Pub Date : 2026-01-02DOI: 10.1016/j.prmcm.2026.100750
Linxin Zheng , Bugao Zhou , Miaohua Liu , Yi Xiong , Xin Zeng , Kaien Guo , Duanyong Liu
Objective
To investigate the therapeutic efficacy and underlying mechanisms of Pien Tze Huang (PTH) in a murine autoimmune hepatitis (AIH) model through assessment of memory regulatory T cells (mTreg)/memory T helper cell 17 (mTh17) cell equilibrium and glycolytic metabolism.
Methods
AIH was induced through intravenous concanavalin A (ConA) administration via tail vein injection with prophylactic PTH treatment over 10 days. Hepatic histopathological alterations were evaluated using H&E staining, while serum transaminase levels were quantified through biochemical analysis. ELISA was employed to determine immunoglobulin concentrations and hepatic tissue levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 21 (IL-21), interleukin 10 (IL-10), interleukin 4 (IL-4), tumor necrosis factor α (TNF-α), interferon-gamma (IFN-γ), Immunoglobulin G (IgG), Immunoglobulin A (IgA), Immunoglobulin M (IgM), glycolysis hexokinase 2 (HK2), pyruvate kinase (PK), glucose-6-phosphatase (G6pase), phosphoenolpyruvate carboxykinase (PEPCK), aldolase A (ALDOA), glucokinase (GCK), lactate dehydrogenase A (LDHA). Flow cytometric analysis was performed to quantify Treg, mTreg, Th17, and mTh17 cell populations. Protein expression of glucose transporter protein 1 (Glut1), glucose transporter protein 2 (Glut2), glucose transporter protein 3 (Glut3), glucose transporter protein 4 (Glut4), hypoxia-inducible factor-1α subunit (HIF-1α), signal transducer and activator of transcription 3 (STAT3), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), T-cell transcription factor (T-bet), and retinoic acid receptor-related orphan receptor gamma (RORγt) was analyzed by Western blotting.
Results
Relative to the model group, PTH administration significantly ameliorated hepatocellular injury, as evidenced by reduced serum ALT and AST levels, decreased immunoglobulin concentrations, and attenuated hepatic pathological damage (p < 0.05 or p < 0.01). Furthermore, PTH treatment resulted in significant suppression of proinflammatory cytokine expression in murine hepatic tissue (p < 0.05 or p < 0.01). PTH treatment increased the proportions of Treg and mTreg cells while reducing Th17 and mTh17 cell populations (p < 0.05 or p < 0.01). Mechanistic investigations revealed that PTH significantly downregulated the expression of critical glycolytic enzymes and glycolysis-associated proteins in hepatic tissue of AIH model mice (p < 0.05 or p < 0.01).
Conclusions
PTH effectively attenuates ConA-induced AIH by modulating the balance of memory Treg/Th17 cells and glycolytic pathways.
{"title":"Regulatory effect of Pien Tze Huang on the mTreg/mTh17 balance in mice with autoimmune hepatitis","authors":"Linxin Zheng , Bugao Zhou , Miaohua Liu , Yi Xiong , Xin Zeng , Kaien Guo , Duanyong Liu","doi":"10.1016/j.prmcm.2026.100750","DOIUrl":"10.1016/j.prmcm.2026.100750","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the therapeutic efficacy and underlying mechanisms of Pien Tze Huang (PTH) in a murine autoimmune hepatitis (AIH) model through assessment of memory regulatory T cells (mTreg)/memory T helper cell 17 (mTh17) cell equilibrium and glycolytic metabolism.</div></div><div><h3>Methods</h3><div>AIH was induced through intravenous concanavalin A (ConA) administration <em>via</em> tail vein injection with prophylactic PTH treatment over 10 days. Hepatic histopathological alterations were evaluated using H&E staining, while serum transaminase levels were quantified through biochemical analysis. ELISA was employed to determine immunoglobulin concentrations and hepatic tissue levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 21 (IL-21), interleukin 10 (IL-10), interleukin 4 (IL-4), tumor necrosis factor α (TNF-α), interferon-gamma (IFN-γ), Immunoglobulin G (IgG), Immunoglobulin A (IgA), Immunoglobulin M (IgM), glycolysis hexokinase 2 (HK2), pyruvate kinase (PK), glucose-6-phosphatase (G6pase), phosphoenolpyruvate carboxykinase (PEPCK), aldolase A (ALDOA), glucokinase (GCK), lactate dehydrogenase A (LDHA). Flow cytometric analysis was performed to quantify Treg, mTreg, Th17, and mTh17 cell populations. Protein expression of glucose transporter protein 1 (Glut1), glucose transporter protein 2 (Glut2), glucose transporter protein 3 (Glut3), glucose transporter protein 4 (Glut4), hypoxia-inducible factor-1α subunit (HIF-1α), signal transducer and activator of transcription 3 (STAT3), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), T-cell transcription factor (T-bet), and retinoic acid receptor-related orphan receptor gamma (RORγt) was analyzed by Western blotting.</div></div><div><h3>Results</h3><div>Relative to the model group, PTH administration significantly ameliorated hepatocellular injury, as evidenced by reduced serum ALT and AST levels, decreased immunoglobulin concentrations, and attenuated hepatic pathological damage (<em>p</em> < 0.05 or <em>p</em> < 0.01). Furthermore, PTH treatment resulted in significant suppression of proinflammatory cytokine expression in murine hepatic tissue (<em>p</em> < 0.05 or <em>p</em> < 0.01). PTH treatment increased the proportions of Treg and mTreg cells while reducing Th17 and mTh17 cell populations (<em>p</em> < 0.05 or <em>p</em> < 0.01). Mechanistic investigations revealed that PTH significantly downregulated the expression of critical glycolytic enzymes and glycolysis-associated proteins in hepatic tissue of AIH model mice (<em>p</em> < 0.05 or <em>p</em> < 0.01).</div></div><div><h3>Conclusions</h3><div>PTH effectively attenuates ConA-induced AIH by modulating the balance of memory Treg/Th17 cells and glycolytic pathways.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100750"},"PeriodicalIF":0.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.prmcm.2025.100749
Akash Bhati, Hemanth Kumar Boyina, Navneet Sharma
Introduction
Various parts of the Morus species have long been used in TCM, which are increasingly known for their anti-oxidant and anti-inflammatory properties. This review systematically explores the phytochemical composition and therapeutic relevance of Morus species within the TCM framework.
Methods
A comprehensive literature analysis was conducted across ScienceDirect.PubMed and Google Scholar, concentrating more on peer-reviewed English-language articles, clinical trials, and reviews published up to 2025.
Results
Out of the initial 297 sources identified, 165 were selected for relevance to Morus and its bioactive constituents. More emphasis has been placed on those studies providing part-specific information on leaves, bark, stems, fruits, twigs, and roots, which are commonly used in traditional formulations. The review maps the distribution of phytochemicals across these botanical parts and highlights their pharmacological actions with special attention to anti-inflammatory and antioxidant mechanisms. Key compounds discussed in relation to modulation of oxidative stress, inflammatory pathways, and possible clinical applications include flavonoids, alkaloids, and polyphenols.
Discussion
The current synthesis provides a comprehensive phytochemical profile of Morus species and emphasizes their therapeutic potential in the management of chronic inflammatory-degenerative disorders. Despite this promise, the effects await further confirmation by targeted pharmacological studies and well-designed clinical trials. Elucidation of the role of bioactive compounds from Morus species might help to include such compounds in evidence-based complementary medicine and drug development strategies.
{"title":"Anti-inflammatory and antioxidant mechanisms of Morus species: Part-specific insights from traditional Chinese medicine","authors":"Akash Bhati, Hemanth Kumar Boyina, Navneet Sharma","doi":"10.1016/j.prmcm.2025.100749","DOIUrl":"10.1016/j.prmcm.2025.100749","url":null,"abstract":"<div><h3>Introduction</h3><div>Various parts of the Morus species have long been used in TCM, which are increasingly known for their anti-oxidant and anti-inflammatory properties. This review systematically explores the phytochemical composition and therapeutic relevance of Morus species within the TCM framework.</div></div><div><h3>Methods</h3><div>A comprehensive literature analysis was conducted across ScienceDirect.PubMed and Google Scholar, concentrating more on peer-reviewed English-language articles, clinical trials, and reviews published up to 2025.</div></div><div><h3>Results</h3><div>Out of the initial 297 sources identified, 165 were selected for relevance to Morus and its bioactive constituents. More emphasis has been placed on those studies providing part-specific information on leaves, bark, stems, fruits, twigs, and roots, which are commonly used in traditional formulations. The review maps the distribution of phytochemicals across these botanical parts and highlights their pharmacological actions with special attention to anti-inflammatory and antioxidant mechanisms. Key compounds discussed in relation to modulation of oxidative stress, inflammatory pathways, and possible clinical applications include flavonoids, alkaloids, and polyphenols.</div></div><div><h3>Discussion</h3><div>The current synthesis provides a comprehensive phytochemical profile of Morus species and emphasizes their therapeutic potential in the management of chronic inflammatory-degenerative disorders. Despite this promise, the effects await further confirmation by targeted pharmacological studies and well-designed clinical trials. Elucidation of the role of bioactive compounds from Morus species might help to include such compounds in evidence-based complementary medicine and drug development strategies.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100749"},"PeriodicalIF":0.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.prmcm.2025.100747
Thi Hong Tuoi Do , Van Ho Nam Phan , Thi Kim Anh Le , Phuong Ngoc Anh Le , Le Dan Thao Ha , Phan Thao Trang Nguyen , Truong Hoan Trong Nguyen , Thi Thu Hien Vo , Huong-Giang Le , Thi Van Anh Tran
Introduction
Many species belonging to the genus Helicteres are used in the traditional medicine of Asian countries. Helicteres hirsuta (雁婆麻) is widely distributed and cultivated in China but not used for medicinal purposes. However, the decoction of H. hirsuta has long been employed in Vietnamese folk medicine for managing hepatic disorders. The systematic pharmacological validation and phytochemical characterization of this plant remain inadequate. This study sought to elucidate the chemical constituents of the H. hirsuta water extract (HWE) and to assess its hepatoprotective efficacy through in vitro and in vivo models. The findings are expected to not only provide scientific evidence for its traditional use in Vietnam but also highlight the potential of H. hirsuta as a new, untapped therapeutic resource for Traditional Chinese Medicine.
Methods
HWE was fractionated by column chromatography, and isolated constituents were identified using spectroscopic techniques. Hepatoprotective activity was examined against paracetamol-induced cytotoxicity in HepG2 cells, while antioxidant capacity with DPPH radical scavenging and lipid peroxidation assays were assessed. Main bioactive constituents identified by UPLC–MS were quantified in HWE which was further investigated in vivo. Hepatoprotective effects of HWE (412.5 and 825 mg/kg) were evaluated in mice with paracetamol-induced hepatotoxicity (400 mg/kg). Serum biomarkers (ALT, AST, ALP, bilirubin), oxidative stress parameters (GSH, MDA), and histopathology were analyzed, using silymarin (100 mg/kg) as positive control.
Results
HWE exhibited pronounced hepatoprotective activity in vitro (EC₅₀ = 20.12 ± 0.15 µg/mL) with strong antioxidant potential (DPPH, IC₅₀ = 33.91 ± 0.48 µg/mL; MDA, IC₅₀ = 165.07 ± 8.60 µg/mL). Nine compounds were identified, including danshensu (>2 % w/w) as predominant constituent, rosmarinic acid, tiliroside, isoacteoside, forsythoside B, and four flavonoid glucuronides. In vivo, HWE significantly ameliorated biochemical and oxidative stress markers, with greater efficacy at 825 mg/kg.
Conclusion
HWE, particularly at 825 mg/kg, demonstrated significant hepatoprotective activity, attributable to polyphenolic constituents, notably danshensu. These findings scientifically substantiate traditional use and provide a foundation for therapeutic development.
{"title":"The hepatoprotective activity and chemical constituents of Helicteres hirsuta water extract","authors":"Thi Hong Tuoi Do , Van Ho Nam Phan , Thi Kim Anh Le , Phuong Ngoc Anh Le , Le Dan Thao Ha , Phan Thao Trang Nguyen , Truong Hoan Trong Nguyen , Thi Thu Hien Vo , Huong-Giang Le , Thi Van Anh Tran","doi":"10.1016/j.prmcm.2025.100747","DOIUrl":"10.1016/j.prmcm.2025.100747","url":null,"abstract":"<div><h3>Introduction</h3><div>Many species belonging to the genus <em>Helicteres</em> are used in the traditional medicine of Asian countries. <em>Helicteres hirsuta</em> (雁婆麻) is widely distributed and cultivated in China but not used for medicinal purposes. However, the decoction of <em>H. hirsuta</em> has long been employed in Vietnamese folk medicine for managing hepatic disorders. The systematic pharmacological validation and phytochemical characterization of this plant remain inadequate. This study sought to elucidate the chemical constituents of the <em>H. hirsuta</em> water extract (HWE) and to assess its hepatoprotective efficacy through <em>in vitro</em> and <em>in vivo</em> models. The findings are expected to not only provide scientific evidence for its traditional use in Vietnam but also highlight the potential of <em>H. hirsuta</em> as a new, untapped therapeutic resource for Traditional Chinese Medicine.</div></div><div><h3>Methods</h3><div>HWE was fractionated by column chromatography, and isolated constituents were identified using spectroscopic techniques. Hepatoprotective activity was examined against paracetamol-induced cytotoxicity in HepG2 cells, while antioxidant capacity with DPPH radical scavenging and lipid peroxidation assays were assessed. Main bioactive constituents identified by UPLC–MS were quantified in HWE which was further investigated <em>in vivo</em>. Hepatoprotective effects of HWE (412.5 and 825 mg/kg) were evaluated in mice with paracetamol-induced hepatotoxicity (400 mg/kg). Serum biomarkers (ALT, AST, ALP, bilirubin), oxidative stress parameters (GSH, MDA), and histopathology were analyzed, using silymarin (100 mg/kg) as positive control.</div></div><div><h3>Results</h3><div>HWE exhibited pronounced hepatoprotective activity <em>in vitro</em> (EC₅₀ = 20.12 ± 0.15 µg/mL) with strong antioxidant potential (DPPH, IC₅₀ = 33.91 ± 0.48 µg/mL; MDA, IC₅₀ = 165.07 ± 8.60 µg/mL). Nine compounds were identified, including danshensu (>2 % w/w) as predominant constituent, rosmarinic acid, tiliroside, isoacteoside, forsythoside B, and four flavonoid glucuronides. <em>In vivo</em>, HWE significantly ameliorated biochemical and oxidative stress markers, with greater efficacy at 825 mg/kg.</div></div><div><h3>Conclusion</h3><div>HWE, particularly at 825 mg/kg, demonstrated significant hepatoprotective activity, attributable to polyphenolic constituents, notably danshensu. These findings scientifically substantiate traditional use and provide a foundation for therapeutic development.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100747"},"PeriodicalIF":0.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.prmcm.2025.100748
Jinzhe Luo, Weibo Shao, Xiaojie Xue
<div><h3>Introduction</h3><div>Buyang Huanwu Decoction (BHD) is a traditional Chinese medicine (TCM) formula created by Wang Qingren during the Qing dynasty. It is renowned for its effects of <em>Tonify qi,</em><span><span><sup>1</sup></span></span> <em>Circulate blood, and Unblock meridians</em><span><span><sup>2</sup></span></span> and is widely used in the treatment of stroke, for conditions such as hemiplegia and facial paralysis. The formula comprises seven herbs (see Table 2 for the complete list), including <em>Astragalus membranaceus (Fisch.) Bunge, Angelica sinensis (Oliv.) Diels and Paeonia lactiflora Pall.</em> This paper aims to provide a systematic review of the research progress on BHD for stroke treatment from 2019 to December 2025, covering both clinical efficacy and the multidimensional mechanisms of action. The review seeks to address the shortcomings of previous reviews regarding the comprehensive of mechanisms and their timeliness, while providing references for the modernisation of TCM.</div></div><div><h3>Method</h3><div>In order to evaluate the therapeutic effects of BHD on stroke comprehensively, we retrieved relevant literature published between 2019 and December 2025 from Chinese and English databases, including CNKI, Wanfang Database, PubMed and Web of Science. Search keywords included “Buyang Huanwu Decoction”, “stroke”, “mechanism”, “neuroinflammation”, “gut-brain axis” and the herbs that make up the decoction. This review was compiled by synthesising findings from animal experiments and clinical studies.</div></div><div><h3>Results</h3><div>Preliminary, low-certainty evidence from the 19 included RCTs suggests that BHD, when combined with Western medicine or acupuncture, may be associated with potential improvements in certain clinical outcomes such as National Institutes of Health Stroke Scale (NIHSS) and Barthel Index(BL) scores; however, these findings are derived from studies with methodological limitations and require validation in more robust trials. Its mechanism of action is complex, characterized by multi-component, multi-target, and multi-pathway effects. More specifically, this formula regulates cerebral blood circulation, protects neurons, promotes regeneration and stabilises the blood-brain barrier (BBB). It also modulates the gut-brain axis.</div></div><div><h3>Discussion</h3><div>This review summarises the available evidence on the efficacy and pharmacological mechanisms of BHD at different stages of stroke. While the findings may inform targeted clinical applications, further validation is required. However, current research is largely confined to animal or cellular experiments and lacks direct evidence from human studies. There are ongoing challenges in clinical practice, including dosage optimisation and herb-drug interactions. Future studies may overcome these limitations by leveraging systems biology and metabolomics, and through deeper exploration of gut-brain axis mechanisms. Concurrently, the d
补阳还五汤（BHD）是清朝王庆仁发明的传统中药配方。它以其补气、活血、通络的功效而闻名，被广泛用于治疗中风、偏瘫和面瘫等病症。该配方由七种草药组成（完整列表见表2），其中包括黄芪（黄芪属）。邦吉，当归（橄榄）丹参与芍药。本文旨在对2019年至2025年12月BHD治疗脑卒中的研究进展进行系统综述，包括临床疗效和多维作用机制。本综述旨在弥补以往综述在机制综合性和及时性方面的不足，同时为中医药现代化提供参考。方法为了全面评价BHD对脑卒中的治疗效果，我们从CNKI、万方数据库、PubMed、Web of Science等中英文数据库中检索2019年至2025年12月发表的相关文献。搜索关键词包括“补阳还五汤”、“中风”、“机制”、“神经炎症”、“肠脑轴”以及组成该汤的草药。这篇综述是通过综合动物实验和临床研究的结果编写的。结果19项纳入的随机对照试验的初步、低确定性证据表明，BHD与西药或针灸联合治疗可能与某些临床结果的潜在改善有关，如美国国立卫生研究院卒中量表（NIHSS）和Barthel指数（BL）评分；然而，这些发现来自有方法学局限性的研究，需要在更可靠的试验中进行验证。其作用机制复杂，具有多组分、多靶点、多途径作用的特点。更具体地说，这个配方调节脑血循环，保护神经元，促进再生和稳定血脑屏障（BBB）。它还调节肠脑轴。本文综述了BHD在脑卒中不同阶段的疗效和药理机制的现有证据。虽然这些发现可能为有针对性的临床应用提供信息，但还需要进一步的验证。然而，目前的研究主要局限于动物或细胞实验，缺乏来自人体研究的直接证据。在临床实践中存在持续的挑战，包括剂量优化和草药-药物相互作用。未来的研究可能会通过利用系统生物学和代谢组学，以及通过对肠-脑轴机制的更深入探索来克服这些局限性。同时，新配方的开发，如纳米载体，有望提高生物利用度和疗效，从而最大限度地发挥其治疗潜力
{"title":"Buyang Huanwu decoction in the treatment of stroke: A review","authors":"Jinzhe Luo, Weibo Shao, Xiaojie Xue","doi":"10.1016/j.prmcm.2025.100748","DOIUrl":"10.1016/j.prmcm.2025.100748","url":null,"abstract":"<div><h3>Introduction</h3><div>Buyang Huanwu Decoction (BHD) is a traditional Chinese medicine (TCM) formula created by Wang Qingren during the Qing dynasty. It is renowned for its effects of <em>Tonify qi,</em><span><span><sup>1</sup></span></span> <em>Circulate blood, and Unblock meridians</em><span><span><sup>2</sup></span></span> and is widely used in the treatment of stroke, for conditions such as hemiplegia and facial paralysis. The formula comprises seven herbs (see Table 2 for the complete list), including <em>Astragalus membranaceus (Fisch.) Bunge, Angelica sinensis (Oliv.) Diels and Paeonia lactiflora Pall.</em> This paper aims to provide a systematic review of the research progress on BHD for stroke treatment from 2019 to December 2025, covering both clinical efficacy and the multidimensional mechanisms of action. The review seeks to address the shortcomings of previous reviews regarding the comprehensive of mechanisms and their timeliness, while providing references for the modernisation of TCM.</div></div><div><h3>Method</h3><div>In order to evaluate the therapeutic effects of BHD on stroke comprehensively, we retrieved relevant literature published between 2019 and December 2025 from Chinese and English databases, including CNKI, Wanfang Database, PubMed and Web of Science. Search keywords included “Buyang Huanwu Decoction”, “stroke”, “mechanism”, “neuroinflammation”, “gut-brain axis” and the herbs that make up the decoction. This review was compiled by synthesising findings from animal experiments and clinical studies.</div></div><div><h3>Results</h3><div>Preliminary, low-certainty evidence from the 19 included RCTs suggests that BHD, when combined with Western medicine or acupuncture, may be associated with potential improvements in certain clinical outcomes such as National Institutes of Health Stroke Scale (NIHSS) and Barthel Index(BL) scores; however, these findings are derived from studies with methodological limitations and require validation in more robust trials. Its mechanism of action is complex, characterized by multi-component, multi-target, and multi-pathway effects. More specifically, this formula regulates cerebral blood circulation, protects neurons, promotes regeneration and stabilises the blood-brain barrier (BBB). It also modulates the gut-brain axis.</div></div><div><h3>Discussion</h3><div>This review summarises the available evidence on the efficacy and pharmacological mechanisms of BHD at different stages of stroke. While the findings may inform targeted clinical applications, further validation is required. However, current research is largely confined to animal or cellular experiments and lacks direct evidence from human studies. There are ongoing challenges in clinical practice, including dosage optimisation and herb-drug interactions. Future studies may overcome these limitations by leveraging systems biology and metabolomics, and through deeper exploration of gut-brain axis mechanisms. Concurrently, the d","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100748"},"PeriodicalIF":0.0,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.prmcm.2025.100745
Doaa Muwafaq Nassrullah, Huda I. Al Qadhi
Introduction
Psoriasis is a long-lasting, inflammatory autoimmune condition that primarily affects the skin and those with a significant genetic susceptibility. Hesperidin is a polyphenolic bioflavonoid belonging to the flavanone glycoside class that exhibits antioxidant and anti-inflammatory actions. Hesperidin is found in many herbs used in traditional Chinese medicine (TCM), especially Zhiqiao (枳壳, Zhỹ Qiào; dried Citrus aurantium peel) and Chenpi (陳皮, Chén Pí; dried Citrus reticulata peel).
Methods
A total of 48 albino mice were divided into 6 groups, each of 8 mice. The effects of clinical observation, histopathological examination, and biomarker analysis were evaluated.
Results
Hesperidin and its combination with clobetasol significantly reduced imiquimod-induced elevations in the Psoriasis Area and Severity Index (PASI) and Baker’s scores (P<0.001), also significantly diminished inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-17A (IL-17A) as well as oxidative markers malondialdehyde (MDA) (P<0.001), while increasing superoxide dismutase (SOD) levels (P<0.001).
Conclusion
Topical administration of hesperidin may be a promising agent for psoriasis treatment alone or in combination with clobetasol. This is due to the significant anti-inflammatory and antioxidant effects. The study's findings align with the traditional use of hesperidin-rich TCM herbs, including Zhiqiao and Chenpi.
{"title":"The effect of topically applied Hesperidin on Imiquimod-induced Psoriasis in a mouse model","authors":"Doaa Muwafaq Nassrullah, Huda I. Al Qadhi","doi":"10.1016/j.prmcm.2025.100745","DOIUrl":"10.1016/j.prmcm.2025.100745","url":null,"abstract":"<div><h3>Introduction</h3><div>Psoriasis is a long-lasting, inflammatory autoimmune condition that primarily affects the skin and those with a significant genetic susceptibility. Hesperidin is a polyphenolic bioflavonoid belonging to the flavanone glycoside class that exhibits antioxidant and anti-inflammatory actions. Hesperidin is found in many herbs used in traditional Chinese medicine (TCM), especially Zhiqiao (<strong>枳壳</strong>, Zhỹ Qiào; dried Citrus aurantium peel) and Chenpi (<strong>陳皮</strong>, Chén Pí; dried Citrus reticulata peel).</div></div><div><h3>Methods</h3><div>A total of 48 albino mice were divided into 6 groups, each of 8 mice. The effects of clinical observation, histopathological examination, and biomarker analysis were evaluated.</div></div><div><h3>Results</h3><div>Hesperidin and its combination with clobetasol significantly reduced imiquimod-induced elevations in the Psoriasis Area and Severity Index (PASI) and Baker’s scores (P<0.001), also significantly diminished inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-17A (IL-17A) as well as oxidative markers malondialdehyde (MDA) (P<0.001), while increasing superoxide dismutase (SOD) levels (P<0.001).</div></div><div><h3>Conclusion</h3><div>Topical administration of hesperidin may be a promising agent for psoriasis treatment alone or in combination with clobetasol. This is due to the significant anti-inflammatory and antioxidant effects<strong>.</strong> The study's findings align with the traditional use of hesperidin-rich TCM herbs, including Zhiqiao and Chenpi.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100745"},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahua (Madhuca longifolia) is a tree commonly found in tropical regions (family: Sapotaceae). The main phytoconstituents present in flowers and other parts of the plant (known as sweet flower) have a wide range of Traditional Chinese Medicine (TCM) and Ayurvedic applications in the treatment of various disease conditions, including hepatoprotective, anti-inflammatory, and antihyperglycemic activities, especially for kidney stones. Recently, research publications have highlighted greater concern about the application of bioactive constituents and the identification of genes related to stress tolerance, which may help breed or engineer M. longifolia varieties with enhanced medicinal compound production, supporting consistent quality and efficacy in herbal products. The review further highlights the phytochemical composition of mahua, its pharmacological actions in treating certain diseases, and its full mechanism of action, including its pharmacological activities in treating various diseases and ailments.
Methodology
The main study aims to collect all data and information that are collected from previously published reports that are related to “Madhuca longifolia”, “Pharmacological activities of mahua”“, traditional chinese medicine” and their constituents, “mahua phytoconstituents”, which were retrieved from different databases (Scopus, Google Scholar, and PubMed). Hence, ethical authorisation is not required. We retrieved, finalised, and utilised a comprehensive review of 81 articles from 2000 to 2025.
Results
Data from different sources have been collected, and each research publication related to our objective is being analysed. This review further highlights the phytochemical composition of other parts of the mahua plant and the reported pharmacological activities. This review suggested that its various applications warrant further research and investigation.
Conclusion
Mahua’s flower is used as an ayurvedic formulation, and its extracts have potential for the treatment of various disease conditions and also boost immunity.
麻花（madhua long gifolia）是一种常见于热带地区的树（科：槭树科）。花和植物的其他部分（被称为花）中存在的主要植物成分在治疗各种疾病方面具有广泛的传统中医（TCM）和阿育吠陀应用，包括保护肝脏，抗炎和降糖活性，特别是肾结石。最近，研究出版物强调了对生物活性成分的应用和与胁迫耐受性相关基因的鉴定的更大关注，这可能有助于培育或改造长叶支曲品种，提高药用化合物的产量，支持草药产品的质量和功效的一致性。综述进一步强调了麻花的植物化学成分、治疗某些疾病的药理作用及其全部作用机制，包括治疗各种疾病的药理活性。方法本研究主要收集从不同数据库（Scopus、谷歌Scholar和PubMed）中检索到的与“madhua longifolia”、“麻花药理活性”、“中药”及其成分、“麻花植物成分”相关的文献资料。因此，不需要伦理授权。我们检索、整理并利用了2000年至2025年间81篇文章的综合综述。收集了不同来源的数据，并分析了与我们目标相关的每个研究出版物。本文将进一步介绍麻花植物其他部分的植物化学成分和已报道的药理活性。这一综述表明，其各种应用值得进一步研究和探索。结论麻花可作为一种阿育吠陀制剂，其提取物具有治疗多种疾病和提高免疫力的潜力。
{"title":"A comprehensive review of the bioactive compounds and the various pharmacological activities of Mahua (Madhuca longifolia) plant","authors":"Sabina Yasmin , Rasmita Nayak , Fatima M Al-Salam , Anupama Diwan , Rani Mansuri , Sumel Ashique , Md Yousuf Ansari","doi":"10.1016/j.prmcm.2025.100746","DOIUrl":"10.1016/j.prmcm.2025.100746","url":null,"abstract":"<div><h3>Introduction</h3><div>Mahua (<em>Madhuca longifolia</em>) is a tree commonly found in tropical regions (family: Sapotaceae). The main phytoconstituents present in flowers and other parts of the plant (known as sweet flower) have a wide range of Traditional Chinese Medicine (TCM) and Ayurvedic applications in the treatment of various disease conditions, including hepatoprotective, anti-inflammatory, and antihyperglycemic activities, especially for kidney stones. Recently, research publications have highlighted greater concern about the application of bioactive constituents and the identification of genes related to stress tolerance, which may help breed or engineer <em>M. longifolia</em> varieties with enhanced medicinal compound production, supporting consistent quality and efficacy in herbal products. The review further highlights the phytochemical composition of mahua, its pharmacological actions in treating certain diseases, and its full mechanism of action, including its pharmacological activities in treating various diseases and ailments.</div></div><div><h3>Methodology</h3><div>The main study aims to collect all data and information that are collected from previously published reports that are related to “<em>Madhuca longifolia</em>”, “Pharmacological activities of mahua”“, traditional chinese medicine” and their constituents, “mahua phytoconstituents”, which were retrieved from different databases (Scopus, Google Scholar, and PubMed). Hence, ethical authorisation is not required. We retrieved, finalised, and utilised a comprehensive review of 81 articles from 2000 to 2025.</div></div><div><h3>Results</h3><div>Data from different sources have been collected, and each research publication related to our objective is being analysed. This review further highlights the phytochemical composition of other parts of the mahua plant and the reported pharmacological activities. This review suggested that its various applications warrant further research and investigation.</div></div><div><h3>Conclusion</h3><div>Mahua’s flower is used as an ayurvedic formulation, and its extracts have potential for the treatment of various disease conditions and also boost immunity.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100746"},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.prmcm.2025.100743
Sampat Singh Tanwar, Seema Sharma
<div><h3>Introduction</h3><div>Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease worldwide, affecting around 24% of the population, with regional prevalence ranging from 31.8% in the Middle East to 13.5% in Africa (WHO). MASLD encompasses a spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Its complex pathogenesis involves insulin resistance, obesity, genetic factors, and chronic inflammation, leading to excessive lipid accumulation in hepatocytes. Current Western treatments primarily address symptoms but offer limited efficacy. Traditional Chinese Medicine (TCM) provides a holistic approach focused on restoring Yin-Yang balance and Qi flow, viewing liver dysfunction as related to dampness and Qi stagnation. Modern research supports TCM’s multi-target actions, showing herbal medicines improve gut microbiota, strengthen the intestinal barrier, reduce inflammation, and modulate adipokines and insulin sensitivity. These mechanisms support TCM’s potential systemic efficacy in managing MASLD, integrating traditional theory with modern pharmacology.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted across major databases including PubMed, Scopus, and Web of Science to identify relevant preclinical and clinical studies published up to 2025. The search strategy employed combinations of keywords such as “Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD),” “Traditional Chinese Medicine (TCM),” “gut-liver axis,” “adipose-liver axis,” “herbal medicine,” “gut microbiota,” and “adipokines.” Studies were included if they investigated molecular mechanisms or therapeutic effects of Chinese herbal medicines in MASLD models, particularly focusing on modulation of the gut-liver and adipose tissue-liver axes. Both in vitro and in vivo experimental studies, as well as relevant clinical trials, were considered. Studies were excluded if they were non-English, case reports, reviews without original data, or lacked mechanistic or therapeutic relevance. This approach aimed to ensure a comprehensive and focused synthesis of high-quality evidence supporting the systemic effects of TCM in MASLD.</div></div><div><h3>Results</h3><div>Recent studies highlight the gut-liver and adipose-liver axes as key contributors to MASLD progression. Gut dysbiosis alters bile acids, tryptophan catabolites, and BCAAs, where <em>Bacteroides</em> species promote secondary bile acid accumulation, disrupting FXR signaling and causing lipid imbalance and inflammation. Tryptophan-derived indoles impair gut barrier integrity, worsening liver inflammation and fibrosis, while elevated BCAAs associate with insulin resistance and hepatocyte damage. Obesity-induced adipose dysfunction drives MASLD by releasing excess FFAs, activating NF-κB and PPAR-γ pathways, and secreting pro-inflammatory cytokines (TNF-α, IL-6), further impairing
代谢功能障碍相关脂肪变性肝病（MASLD）是全球最常见的慢性肝病，影响约24%的人口，区域患病率从中东的31.8%到非洲的13.5%不等（WHO）。MASLD包括从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH）、纤维化、肝硬化和肝细胞癌。其复杂的发病机制涉及胰岛素抵抗、肥胖、遗传因素和慢性炎症，导致肝细胞内脂质过度积累。目前的西方治疗主要针对症状，但疗效有限。传统中医（TCM）提供了一种整体的方法，专注于恢复阴阳平衡和气的流动，将肝功能障碍视为与湿气和气滞有关。现代研究支持中药的多靶点作用，表明草药可以改善肠道微生物群，增强肠道屏障，减少炎症，调节脂肪因子和胰岛素敏感性。这些机制支持中医治疗MASLD的潜在系统性疗效，将传统理论与现代药理学相结合。方法系统检索PubMed、Scopus、Web of Science等主要数据库，筛选截至2025年发表的相关临床前和临床研究。搜索策略采用了诸如“代谢功能障碍相关脂肪性肝病（MASLD）”、“中医（TCM）”、“肠-肝轴”、“脂肪-肝轴”、“草药”、“肠道微生物群”和“脂肪因子”等关键词的组合。如果研究中草药在MASLD模型中的分子机制或治疗效果，特别是关注肠-肝和脂肪组织-肝轴的调节，则纳入研究。考虑了体外和体内实验研究以及相关的临床试验。非英语、病例报告、没有原始数据的综述或缺乏机制或治疗相关性的研究被排除。该方法旨在确保综合和集中高质量的证据，支持中医在MASLD中的全身作用。最近的研究强调肠-肝和脂肪-肝轴是MASLD进展的关键因素。肠道生态失调改变胆汁酸、色氨酸分解代谢物和支链氨基酸，其中拟杆菌类促进继发胆汁酸积累，破坏FXR信号并引起脂质失衡和炎症。色氨酸衍生的吲哚损害肠道屏障完整性，加重肝脏炎症和纤维化，而BCAAs升高与胰岛素抵抗和肝细胞损伤有关。肥胖诱导的脂肪功能障碍通过释放过量的FFAs，激活NF-κB和PPAR-γ途径，分泌促炎细胞因子（TNF-α, IL-6），进一步损害胰岛素敏感性，从而驱动MASLD。多种中药制剂通过调节这些轴在临床前MASLD模型中显示出治疗潜力。四妙散增加乳酸菌和双歧杆菌，减少厚壁菌门和变形菌门，改善菌群平衡，减少肝脏脂肪变性。调肝消脂增强肠道屏障完整性，减少全身炎症。降脂胶囊通过下调SREBP通路抑制肝脏脂质积累。这些发现支持了中医药在改善MASLD肠道菌群组成、增强屏障功能、减轻炎症和调节脂质代谢方面的多靶点机制。这篇综述表明，中医药通过调节关键的代谢和炎症途径，特别是肠-肝和脂肪组织-肝轴，为MASLD的管理提供了多靶点的方法。这些机制与现代药理学发现一致，为古代医学实践提供了科学依据。然而，临床证据仍然有限，需要标准化、高质量的临床试验来验证特定草药干预措施的有效性和安全性。未来的研究应集中在阐明精确的分子靶点和优化处方策略，以提高中医治疗MASLD的临床转化。
{"title":"Modulatory Role of Traditional Chinese Medicine in Gut–Liver and Adipose–Liver Axis Dysfunction in MASLD","authors":"Sampat Singh Tanwar, Seema Sharma","doi":"10.1016/j.prmcm.2025.100743","DOIUrl":"10.1016/j.prmcm.2025.100743","url":null,"abstract":"<div><h3>Introduction</h3><div>Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease worldwide, affecting around 24% of the population, with regional prevalence ranging from 31.8% in the Middle East to 13.5% in Africa (WHO). MASLD encompasses a spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Its complex pathogenesis involves insulin resistance, obesity, genetic factors, and chronic inflammation, leading to excessive lipid accumulation in hepatocytes. Current Western treatments primarily address symptoms but offer limited efficacy. Traditional Chinese Medicine (TCM) provides a holistic approach focused on restoring Yin-Yang balance and Qi flow, viewing liver dysfunction as related to dampness and Qi stagnation. Modern research supports TCM’s multi-target actions, showing herbal medicines improve gut microbiota, strengthen the intestinal barrier, reduce inflammation, and modulate adipokines and insulin sensitivity. These mechanisms support TCM’s potential systemic efficacy in managing MASLD, integrating traditional theory with modern pharmacology.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted across major databases including PubMed, Scopus, and Web of Science to identify relevant preclinical and clinical studies published up to 2025. The search strategy employed combinations of keywords such as “Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD),” “Traditional Chinese Medicine (TCM),” “gut-liver axis,” “adipose-liver axis,” “herbal medicine,” “gut microbiota,” and “adipokines.” Studies were included if they investigated molecular mechanisms or therapeutic effects of Chinese herbal medicines in MASLD models, particularly focusing on modulation of the gut-liver and adipose tissue-liver axes. Both in vitro and in vivo experimental studies, as well as relevant clinical trials, were considered. Studies were excluded if they were non-English, case reports, reviews without original data, or lacked mechanistic or therapeutic relevance. This approach aimed to ensure a comprehensive and focused synthesis of high-quality evidence supporting the systemic effects of TCM in MASLD.</div></div><div><h3>Results</h3><div>Recent studies highlight the gut-liver and adipose-liver axes as key contributors to MASLD progression. Gut dysbiosis alters bile acids, tryptophan catabolites, and BCAAs, where <em>Bacteroides</em> species promote secondary bile acid accumulation, disrupting FXR signaling and causing lipid imbalance and inflammation. Tryptophan-derived indoles impair gut barrier integrity, worsening liver inflammation and fibrosis, while elevated BCAAs associate with insulin resistance and hepatocyte damage. Obesity-induced adipose dysfunction drives MASLD by releasing excess FFAs, activating NF-κB and PPAR-γ pathways, and secreting pro-inflammatory cytokines (TNF-α, IL-6), further impairing","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100743"},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.prmcm.2025.100744
Yutong Qi , Zixia Chen , Jiantang Zhang , Ruilan Du , Jingwen Shi , Qizhu Chen , Jun Chen , Huaben Bo
Introduction
Danggui Buxue Tang (DBT) is a classic herbal formula traditionally used to "tonify Qi and generate blood." Its efficacy is believed to depend on the biotransformation of its bioactive compounds by the gut microbiota; however, the specific metabolic profile and the key bacterial taxa involved remain unclear.
Methods
An in vitro anaerobic fermentation model was established to simulate gut microbial biotransformation of DBT. This model allowed for a controlled and reproducible investigation of DBT-microbiota interactions. We integrated untargeted metabolomics (LC-MS) with 16S rRNA gene sequencing to analyze the concomitant changes in metabolites and the microbial community. PICRUSt2 was used for functional prediction. Additionally, network pharmacology and molecular docking were employed to construct a "microbiota-enzyme-metabolite-target" network.
Results
Untargeted metabolomics analysis identified 734 significantly altered metabolites following DBT fermentation, including notable increases in formononetin, biochanin A, and xenognosin B. 16S rRNA gene sequencing revealed that DBT markedly increased the relative abundance of Bifidobacterium (from 0.05 % to 25.5 %) while suppressing Porphyromonas. Functional prediction indicated significant enrichment in the "Drug metabolism - other enzymes" pathway. Correlation analysis revealed significant associations between specific gut microbiota and metabolites. A three-step metabolic cascade (glycoside hydrolysis → methylation → hydroxylation) was identified, which reduced toxicity by 90 % and increased clearance twofold. The metabolites exhibited strong binding to targets such as CDK2 (binding energy ≤ -7.24 kcal/mol) and were enriched in hematopoiesis-related pathways, including the PI3K-Akt signaling pathway.
Discussion
This study systematically elucidates how the gut microbiota transforms DBT isoflavones into active aglycones that target core hematopoietic proteins, providing a novel perspective on the mechanism of orally administered, poorly absorbable traditional Chinese medicine formulas. Our results confirm that the gut microbiota is indispensable for the efficacy of DBT.
{"title":"Integrative multi-omics analysis to decipher the mechanism by which the interaction between Danggui Buxue Tang and gut microbiota drives isoflavone metabolic transformation","authors":"Yutong Qi , Zixia Chen , Jiantang Zhang , Ruilan Du , Jingwen Shi , Qizhu Chen , Jun Chen , Huaben Bo","doi":"10.1016/j.prmcm.2025.100744","DOIUrl":"10.1016/j.prmcm.2025.100744","url":null,"abstract":"<div><h3>Introduction</h3><div>Danggui Buxue Tang (DBT) is a classic herbal formula traditionally used to \"tonify Qi and generate blood.\" Its efficacy is believed to depend on the biotransformation of its bioactive compounds by the gut microbiota; however, the specific metabolic profile and the key bacterial taxa involved remain unclear.</div></div><div><h3>Methods</h3><div>An in vitro anaerobic fermentation model was established to simulate gut microbial biotransformation of DBT. This model allowed for a controlled and reproducible investigation of DBT-microbiota interactions. We integrated untargeted metabolomics (LC-MS) with 16S rRNA gene sequencing to analyze the concomitant changes in metabolites and the microbial community. PICRUSt2 was used for functional prediction. Additionally, network pharmacology and molecular docking were employed to construct a \"microbiota-enzyme-metabolite-target\" network.</div></div><div><h3>Results</h3><div>Untargeted metabolomics analysis identified 734 significantly altered metabolites following DBT fermentation, including notable increases in formononetin, biochanin A, and xenognosin B. 16S rRNA gene sequencing revealed that DBT markedly increased the relative abundance of Bifidobacterium (from 0.05 % to 25.5 %) while suppressing Porphyromonas. Functional prediction indicated significant enrichment in the \"Drug metabolism - other enzymes\" pathway. Correlation analysis revealed significant associations between specific gut microbiota and metabolites. A three-step metabolic cascade (glycoside hydrolysis → methylation → hydroxylation) was identified, which reduced toxicity by 90 % and increased clearance twofold. The metabolites exhibited strong binding to targets such as CDK2 (binding energy ≤ -7.24 kcal/mol) and were enriched in hematopoiesis-related pathways, including the PI3K-Akt signaling pathway.</div></div><div><h3>Discussion</h3><div>This study systematically elucidates how the gut microbiota transforms DBT isoflavones into active aglycones that target core hematopoietic proteins, providing a novel perspective on the mechanism of orally administered, poorly absorbable traditional Chinese medicine formulas. Our results confirm that the gut microbiota is indispensable for the efficacy of DBT.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100744"},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-13DOI: 10.1016/j.prmcm.2025.100742
Shanmugham Poongkuzhali, Natarajan Muninathan, Arumugam Suresh, Christina Beula
<div><h3>Introduction</h3><div>Cordycepin (CD), 3′- deoxy adenosine, is a major bioactive compound secreted by the entomopathogenic fungus <em>Cordyceps militaris</em> and <em>Cordyceps sinensis. Cordyceps sinensis</em> is known as <em>DongChongXiaCa</em> in Traditional Chinese Medicine (TCM). It possesses various pharmacological properties such as anti-inflammatory, immunomodulatory, anti-tumor activities. It also alleviates fatigue. Its therapeutic potential extends from cancer to several metabolic disorders. The therapeutic efficacy of CD in preclinical breast cancer (BC) studies has been highlighted with a focus on molecular pathways modulated by the compound.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted across various electronic databases such as Google Scholar and PubMed in order to identify the relevant <em>in vitro</em> and <em>in vivo</em> studies. The chosen articles focused on the molecular mechanisms modulated by CD in BC and in other cancers. Articles related to therapeutic effects of CD against metabolic disorders, synergistic mechanisms with conventional treatments, bioavailability and pharmacokinetic limitations, clinical prospects and challenges of CD were also retrieved.</div></div><div><h3>Results</h3><div>Pre-clinical studies reported that CD possesses broad spectrum of biological properties, such as anti-tumor, anti-aging, anti-hyperlipidemic, inhibition of fat accumulation, reduction of body weight, anti-viral, anti-SARS-CoV-2, anti-hyperglycemic and skin-lightening properties<em>. In vitro</em> and <em>in vivo</em> studies highlighted the anti-cancer property of CD against BC. It covers the molecular pathways modulated by the natural compound in BC. CD induced apoptosis by upregulating Bax/BcL ratio, cleaved caspases 8 and 7 and downregulating BcL-2 in BC cell lines as well as in Triple Negative Breast Cancer (TNBC) xenograft models. It initiated autophagy in MCF-7 cells and apoptosis in MDA-MB-231 cells. CD inhibited cell invasion and metastasis by downregulating matrix metalloproteinases (MMP’s), epithelial-mesenchymal transition (EMT) markers in TNBC xenograft model. It also downregulated EMT transcription factors in TNBC cancer cell lines, inhibited markers of hedgehog signaling pathway. Several other BC molecular pathways regulated by CD are also covered. Apart from anti-BC activity, it also possesses anti-hyperlipidemic, anti-hyperglycemic, immunomodulatory, anti-obesity, anti-pigmentation, anti-anxiety, stress lowering, and anti-hypertensive properties. Pre-clinical studies on CD’s anti-cancer activity against colon, hepatocellular, leukemia and other cancers have been included. It displayed synergistic effects when combined with conventional chemotherapeutic drugs, including doxorubicin, cisplatin, gemcitabine and apatinib. One of the major limitations of CD is the bioavailability of the compound inside the human body. As CD is susceptible to degradation by adenosine deaminase (A
{"title":"Harnessing cordycepin’s therapeutic potential: A review with special focus on breast cancer","authors":"Shanmugham Poongkuzhali, Natarajan Muninathan, Arumugam Suresh, Christina Beula","doi":"10.1016/j.prmcm.2025.100742","DOIUrl":"10.1016/j.prmcm.2025.100742","url":null,"abstract":"<div><h3>Introduction</h3><div>Cordycepin (CD), 3′- deoxy adenosine, is a major bioactive compound secreted by the entomopathogenic fungus <em>Cordyceps militaris</em> and <em>Cordyceps sinensis. Cordyceps sinensis</em> is known as <em>DongChongXiaCa</em> in Traditional Chinese Medicine (TCM). It possesses various pharmacological properties such as anti-inflammatory, immunomodulatory, anti-tumor activities. It also alleviates fatigue. Its therapeutic potential extends from cancer to several metabolic disorders. The therapeutic efficacy of CD in preclinical breast cancer (BC) studies has been highlighted with a focus on molecular pathways modulated by the compound.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted across various electronic databases such as Google Scholar and PubMed in order to identify the relevant <em>in vitro</em> and <em>in vivo</em> studies. The chosen articles focused on the molecular mechanisms modulated by CD in BC and in other cancers. Articles related to therapeutic effects of CD against metabolic disorders, synergistic mechanisms with conventional treatments, bioavailability and pharmacokinetic limitations, clinical prospects and challenges of CD were also retrieved.</div></div><div><h3>Results</h3><div>Pre-clinical studies reported that CD possesses broad spectrum of biological properties, such as anti-tumor, anti-aging, anti-hyperlipidemic, inhibition of fat accumulation, reduction of body weight, anti-viral, anti-SARS-CoV-2, anti-hyperglycemic and skin-lightening properties<em>. In vitro</em> and <em>in vivo</em> studies highlighted the anti-cancer property of CD against BC. It covers the molecular pathways modulated by the natural compound in BC. CD induced apoptosis by upregulating Bax/BcL ratio, cleaved caspases 8 and 7 and downregulating BcL-2 in BC cell lines as well as in Triple Negative Breast Cancer (TNBC) xenograft models. It initiated autophagy in MCF-7 cells and apoptosis in MDA-MB-231 cells. CD inhibited cell invasion and metastasis by downregulating matrix metalloproteinases (MMP’s), epithelial-mesenchymal transition (EMT) markers in TNBC xenograft model. It also downregulated EMT transcription factors in TNBC cancer cell lines, inhibited markers of hedgehog signaling pathway. Several other BC molecular pathways regulated by CD are also covered. Apart from anti-BC activity, it also possesses anti-hyperlipidemic, anti-hyperglycemic, immunomodulatory, anti-obesity, anti-pigmentation, anti-anxiety, stress lowering, and anti-hypertensive properties. Pre-clinical studies on CD’s anti-cancer activity against colon, hepatocellular, leukemia and other cancers have been included. It displayed synergistic effects when combined with conventional chemotherapeutic drugs, including doxorubicin, cisplatin, gemcitabine and apatinib. One of the major limitations of CD is the bioavailability of the compound inside the human body. As CD is susceptible to degradation by adenosine deaminase (A","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100742"},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.prmcm.2025.100739
Md. Sanower Hossain
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