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
{"title":"Reframing antimicrobial synergy through traditional and translational lenses","authors":"Md. Sanower Hossain","doi":"10.1016/j.prmcm.2025.100739","DOIUrl":"10.1016/j.prmcm.2025.100739","url":null,"abstract":"","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100739"},"PeriodicalIF":0.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750390","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.2025.100740
Muhammad Sani Ismaila , Ismail Sulaiman , Abdulbariu Ogirima Uhuami , Venkatesan Sundaram , Mustapha Umar Imam
Introduction
Type 2 diabetes mellitus (T2DM) is increasing globally, creating a need for natural and functional food–based therapeutic interventions. Quail egg yolk oil (QEYO), traditionally used in Chinese medicine as 鹌鹑蛋黄油 (ānchún dànhuáng yóu) for nourishing Yin and supporting metabolic balance, contains bioactive lipids and antioxidants with potential relevance for glycemic and redox regulation. This study investigated the antidiabetic and antioxidant effects of QEYO in a high-sugar diet (HSD)–induced metabolic dysfunction model in Drosophila melanogaster.
Methods
Adult male Drosophila melanogaster were fed a high-sugar diet (30% sucrose) to induce metabolic dysfunction and allocated into five groups: control, HSD, QEYO (62.5 or 125 mg/10 mL diet), and metformin (16 mg/10 mL). After 14 days of HSD induction followed by 7 days of treatment, physiological parameters, glucose and lipid biomarkers, oxidative stress indicators, and expression of key metabolic genes were assessed using enzymatic assays and RT-qPCR.
Results
HSD-fed flies developed obesity, hyperglycemia, elevated triglycerides, oxidative stress, and dysregulation of insulin pathway–related genes. QEYO significantly ameliorated these abnormalities in a dose-dependent manner. The 62.5 mg dose produced stronger glucose-lowering effects, while the 125 mg dose showed greater antioxidant enhancement and improved expression of SOD, CAT, IRS, and DILP2. Metformin produced comparable metabolic benefits.
Discussion
QEYO improved glucose homeostasis, lipid metabolism, and insulin pathway activity, and reduced markers of insulin resistance and oxidative imbalance in HSD-induced flies. These findings support its potential as a functional food–based intervention for T2DM and correspond with its traditional role in Chinese dietary therapy for metabolic regulation. Further mammalian studies are required for translational confirmation.
{"title":"Quail egg yolk oil attenuates insulin resistance and redox imbalance in a high-sugar-diet drosophila model","authors":"Muhammad Sani Ismaila , Ismail Sulaiman , Abdulbariu Ogirima Uhuami , Venkatesan Sundaram , Mustapha Umar Imam","doi":"10.1016/j.prmcm.2025.100740","DOIUrl":"10.1016/j.prmcm.2025.100740","url":null,"abstract":"<div><h3>Introduction</h3><div>Type 2 diabetes mellitus (T2DM) is increasing globally, creating a need for natural and functional food–based therapeutic interventions. Quail egg yolk oil (QEYO), traditionally used in Chinese medicine as 鹌鹑蛋黄油 (ānchún dànhuáng yóu) for nourishing Yin and supporting metabolic balance, contains bioactive lipids and antioxidants with potential relevance for glycemic and redox regulation. This study investigated the antidiabetic and antioxidant effects of QEYO in a high-sugar diet (HSD)–induced metabolic dysfunction model in <em>Drosophila melanogaster</em>.</div></div><div><h3>Methods</h3><div>Adult male <em>Drosophila melanogaster</em> were fed a high-sugar diet (30% sucrose) to induce metabolic dysfunction and allocated into five groups: control, HSD, QEYO (62.5 or 125 mg/10 mL diet), and metformin (16 mg/10 mL). After 14 days of HSD induction followed by 7 days of treatment, physiological parameters, glucose and lipid biomarkers, oxidative stress indicators, and expression of key metabolic genes were assessed using enzymatic assays and RT-qPCR.</div></div><div><h3>Results</h3><div>HSD-fed flies developed obesity, hyperglycemia, elevated triglycerides, oxidative stress, and dysregulation of insulin pathway–related genes. QEYO significantly ameliorated these abnormalities in a dose-dependent manner. The 62.5 mg dose produced stronger glucose-lowering effects, while the 125 mg dose showed greater antioxidant enhancement and improved expression of SOD, CAT, IRS, and DILP2. Metformin produced comparable metabolic benefits.</div></div><div><h3>Discussion</h3><div>QEYO improved glucose homeostasis, lipid metabolism, and insulin pathway activity, and reduced markers of insulin resistance and oxidative imbalance in HSD-induced flies. These findings support its potential as a functional food–based intervention for T2DM and correspond with its traditional role in Chinese dietary therapy for metabolic regulation. Further mammalian studies are required for translational confirmation.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100740"},"PeriodicalIF":0.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750151","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}
Aganope thyrsiflora (Benth.) Polhill, is a lesser-known ethnomedicinal plant traditionally used to treat gastrointestinal ailments. Despite its use in folk medicine, its pharmacological efficacy and safety profile remain largely unexamined.
Aim of the study
To evaluate the systemic effects and potential toxicological risks of the methanolic extract of A. thyrsiflora through combined experimental and computational approaches.
Materials and methods
In vivo acute and sub-acute toxicity were assessed via biochemical analysis, liver histopathology, and serum electrolyte analysis. LC-MS identified major phytoconstituents, which were further evaluated using in silico toxicity prediction tools.
Results
Extract treatment increased serum cholesterol, triglycerides, and very low-density lipoproteins (VLDL), while reducing low-density lipoprotein (LDL) levels. Liver function markers remained within physiological ranges, though serum alkaline phosphatase (SAP) increased at higher doses. Histopathology confirmed preserved hepatic structure without pathological changes. A remarkable hypoglycemic effect were observed. LC-MS identified fifteen major compounds, several of which were flagged with organ-specific toxicity alerts in silico.
Conclusion
The methanolic extract of A. thyrsiflora shows hypoglycemic potential and general hepatic safety at tested doses. However, its metabolic effects and predicted compound-specific toxicities highlight the need for further investigation. This study provides the first toxicological basis for future pharmacological validation of this underexplored ethnomedicinal species.
{"title":"Aganope thyrsiflora (Benth.) Polhill: Acute, sub-acute, and in silico toxicological evaluation of an underexplored ethnomedicinal plant","authors":"Lalnun Hruaitluangi , Lalduhawma Chhakchhuak , Anima Debbarma , C. Malsawmtluangi , Hauzel Lalhlenmawia , Ajmal Koya Pulikkal , Lalzikpuii Sailo","doi":"10.1016/j.prmcm.2025.100735","DOIUrl":"10.1016/j.prmcm.2025.100735","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Aganope thyrsiflora</em> (Benth.) Polhill, is a lesser-known ethnomedicinal plant traditionally used to treat gastrointestinal ailments. Despite its use in folk medicine, its pharmacological efficacy and safety profile remain largely unexamined.</div></div><div><h3>Aim of the study</h3><div>To evaluate the systemic effects and potential toxicological risks of the methanolic extract of <em>A. thyrsiflora</em> through combined experimental and computational approaches.</div></div><div><h3>Materials and methods</h3><div><em>In vivo</em> acute and sub-acute toxicity were assessed via biochemical analysis, liver histopathology, and serum electrolyte analysis. LC-MS identified major phytoconstituents, which were further evaluated using <em>in silico</em> toxicity prediction tools.</div></div><div><h3>Results</h3><div>Extract treatment increased serum cholesterol, triglycerides, and very low-density lipoproteins (VLDL), while reducing low-density lipoprotein (LDL) levels. Liver function markers remained within physiological ranges, though serum alkaline phosphatase (SAP) increased at higher doses. Histopathology confirmed preserved hepatic structure without pathological changes. A remarkable hypoglycemic effect were observed. LC-MS identified fifteen major compounds, several of which were flagged with organ-specific toxicity alerts <em>in silico</em>.</div></div><div><h3>Conclusion</h3><div>The methanolic extract of <em>A. thyrsiflora</em> shows hypoglycemic potential and general hepatic safety at tested doses. However, its metabolic effects and predicted compound-specific toxicities highlight the need for further investigation. This study provides the first toxicological basis for future pharmacological validation of this underexplored ethnomedicinal species.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100735"},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799891","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}
Syzygium grande (syn. Eugenia grandis), commonly known as the sea apple, is a medicinally important plant that has been traditionally used to treat various ailments, including coughs, hemorrhoids (piles), dental problems, dysentery, bronchitis, and diabetes. This study aimed to evaluate the in vitro anthelmintic, in vivo analgesic, and antidiarrheal activities of the methanolic extract of S. grande (MESG) using Swiss albino mice.
Methods
The anthelmintic activity was tested on the earthworm Pheretima posthuma. At the same time, analgesic effects were assessed using three models: the acetic acid-induced writhing test, the formalin-induced paw licking test, and the hot plate test. Antidiarrheal activity was evaluated using castor oil-induced diarrhea and the gastrointestinal motility test with charcoal meal. To support experimental findings, in silico methods such as molecular docking, ADME/T, PASS prediction, and network pharmacology were employed.
Results
Significant writhing inhibition was shown by MESG at 400 mg/kg—66.82% in the acetic acid test and 63.38% in the formalin test (p < 0.001), and showed marked analgesic activity in the hot plate test. At 200 mg/kg, the extract also exhibited strong antidiarrheal effects (p < 0.001). In the anthelmintic test, MESG at 10 μg/mL showed maximum efficacy comparable to levamisole (10 μg/mL). To clarify the multi-target potential of S. grande phytochemicals in modifying key proteins involved in pharmacological processes, this study combines network pharmacology with molecular docking. Molecular docking results revealed that gamma-sitosterol exhibited the highest binding affinity against 6COX, 5ZHP, and 1SA0 protein targets, suggesting strong potential as a drug candidate due to its favorable interactions.
Conclusion
Based on both experimental and computational evidence, MESG shows promise as a potential source of natural analgesic, antidiarrheal, and anthelmintic agents, warranting further research for drug development.
{"title":"In vivo, in vitro, and in silico evaluation of the analgesic, antidiarrheal, and anthelmintic activities of methanolic extract of Syzygium grande (Wight) Walp","authors":"Md. Jahirul Islam Mamun, Md. Hossain Rasel, Zobayed Islam, Khurshida Jahan Suma, Mohi Uddin","doi":"10.1016/j.prmcm.2025.100734","DOIUrl":"10.1016/j.prmcm.2025.100734","url":null,"abstract":"<div><h3>Background</h3><div><em>Syzygium grande</em> (syn. Eugenia grandis), commonly known as the sea apple, is a medicinally important plant that has been traditionally used to treat various ailments, including coughs, hemorrhoids (piles), dental problems, dysentery, bronchitis, and diabetes. This study aimed to evaluate the <em>in vitro</em> anthelmintic, <em>in vivo</em> analgesic, and antidiarrheal activities of the methanolic extract of <em>S. grande</em> (MESG) using Swiss albino mice.</div></div><div><h3>Methods</h3><div>The anthelmintic activity was tested on the earthworm <em>Pheretima posthuma</em>. At the same time, analgesic effects were assessed using three models: the acetic acid-induced writhing test, the formalin-induced paw licking test, and the hot plate test. Antidiarrheal activity was evaluated using castor oil-induced diarrhea and the gastrointestinal motility test with charcoal meal. To support experimental findings, in silico methods such as molecular docking, ADME/T, PASS prediction, and network pharmacology were employed.</div></div><div><h3>Results</h3><div>Significant writhing inhibition was shown by MESG at 400 mg/kg—66.82% in the acetic acid test and 63.38% in the formalin test (p < 0.001), and showed marked analgesic activity in the hot plate test. At 200 mg/kg, the extract also exhibited strong antidiarrheal effects (p < 0.001). In the anthelmintic test, MESG at 10 μg/mL showed maximum efficacy comparable to levamisole (10 μg/mL). To clarify the multi-target potential of <em>S. grande</em> phytochemicals in modifying key proteins involved in pharmacological processes, this study combines network pharmacology with molecular docking. Molecular docking results revealed that gamma-sitosterol exhibited the highest binding affinity against 6COX, 5ZHP, and 1SA0 protein targets, suggesting strong potential as a drug candidate due to its favorable interactions.</div></div><div><h3>Conclusion</h3><div>Based on both experimental and computational evidence, MESG shows promise as a potential source of natural analgesic, antidiarrheal, and anthelmintic agents, warranting further research for drug development.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100734"},"PeriodicalIF":0.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750172","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 : 2025-12-02DOI: 10.1016/j.prmcm.2025.100732
Zhanbiao He , Zhen Wang , Lu Ga , Jun Ai , Xin Tong
<div><h3>Introduction</h3><div>The AS1411 aptamer has shown great potential in the development of targeted anti-tumor drug delivery systems. <strong>Camptothecin (CPT, Xǐshù Jiǎn)</strong>, a cytotoxic quinoline alkaloid first isolated from the traditional Chinese medicine <em>Camptotheca acuminata</em> (Xǐshù), has been extensively used in various Chinese medicinal preparations including Xi Shu Injection and compound formulations combined with other herbs for cancer treatment. Despite its potent antitumor activity demonstrated in both traditional applications and modern clinical studies, the clinical application of CPT is limited by poor water solubility, low stability, and lack of tumor selectivity. Although some studies have combined AS1411 with chemotherapeutic drugs, the precise binding mechanism between the AS1411 G-quadruplex and small molecule drugs like CPT remains unclear. A systematic investigation into their interaction is crucial for the rational design of efficient and targeted drug delivery systems that can enhance the therapeutic potential of this important TCM-derived compound.</div></div><div><h3>Methods</h3><div>In this work, we first synthesized a CPT-AS1411 complex and confirmed its formation. Subsequently, we employed a suite of biophysical techniques to decipher the binding mechanism between CPT and the AS1411 G-quadruplex. UV–Vis absorption and steady-state fluorescence spectroscopy were used to verify complex formation and determine the quenching constant. Ethidium bromide (EtBr) displacement assays were conducted to probe the binding mode (e.g., intercalation or groove binding). Circular dichroism (CD) spectroscopy was utilized to monitor conformational changes in the AS1411 structure upon CPT binding. Furthermore, the effects of ionic strength and the stability of the complex under different storage conditions were evaluated.</div></div><div><h3>Results</h3><div>UV–Vis and fluorescence spectroscopy confirmed the formation of the CPT-AS1411 complex. The calculated quenching constant (K∼SV∼ = 0.5135 M⁻¹, K∼q∼ = 5.135 × 10⁷ M⁻¹·S⁻¹) indicated a static quenching process, suggesting the formation of a ground-state complex. EtBr displacement studies and CD spectral analysis collectively demonstrated a non-intercalative binding mode between CPT and AS1411. Investigations into ionic strength revealed that electrostatic interactions played a minor role in complex formation. Stability studies indicated that the CPT-AS1411 complex was more stable when stored at -4 °C compared to room temperature.</div></div><div><h3>Conclusion</h3><div>This study comprehensively elucidates the non-intercalative binding mechanism between CPT and the AS1411 G-quadruplex through multi-spectroscopic methods. Our findings provide crucial molecular-level insights and a solid experimental foundation for the future development of AS1411-based targeted delivery systems for camptothecin and its derivatives, potentially enhancing their therapeutic efficacy a
AS1411适体在靶向抗肿瘤药物递送系统的开发中显示出巨大的潜力。喜树碱(CPT, Xǐshù Jiǎn)是一种细胞毒性喹啉类生物碱,最早从中药喜树(Xǐshù)中分离出来,已广泛用于各种中药制剂,包括喜树注射液和与其他草药联合治疗癌症的复方制剂。尽管CPT在传统应用和现代临床研究中都显示出强大的抗肿瘤活性,但其水溶性差、稳定性低、缺乏肿瘤选择性等限制了CPT的临床应用。虽然有研究将AS1411与化疗药物结合,但AS1411 g -四联体与CPT等小分子药物的确切结合机制尚不清楚。系统地研究它们之间的相互作用对于合理设计有效的靶向给药系统至关重要,从而提高这种重要的中药衍生化合物的治疗潜力。方法首次合成了CPT-AS1411配合物,并对其形成进行了确证。随后,我们采用了一套生物物理技术来破译CPT与AS1411 g -四重体之间的结合机制。采用紫外可见吸收和稳态荧光光谱法验证了络合物的形成并测定了猝灭常数。采用溴化乙啶(EtBr)置换法检测其结合方式(如插层或凹槽结合)。利用圆二色性(CD)光谱监测CPT结合后AS1411结构的构象变化。此外,还考察了不同贮存条件对络合物离子强度和稳定性的影响。结果紫外可见光谱和荧光光谱证实了CPT-AS1411配合物的形成。计算出的猝灭常数(K ~ SV ~ = 0.5135 M⁻,K ~ q ~ = 5.135 × 10⁷M⁻·S⁻)表明这是一个静态猝灭过程,表明基态复合物的形成。EtBr置换研究和CD光谱分析共同证明了CPT和AS1411之间的非插层结合模式。对离子强度的研究表明,静电相互作用在络合物的形成中起着次要作用。稳定性研究表明,与室温相比,CPT-AS1411配合物在-4℃保存时更稳定。结论本研究通过多光谱方法全面阐明了CPT与AS1411 g -四联体的非插层结合机制。我们的研究结果提供了关键的分子水平的见解和坚实的实验基础,为未来发展基于as1411的喜树碱及其衍生物靶向递送系统,潜在地提高其治疗效果和降低全身毒性。
{"title":"The anti-tumor effect of chinese medicine extracts camptothecin -AS1411 system","authors":"Zhanbiao He , Zhen Wang , Lu Ga , Jun Ai , Xin Tong","doi":"10.1016/j.prmcm.2025.100732","DOIUrl":"10.1016/j.prmcm.2025.100732","url":null,"abstract":"<div><h3>Introduction</h3><div>The AS1411 aptamer has shown great potential in the development of targeted anti-tumor drug delivery systems. <strong>Camptothecin (CPT, Xǐshù Jiǎn)</strong>, a cytotoxic quinoline alkaloid first isolated from the traditional Chinese medicine <em>Camptotheca acuminata</em> (Xǐshù), has been extensively used in various Chinese medicinal preparations including Xi Shu Injection and compound formulations combined with other herbs for cancer treatment. Despite its potent antitumor activity demonstrated in both traditional applications and modern clinical studies, the clinical application of CPT is limited by poor water solubility, low stability, and lack of tumor selectivity. Although some studies have combined AS1411 with chemotherapeutic drugs, the precise binding mechanism between the AS1411 G-quadruplex and small molecule drugs like CPT remains unclear. A systematic investigation into their interaction is crucial for the rational design of efficient and targeted drug delivery systems that can enhance the therapeutic potential of this important TCM-derived compound.</div></div><div><h3>Methods</h3><div>In this work, we first synthesized a CPT-AS1411 complex and confirmed its formation. Subsequently, we employed a suite of biophysical techniques to decipher the binding mechanism between CPT and the AS1411 G-quadruplex. UV–Vis absorption and steady-state fluorescence spectroscopy were used to verify complex formation and determine the quenching constant. Ethidium bromide (EtBr) displacement assays were conducted to probe the binding mode (e.g., intercalation or groove binding). Circular dichroism (CD) spectroscopy was utilized to monitor conformational changes in the AS1411 structure upon CPT binding. Furthermore, the effects of ionic strength and the stability of the complex under different storage conditions were evaluated.</div></div><div><h3>Results</h3><div>UV–Vis and fluorescence spectroscopy confirmed the formation of the CPT-AS1411 complex. The calculated quenching constant (K∼SV∼ = 0.5135 M⁻¹, K∼q∼ = 5.135 × 10⁷ M⁻¹·S⁻¹) indicated a static quenching process, suggesting the formation of a ground-state complex. EtBr displacement studies and CD spectral analysis collectively demonstrated a non-intercalative binding mode between CPT and AS1411. Investigations into ionic strength revealed that electrostatic interactions played a minor role in complex formation. Stability studies indicated that the CPT-AS1411 complex was more stable when stored at -4 °C compared to room temperature.</div></div><div><h3>Conclusion</h3><div>This study comprehensively elucidates the non-intercalative binding mechanism between CPT and the AS1411 G-quadruplex through multi-spectroscopic methods. Our findings provide crucial molecular-level insights and a solid experimental foundation for the future development of AS1411-based targeted delivery systems for camptothecin and its derivatives, potentially enhancing their therapeutic efficacy a","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"18 ","pages":"Article 100732"},"PeriodicalIF":0.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694951","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}