Pub Date : 2026-02-10DOI: 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.
{"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 , Minghao Lu , Xin Sun , Hong Zhu , Baoping Jiang , Lingling Zhou , 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}
Pub Date : 2026-02-10DOI: 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.
{"title":"Sangbaipi Decoction mitigates influenza pneumonia in mice by inhibiting ZBP1-mediated PANoptosis","authors":"Chengcheng Zhang , Guofeng Yu , Miaomiao Liu , Ruikun Du , Jing Ma , Xuran Gu , Lijun Rong , Xuxiao Lv , 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}
Pub Date : 2026-02-10DOI: 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.
{"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}
Pub Date : 2026-02-09DOI: 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.
{"title":"Gancao decoction ameliorated senecionine-induced Hepatic Sinusoidal Obstruction Syndrome in mice by inhibiting NET formation and senecionine bioactivation in liver","authors":"Shuang Zhang , Dongming Yan , Si Cheng , Jingyi Jin , Jiamin Cui , Chenghai Liu , Yue Li , 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}
Pub Date : 2026-02-09DOI: 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
{"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 , 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","doi":"10.1016/j.jep.2026.121349","DOIUrl":"10.1016/j.jep.2026.121349","url":null,"abstract":"<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","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}
Pub Date : 2026-02-09DOI: 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.
{"title":"Long Gu (Os Draconis): Textual research, modern scientific evaluation, and quality control challenges","authors":"Sun Xiujia , Li Zhan Hua , Gao Yuanze , Kumar Ganesan , Liu Jing , Li Li , Zhang Chao , 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 (>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}
Pub Date : 2026-02-09DOI: 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.
{"title":"Metabolomic profiling of Cordia africana Lam. and its anti-asthmatic effect in an ovalbumin-induced allergic airway inflammation model","authors":"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","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}
Pub Date : 2026-02-08DOI: 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
{"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 , Min Xiang , Yuan Li , Zizhong Wang , Jiangtao Lin","doi":"10.1016/j.jep.2026.121347","DOIUrl":"10.1016/j.jep.2026.121347","url":null,"abstract":"<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","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}
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.
{"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, Yuling Liu, Qi Song, Lixia Song, Jiameng Li, Yanmin Zhang, Jing Meng, Baokai Dou, Xiaoyu Hu, Lv Gao, Qinghe Zhao, Hairu Huo, 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}
Pub Date : 2026-02-07DOI: 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.
{"title":"Neuroprotective and antioxidant properties of Polygala virgata fractions in a 6-hydroxydopamine-induced neurotoxicity model","authors":"A.D. de Beer , W. Rudolph , V. Maharaj , V. Steenkamp , M. Balmith , 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 < 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}