that the MAPK signaling pathway plays a pivotal role in the therapeutic effects of LGWWJXD. WGCNA and machine learning algorithms identified two key genes, <em>Bmal1</em> and <em>Per2</em>. The integration of metabolomics and transcriptomics results revealed both to stem from inflammatory factor release. inflammatory factors. Molecular docking, molecular dynamics simulation, western blotting, and R
民族药理学相关性:慢性阻塞性肺疾病(COPD)是一种常见的呼吸道疾病。其临床症状以长期咳嗽、咳痰等气道症状为特征,危害显著。灵肝无味降心汤具有温肺、化瘀、止咳、平喘等功效,是治疗慢性阻塞性肺病的经典方药。研究目的:本研究旨在确定LGWWJXD预防和治疗COPD的作用机制。材料和方法:采用暴露于香烟烟雾(CS)、低温和脂多糖(LPS)相结合的方法建立COPD大鼠模型。模型大鼠灌胃LGWWJXD。采用苏木精-伊红(H&E)染色联合透射电镜观察肺组织组织学变化。采用酶联免疫吸附法测定支气管肺泡灌洗液、血清和细胞培养基中的炎症因子。采用超高效液相色谱-质谱联用(UPLC-MS/MS)技术鉴定了LGWWJXD的有效成分及其能进入体循环的成分。代谢组学分析表征了不同的代谢物和相关途径,转录组学用于鉴定差异基因和确定差异富集途径。通过WGCNA结合三种机器学习算法对核心基因进行鉴定。通过免疫细胞浸润分析和单细胞RNA测序研究细胞亚型之间的相互作用。通过分子对接和分子动力学模拟,筛选关键基因和核心化合物。随后,用CS和LPS刺激BEAS-2B细胞建立COPD细胞模型,旨在阐明关键化合物的治疗作用机制。最后,综合上述结果,系统探讨LGWWJXD治疗COPD的潜在机制。最后通过western blotting和RT-PCR进行验证。结果:LGWWJXD减轻大鼠肺部炎症,减轻病理性肺损伤,帮助改善肺功能,降低香烟烟雾- lps -低温COPD。代谢组学结果显示,LGWWJXD干预后,大多数差异代谢物水平正常,精氨酸生物合成和嘌呤代谢是主要途径。转录组学分析显示,MAPK信号通路在LGWWJXD的治疗效果中起关键作用。WGCNA和机器学习算法确定了两个关键基因Bmal1和Per2。代谢组学和转录组学的综合结果显示,两者都源于炎症因子的释放。炎症因子。分子对接、分子动力学模拟、western blotting和RT-PCR共同验证了LGWWJXD的潜在活性成分,包括Asarinin、6-Shogaol和Isoliquiritigenin,通过调控昼夜节律相关基因Bmal1、Per2和Nr1d1,抑制p38/JNK MAPK信号通路,缓解COPD。在体外,不同浓度细辛素干预BEAS-2B细胞后,TNF-α、IL-1β、IL-6水平均显著降低。同时,我们发现细辛素发挥抗炎作用的机制是上调Bmal1蛋白的表达,从而抑制p38/JNK MAPK信号通路,从而抑制炎症因子的释放。结论:LGWWJXD减轻大鼠肺炎症,保护细胞凋亡,减轻病理性肺损伤,有助于改善肺功能。LGWWJXD中潜在的活性成分,包括细辛素、6-Shogaol、异黄酮等,可能通过与精氨酸生物合成和嘌呤代谢途径联合,调控昼夜节律相关基因的表达,抑制p38/JNK MAPK通路,共同抑制炎症反应。为临床应用LGWWJXD治疗COPD奠定了科学基础。
{"title":"Inhibition of the p38/JNK MAPK pathway mediated by circadian rhythm genes: Study of the mechanism of Linggan Wuwei Jiangxin decoction in the treatment of COPD","authors":"Shihao Li ,&nbsp;Ping Huang ,&nbsp;Jingjing Li ,&nbsp;Zhuang Huang ,&nbsp;Kairui Zhang ,&nbsp;Kai Chang ,&nbsp;Huangen Kou ,&nbsp;Benjiang Xiao ,&nbsp;Meng Chen ,&nbsp;Kaojiang Zhu ,&nbsp;Rui Qian ,&nbsp;Xing Hong ,&nbsp;Yuxin Wen ,&nbsp;Pengyu Chen ,&nbsp;Qiong Wang ,&nbsp;Fang Huang","doi":"10.1016/j.jep.2026.121349","DOIUrl":"10.1016/j.jep.2026.121349","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Chronic obstructive pulmonary disease (COPD) is a frequently encountered respiratory disease. Its clinical symptoms are characterized by long-term coughing, expectoration, and other airway symptoms, resulting in significant harm. Linggan Wuwei Jiangxin Decoction (LGWWJXD) has the effects of warming the lungs, transforming fluid retention, and relieving cough and asthma, and is a classic prescription for treating COPD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This study aims to determine the mechanism of action of LGWWJXD in preventing and treating COPD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;COPD rat models were established using a combination of exposure to cigarette smoke (CS), hypothermia, and lipopolysaccharide (LPS). Model rats were administered LGWWJXD. Histological changes in lung tissues were detected via hematoxylin-eosin (H&amp;E) staining combined with transmission electron microscopy. Quantification of inflammatory factors in the bronchoalveolar lavage fluid, serum and cell culture medium were determined using enzyme-linked immunosorbent assays. The active ingredients of LGWWJXD and its components that could enter the systemic circulation were identified using UPLC-MS/MS. Metabolomic analysis characterized distinctive metabolites and associated pathways, and transcriptomics was used to identify differential genes and determine differential enrichment pathways. Core genes were identified through WGCNA combined with three machine learning algorithms. The interactions between cell subtypes was investigated through immune cell infiltration analysis and single-cell RNA sequencing. Molecular docking and molecular dynamics simulations were performed to screen key genes and core compounds. Subsequently, BEAS-2B cells were stimulated with CS and LPS to establish a COPD cell model, aiming to elucidate the mechanisms underlying the therapeutic effects of the key compounds. Finally, the aforementioned results were integrated to systematically explore the potential mechanism of LGWWJXD in the treatment of COPD. Finally, it was verified through western blotting and RT-PCR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;LGWWJXD alleviated lung inflammation in rats, reduced pathological lung damage to help improve lung function, and reduced cigarette smoke-LPS-low temperature COPD. Metabolomics results showed that the levels of most differential metabolites were normal after LGWWJXD intervention, with arginine biosynthesis and purine metabolism being the main pathways. Transcriptomic analysis revealed that the MAPK signaling pathway plays a pivotal role in the therapeutic effects of LGWWJXD. WGCNA and machine learning algorithms identified two key genes, &lt;em&gt;Bmal1&lt;/em&gt; and &lt;em&gt;Per2&lt;/em&gt;. The integration of metabolomics and transcriptomics results revealed both to stem from inflammatory factor release. inflammatory factors. Molecular docking, molecular dynamics simulation, western blotting, and R","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121349"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165470","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}
引用次数: 0
Long Gu (Os Draconis): Textual research, modern scientific evaluation, and quality control challenges 龙骨:考证、现代科学评价与质量控制挑战。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-09 DOI: 10.1016/j.jep.2026.121354
Sun Xiujia , Li Zhan Hua , Gao Yuanze , Kumar Ganesan , Liu Jing , Li Li , Zhang Chao , Jianping Chen

Ethnopharmacological relevance

Long Gu (Os Draconis), a mineral medicine with over 2000 years of use in traditional Chinese medicine, is facing a critical juncture. Its identity has been clarified scientifically—from a mythologized “dragon bone” to a fossilized mammalian bioapatite—yet its sustainable clinical application is threatened by resource depletion, widespread domestic and international adulteration, and the lack of modern quality standards.

Aim of the study

This review aims to systematically analyze the evolution of Long Gu through historical materia medica, define its authentic characteristics using modern science, diagnose the root causes of its current market and regulatory crisis, and propose a robust, multi-dimensional framework for quality evaluation and sustainable sourcing.

Materials and methods

A systematic review of Chinese materia medica literature from the Pre-Qin to Qing Dynasties was conducted. Historical textual research was integrated with evidence from modern mineralogy, paleontology, geochemistry, and pharmacology to validate traditional knowledge and establish scientific identification criteria.

Results

The understanding of Long Gu evolved from mythological origins to a scientific conclusion in the Ming Dynasty, with Li Shizhen correctly identifying it as fossilized ancient mammalian bones. Modern research confirms authentic “Wuhua Long Gu” from the Shanxi-Shaanxi region is primarily carbonated hydroxyapatite, characterized by high porosity (>35%), significant hygroscopicity, and a unique trace element profile (Zn, Sr). These properties underpin its advertised therapeutic effects. However, the market is now saturated with dangerous adulterants, including fluoride-rich dinosaur fossils and processed modern bones, due to resource exhaustion and inadequate pharmacopoeial standards focused solely on calcium content.

Conclusion

The future of Long Gu depends on transcending outdated quality controls. Ensuring its efficacy and safety necessitates a paradigm shift to a comprehensive standard system that combines paleontological and geochronological origin verification, quantitative microstructural analysis, chemical fingerprinting of key components, and strict safety monitoring. Complementary research into biomimetic synthesis and accelerated mineralization is urgently needed to develop sustainable alternatives for this invaluable yet endangered medicinal resource.
民族药理学相关性:龙骨是一种具有2000多年历史的中药矿物药物,目前正面临着关键时刻。它的身份已经被科学地澄清——从神话中的“龙骨”到哺乳动物生物磷灰石化石——然而,它的可持续临床应用受到资源枯竭、国内外普遍掺假和缺乏现代质量标准的威胁。研究目的:系统分析龙骨药材的历史沿路,运用现代科学手段厘清龙骨药材的原汁原味,诊断龙骨药材市场和监管危机的根源,提出龙骨药材质量评价和可持续采购的多维框架。材料与方法:对先秦至清代的中药材文献进行了系统的综述。历史文本研究与现代矿物学、古生物学、地球化学和药理学的证据相结合,以验证传统知识并建立科学的鉴定标准。结果:对龙骨的认识从神话起源发展到明代的科学结论,李时珍正确地将其鉴定为古代哺乳动物骨骼化石。现代研究证实,陕陕地区真品“五花龙骨”主要为碳酸羟基磷灰石,具有孔隙度高(> ~ 35%)、吸湿性强、微量元素(Zn、Sr)剖面独特的特点。这些特性巩固了它所宣传的治疗效果。然而,由于资源枯竭和仅关注钙含量的药典标准不完善,现在市场上充斥着危险的掺假物,包括富含氟的恐龙化石和加工过的现代骨头。结论:龙骨的未来取决于超越过时的质量控制。为了确保其有效性和安全性,必须将范式转变为综合标准体系,该体系结合古生物学和地质年代学起源验证、定量微观结构分析、关键成分的化学指纹识别和严格的安全监测。迫切需要对仿生合成和加速矿化进行补充研究,以开发这种宝贵但濒危的药用资源的可持续替代品。
{"title":"Long Gu (Os Draconis): Textual research, modern scientific evaluation, and quality control challenges","authors":"Sun Xiujia ,&nbsp;Li Zhan Hua ,&nbsp;Gao Yuanze ,&nbsp;Kumar Ganesan ,&nbsp;Liu Jing ,&nbsp;Li Li ,&nbsp;Zhang Chao ,&nbsp;Jianping Chen","doi":"10.1016/j.jep.2026.121354","DOIUrl":"10.1016/j.jep.2026.121354","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Long Gu (Os Draconis), a mineral medicine with over 2000 years of use in traditional Chinese medicine, is facing a critical juncture. Its identity has been clarified scientifically—from a mythologized “dragon bone” to a fossilized mammalian bioapatite—yet its sustainable clinical application is threatened by resource depletion, widespread domestic and international adulteration, and the lack of modern quality standards.</div></div><div><h3>Aim of the study</h3><div>This review aims to systematically analyze the evolution of Long Gu through historical materia medica, define its authentic characteristics using modern science, diagnose the root causes of its current market and regulatory crisis, and propose a robust, multi-dimensional framework for quality evaluation and sustainable sourcing.</div></div><div><h3>Materials and methods</h3><div>A systematic review of Chinese materia medica literature from the Pre-Qin to Qing Dynasties was conducted. Historical textual research was integrated with evidence from modern mineralogy, paleontology, geochemistry, and pharmacology to validate traditional knowledge and establish scientific identification criteria.</div></div><div><h3>Results</h3><div>The understanding of Long Gu evolved from mythological origins to a scientific conclusion in the Ming Dynasty, with Li Shizhen correctly identifying it as fossilized ancient mammalian bones. Modern research confirms authentic “Wuhua Long Gu” from the Shanxi-Shaanxi region is primarily carbonated hydroxyapatite, characterized by high porosity (&gt;35%), significant hygroscopicity, and a unique trace element profile (Zn, Sr). These properties underpin its advertised therapeutic effects. However, the market is now saturated with dangerous adulterants, including fluoride-rich dinosaur fossils and processed modern bones, due to resource exhaustion and inadequate pharmacopoeial standards focused solely on calcium content.</div></div><div><h3>Conclusion</h3><div>The future of Long Gu depends on transcending outdated quality controls. Ensuring its efficacy and safety necessitates a paradigm shift to a comprehensive standard system that combines paleontological and geochronological origin verification, quantitative microstructural analysis, chemical fingerprinting of key components, and strict safety monitoring. Complementary research into biomimetic synthesis and accelerated mineralization is urgently needed to develop sustainable alternatives for this invaluable yet endangered medicinal resource.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121354"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165529","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}
引用次数: 0
Metabolomic profiling of Cordia africana Lam. and its anti-asthmatic effect in an ovalbumin-induced allergic airway inflammation model 非洲考迪亚的代谢组学分析。观察其在卵清蛋白致变应性气道炎症模型中的抗哮喘作用。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-09 DOI: 10.1016/j.jep.2026.121346
Manal M. Sabry , Heba A. El Gizawy , Ahlam M. El-Fishawy , Mohammed A. Hussein , Basma M. Eltanany , Laura Pont , Fernando Benavente , Rania A. El Gedaily , Rana M. Ibrahim

Ethnopharmacological relevance

Cordia africana Lam. (C. africana) (Boraginaceae) is traditionally used in Africa to manage inflammatory disorders.

Aim of the study

This study aimed to investigate the metabolome of C. africana cultivated in Sudan and evaluate its potential against allergic severe asthma - a chronic, and complex inflammatory airway condition.

Material and methods

Phytoconstituents of C. africana leaf (CL), stem bark (CSB), and root bark (CRB) were identified by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The antiallergic effect of CL (200 and 400 mg/kg b.wt.) was investigated in an ovalbumin (OVA)-induced airway inflammation and allergic asthma rat model, using dexamethasone (0.5 mg/kg b.wt.) as a standard.

Results

A total of 65 metabolites were identified, including carbohydrates, organic and fatty acids, phenolic acids, coumarins, and flavonoids. Hierarchical clustering heatmap analysis revealed significant metabolite discrepancies between the organs, with CL treatment exhibiting the highest number of unique metabolites (24 compounds). CL extract significantly reduced sneezing frequency, eosinophils count, plasma immunoglobulin E, histamine, complements C3 and C4, lung vascular endothelial growth factor, phosphorylated Akt, interleukin-6 (IL-6), IL-23, transforming growth factor-beta (TGF-β), malondialdehyde, while significantly increasing glutathione, and superoxide dismutase. Furthermore, lung NLRP3 and AhR gene expression were markedly reduced. These biochemical findings, suggesting anti-allergic, anti-inflammatory and antioxidant effects, were further supported by histological analysis after proper clinical trials.

Conclusion

The results suggest that C. africana could serve as a promising source of bioactive metabolites with anti-asthmatic potential. However, further pre-clinical and clinical studies are required to validate its efficacy and safety for developing novel therapies.
民族药理学相关性:非洲考迪亚Lam。(C. africana) (Boraginaceae)在非洲传统上用于治疗炎症性疾病。研究目的:本研究旨在调查在苏丹种植的非洲假药的代谢组,并评估其对抗过敏性严重哮喘(一种慢性、复杂的气道炎症)的潜力。材料与方法:采用液相色谱-四极杆飞行时间串联质谱法(LC-QTOF-MS/MS)对非洲竹叶(CL)、茎皮(CSB)和根皮(CRB)的植物成分进行鉴定。以地塞米松(0.5 mg/kg b.wt.)为标准,在卵清蛋白(OVA)诱导的气道炎症和过敏性哮喘大鼠模型中,研究CL(200和400 mg/kg b.wt.)的抗过敏作用。结果:共鉴定出65种代谢物,包括碳水化合物、有机脂肪酸、脂肪酸、酚酸、香豆素和类黄酮。分层聚类热图分析显示各器官之间代谢物存在显著差异,CL处理显示出最多的独特代谢物(24种化合物)。CL提取物显著降低打喷嚏频率、嗜酸性粒细胞计数、血浆免疫球蛋白E、组胺、补体C3和C4、肺血管内皮生长因子、磷酸化Akt、白细胞介素-6 (IL-6)、IL-23、转化生长因子-β (TGF-β)、丙二醛,同时显著升高谷胱甘肽和超氧化物歧化酶。肺NLRP3、AhR基因表达明显降低。这些生化结果提示具有抗过敏、抗炎和抗氧化作用,并在适当的临床试验后得到组织学分析的进一步支持。结论:非洲曲霉是一种具有抗哮喘潜能的生物活性代谢物来源。然而,需要进一步的临床前和临床研究来验证其有效性和安全性,以开发新的治疗方法。
{"title":"Metabolomic profiling of Cordia africana Lam. and its anti-asthmatic effect in an ovalbumin-induced allergic airway inflammation model","authors":"Manal M. Sabry ,&nbsp;Heba A. El Gizawy ,&nbsp;Ahlam M. El-Fishawy ,&nbsp;Mohammed A. Hussein ,&nbsp;Basma M. Eltanany ,&nbsp;Laura Pont ,&nbsp;Fernando Benavente ,&nbsp;Rania A. El Gedaily ,&nbsp;Rana M. Ibrahim","doi":"10.1016/j.jep.2026.121346","DOIUrl":"10.1016/j.jep.2026.121346","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cordia africana</em> Lam. (<em>C. africana</em>) (Boraginaceae) is traditionally used in Africa to manage inflammatory disorders.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the metabolome of <em>C. africana</em> cultivated in Sudan and evaluate its potential against allergic severe asthma - a chronic, and complex inflammatory airway condition.</div></div><div><h3>Material and methods</h3><div>Phytoconstituents of <em>C. africana</em> leaf (CL), stem bark (CSB), and root bark (CRB) were identified by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The antiallergic effect of CL (200 and 400 mg/kg b.wt.) was investigated in an ovalbumin (OVA)-induced airway inflammation and allergic asthma rat model, using dexamethasone (0.5 mg/kg b.wt.) as a standard.</div></div><div><h3>Results</h3><div>A total of 65 metabolites were identified, including carbohydrates, organic and fatty acids, phenolic acids, coumarins, and flavonoids. Hierarchical clustering heatmap analysis revealed significant metabolite discrepancies between the organs, with CL treatment exhibiting the highest number of unique metabolites (24 compounds). CL extract significantly reduced sneezing frequency, eosinophils count, plasma immunoglobulin E, histamine, complements C3 and C4, lung vascular endothelial growth factor, phosphorylated Akt, interleukin-6 (IL-6), IL-23, transforming growth factor-beta (TGF-β), malondialdehyde, while significantly increasing glutathione, and superoxide dismutase. Furthermore, lung NLRP3 and AhR gene expression were markedly reduced. These biochemical findings, suggesting anti-allergic, anti-inflammatory and antioxidant effects, were further supported by histological analysis after proper clinical trials.</div></div><div><h3>Conclusion</h3><div>The results suggest that <em>C. africana</em> could serve as a promising source of bioactive metabolites with anti-asthmatic potential. However, further pre-clinical and clinical studies are required to validate its efficacy and safety for developing novel therapies.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121346"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165625","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}
引用次数: 0
Danlong oral liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells 丹龙口服液通过靶向气道平滑肌细胞的S1PR2/ROCK1/YAP信号通路缓解哮喘气道重构。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-08 DOI: 10.1016/j.jep.2026.121347
Mengqi Zhou , Min Xiang , Yuan Li , Zizhong Wang , Jiangtao Lin
<div><h3>Ethnopharmacological relevance</h3><div>Danlong Oral Liquid (DLOL) is a proprietary Traditional Chinese Medicine (TCM) with documented clinical efficacy against asthma, yet its underlying mechanism of action remains incompletely understood. The bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and its receptor S1PR2 signaling axis are critically implicated in asthma pathogenesis, particularly in driving airway smooth muscle cell (ASMC) remodeling, a key pathological feature of asthma. Despite this, the mechanistic involvement of DLOL in this specific pathway has not been explored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to validate the effect of DLOL against asthma-associated airway remodeling and to elucidate whether its mechanism of action involves the modulation of the S1PR2/ROCK1/YAP signaling pathway in ASMCs.</div></div><div><h3>Materials and methods</h3><div>The therapeutic effects and mechanisms of DLOL were investigated using a combination of <em>in vivo</em> and <em>in vitro</em> approaches. An <em>in vivo</em> rat model of allergic asthma was induced by ovalbumin (OVA) sensitization and challenge. We assessed airway hyperresponsiveness (AHR) and performed inflammatory cell counts in bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining. Lung histopathology was evaluated by Hematoxylin and Eosin (H&E) staining, Periodic Acid-Schiff (PAS) staining, and Masson's trichrome staining to assess inflammation, goblet cell hyperplasia, and collagen deposition. Levels of S1P and cytokines (IL-4, IL-5, IL-13) in BALF and serum, along with OVA-IgE in serum, were measured by enzyme-linked immunosorbent assay (ELISA). The protein and gene expression of key molecules in the S1PR2/ROCK1/YAP signaling pathway were analyzed by Western blotting (WB), immunohistochemistry (IHC), and Real-time quantitative polymerase chain reaction (RT-qPCR). For <em>in vitro</em> studies, primary rat ASMCs were stimulated with S1P. The impact of DLOL-containing serum (DL-CS) on proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) incorporation assays. Cell migration and contraction were evaluated by scratch assay and collagen gel contraction assay, respectively. Underlying mechanisms were further examined by WB, RT-qPCR, and immunofluorescence (IF).</div></div><div><h3>Results</h3><div>DLOL administration significantly alleviated AHR, airway inflammation, and remodeling in a rat model of asthma. Mechanistically, DLOL downregulated the S1PR2/ROCK1/YAP signaling axis in lung tissues, inhibiting the expression of S1PR2, RhoA, and ROCK1, promoting YAP inactivation, and suppressing the downstream targets FOXM1 and CyclinD1. Consistently, DL-CS potently inhibited S1P-induced proliferation, migration, and contraction of ASMCs <em>in vitro</em>, further confirming its robust anti-remodeling activity.</div></div><div><h3>Conclusions</h3><div>Our integrated findings demonstrate
民族药理学相关性:丹龙口服液(DLOL)是一种具有临床疗效的中药,但其作用机制尚不完全清楚。生物活性鞘脂介质鞘鞘醇-1-磷酸(S1P)及其受体S1PR2信号轴在哮喘发病中起关键作用,特别是在驱动气道平滑肌细胞(ASMC)重塑中,这是哮喘的一个关键病理特征。尽管如此,DLOL在这一特定途径中的机制参与尚未被探索。研究目的:本研究旨在验证DLOL对哮喘相关气道重塑的作用,并阐明其作用机制是否涉及ASMCs中S1PR2/ROCK1/YAP信号通路的调节。材料与方法:采用体内与体外相结合的方法研究DLOL的治疗效果及作用机制。采用卵清蛋白(OVA)致敏和激发诱导大鼠体内变应性哮喘模型。我们评估气道高反应性(AHR),并使用Wright-Giemsa染色对支气管肺泡灌洗液(BALF)进行炎症细胞计数。肺组织病理学采用苏木精和伊红(H&E)染色、周期性酸-希夫(PAS)染色和马森三色染色评估炎症、杯状细胞增生和胶原沉积。采用酶联免疫吸附试验(ELISA)检测BALF和血清中S1P、细胞因子(IL-4、IL-5、IL-13)及血清中OVA-IgE水平。采用Western blotting (WB)、免疫组化(IHC)、实时定量聚合酶链反应(RT-qPCR)等方法分析S1PR2/ROCK1/YAP信号通路关键分子的蛋白及基因表达情况。在体外研究中,用S1P刺激原代大鼠ASMCs。采用细胞计数试剂盒-8 (CCK-8)和5-乙基-2′-脱氧尿苷(EdU)掺入法评估含dloll血清(DL-CS)对增殖的影响。分别用抓痕法和胶原凝胶收缩法评价细胞迁移和收缩。通过WB、RT-qPCR和免疫荧光(IF)进一步研究其潜在机制。结果:大鼠哮喘模型中给药DLOL可显著减轻AHR、气道炎症和气道重塑。在机制上,DLOL下调肺组织中S1PR2/ROCK1/YAP信号轴,抑制S1PR2、RhoA和ROCK1的表达,促进YAP失活,抑制下游靶点FOXM1和CyclinD1。DL-CS能够有效抑制s1p诱导的体外ASMCs的增殖、迁移和收缩,进一步证实了其强大的抗重塑活性。结论:我们的综合研究结果表明,DLOL通过抑制ASMCs的S1PR2/ROCK1/YAP信号通路,从而抑制ASMCs的促重塑表型,从而减轻过敏性哮喘和气道重塑。这项工作不仅为DLOL的临床应用提供了坚实的机制基础,而且将其定位为一种有前景的哮喘多靶点治疗药物。
{"title":"Danlong oral liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells","authors":"Mengqi Zhou ,&nbsp;Min Xiang ,&nbsp;Yuan Li ,&nbsp;Zizhong Wang ,&nbsp;Jiangtao Lin","doi":"10.1016/j.jep.2026.121347","DOIUrl":"10.1016/j.jep.2026.121347","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Danlong Oral Liquid (DLOL) is a proprietary Traditional Chinese Medicine (TCM) with documented clinical efficacy against asthma, yet its underlying mechanism of action remains incompletely understood. The bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and its receptor S1PR2 signaling axis are critically implicated in asthma pathogenesis, particularly in driving airway smooth muscle cell (ASMC) remodeling, a key pathological feature of asthma. Despite this, the mechanistic involvement of DLOL in this specific pathway has not been explored.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This study aimed to validate the effect of DLOL against asthma-associated airway remodeling and to elucidate whether its mechanism of action involves the modulation of the S1PR2/ROCK1/YAP signaling pathway in ASMCs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;The therapeutic effects and mechanisms of DLOL were investigated using a combination of &lt;em&gt;in vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt; approaches. An &lt;em&gt;in vivo&lt;/em&gt; rat model of allergic asthma was induced by ovalbumin (OVA) sensitization and challenge. We assessed airway hyperresponsiveness (AHR) and performed inflammatory cell counts in bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining. Lung histopathology was evaluated by Hematoxylin and Eosin (H&amp;E) staining, Periodic Acid-Schiff (PAS) staining, and Masson's trichrome staining to assess inflammation, goblet cell hyperplasia, and collagen deposition. Levels of S1P and cytokines (IL-4, IL-5, IL-13) in BALF and serum, along with OVA-IgE in serum, were measured by enzyme-linked immunosorbent assay (ELISA). The protein and gene expression of key molecules in the S1PR2/ROCK1/YAP signaling pathway were analyzed by Western blotting (WB), immunohistochemistry (IHC), and Real-time quantitative polymerase chain reaction (RT-qPCR). For &lt;em&gt;in vitro&lt;/em&gt; studies, primary rat ASMCs were stimulated with S1P. The impact of DLOL-containing serum (DL-CS) on proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) incorporation assays. Cell migration and contraction were evaluated by scratch assay and collagen gel contraction assay, respectively. Underlying mechanisms were further examined by WB, RT-qPCR, and immunofluorescence (IF).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;DLOL administration significantly alleviated AHR, airway inflammation, and remodeling in a rat model of asthma. Mechanistically, DLOL downregulated the S1PR2/ROCK1/YAP signaling axis in lung tissues, inhibiting the expression of S1PR2, RhoA, and ROCK1, promoting YAP inactivation, and suppressing the downstream targets FOXM1 and CyclinD1. Consistently, DL-CS potently inhibited S1P-induced proliferation, migration, and contraction of ASMCs &lt;em&gt;in vitro&lt;/em&gt;, further confirming its robust anti-remodeling activity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Our integrated findings demonstrate","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121347"},"PeriodicalIF":5.4,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157248","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}
引用次数: 0
Integration of non-targeted metabolomics and transcriptomics reveals the mechanistic rationale of Coptidis Rhizoma's cold property via systemic energy homeostasis and adaptive thermogenesis in mice 非靶向代谢组学和转录组学的整合揭示了黄连低温特性通过小鼠全身能量稳态和适应性产热的机制原理。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-07 DOI: 10.1016/j.jep.2026.121344
Ran Xie, Yuling Liu, Qi Song, Lixia Song, Jiameng Li, Yanmin Zhang, Jing Meng, Baokai Dou, Xiaoyu Hu, Lv Gao, Qinghe Zhao, Hairu Huo, Feng Sui

Ethnopharmacological relevance

Coptidis Rhizoma (CR), a typical bitter-cold herbal medicine in traditional Chinese medicine (TCM), is commonly employed in treating metabolic diseases like diabetes.

Aim of the study

This study investigated the effects of CR on whole-body metabolic status and elucidate the scientific basis of its “cold” property.

Materials and methods

A CR water decoction was prepared and its major constituents were identified and quantified. C57BL/6J mice were orally administered the CR decoction, and changes in core body temperature (CBT) were monitored using thermocouples. The thermal preference was assessed using dual-temperature choice tests and thermal gradient experiment. Serum metabolomic profiling and transcriptomic analysis of brown adipose tissue (BAT) was conducted. Key targets were validated using RT-qPCR and immunoblotting. Integrated multi-omics analysis was carried out via MetaboAnalyst online database.

Results

The prepared CR decoction identified 11 components. CR administration significantly reduced CBT and altered behavioral thermal preference. Metabolomics identified 45 differential metabolites, enriched in 9 metabolic pathways like the TCA cycle. Transcriptomics revealed 711 significantly differentially expressed genes, prominently associated with thermogenesis and the TCA cycle. Key genes (Acsl1, Elovl3, Hadh, Dio2, Scd1, and Lep) were verified. Integrated metabolomic and transcriptomic analysis underscored CR's impact on the TCA cycle and fatty acid degradation.

Conclusion

CR enhances adaptive thermogenesis in BAT, accelerates the TCA cycle and lipid metabolism, and promotes energy substrate consumption, thereby modulating systemic energy homeostasis. These effects are similar to physiological responses to cold stimulation, providing a mechanistic rationale for the “cold” property of CR in TCM.
民族药理学相关性:黄连(Coptidis Rhizoma, CR)是一种典型的中药苦寒药,常用于治疗糖尿病等代谢性疾病。研究目的:研究CR对全身代谢状态的影响,阐明其“冷”特性的科学依据。材料与方法:制备CR水煎剂,对其主要成分进行鉴定和定量。给C57BL/6J小鼠灌胃CR汤,采用热电偶法监测小鼠核心体温的变化。采用双温度选择试验和热梯度试验评价热偏好。进行了褐色脂肪组织(BAT)的血清代谢组学分析和转录组学分析。利用RT-qPCR和免疫印迹技术对关键靶点进行验证。综合多组学分析通过MetaboAnalyst在线数据库进行。结果:制备的白藜芦醇煎剂鉴定出11种成分。给予CR显著降低CBT和改变行为热偏好。代谢组学鉴定出45种差异代谢物,富集于TCA循环等9种代谢途径。转录组学揭示了711个显著差异表达的基因,这些基因与产热和TCA循环显著相关。对关键基因Acsl1、Elovl3、Hadh、Dio2、Scd1和Lep进行了验证。综合代谢组学和转录组学分析强调了CR对TCA循环和脂肪酸降解的影响。结论:CR增强BAT的适应性产热,加速TCA循环和脂质代谢,促进能量底物消耗,从而调节全身能量稳态。这些作用类似于对冷刺激的生理反应,为中医中CR的“冷”特性提供了机制基础。
{"title":"Integration of non-targeted metabolomics and transcriptomics reveals the mechanistic rationale of Coptidis Rhizoma's cold property via systemic energy homeostasis and adaptive thermogenesis in mice","authors":"Ran Xie,&nbsp;Yuling Liu,&nbsp;Qi Song,&nbsp;Lixia Song,&nbsp;Jiameng Li,&nbsp;Yanmin Zhang,&nbsp;Jing Meng,&nbsp;Baokai Dou,&nbsp;Xiaoyu Hu,&nbsp;Lv Gao,&nbsp;Qinghe Zhao,&nbsp;Hairu Huo,&nbsp;Feng Sui","doi":"10.1016/j.jep.2026.121344","DOIUrl":"10.1016/j.jep.2026.121344","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Coptidis Rhizoma (CR), a typical bitter-cold herbal medicine in traditional Chinese medicine (TCM), is commonly employed in treating metabolic diseases like diabetes.</div></div><div><h3>Aim of the study</h3><div>This study investigated the effects of CR on whole-body metabolic status and elucidate the scientific basis of its “cold” property.</div></div><div><h3>Materials and methods</h3><div>A CR water decoction was prepared and its major constituents were identified and quantified. C57BL/6J mice were orally administered the CR decoction, and changes in core body temperature (CBT) were monitored using thermocouples. The thermal preference was assessed using dual-temperature choice tests and thermal gradient experiment. Serum metabolomic profiling and transcriptomic analysis of brown adipose tissue (BAT) was conducted. Key targets were validated using RT-qPCR and immunoblotting. Integrated multi-omics analysis was carried out <em>via</em> MetaboAnalyst online database.</div></div><div><h3>Results</h3><div>The prepared CR decoction identified 11 components. CR administration significantly reduced CBT and altered behavioral thermal preference. Metabolomics identified 45 differential metabolites, enriched in 9 metabolic pathways like the TCA cycle. Transcriptomics revealed 711 significantly differentially expressed genes, prominently associated with thermogenesis and the TCA cycle. Key genes (Acsl1, Elovl3, Hadh, Dio2, Scd1, and Lep) were verified. Integrated metabolomic and transcriptomic analysis underscored CR's impact on the TCA cycle and fatty acid degradation.</div></div><div><h3>Conclusion</h3><div>CR enhances adaptive thermogenesis in BAT, accelerates the TCA cycle and lipid metabolism, and promotes energy substrate consumption, thereby modulating systemic energy homeostasis. These effects are similar to physiological responses to cold stimulation, providing a mechanistic rationale for the “cold” property of CR in TCM.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121344"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149701","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}
引用次数: 0
Neuroprotective and antioxidant properties of Polygala virgata fractions in a 6-hydroxydopamine-induced neurotoxicity model 6-羟多巴胺诱导的神经毒性模型中茯苓提取物的神经保护和抗氧化作用。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-07 DOI: 10.1016/j.jep.2026.121222
A.D. de Beer , W. Rudolph , V. Maharaj , V. Steenkamp , M. Balmith , W. Cordier

Introduction

Ferroptosis contributes to Parkinson's disease progression given dysregulation of iron homeostasis and redox status. Polygala virgata is used ethnomedicinally for memory enhancement. This study assessed the cytoprotective and antioxidant properties of crude extracts and fractions of P. virgata using a 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y neuroblastoma cytotoxicity model.

Method

Dried roots of P. virgata (14% w/v) were sequentially extracted using dichloromethane/methanol (1:1) and methanol, which was combined to give a crude extract. The crude extract was separated into seven fractions using different ratios of water, acetonitrile and methanol on solid phase extraction (SPE). Inherent cytotoxicity of the samples (10 μg/mL), as well as their ability to reduce 6-OHDA-induced cytotoxicity (35 μM), was determined using the sulforhodamine B (SRB) assay after 48-h (h) exposure. The active fractions' cytoprotective effect in relation to reactive oxygen species (ROS), glutathione levels (GSH), lipid peroxidation, and mitochondrial integrity was determined fluorometrically. Cytoprotective fractions’ phytochemical constituency was elucidated using liquid chromatography high resolution mass-spectrometry (UPLC-HRMS).

Results

Fractions 3 to 7 increased cell density after exposure to 6-OHDA by 31.14%, 28.08%, 30.72%, 40.58% (p < 0.01) and 28.86%, respectively, with no inherent cytotoxicity observed. Fraction 4 reduced 6-OHDA-induced ROS generation (2.09-fold) and lipid peroxidation (0.28-fold). Non-significant increases in GSH were noted (1.34 to 19.25%), while all fractions hyperpolarised the mitochondrial membrane. Multi-hydroxylated xanthones, flavones and flavans were tentatively identified using UPLC-HRMS.

Conclusion

P. virgata fractions reduced 6-OHDA-induced cytotoxicity via decreased oxidative stress and hyperpolarisation of the mitochondrial membrane, most likely ascribed to the identified xanthones, flavones and flavans. Isolation and purification of these compounds are warranted as potential antioxidant scaffolds.
简介:由于铁稳态和氧化还原状态的失调,铁下沉有助于帕金森病的进展。山茱萸在民族医学上被用来增强记忆。本研究采用6-羟多巴胺(6-OHDA) SH-SY5Y神经母细胞瘤细胞毒性模型,评估了荆芥粗提物和组分的细胞保护和抗氧化特性。方法:采用二氯甲烷/甲醇(1:1)和甲醇混合提取粗提物,分别以14% w/v的比例提取荆芥干根。采用固相萃取法(SPE),采用不同比例的水、乙腈和甲醇对粗提物进行分离。暴露48小时(h)后,采用硫代丹B (SRB)法测定样品的固有细胞毒性(10 μg/mL)和降低6- ohda诱导的细胞毒性(35 μM)的能力。荧光法测定活性组分对活性氧(ROS)、谷胱甘肽水平(GSH)、脂质过氧化和线粒体完整性的细胞保护作用。采用液相色谱-高分辨质谱(UPLC-HRMS)分析了细胞保护组分的植物化学成分。结果:6-OHDA处理后,3 ~ 7组分细胞密度分别提高31.14%、28.08%、30.72%、40.58%和28.86% (p < 0.01),未见固有细胞毒性。组分4减少6-羟色胺诱导的ROS生成(2.09倍)和脂质过氧化(0.28倍)。GSH无显著性升高(1.34% ~ 19.25%),而所有组分均使线粒体膜超极化。用UPLC-HRMS初步鉴定了多羟基化的山酮、黄酮和黄烷。结论:荆芥提取物通过降低氧化应激和线粒体膜的超极化来降低6- ohda诱导的细胞毒性,这很可能归因于所鉴定的黄酮、黄酮和黄烷。这些化合物的分离和纯化作为潜在的抗氧化支架是有必要的。
{"title":"Neuroprotective and antioxidant properties of Polygala virgata fractions in a 6-hydroxydopamine-induced neurotoxicity model","authors":"A.D. de Beer ,&nbsp;W. Rudolph ,&nbsp;V. Maharaj ,&nbsp;V. Steenkamp ,&nbsp;M. Balmith ,&nbsp;W. Cordier","doi":"10.1016/j.jep.2026.121222","DOIUrl":"10.1016/j.jep.2026.121222","url":null,"abstract":"<div><h3>Introduction</h3><div>Ferroptosis contributes to Parkinson's disease progression given dysregulation of iron homeostasis and redox status. <em>Polygala virgata</em> is used ethnomedicinally for memory enhancement. This study assessed the cytoprotective and antioxidant properties of crude extracts and fractions of <em>P. virgata</em> using a 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y neuroblastoma cytotoxicity model.</div></div><div><h3>Method</h3><div>Dried roots of <em>P. virgata</em> (14% w/v) were sequentially extracted using dichloromethane/methanol (1:1) and methanol, which was combined to give a crude extract. The crude extract was separated into seven fractions using different ratios of water, acetonitrile and methanol on solid phase extraction (SPE). Inherent cytotoxicity of the samples (10 μg/mL), as well as their ability to reduce 6-OHDA-induced cytotoxicity (35 μM), was determined using the sulforhodamine B (SRB) assay after 48-h (h) exposure. The active fractions' cytoprotective effect in relation to reactive oxygen species (ROS), glutathione levels (GSH), lipid peroxidation, and mitochondrial integrity was determined fluorometrically. Cytoprotective fractions’ phytochemical constituency was elucidated using liquid chromatography high resolution mass-spectrometry (UPLC-HRMS).</div></div><div><h3>Results</h3><div>Fractions 3 to 7 increased cell density after exposure to 6-OHDA by 31.14%, 28.08%, 30.72%, 40.58% (p &lt; 0.01) and 28.86%, respectively, with no inherent cytotoxicity observed. Fraction 4 reduced 6-OHDA-induced ROS generation (2.09-fold) and lipid peroxidation (0.28-fold). Non-significant increases in GSH were noted (1.34 to 19.25%), while all fractions hyperpolarised the mitochondrial membrane. Multi-hydroxylated xanthones, flavones and flavans were tentatively identified using UPLC-HRMS.</div></div><div><h3>Conclusion</h3><div><em>P. virgata</em> fractions reduced 6-OHDA-induced cytotoxicity via decreased oxidative stress and hyperpolarisation of the mitochondrial membrane, most likely ascribed to the identified xanthones, flavones and flavans. Isolation and purification of these compounds are warranted as potential antioxidant scaffolds.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121222"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149710","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}
引用次数: 0
期刊
Journal of ethnopharmacology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1