Pub Date : 2025-10-01DOI: 10.1016/j.prmcm.2025.100698
Weekar Younus Raja , Insha Mushtaq , Nisar Ahmad Dar , Mohmmad Akbar Dar , Ishtiyaq Ahmad Chashoo , Zulfiqar Ali Bhat
Introduction
Ailanthus altissima, also known as Chun Pi, is native to central and northern China, and several other parts of Central Asia. Ailanthus altissima is used traditionally in the treatment of various diseases, such as obesity, dysentery, asthma, spasms, gastric and intestinal upsets, hemorrhoids and cardiac problems.
Methods
The present study aimed to evaluate the effects of A. altissima root bark extracton serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), very low-density lipoprotein cholesterol (VLDL-c), SGOT, SGPT, ALP, total protein, total bilirubin, atherogenic index(AI), cardiac risk index I, atherogenic coefficient, and cardiac risk index II (LDL/HDL ratio). Hyperlipidemia was induced in albino rats via cholesterol administration, and the rats were treated orally with methanol and aqueous extracts at doses of 200 and 400 mg/kg b.w. for 30 days.
Results
Treatment with Ailanthus altissima extract significantly reduced serum TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and low-density lipoprotein cholesterol (VLDL-C) levels and increased high-density lipoprotein cholesterol (HDL-C) levels. The observed effects on the lipid profiles were comparable to those of atorvastatin, a standard antihyperlipidemic drug. Additionally, the plant extracts notably decreased the liver enzyme levels (SGOT, SGPT, and ALP), indicating a protective effect on liver function.
Discussion
Our findings demonstrated that the root bark aqueous extract of Ailanthus altissima effectively reduced hyperlipidemia and improved lipid profiles. The extract significantly improved various atherogenic indices and cardiac risk factors, highlighting its potential as a promising therapeutic agent for preventing atherosclerosis and related cardiovascular diseases. The observed benefits underscore its ability to lower cholesterol levels and reduce cardiovascular risk, suggesting that Ailanthus altissima could be a valuable natural alternative for the management of hyperlipidemia and cardiovascular health.
{"title":"Ailanthus altissima (Mill.) Swingle notably decreases the cholesterol induced hyperlipidemia in albino rats","authors":"Weekar Younus Raja , Insha Mushtaq , Nisar Ahmad Dar , Mohmmad Akbar Dar , Ishtiyaq Ahmad Chashoo , Zulfiqar Ali Bhat","doi":"10.1016/j.prmcm.2025.100698","DOIUrl":"10.1016/j.prmcm.2025.100698","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Ailanthus altissima</em>, also known as Chun Pi, is native to central and northern China, and several other parts of Central Asia. <em>Ailanthus altissima</em> is used traditionally in the treatment of various diseases, such as obesity, dysentery, asthma, spasms, gastric and intestinal upsets, hemorrhoids and cardiac problems.</div></div><div><h3>Methods</h3><div>The present study aimed to evaluate the effects of A. altissima root bark extracton serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), very low-density lipoprotein cholesterol (VLDL-c), SGOT, SGPT, ALP, total protein, total bilirubin, atherogenic index(AI), cardiac risk index I, atherogenic coefficient, and cardiac risk index II (LDL/HDL ratio). Hyperlipidemia was induced in albino rats via cholesterol administration, and the rats were treated orally with methanol and aqueous extracts at doses of 200 and 400 mg/kg b.w. for 30 days.</div></div><div><h3>Results</h3><div>Treatment with <em>Ailanthus altissima</em> extract significantly reduced serum TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and low-density lipoprotein cholesterol (VLDL-C) levels and increased high-density lipoprotein cholesterol (HDL-C) levels. The observed effects on the lipid profiles were comparable to those of atorvastatin, a standard antihyperlipidemic drug. Additionally, the plant extracts notably decreased the liver enzyme levels (SGOT, SGPT, and ALP), indicating a protective effect on liver function.</div></div><div><h3>Discussion</h3><div>Our findings demonstrated that the root bark aqueous extract of Ailanthus altissima effectively reduced hyperlipidemia and improved lipid profiles. The extract significantly improved various atherogenic indices and cardiac risk factors, highlighting its potential as a promising therapeutic agent for preventing atherosclerosis and related cardiovascular diseases. The observed benefits underscore its ability to lower cholesterol levels and reduce cardiovascular risk, suggesting that Ailanthus altissima could be a valuable natural alternative for the management of hyperlipidemia and cardiovascular health.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100698"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268681","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 : 2025-09-29DOI: 10.1016/j.prmcm.2025.100700
Yuan-sheng Guo , Tian-tian Zuo , Hong-yu Jin , Jing Liu , Xian-long Cheng , Feng Wei
Background
Oysters are one of the most important marine biological resources worldwide, with high nutritional and medicinal value. Enhancing the traceability of oyster products can provide crucial information to improve their quality and safety. Methods: This study focuses on oysters from three different production areas. Multi-element analysis was conducted to establish a multi-element fingerprint for oysters from various regions by ICP-MS. Combined with chemometric methods such as Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA), the study aims to trace the geographic origin of the oysters. Additionally, single-factor pollution index and the Nemerow Index were employed to assess the heavy metal contamination levels in oysters from different regions. Based on these findings, a risk assessment was conducted according to industry guidelines to evaluate the potential health risks to humans from consuming oysters from different production areas.
Results
Chemometric analysis revealed that oyster samples from different production areas clustered into distinct groups with significant difference. The elements Na, Rb, Sn, and Fe were identified as the primary factors responsible for these differences. Additionally, a comprehensive evaluation of heavy metal contamination in oysters from various regions was conducted using both the single-factor pollution index method and the Nemerow composite index method, providing insight into their contamination levels. Based on these results, a risk assessment strategy was applied to evaluate the edible safety of the oysters. The findings indicated that, except for some oyster samples from the northeastern region, which posed certain health risks, oysters from other areas were found to have acceptable health risk levels.
Conclusion
This approach effectively distinguishes the geographical origin of oysters and scientifically assess both heavy metal contamination and health risks, offering valuable strategies for the safety risk assessment of oysters and other traditional Chinese medicines.
{"title":"Geographical origin identification, heavy metal contamination evaluation, and risk assessment of oysters from different regions based on multi-element fingerprinting","authors":"Yuan-sheng Guo , Tian-tian Zuo , Hong-yu Jin , Jing Liu , Xian-long Cheng , Feng Wei","doi":"10.1016/j.prmcm.2025.100700","DOIUrl":"10.1016/j.prmcm.2025.100700","url":null,"abstract":"<div><h3>Background</h3><div>Oysters are one of the most important marine biological resources worldwide, with high nutritional and medicinal value. Enhancing the traceability of oyster products can provide crucial information to improve their quality and safety. <em><strong>Methods:</strong></em> This study focuses on oysters from three different production areas. Multi-element analysis was conducted to establish a multi-element fingerprint for oysters from various regions by ICP-MS. Combined with chemometric methods such as Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA), the study aims to trace the geographic origin of the oysters. Additionally, single-factor pollution index and the Nemerow Index were employed to assess the heavy metal contamination levels in oysters from different regions. Based on these findings, a risk assessment was conducted according to industry guidelines to evaluate the potential health risks to humans from consuming oysters from different production areas.</div></div><div><h3>Results</h3><div>Chemometric analysis revealed that oyster samples from different production areas clustered into distinct groups with significant difference. The elements Na, Rb, Sn, and Fe were identified as the primary factors responsible for these differences. Additionally, a comprehensive evaluation of heavy metal contamination in oysters from various regions was conducted using both the single-factor pollution index method and the Nemerow composite index method, providing insight into their contamination levels. Based on these results, a risk assessment strategy was applied to evaluate the edible safety of the oysters. The findings indicated that, except for some oyster samples from the northeastern region, which posed certain health risks, oysters from other areas were found to have acceptable health risk levels.</div></div><div><h3>Conclusion</h3><div>This approach effectively distinguishes the geographical origin of oysters and scientifically assess both heavy metal contamination and health risks, offering valuable strategies for the safety risk assessment of oysters and other traditional Chinese medicines.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100700"},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268682","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 : 2025-09-25DOI: 10.1016/j.prmcm.2025.100694
Xinru Zheng , Runyu Gan , Jingxian Wu , Ruili Xue , Chaoyi Cui , Yuyin Duan
<div><h3>Background</h3><div>Abdominal aortic aneurysm (AAA) represents a fatal vascular disease with prevalence rates of 4–8 % among individuals over 65 years, and rupture mortality rates reaching 60–80 %. With accelerating population aging, AAA incidence continues rising, creating urgent demands for novel therapeutic strategies. Current treatments including surgical intervention and endovascular therapy, while effective, demonstrate significant limitations, and the pathogenic mechanisms remain unclear. The inflammatory microenvironment and macrophages play crucial roles in AAA, yet their immune mechanisms remain controversial. The advancement of single-cell sequencing technology provides new opportunities for elucidating AAA immune mechanisms. This study employed single-cell RNA sequencing (scRNA-seq) and network pharmacology to characterize immune cell features and identify therapeutic targets, exploring the immunomodulatory effects of Radix Salviae miltiorrhizae (RS), aiming to reveal AAA pathogenic mechanisms and provide novel precision treatment strategies.</div></div><div><h3>Method</h3><div>Using scRNA-seq data from healthy and AAA mouse models in the GEO database (GSE239620), we performed preprocessing and quality control through Seurat, employed Harmony to correct batch effects, and combined clustering, pseudotemporal analysis (Monocle2), and cell communication analysis (CellChat) to reveal the characteristics and interactions of immune cells, particularly macrophages, within the AAA inflammatory microenvironment. Network pharmacology utilized TCMSP and SwissADME to screen active components and targets of RS, with molecular docking (AutoDock Vina) validating their binding to target proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses (clusterProfiler) elucidated biological functions. This study integrates scRNA-seq and network pharmacology to explore AAA immune mechanisms and RS therapeutic potential.</div></div><div><h3>Result</h3><div>This study investigated the immune microenvironment of AAA via scRNA-seq, elucidating the pivotal role of macrophages in disease progression. UMAP clustering identified five distinct immune cell types, revealing a significant enrichment of macrophages in AAA samples (<em>P</em> < 0.01). Subsequent sub-clustering analysis distinguished five macrophage subtypes (Mac1–Mac5), each characterized by a unique marker gene expression profile (logFC > 0.5, <em>P</em> < 0.05). Pseudotime analysis using Monocle2 mapped their developmental trajectories and identified key gene modules associated with immune responses and inflammatory regulation (<em>q</em> < 0.1). Furthermore, cell communication analysis with CellChat indicated enhanced interactions between macrophages and T/NK cells, underscored by the robust activation of MHC-I signaling (communication probability > 0.5). GO and KEGG analyses showed that associated genes were primarily enriched in the “re
{"title":"Unveiling macrophage-centric immunomodulatory mechanisms of radix salviae miltiorrhizae in abdominal aortic aneurysm through integrated single-cell transcriptomic, network pharmacological, and molecular docking analyses","authors":"Xinru Zheng , Runyu Gan , Jingxian Wu , Ruili Xue , Chaoyi Cui , Yuyin Duan","doi":"10.1016/j.prmcm.2025.100694","DOIUrl":"10.1016/j.prmcm.2025.100694","url":null,"abstract":"<div><h3>Background</h3><div>Abdominal aortic aneurysm (AAA) represents a fatal vascular disease with prevalence rates of 4–8 % among individuals over 65 years, and rupture mortality rates reaching 60–80 %. With accelerating population aging, AAA incidence continues rising, creating urgent demands for novel therapeutic strategies. Current treatments including surgical intervention and endovascular therapy, while effective, demonstrate significant limitations, and the pathogenic mechanisms remain unclear. The inflammatory microenvironment and macrophages play crucial roles in AAA, yet their immune mechanisms remain controversial. The advancement of single-cell sequencing technology provides new opportunities for elucidating AAA immune mechanisms. This study employed single-cell RNA sequencing (scRNA-seq) and network pharmacology to characterize immune cell features and identify therapeutic targets, exploring the immunomodulatory effects of Radix Salviae miltiorrhizae (RS), aiming to reveal AAA pathogenic mechanisms and provide novel precision treatment strategies.</div></div><div><h3>Method</h3><div>Using scRNA-seq data from healthy and AAA mouse models in the GEO database (GSE239620), we performed preprocessing and quality control through Seurat, employed Harmony to correct batch effects, and combined clustering, pseudotemporal analysis (Monocle2), and cell communication analysis (CellChat) to reveal the characteristics and interactions of immune cells, particularly macrophages, within the AAA inflammatory microenvironment. Network pharmacology utilized TCMSP and SwissADME to screen active components and targets of RS, with molecular docking (AutoDock Vina) validating their binding to target proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses (clusterProfiler) elucidated biological functions. This study integrates scRNA-seq and network pharmacology to explore AAA immune mechanisms and RS therapeutic potential.</div></div><div><h3>Result</h3><div>This study investigated the immune microenvironment of AAA via scRNA-seq, elucidating the pivotal role of macrophages in disease progression. UMAP clustering identified five distinct immune cell types, revealing a significant enrichment of macrophages in AAA samples (<em>P</em> < 0.01). Subsequent sub-clustering analysis distinguished five macrophage subtypes (Mac1–Mac5), each characterized by a unique marker gene expression profile (logFC > 0.5, <em>P</em> < 0.05). Pseudotime analysis using Monocle2 mapped their developmental trajectories and identified key gene modules associated with immune responses and inflammatory regulation (<em>q</em> < 0.1). Furthermore, cell communication analysis with CellChat indicated enhanced interactions between macrophages and T/NK cells, underscored by the robust activation of MHC-I signaling (communication probability > 0.5). GO and KEGG analyses showed that associated genes were primarily enriched in the “re","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100694"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268680","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 : 2025-09-25DOI: 10.1016/j.prmcm.2025.100696
Chenggong Xie , Chujiong Chen , Zelin Ke , Hengyu Tan , Hongze Zhao , Xuxiang Deng , Hao Liang , Yidi Zeng
INTRODUCTION
Pueraria lobata (PL) is a traditional Chinese medicinal herb that is rich in isoflavonoids, such as puerarin and daidzein. It is widely used to treat cardiovascular, metabolic and oncological disorders. As PL is increasingly being co-administered with conventional drugs, herb–drug interactions (HDI) have emerged as a significant clinical concern. A comprehensive synthesis of the current evidence base is required to clarify the pharmacodynamic and pharmacokinetic profiles of PL-related interactions, as well as their implications for clinical practice.
METHODS
We conducted a comprehensive review of experimental and clinical studies on HDI involving PL and its bioactive constituents. Literature was retrieved from PubMed, CNKI, and Google Scholar up to April 2024. Studies were included if they reported on the pharmacodynamic or pharmacokinetic interactions between PL (or its constituents) and therapeutic drugs. Twenty-three studies met the eligibility criteria: Twelve addressed pharmacodynamic interactions and eleven addressed pharmacokinetic interactions.
RESULTS
In terms of pharmacodynamics, PL exhibited both synergistic and antagonistic effects. Synergistic outcomes included enhanced efficacy in terms of cardiovascular protection, osteoporosis prevention, glycaemic control and chemosensitisation in cancer therapy. Conversely, adverse outcomes were observed, including attenuation of the antiplatelet effect when combined with warfarin or dual antiplatelet therapy and increased mortality when combined with methotrexate in animal models. In terms of pharmacokinetics, puerarin and other constituents were found to modulate cytochrome P450 enzymes and transporters. The effects included inhibiting CYP2D6, suppressing CYP3A, inducing CYP1A2 and altering P-glycoprotein activity. These mechanisms contribute to variable drug metabolism and bioavailability across co-administered agents.
DISCUSSION
Evidence suggests that PL can have beneficial or harmful effects on HDI, depending on the therapeutic context. However, the available data is limited and is largely derived from preclinical models. There is a lack of rigorous clinical trials and the roles of minor constituents remain under-explored. Research gaps include a lack of data on high-risk populations and an incomplete understanding of the mechanisms of pharmacodynamic interactions. To ensure the rational and safe integration of PL into modern medical practice, future work should prioritise translational studies and broaden the focus beyond puerarin to establish safety profiles.
{"title":"Herb-drug interactions involving pueraria lobata and its bioactive constituents: A comprehensive review","authors":"Chenggong Xie , Chujiong Chen , Zelin Ke , Hengyu Tan , Hongze Zhao , Xuxiang Deng , Hao Liang , Yidi Zeng","doi":"10.1016/j.prmcm.2025.100696","DOIUrl":"10.1016/j.prmcm.2025.100696","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Pueraria lobata (PL) is a traditional Chinese medicinal herb that is rich in isoflavonoids, such as puerarin and daidzein. It is widely used to treat cardiovascular, metabolic and oncological disorders. As PL is increasingly being co-administered with conventional drugs, herb–drug interactions (HDI) have emerged as a significant clinical concern. A comprehensive synthesis of the current evidence base is required to clarify the pharmacodynamic and pharmacokinetic profiles of PL-related interactions, as well as their implications for clinical practice.</div></div><div><h3>METHODS</h3><div>We conducted a comprehensive review of experimental and clinical studies on HDI involving PL and its bioactive constituents. Literature was retrieved from PubMed, CNKI, and Google Scholar up to April 2024. Studies were included if they reported on the pharmacodynamic or pharmacokinetic interactions between PL (or its constituents) and therapeutic drugs. Twenty-three studies met the eligibility criteria: Twelve addressed pharmacodynamic interactions and eleven addressed pharmacokinetic interactions.</div></div><div><h3>RESULTS</h3><div>In terms of pharmacodynamics, PL exhibited both synergistic and antagonistic effects. Synergistic outcomes included enhanced efficacy in terms of cardiovascular protection, osteoporosis prevention, glycaemic control and chemosensitisation in cancer therapy. Conversely, adverse outcomes were observed, including attenuation of the antiplatelet effect when combined with warfarin or dual antiplatelet therapy and increased mortality when combined with methotrexate in animal models. In terms of pharmacokinetics, puerarin and other constituents were found to modulate cytochrome P450 enzymes and transporters. The effects included inhibiting CYP2D6, suppressing CYP3A, inducing CYP1A2 and altering P-glycoprotein activity. These mechanisms contribute to variable drug metabolism and bioavailability across co-administered agents.</div></div><div><h3>DISCUSSION</h3><div>Evidence suggests that PL can have beneficial or harmful effects on HDI, depending on the therapeutic context. However, the available data is limited and is largely derived from preclinical models. There is a lack of rigorous clinical trials and the roles of minor constituents remain under-explored. Research gaps include a lack of data on high-risk populations and an incomplete understanding of the mechanisms of pharmacodynamic interactions. To ensure the rational and safe integration of PL into modern medical practice, future work should prioritise translational studies and broaden the focus beyond puerarin to establish safety profiles.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100696"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221977","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 : 2025-09-20DOI: 10.1016/j.prmcm.2025.100695
Deepthi D Kini , Tathagata Dey , G Divya Theja , S. Shalini , R. Ruthicshaw , Keshava Murthy SG
Introduction
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a global health threat. Traditional Chinese medicine (TCM), with its extensive use of plant-based compounds, offers a promising alternative for TB treatment. However, the molecular mechanisms underlying the effects of TCM phytoconstituents on TB have not been fully elucidated. This study aims to explore the multitarget therapeutic potential of TCM phytoconstituents for TB management using network pharmacology, molecular docking, and molecular dynamics (MD) simulations.
Methods
Network pharmacology was employed to identify the interactions between phytoconstituents and proteins associated with TB. Molecular docking evaluated compound binding to key TB targets, while MD simulations assessed complex stability and dynamics. Gene expression was analyzed using the eFP server, and mycoCSM predicted bacterial protein responses to compounds, indicating potential drug resistance or susceptibility.
Results
Network pharmacology analysis identified key biological pathways, including the prolactin signalling pathway and the phosphatidylinositol 3-kinase signalling, that may be modulated by these compounds. The docking scores range from -6.5 to -9.0 kcal/mol for Glabroisoflavanone A and B against three major proteins, viz. 1O43, 5XGI, and 6NJS. Both phytoconstituents exhibited a good anti-tubercular sensitivity score. MD simulations (200 ns) further revealed that Glabroisoflavanone A formed the most stable complex with 5XGI.
Discussion
The Glabroisoflavanone A-5XGI complex showed the strongest binding, supported by the most binding free energy (–75.19 ± 4.89 kcal/mol), suggesting a robust interaction. These findings highlight the differential binding and dynamic behavior of phytoconstituents, offering potential insights for therapeutic development.
由结核分枝杆菌引起的结核病是一种全球性的健康威胁。传统中药（TCM）广泛使用植物基化合物，为结核病治疗提供了一个有希望的替代方案。然而，中药植物成分治疗结核的分子机制尚未完全阐明。本研究旨在通过网络药理学、分子对接和分子动力学（MD）模拟，探索中药植物成分在结核病治疗中的多靶点治疗潜力。方法采用网络药理学方法鉴定结核相关蛋白与植物成分的相互作用。分子对接评估了化合物与关键结核靶点的结合，而MD模拟评估了复合物的稳定性和动力学。使用eFP服务器分析基因表达，mycoCSM预测细菌对化合物的蛋白质反应，表明潜在的耐药性或易感性。结果网络药理学分析确定了这些化合物可能调节的关键生物学通路，包括催乳素信号通路和磷脂酰肌醇3-激酶信号通路。Glabroisoflavanone A和B对3种主要蛋白（即1043、5XGI和6NJS）的对接分数在-6.5 ~ -9.0 kcal/mol之间。两种植物成分均表现出良好的抗结核敏感性评分。MD模拟（200 ns）进一步表明，光异黄酮A与5XGI形成了最稳定的配合物。Glabroisoflavanone a - 5xgi配合物结合最强，结合自由能最高（-75.19±4.89 kcal/mol），表明其相互作用强。这些发现突出了植物成分的差异结合和动态行为，为治疗开发提供了潜在的见解。
{"title":"Multitarget insights into traditional Chinese phytoconstituents against tuberculosis via network pharmacology, molecular docking, and MD simulation","authors":"Deepthi D Kini , Tathagata Dey , G Divya Theja , S. Shalini , R. Ruthicshaw , Keshava Murthy SG","doi":"10.1016/j.prmcm.2025.100695","DOIUrl":"10.1016/j.prmcm.2025.100695","url":null,"abstract":"<div><h3>Introduction</h3><div>Tuberculosis (TB), caused by <em>Mycobacterium tuberculosis</em>, is a global health threat. Traditional Chinese medicine (TCM), with its extensive use of plant-based compounds, offers a promising alternative for TB treatment. However, the molecular mechanisms underlying the effects of TCM phytoconstituents on TB have not been fully elucidated. This study aims to explore the multitarget therapeutic potential of TCM phytoconstituents for TB management using network pharmacology, molecular docking, and molecular dynamics (MD) simulations.</div></div><div><h3>Methods</h3><div>Network pharmacology was employed to identify the interactions between phytoconstituents and proteins associated with TB. Molecular docking evaluated compound binding to key TB targets, while MD simulations assessed complex stability and dynamics. Gene expression was analyzed using the eFP server, and mycoCSM predicted bacterial protein responses to compounds, indicating potential drug resistance or susceptibility.</div></div><div><h3>Results</h3><div>Network pharmacology analysis identified key biological pathways, including the prolactin signalling pathway and the phosphatidylinositol 3-kinase signalling, that may be modulated by these compounds. The docking scores range from -6.5 to -9.0 kcal/mol for Glabroisoflavanone A and B against three major proteins, viz. 1O43, 5XGI, and 6NJS. Both phytoconstituents exhibited a good anti-tubercular sensitivity score. MD simulations (200 ns) further revealed that Glabroisoflavanone A formed the most stable complex with 5XGI.</div></div><div><h3>Discussion</h3><div>The Glabroisoflavanone A-5XGI complex showed the strongest binding, supported by the most binding free energy (–75.19 ± 4.89 kcal/mol), suggesting a robust interaction. These findings highlight the differential binding and dynamic behavior of phytoconstituents, offering potential insights for therapeutic development.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100695"},"PeriodicalIF":0.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159698","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 : 2025-09-20DOI: 10.1016/j.prmcm.2025.100693
Dan-dan Guo , Zhen Tian , Ru-jin Liang , Ting-ting Tan , Yu-wei Hu , Hua Zhu , Jing Zhao , Peng-zhou Hang
Introduction
Arsenic trioxide (ATO) has a well-documented history in traditional Chinese medicine as an effective treatment for acute promyelocytic leukemia and certain solid tumors; however, its efficacy as a standalone chemotherapy agent is limited. 7,8-Dihydroxyflavone (DHF), a TrkB receptor agonist, has shown promising anticancer effects across various malignancies. This study aimed to investigate the therapeutic potential of DHF, both alone and in combination with ATO, in hepatocellular carcinoma (HCC) cells.
Methods
The HCCLM3 and HepG2 cell lines were treated with ATO and DHF, alone or in combination. Cell viability and death ratio were assessed using MTT and live/dead staining. Proliferation and migration were evaluated through EdU staining, wound-healing assays, and colony formation assays. Apoptosis was detected via TUNEL staining, while changes in morphology and mitochondrial function were assessed using Mito-Tracker, transmission electron microscopy, mito-SOX, and JC-1 staining.
Results
The combination of DHF and ATO significantly reduced cell viability, proliferation, and migration, while concurrently increasing cell death and apoptosis compared to monotherapy. Mechanistically, combination treatment notably decreased mitochondrial membrane potential, increased the production of mitochondrial reactive oxygen species (ROS), and suppressed mitochondrial respiration, which was accompanied by reduced protein levels of mitochondrial complexes I, II, III, and V. Furthermore, these effects were reversed by the mitochondrial uncoupler CCCP at a low dose.
Conclusion
These findings suggest that the DHF-ATO combination suppresses HCC progression by impairing mitochondrial oxidative phosphorylation, providing a promising strategy to enhance chemotherapeutic efficacy.
{"title":"7,8-Dihydroxyflavone enhances the chemosensitivity of hepatocellular carcinoma cells to arsenic trioxide by disrupting mitochondrial oxidative phosphorylation","authors":"Dan-dan Guo , Zhen Tian , Ru-jin Liang , Ting-ting Tan , Yu-wei Hu , Hua Zhu , Jing Zhao , Peng-zhou Hang","doi":"10.1016/j.prmcm.2025.100693","DOIUrl":"10.1016/j.prmcm.2025.100693","url":null,"abstract":"<div><h3>Introduction</h3><div>Arsenic trioxide (ATO) has a well-documented history in traditional Chinese medicine as an effective treatment for acute promyelocytic leukemia and certain solid tumors; however, its efficacy as a standalone chemotherapy agent is limited. 7,8-Dihydroxyflavone (DHF), a TrkB receptor agonist, has shown promising anticancer effects across various malignancies. This study aimed to investigate the therapeutic potential of DHF, both alone and in combination with ATO, in hepatocellular carcinoma (HCC) cells.</div></div><div><h3>Methods</h3><div>The HCCLM3 and HepG2 cell lines were treated with ATO and DHF, alone or in combination. Cell viability and death ratio were assessed using MTT and live/dead staining. Proliferation and migration were evaluated through EdU staining, wound-healing assays, and colony formation assays. Apoptosis was detected via TUNEL staining, while changes in morphology and mitochondrial function were assessed using Mito-Tracker, transmission electron microscopy, mito-SOX, and JC-1 staining.</div></div><div><h3>Results</h3><div>The combination of DHF and ATO significantly reduced cell viability, proliferation, and migration, while concurrently increasing cell death and apoptosis compared to monotherapy. Mechanistically, combination treatment notably decreased mitochondrial membrane potential, increased the production of mitochondrial reactive oxygen species (ROS), and suppressed mitochondrial respiration, which was accompanied by reduced protein levels of mitochondrial complexes I, II, III, and V. Furthermore, these effects were reversed by the mitochondrial uncoupler CCCP at a low dose.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the DHF-ATO combination suppresses HCC progression by impairing mitochondrial oxidative phosphorylation, providing a promising strategy to enhance chemotherapeutic efficacy.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100693"},"PeriodicalIF":0.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160136","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 : 2025-09-12DOI: 10.1016/j.prmcm.2025.100685
Poloko Stephen Kheoane , Kingsley Chimaeze Mbara , Mosoatsi Lawrence Mputi , Ts’epo Arnold Lenkoe , Sebusiswe Magama , Mokonyana Mohale , Clemence Tarirai
<div><h3>Background</h3><div>Medicinal plants have been used traditionally as oral and topical herbs for treating inflammation and alleviating pain. Particularly in traditional Chinese medicine (TCM) practices, many plants from the genera <em>Malva, Prunus</em>, and <em>Cupressus</em> are used to treat various inflammation-related diseases. This study investigated <em>in vitro</em> and <em>in vivo</em> anti-inflammatory activity of the root extracts of <em>Malva parviflora</em>, the exudates of <em>Prunus persica, Cupressus sempervirens</em> and their chitosan nanoparticles and chitosan nanogels.</div></div><div><h3>Methods</h3><div><em>In vitro</em> anti-inflammatory activities of <em>M. parviflora</em> root extracts, <em>P. persica</em> and <em>C. sempervirens</em> exudates were investigated using the protein denaturation assay method. A 1% bovine albumin reaction mixture in phosphate buffer and 80% (v/v) methanol was incubated with plant extracts or exudates at 37 °C and 70 °C. Cross-linked chitosan nanoparticles loaded with plant extracts or exudates were prepared by the gelation method. The entrapment efficiency of the plants in the chitosan nanoformulation was estimated using the phenolic content of plant materials. The nanoparticles-based nanogel was formulated by suspending nanoparticles in a gel base. Inflammation was induced in Wistar rats (230 – 270 g) by subcutaneous injection of 0.1 mL of 1% (w/v) carrageenan in the plantar tissue of the right hind paw of the rats. The rats (<em>n</em> = 48) were randomly divided into two experimental groups (A and B) of 24 rats each for oral and topical administration of nanoformulations, respectively. Each group (<em>n</em> = 24) was subdivided into 6 test group (<em>n</em> = 4), where test groups 1, 2, and 3 were treated with 500 mg/kg/BW each of <em>M. parviflora, C. sempervirens</em>, and <em>P. persica</em> nanoparticle/nanogel, either orally or topically, respectively. Test groups 4, 5, and 6, respectively served as positive control, placebo nanoparticles (<em>i.e.</em>, chitosan nanoparticles), and negative control, treated orally or topically with indomethacin (50 mg/kg/BW), chitosan nanoparticle/nanogel alone (500 mg/kg/BW/100 mg/kg/BW), and saline (3 mL).</div></div><div><h3>Results</h3><div><em>P. persica</em> exudate had the highest TPC of 70.42 ± 0.53 µg of GAE/mg compared to <em>M. parviflora</em> root extract and <em>C. sempervirens</em> exudate with the 30.93 ± 1.65 µg of GAE/mg and 9.99 ± 0.65 µg of GAE/mg, respectively. <em>M. parviflora</em> root extracts had the highest <em>in vitro</em> protein denaturation (92.40%) compared to leaves and stem extracts. <em>P. persica</em> and <em>C. sempervirens</em> nanoparticles had the highest entrapment efficiencies (99.46% and 99.56%). <em>M. parviflora</em> root extract nanoparticles showed the greatest inhibition of oedema (90%) with oral administration, outperforming <em>P. persica</em> and <em>C. sempervirens</em> exudates nanoparticle
{"title":"Anti-inflammatory effects of orally and topically administered nanoformulations of Malva parviflora root extracts, and Prunus persica and Cupressus sempervirens exudates","authors":"Poloko Stephen Kheoane , Kingsley Chimaeze Mbara , Mosoatsi Lawrence Mputi , Ts’epo Arnold Lenkoe , Sebusiswe Magama , Mokonyana Mohale , Clemence Tarirai","doi":"10.1016/j.prmcm.2025.100685","DOIUrl":"10.1016/j.prmcm.2025.100685","url":null,"abstract":"<div><h3>Background</h3><div>Medicinal plants have been used traditionally as oral and topical herbs for treating inflammation and alleviating pain. Particularly in traditional Chinese medicine (TCM) practices, many plants from the genera <em>Malva, Prunus</em>, and <em>Cupressus</em> are used to treat various inflammation-related diseases. This study investigated <em>in vitro</em> and <em>in vivo</em> anti-inflammatory activity of the root extracts of <em>Malva parviflora</em>, the exudates of <em>Prunus persica, Cupressus sempervirens</em> and their chitosan nanoparticles and chitosan nanogels.</div></div><div><h3>Methods</h3><div><em>In vitro</em> anti-inflammatory activities of <em>M. parviflora</em> root extracts, <em>P. persica</em> and <em>C. sempervirens</em> exudates were investigated using the protein denaturation assay method. A 1% bovine albumin reaction mixture in phosphate buffer and 80% (v/v) methanol was incubated with plant extracts or exudates at 37 °C and 70 °C. Cross-linked chitosan nanoparticles loaded with plant extracts or exudates were prepared by the gelation method. The entrapment efficiency of the plants in the chitosan nanoformulation was estimated using the phenolic content of plant materials. The nanoparticles-based nanogel was formulated by suspending nanoparticles in a gel base. Inflammation was induced in Wistar rats (230 – 270 g) by subcutaneous injection of 0.1 mL of 1% (w/v) carrageenan in the plantar tissue of the right hind paw of the rats. The rats (<em>n</em> = 48) were randomly divided into two experimental groups (A and B) of 24 rats each for oral and topical administration of nanoformulations, respectively. Each group (<em>n</em> = 24) was subdivided into 6 test group (<em>n</em> = 4), where test groups 1, 2, and 3 were treated with 500 mg/kg/BW each of <em>M. parviflora, C. sempervirens</em>, and <em>P. persica</em> nanoparticle/nanogel, either orally or topically, respectively. Test groups 4, 5, and 6, respectively served as positive control, placebo nanoparticles (<em>i.e.</em>, chitosan nanoparticles), and negative control, treated orally or topically with indomethacin (50 mg/kg/BW), chitosan nanoparticle/nanogel alone (500 mg/kg/BW/100 mg/kg/BW), and saline (3 mL).</div></div><div><h3>Results</h3><div><em>P. persica</em> exudate had the highest TPC of 70.42 ± 0.53 µg of GAE/mg compared to <em>M. parviflora</em> root extract and <em>C. sempervirens</em> exudate with the 30.93 ± 1.65 µg of GAE/mg and 9.99 ± 0.65 µg of GAE/mg, respectively. <em>M. parviflora</em> root extracts had the highest <em>in vitro</em> protein denaturation (92.40%) compared to leaves and stem extracts. <em>P. persica</em> and <em>C. sempervirens</em> nanoparticles had the highest entrapment efficiencies (99.46% and 99.56%). <em>M. parviflora</em> root extract nanoparticles showed the greatest inhibition of oedema (90%) with oral administration, outperforming <em>P. persica</em> and <em>C. sempervirens</em> exudates nanoparticle","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100685"},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107940","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 : 2025-09-12DOI: 10.1016/j.prmcm.2025.100689
Kingsley Chimaeze Mbara , Poloko Stephen Kheoane , Clemence Tarirai
<div><h3>Introduction</h3><div>Berberine (黄连素, huáng lián sù) is a time-honored remedy in Traditional Chinese Medicine (TCM) that is found in various medicinal herbs and used to treat diabetes mellitus (DM), infections, diarrhea, and dysentery. Berberine, the major active component of <em>Coptidis rhizome</em> (黄连, huanglian), <em>Phellodendri cortex</em> (黄柏, huangbai), and <em>Mahoniae caulis</em> (亮叶十大功劳, Gong Lao Mu), exhibits several pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, cardioprotective, antineoplastic, antimicrobial, and antidiabetic effects. Antidiabetic effects of berberine are partly attributed to the activation of AMP-activated protein kinase (AMPK), which is a key mechanism and a potential treatment strategy for DM and its complications. This review discusses recent studies on the significant roles of berberine in activating AMPK for treating DM and its complications.</div></div><div><h3>Method</h3><div>We have comprehensively searched online databases like Scopus, PubMed, and Google Scholar for articles published in English between 2016 and 2025 using different permutations of these keywords: “Berberine”, “AMPK”, “Diabetes Mellitus”, “Diabetic nephropathy”, “Diabetic neuropathy”, “Diabetic retinopathy”, “Diabetic cardiomyopathy”, “Diabetic hepatic steatosis,” “Diabetic bone diseases”, “Diabetic atherosclerosis”, “Diabetic cognitive dysfunction”, “Diabetic lung injury” and “Other diabetic complications” to compile this narrative review. Out of 1750 initially retrieved articles, 183 were included based on their relevance to treating DM or its complications through the AMPK signaling pathway, pharmacokinetics, and translational potential. Non-English articles and studies not focused on AMPK activation by berberine and that did not address DM and its complications were excluded.</div></div><div><h3>Results</h3><div>The literature review found that berberine consistently activates AMPK across various preclinical studies of DM. The activation of AMPK is frequently mediated by pathways involving LKB1 and CAMKKβ. Berberine's activation of AMPK positively impacts glucose uptake, insulin sensitivity, lipid metabolism, oxidative stress, and inflammatory responses. Evidence from animal models demonstrated its efficacy in ameliorating complications such as diabetic nephropathy, neuropathy, retinopathy, cardiomyopathy, hepatic steatosis, bone diseases, atherosclerosis, cognitive dysfunction, and lung injury. Clinical trials reported significant reductions in fasting blood glucose (FBG), HbA1c, and lipid levels, with minimal side effects, at standard doses.</div></div><div><h3>Discussion</h3><div>AMPK activation by berberine plays a central role in cellular energy homeostasis, modulating key processes such as gluconeogenesis, lipogenesis, oxidative stress, and inflammation, which contribute to its therapeutic efficacy in metabolic dysfunction and DM-related complications. However, challenges remain re
{"title":"Targeting AMPK signaling: The therapeutic potential of berberine in diabetes and its complications","authors":"Kingsley Chimaeze Mbara , Poloko Stephen Kheoane , Clemence Tarirai","doi":"10.1016/j.prmcm.2025.100689","DOIUrl":"10.1016/j.prmcm.2025.100689","url":null,"abstract":"<div><h3>Introduction</h3><div>Berberine (黄连素, huáng lián sù) is a time-honored remedy in Traditional Chinese Medicine (TCM) that is found in various medicinal herbs and used to treat diabetes mellitus (DM), infections, diarrhea, and dysentery. Berberine, the major active component of <em>Coptidis rhizome</em> (黄连, huanglian), <em>Phellodendri cortex</em> (黄柏, huangbai), and <em>Mahoniae caulis</em> (亮叶十大功劳, Gong Lao Mu), exhibits several pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, cardioprotective, antineoplastic, antimicrobial, and antidiabetic effects. Antidiabetic effects of berberine are partly attributed to the activation of AMP-activated protein kinase (AMPK), which is a key mechanism and a potential treatment strategy for DM and its complications. This review discusses recent studies on the significant roles of berberine in activating AMPK for treating DM and its complications.</div></div><div><h3>Method</h3><div>We have comprehensively searched online databases like Scopus, PubMed, and Google Scholar for articles published in English between 2016 and 2025 using different permutations of these keywords: “Berberine”, “AMPK”, “Diabetes Mellitus”, “Diabetic nephropathy”, “Diabetic neuropathy”, “Diabetic retinopathy”, “Diabetic cardiomyopathy”, “Diabetic hepatic steatosis,” “Diabetic bone diseases”, “Diabetic atherosclerosis”, “Diabetic cognitive dysfunction”, “Diabetic lung injury” and “Other diabetic complications” to compile this narrative review. Out of 1750 initially retrieved articles, 183 were included based on their relevance to treating DM or its complications through the AMPK signaling pathway, pharmacokinetics, and translational potential. Non-English articles and studies not focused on AMPK activation by berberine and that did not address DM and its complications were excluded.</div></div><div><h3>Results</h3><div>The literature review found that berberine consistently activates AMPK across various preclinical studies of DM. The activation of AMPK is frequently mediated by pathways involving LKB1 and CAMKKβ. Berberine's activation of AMPK positively impacts glucose uptake, insulin sensitivity, lipid metabolism, oxidative stress, and inflammatory responses. Evidence from animal models demonstrated its efficacy in ameliorating complications such as diabetic nephropathy, neuropathy, retinopathy, cardiomyopathy, hepatic steatosis, bone diseases, atherosclerosis, cognitive dysfunction, and lung injury. Clinical trials reported significant reductions in fasting blood glucose (FBG), HbA1c, and lipid levels, with minimal side effects, at standard doses.</div></div><div><h3>Discussion</h3><div>AMPK activation by berberine plays a central role in cellular energy homeostasis, modulating key processes such as gluconeogenesis, lipogenesis, oxidative stress, and inflammation, which contribute to its therapeutic efficacy in metabolic dysfunction and DM-related complications. However, challenges remain re","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100689"},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108034","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 : 2025-09-12DOI: 10.1016/j.prmcm.2025.100692
Y. Yan , X. Liu , Y. Sun, H. Wang
Introduction
Gambogic acid (GA), a caged xanthone derived from the resin of Garcinia hanburyi (known as Téng Huáng in traditional Chinese medicine), has been historically utilized in TCM for its properties of “combating toxins, eroding sores, dispelling blood stasis, and resolving masses” in the treatment of abscesses, boils, and refractory skin diseases. In recent decades, GA has gained significant attention as a promising multi-target anticancer agent. This review aims to synthesize current preclinical evidence regarding GA’s antitumor mechanisms, its efficacy in combination therapies, and strategies to overcome its pharmacological limitations.
Methods
A systematic literature search was conducted across electronic databases including PubMed, Web of Science, and CNKI to identify relevant preclinical studies investigating the anticancer mechanisms and delivery strategies of GA. Articles were selected based on their relevance to GA’s molecular targets, efficacy in mono- and combination therapy, and novel formulation approaches.
Results
Preclinical studies demonstrate that GA exerts broad-spectrum antitumor effects through multiple mechanisms: induction of apoptosis via mitochondrial and death receptor pathways; cell cycle arrest at G0/G1 or G2/M phases; inhibition of angiogenesis via HIF-1α/VEGF/MMPs suppression; and reduction of metastasis through downregulation of MMPs. GA modulates key oncogenic pathways including NF-κB, PI3K/Akt/mTOR, and MAPKs. It overcomes drug resistance by targeting P-glycoprotein, Bcr-Abl, and SHH pathways. Notably, GA induces immunogenic pyroptosis via caspase-3/GSDME activation and reprograms tumor-associated macrophages by suppressing extracellular vesicle-mediated miR-21 transfer. Synergistic effects are observed when GA is combined with chemotherapy, targeted agents (e.g., bortezomib, gefitinib), radiotherapy, or photothermal therapy. However, GA’s clinical application is limited by poor solubility and bioavailability. Nanocarrier systems—such as polymeric nanoparticles, protein-based carriers, biomimetic designs, and stimuli-responsive formulations—have significantly improved GA’s stability, tumor targeting, and therapeutic index.
Discussion
GA represents a multi-mechanistic anticancer agent derived from TCM with high translational potential. Despite compelling preclinical results, further well-designed clinical trials are essential to validate its efficacy and safety in humans. The integration of GA with modern drug delivery technologies, especially nanotechnology, provides a promising approach to overcoming its physicochemical limitations. Future research should focus on context-dependent pathway modulation, immune microenvironment interactions, and clinical translation of advanced GA formulations.
黄曲霉酸（GA）是一种笼状的山酮，从黄曲霉的树脂中提取（在中医中称为黄曲霉Huáng），因其具有“抗毒素、腐蚀疮、化瘀、化块”的功效，在中医中一直被用于治疗脓肿、疖子和难治性皮肤病。近几十年来，GA作为一种有前景的多靶点抗癌药物受到了广泛的关注。本综述旨在综合目前关于GA抗肿瘤机制的临床前证据，其在联合治疗中的疗效，以及克服其药理学局限性的策略。方法系统检索PubMed、Web of Science、中国知网等电子数据库，收集GA抗癌机制和给药策略的相关临床前研究。文章的选择是基于它们与GA的分子靶点的相关性，单一和联合治疗的疗效，以及新的配方方法。结果临床前期研究表明，GA可通过多种机制发挥广谱抗肿瘤作用：通过线粒体和死亡受体途径诱导细胞凋亡；细胞周期阻滞于G0/G1或G2/M期；通过抑制HIF-1α/VEGF/MMPs抑制血管生成；并通过下调MMPs来减少转移。GA调节NF-κB、PI3K/Akt/mTOR和MAPKs等关键的致癌途径。它通过靶向p -糖蛋白、Bcr-Abl和SHH通路来克服耐药性。值得注意的是，GA通过caspase-3/GSDME激活诱导免疫原性焦亡，并通过抑制细胞外囊泡介导的miR-21转移对肿瘤相关巨噬细胞进行重编程。当GA与化疗、靶向药物（如硼替佐米、吉非替尼）、放疗或光热疗法联合使用时，可以观察到协同效应。然而，GA的临床应用受到溶解度和生物利用度差的限制。纳米载体系统，如聚合纳米颗粒、蛋白质载体、仿生设计和刺激反应配方，显著提高了GA的稳定性、肿瘤靶向性和治疗指数。ga是一种来自中药的多机制抗癌药物，具有很高的转化潜力。尽管有令人信服的临床前结果，但进一步精心设计的临床试验对于验证其在人体中的有效性和安全性至关重要。遗传基因与现代药物传递技术，特别是纳米技术的结合，为克服其物理化学局限性提供了一条有前途的途径。未来的研究应集中在上下文依赖性通路调节、免疫微环境相互作用和高级GA配方的临床翻译上。
{"title":"Gambogic acid: A review of its pharmacological mechanisms against cancer","authors":"Y. Yan , X. Liu , Y. Sun, H. Wang","doi":"10.1016/j.prmcm.2025.100692","DOIUrl":"10.1016/j.prmcm.2025.100692","url":null,"abstract":"<div><h3>Introduction</h3><div>Gambogic acid (GA), a caged xanthone derived from the resin of Garcinia hanburyi (known as <em>Téng Huáng</em> in traditional Chinese medicine), has been historically utilized in TCM for its properties of “combating toxins, eroding sores, dispelling blood stasis, and resolving masses” in the treatment of abscesses, boils, and refractory skin diseases. In recent decades, GA has gained significant attention as a promising multi-target anticancer agent. This review aims to synthesize current preclinical evidence regarding GA’s antitumor mechanisms, its efficacy in combination therapies, and strategies to overcome its pharmacological limitations.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted across electronic databases including PubMed, Web of Science, and CNKI to identify relevant preclinical studies investigating the anticancer mechanisms and delivery strategies of GA. Articles were selected based on their relevance to GA’s molecular targets, efficacy in mono- and combination therapy, and novel formulation approaches.</div></div><div><h3>Results</h3><div>Preclinical studies demonstrate that GA exerts broad-spectrum antitumor effects through multiple mechanisms: induction of apoptosis via mitochondrial and death receptor pathways; cell cycle arrest at G0/G1 or G2/M phases; inhibition of angiogenesis via HIF-1α/VEGF/MMPs suppression; and reduction of metastasis through downregulation of MMPs. GA modulates key oncogenic pathways including NF-κB, PI3K/Akt/mTOR, and MAPKs. It overcomes drug resistance by targeting P-glycoprotein, Bcr-Abl, and SHH pathways. Notably, GA induces immunogenic pyroptosis via caspase-3/GSDME activation and reprograms tumor-associated macrophages by suppressing extracellular vesicle-mediated miR-21 transfer. Synergistic effects are observed when GA is combined with chemotherapy, targeted agents (<em>e.g.</em>, bortezomib, gefitinib), radiotherapy, or photothermal therapy. However, GA’s clinical application is limited by poor solubility and bioavailability. Nanocarrier systems—such as polymeric nanoparticles, protein-based carriers, biomimetic designs, and stimuli-responsive formulations—have significantly improved GA’s stability, tumor targeting, and therapeutic index.</div></div><div><h3>Discussion</h3><div>GA represents a multi-mechanistic anticancer agent derived from TCM with high translational potential. Despite compelling preclinical results, further well-designed clinical trials are essential to validate its efficacy and safety in humans. The integration of GA with modern drug delivery technologies, especially nanotechnology, provides a promising approach to overcoming its physicochemical limitations. Future research should focus on context-dependent pathway modulation, immune microenvironment interactions, and clinical translation of advanced GA formulations.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100692"},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107937","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 : 2025-09-11DOI: 10.1016/j.prmcm.2025.100690
Kiren Mustafa , Noreen Akhtar , Hina Khalid , Madiha Younas , Muhammad Tariq Saeed , Yuanda Song , Zhihe Li , Hassan Mohamed
Background
Ficus carica (无花果 wúhuāguǒ) is valued in traditional Chinese medicine (TCM) and nutrition for its rich phytochemical content. Our prior research showed a crude fig extract (FLA) selectively fought liver cancer cells (HepG2) in vitro while sparing normal cells.
Purpose
We aimed to isolate an active compound from FLA and analyze the potent bioactivities, particularly anticancer potential, through in vitro and computational studies.
Method
An innovative strategy combined fractionation by vacuum liquid chromatography (VLC) on silica gel (using six non-polar to polar solvent gradients) with thin layer chromatography (TLC) and bioactivity screening on liver (HepG2) and gastric (SGC-7901) cancer cell lines, and antimicrobial assay. The active Fraction 2 (Fr-2) was repeatedly sub-fractionated using Sephadex LH-20 column chromatography and TLC to isolate psoralen. Its mechanism of action against key cancer markers was evaluated via RT-qPCR, molecular docking, and ADMET pharmacokinetic analysis, with silymarin as a comparator.
Results
Fractionation of FLA yielded Fr- 2 (Hexane: Ethyl acetate, 50:50) with the IC50 (mg/mL) against HepG2 (0.31 ± 0.1) and SGC-7901 (0.124 ± 0.05) among the six tested fractions. It also exhibited antimicrobial activity, showing maximum inhibition zones (mm) against Aspergillus flavus FL (18± 0.4 mm), Penicillium chrysogenum FL (20 ± 0.7 mm), and Pseudomonas aeruginosa (17 ± 0.8 mm). Sub-fractionation of Fr- 2 led to the identification of psoralen, which decreased the genetic expression of tumor suppressor Tp53, anti-apoptotic (Bcl2) and Cell cycle kinases (CDK1 and CDK5). Molecular interaction via molecular docking against critical cancer regulators: Tp53, oncoproteins MDM2 and Bcl2, and CDK1/CDK5 also revealed the strong binding affinity of Psoralen. Psoralen demonstrates a novel mechanism of action by dual targeting of the MDM2-p53 axis: it binds p53′s N-TAD (Arg23, -8.8 kcal/mol) to reduce ubiquitination, while competitively inhibiting MDM2 (-5.8 kcal/mol) to stabilize Tp53 and induce apoptosis. Comparative ADMET analysis revealed psoralen's superior water solubility and oral bioavailability (96.67 % absorption) versus silymarin.
Conclusion
The active Fr-2, featuring psoralen, demonstrates broad antimicrobial and anticancer activity by potentially inhibiting the MDM2-p53 pathway to induce apoptosis, and it exhibits a superior ADMET profile compared to silymarin.
{"title":"Psoralen from Ficus carica: Fractionation, bioactivity, and toxicological-pharmacokinetic comparison with silymarin","authors":"Kiren Mustafa , Noreen Akhtar , Hina Khalid , Madiha Younas , Muhammad Tariq Saeed , Yuanda Song , Zhihe Li , Hassan Mohamed","doi":"10.1016/j.prmcm.2025.100690","DOIUrl":"10.1016/j.prmcm.2025.100690","url":null,"abstract":"<div><h3>Background</h3><div><em>Ficus carica</em> (无花果 <em>wúhuāguǒ</em>) is valued in traditional Chinese medicine (TCM) and nutrition for its rich phytochemical content. Our prior research showed a crude fig extract (FLA) selectively fought liver cancer cells (HepG2) in vitro while sparing normal cells.</div></div><div><h3>Purpose</h3><div>We aimed to isolate an active compound from FLA and analyze the potent bioactivities, particularly anticancer potential, through in vitro and computational studies.</div></div><div><h3>Method</h3><div>An innovative strategy combined fractionation by vacuum liquid chromatography (VLC) on silica gel (using six non-polar to polar solvent gradients) with thin layer chromatography (TLC) and bioactivity screening on liver (HepG2) and gastric (SGC-7901) cancer cell lines, and antimicrobial assay. The active Fraction 2 (Fr-2) was repeatedly sub-fractionated using Sephadex LH-20 column chromatography and TLC to isolate psoralen. Its mechanism of action against key cancer markers was evaluated via RT-qPCR, molecular docking, and ADMET pharmacokinetic analysis, with silymarin as a comparator.</div></div><div><h3>Results</h3><div>Fractionation of FLA yielded Fr- 2 (Hexane: Ethyl acetate, 50:50) with the IC50 (mg/mL) against HepG2 (0.31 ± 0.1) and SGC-7901 (0.124 ± 0.05) among the six tested fractions. It also exhibited antimicrobial activity, showing maximum inhibition zones (mm) against <em>Aspergillus flavus</em> FL (18± 0.4 mm), <em>Penicillium chrysogenum</em> FL (20 ± 0.7 mm), and <em>Pseudomonas aeruginosa</em> (17 ± 0.8 mm). Sub-fractionation of Fr- 2 led to the identification of psoralen, which decreased the genetic expression of tumor suppressor Tp53, anti-apoptotic (Bcl2) and Cell cycle kinases (CDK1 and CDK5). Molecular interaction via molecular docking against critical cancer regulators: Tp53, oncoproteins MDM2 and Bcl2, and CDK1/CDK5 also revealed the strong binding affinity of Psoralen. Psoralen demonstrates a novel mechanism of action by dual targeting of the MDM2-p53 axis: it binds p53′s N-TAD (Arg23, -8.8 kcal/mol) to reduce ubiquitination, while competitively inhibiting MDM2 (-5.8 kcal/mol) to stabilize Tp53 and induce apoptosis. Comparative ADMET analysis revealed psoralen's superior water solubility and oral bioavailability (96.67 % absorption) versus silymarin.</div></div><div><h3>Conclusion</h3><div>The active Fr-2, featuring psoralen, demonstrates broad antimicrobial and anticancer activity by potentially inhibiting the MDM2-p53 pathway to induce apoptosis, and it exhibits a superior ADMET profile compared to silymarin.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100690"},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107938","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}
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