Pharmacological Research - Modern Chinese Medicine最新文献

{"title":"Melanogenesis inhibition by (2-Methylbutyryl) Shikonin, a naturally occurring naphthoquinone potentiates dacarbazine anti-melanoma efficacy via ROS mediated apoptotic pathway","authors":"Aalim Maqsood Bhat ,&nbsp;Irshad Ahmad Bhat ,&nbsp;Sheikh Tasduq Abdullah","doi":"10.1016/j.prmcm.2025.100651","DOIUrl":"10.1016/j.prmcm.2025.100651","url":null,"abstract":"<div><h3>Introduction</h3><div>Melanoma is a highly aggressive skin cancer with strong metastatic potential and resistance to conventional chemotherapy. Dacarbazine (DTIC) is widely used for melanoma treatment, but its effectiveness is often compromised by acquired resistance, resulting in relapse and poor prognosis. (2-Methylbutyryl) Shikonin (BSHK), a naturally derived naphthoquinone pigment isolated from Lithospermum erythrorhizon, is a bioactive derivative of shikonin—an established compound in Traditional Chinese Medicine (TCM). In TCM, shikonin and its derivatives are key constituents of formulations such as Zicao (purple gromwell root), traditionally used for detoxification, reducing inflammation, and treating skin disorders, including eczema, burns, and malignancies. BSHK has demonstrated broad anti-cancer activity by inhibiting cancer cell proliferation and possesses the ability to suppress tyrosinase enzyme activity, a key enzyme in melanogenesis. This study investigates whether BSHK can enhance the therapeutic efficacy of dacarbazine in melanoma cells and explores the molecular mechanisms underlying their combined effect, while also highlighting its traditional use and therapeutic relevance in Chinese herbal medicine.</div></div><div><h3>Methods</h3><div>Melanoma cells were treated with BSHK, dacarbazine, or their combination. Cell viability was assessed by MTT assay. Apoptosis was analyzed using Annexin-V/FITC staining and flow cytometry. Protein expression levels of key Oxidative stress, apoptotic and melanogenic markers such as SOD, Catalase, Nrf-2 Bcl-2, BAX, Caspase-3, and MITF was evaluated by immunoblotting.</div></div><div><h3>Results</h3><div>BSHK significantly enhanced the anti-proliferative effect of dacarbazine on melanoma cells. Co-treatment increased apoptotic cell populations and ROS levels compared to single treatments. Western blot analysis revealed that combination therapy downregulated MITF and Bcl-2, while upregulating BAX and cleaved Caspase-3, indicating enhanced apoptotic signaling and melanogenesis inhibition.</div></div><div><h3>Discussion</h3><div>In conclusion, (2-Methylbutyryl) Shikonin sensitizes melanoma cells to dacarbazine by inhibiting melanogensis thereby increasing their susceptibility to apoptosis. The synergistic anticancer effects of (2-Methylbutyryl) Shikonin and dacarbazine suggest that their combination could be a promising therapeutic strategy for treating melanoma</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100651"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523870","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}

{"title":"Integrated In Silico and In Vivo evaluation of Cassytha filiformis: Molecular insights into caspase-3/8 binding and wound healing effect","authors":"Soosamma John ,&nbsp;Nisha Shri Chengamaraju ,&nbsp;Navya A S ,&nbsp;Agasa Ramu Mahesh ,&nbsp;Bincy Raj","doi":"10.1016/j.prmcm.2025.100650","DOIUrl":"10.1016/j.prmcm.2025.100650","url":null,"abstract":"<div><h3>Background</h3><div><em>Cassytha filiformis</em> is a parasitic vine traditionally used in Chinese traditional medicine (CTM) for its anti-inflammatory, detoxifying, and wound-healing properties. Despite its ethnomedical significance, scientific validation of its therapeutic mechanisms-particularly its interaction with apoptotic pathways-remains limited.</div></div><div><h3>Objective</h3><div>This study investigated the wound healing potential of <em>Cassytha filiformis</em> through <em>in vivo</em> and in silico approaches, alongside phytochemical isolation and characterization.</div></div><div><h3>Methods</h3><div>Successive solvent extraction was performed using petroleum ether, chloroform, ethyl acetate, and methanol. Phytochemical screening confirmed the presence of flavonoids, phenolics, and phytosterols. Isolation and spectroscopic characterization identified pseudohypericin as key constituents. Gas chromatography-mass spectroscopy (GC–MS) analysis revealed additional 25 bioactive compounds.</div></div><div><h3>Results</h3><div>Among all extracts, the 5 % chloroform extract showed the most significant activity in excision and incision wound models, achieving 100 % wound contraction by day 16 and a tensile strength of 425.5 ± 4.89 g, outperforming the standard drug framycetin. In silico docking result showed strong binding affinity of quercetin 3-O-rutinoside (−11.9 kcal/mol) and pseudohypericin (−10.0 kcal/mol) with Caspase-3, supported by favorable ADMET and toxicity profiles. Similarly, Quercetin 3-O-rutinoside and Pseudohypericin exhibited significant binding affinities against Caspase-8 with binding score of -8.1 and -8.0 kcal/mol respectively. Both phytoconstituents showed significant binding affinity against Caspase-8. The stability of complex was validated through 100 ns molecular dynamic (MD) simulation results.</div></div><div><h3>Conclusion</h3><div><em>Cassytha filiformis</em> demonstrated potent wound healing activity, suggesting its potential for development into safe, effective plant-based therapeutics.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100650"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563630","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}

{"title":"Progress in the application of AI in the standardization of traditional Chinese medicine: A review based on machine learning and deep learning","authors":"Xianglong Meng ,&nbsp;Yijing Lang ,&nbsp;Xiaofen Li ,&nbsp;Yuting Li ,&nbsp;Zhulin Bu ,&nbsp;Yuhui Wu ,&nbsp;Shuosheng Zhang","doi":"10.1016/j.prmcm.2025.100639","DOIUrl":"10.1016/j.prmcm.2025.100639","url":null,"abstract":"<div><h3>Introduction</h3><div>The Fourth Industrial Revolution, propelled by advancements in the internet, big data, robotics, and artificial intelligence (AI), has not only accelerated technological progress but also heralded a new era of intelligent healthcare. Nowadays, traditional Chinese medicine (TCM) is moving towards the road of intelligent transformation, in which the urgency of integrating the advanced insights of modern medicine is becoming more and more obvious. At the same time, with the full use of various types of artificial intelligence technology, to explore the potential of Chinese medicine, prompting it to embark on a standardized development track, in order to let the ancient Chinese medicine in the wave of modern science and technology renewed new life.</div></div><div><h3>Methods</h3><div>Through a systematic exploration utilizing keywords such as “AI”, “TCM”, and “Standardization”, we conducted an extensive search across major repositories including Web of Science, PubMed, CNKI, and other databases, analyzing approximately 1000 scholarly works. We strive to deepen our understanding of TCM while fully exploiting the integration potential of AI and TCM, and to effectively promote TCM to make great strides towards more scientific, standardized and efficient standardization.</div></div><div><h3>Results</h3><div>This review explores six critical areas where AI techniques such as machine learning (ML) and deep learning (DL) contribute: disease diagnosis, prevention and treatment, herbal medicine quality evaluation, pharmacokinetics, mechanisms of action, and non-drug therapy. Examples include: using ML to predict disease outcomes; modeling pharmacokinetics using DL; and using AI techniques to assess the quality grade of herbal medicines etc.. It examines the systemic responses driven by complex interactions between internal and environmental factors during disease progression, grounded in fundamental human biology. Through rigorous high-throughput screening and analysis, this review elucidates intricate biological interaction networks and achieves comprehensive holistic regulation, thereby furthering the standardization of Traditional Chinese Medicine.</div></div><div><h3>Conclusion</h3><div>This review explores the complex dimensions of TCM using cutting-edge AI techniques to provide strategic guidance for promoting standardization and evolutionary development in the field.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100639"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523869","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}

{"title":"Network Pharmacology and Computational Validation Uncover the Multi-Target Mechanisms of Spleen-Strengthening and Dampness-resolving Herb pair against Gastric Cancer","authors":"Shuping Qiu ,&nbsp;Zhe Jing ,&nbsp;Rong Su ,&nbsp;Xinhong Chen ,&nbsp;Meiyan Zhu ,&nbsp;Yuhong Wu ,&nbsp;Jing Han ,&nbsp;Hailong Li","doi":"10.1016/j.prmcm.2025.100648","DOIUrl":"10.1016/j.prmcm.2025.100648","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigates the correlation between various spleen-invigorating and dampness-removing herb pairs, including Poria Cocos (Schw.) Wolf with Polyporus Umbellatus (Pers.) Fr., Poria Cocos (Schw.) Wolf with Coicis Semen, Polyporus Umbellatus (Pers.) Fr. with Scutellariae Barbatae Herba, and Coicis Semen with Mume Fructus, and gastric cancer and its subtypes, utilizing network pharmacology, molecular docking, and dynamic simulations.</div></div><div><h3>Methods</h3><div>Active components and targets were identified from TCMSP and supplemented using SwissTargetPrediction. GC-related targets were retrieved from GeneCards, OMIM, and TTD. Intersections were analyzed with Venny 2.1.0, and PPI networks were constructed using STRING and Cytoscape 3.9.1. GO and KEGG analyses were conducted with DAVID and the Bioinformatics websites. Kaplan-Meier survival analysis was performed using the Kaplan-Meier Plotter. Molecular docking and dynamics simulations were carried out with CB-Dock2, AutoDock Vina1.5.6, PyMol, Discovery Studio 2019, GROMACS 2023, CHARMM 36, Ewald (PME), and Verlet.</div></div><div><h3>Results</h3><div>We identified 15, 11, 9, 29, and 8 active components in the respective herbs. Common targets such as IL6, TNF, BCL2, and MMP9 were recognized as potential key targets for GC treatment. GO and KEGG analyses highlighted phosphorylation-related pathways mediated through the STAT3/VEGF axis. Kaplan-Meier analysis indicated that TNF, MMP9, HIF1A, CASP3, AKT1, CCND1, ESR1, BCL2L1, MAPK1, TP53, MYC, and PTGS2 significantly correlated with the overall survival of GC patients. Molecular docking and dynamics simulations demonstrated favorable binding affinities between IL6 and luteolin, TNF and poricoic acid C, BCL2 and wogonin, and MMP9 and quercetin.</div></div><div><h3>Conclusion</h3><div>It is suggested that the pairing of herbs that are both spleen-invigorating and dampness-removing may exert anti-inflammatory, antioxidant, anti-proliferative, and pro-apoptotic effects by modulating signalling pathways through interactions with key targets. This suggests that there is therapeutic potential for GC treatment.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100648"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549413","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}

{"title":"Efficacy and safety of Bufei Huoxue capsules in the treatment of stable COPD: A multicenter, double-blind, placebo-controlled, randomized clinical trial","authors":"Yuqin Chen ,&nbsp;Bihua Zhong ,&nbsp;Zhiwan Wang ,&nbsp;Lei Xu ,&nbsp;Zhe Cheng ,&nbsp;Wenjun He ,&nbsp;Jingjing Qi ,&nbsp;Yinji Xu ,&nbsp;Xiaoying Huang ,&nbsp;Li Li ,&nbsp;Minfang Li ,&nbsp;Yingyun Fu ,&nbsp;Peifang Zhang ,&nbsp;Weike Li ,&nbsp;Huijie Wang ,&nbsp;Qian Jiang ,&nbsp;Junzhen Gao ,&nbsp;Tianci Jiang ,&nbsp;Lingling Dai ,&nbsp;Yan Cai ,&nbsp;Jian Wang","doi":"10.1016/j.prmcm.2025.100647","DOIUrl":"10.1016/j.prmcm.2025.100647","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition characterized by irreversible airflow limitation, resulting in significant morbidity and mortality. Bufei Huoxue capsules (BFHX) have demonstrated potential benefits in small-scale clinical studies, including the improvement of cardiopulmonary function, reduction of blood viscosity, and enhancement of immune responses. These findings support the promise of BFHX for COPD treatment. Therefore, large-scale, standardized, multicenter clinical trials are urgently needed to validate these results.</div></div><div><h3>Methods</h3><div>Patients with stable COPD who met the inclusion and exclusion criteria were recruited. BFHX or placebo was given orally three times a day (1.4 g/dose) for 12 months. The primary outcome was the 6 min walk distance (6MWD).</div></div><div><h3>Results</h3><div>Among 208 patients (one patient did not receive the placebo) with COPD, 154 successfully completed the study, including 83 patients in the BFHX group and 71 patients in the placebo group. 6MWD tended to increase in the BFHX group and decrease in the placebo group. After 9 and 12 months of treatment, the improvement in 6MWD compared with baseline was significantly better in the BFHX group than in the placebo group (full analysis set after 9 months: 36.81 ± 8.06 m vs. −12.11 ± 8.41 m; 95 % confidence interval = 25.50–72.34; <em>p</em> &lt; 0.0001. full analysis set after 12 months: 36.65 ± 8.47 m vs. −18.24 ± 9.26 m; 95 % confidence interval = 29.82–79.96; <em>p</em> &lt; 0.0001). Furthermore, BFHX effectively alleviated fatigue, dyspnea, coughing, and sputum in patients with stable COPD while improving their quality of life and pulmonary function.</div></div><div><h3>Discussion</h3><div>BFHX administration significantly enhanced exercise tolerance in patients with stable COPD, alleviated fatigue and dyspnea, improved pulmonary function, ameliorated cough and sputum production, and enhanced overall quality of life. Moreover, the safety profile of BFHX was commendable, making it a demonstrating potential therapeutic value.</div></div><div><h3>Trial registration</h3><div>The China Clinical Trial Registry (ID: ChiCTR1800016955)</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100647"},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489507","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}

{"title":"Mechanism of Tetrastigma hemsleyanum extracts on diabetic retinopathy based on network pharmacology and experimental verification","authors":"Jie Zhou ,&nbsp;Xuan Chen ,&nbsp;Baisheng Xu ,&nbsp;Xuechun Jiang ,&nbsp;Jie Wang ,&nbsp;Huan An","doi":"10.1016/j.prmcm.2025.100646","DOIUrl":"10.1016/j.prmcm.2025.100646","url":null,"abstract":"<div><h3>Introduction</h3><div>Diabetic retinopathy (DR) is a prevalent ocular complication of diabetes, with advanced stages potentially leading to blindness. <em>Tetrastigma hemsleyanum</em> (San ye qing, SYQ) has traditionally been employed in addressing ailments such as fever, asthma, hepatitis, infantile febrile seizures, pneumonia, rheumatism, and sore throats. Initial animal studies have suggested that SYQ may significantly curb the progression of DR. This study utilized network pharmacology to explore the mechanism of <em>Tetrastigma hemsleyanum</em> (San ye qing, SYQ) in diabetes retinopathy (DR), with subsequent validation through molecular docking and experiments.</div></div><div><h3>Methods</h3><div>Male C57BL/6 J mice were applied to establish a type Ⅰ diabetes model. Hemoxylin &amp; eosin staining and western blotting were then used to evaluate the efficacy of SYQ. Databases including Swiss Target Prediction, GeneCards, and DisGeNet were used to filter targets related to DR. The STRING database and Cytoscape software were used to create a protein-protein interaction network. The Metascape database was used to conduct Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of mutual targets. The active compounds were subjected to molecular docking with core targets using AutoDock software, and the predicted outcomes from network pharmacology were verified in vitro. Tube formation and migration experiments were conducted to evaluate the anti-angiogenic effect and mechanism of SYQ on high glucose-induced EA.hy926 cells.</div></div><div><h3>Results</h3><div>SYQ demonstrated an inhibitory effect on angiogenesis within the DR model and decreased the expression of proteins related to angiogenesis. Network pharmacology analyses revealed that SYQ targeted 127 proteins, with implications for pathways including the HIF-1 signaling pathway. Molecular docking illuminated that β-sitosterol, Procyanidin-B1, and Emodion-1-O-β-<span>d</span>-glucopyranoside exhibited strong binding affinities with AKT1 core target proteins. In vitro experiments corroborated that SYQ diminished tube formation and migration of EA.hy926 cells under high glucose conditions, in a dose-dependent manner. The pro-angiogenic influence of an AKT1 agonist was counteracted by SYQ. Additionally, administration of SYQ led to reduced expression of p-AKT, HIF-1, and angiogenesis-related proteins, suggesting an inhibitory mechanism via AKT1 against high glucose-induced angiogenesis. These observations confirmed the network pharmacology insights.</div></div><div><h3>Discussion</h3><div>SYQ emerged as a potential therapeutic agent for DR, primarily by inhibiting angiogenesis. Its anti-angiogenetic effect was mediated via the AKT1/HIF-1/VEGF pathway, indicating a promising avenue for further research and potential clinical application in DR management.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100646"},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313077","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}

{"title":"Effect of the aqueous extract of Gymnema sylvestre on some metabolic disturbances in a model of insulin resistant induced by dexamethasone and high sucrose diet on rat","authors":"Barnabé Lucien NKONO  YA  NKONO ,&nbsp;Danielle Claude BILANDA ,&nbsp;Balthazar TCHEUDI ,&nbsp;Georges Ramone ADINGA ,&nbsp;Paul Désiré DZEUFIET ,&nbsp;Sélestin SOKENG ,&nbsp;Pierre KAMTCHOUING","doi":"10.1016/j.prmcm.2025.100642","DOIUrl":"10.1016/j.prmcm.2025.100642","url":null,"abstract":"<div><h3>Introduction</h3><div>Insulin resistance (IR) is when cells don’t respond well to insulin and can’t easily take up glucose from the blood. Such situation may lead to chronic hyperglycemia and even diabetes. Gymnema sylvestre aqueous extract is known in traditional Chinese medicine for its hypoglycemic activity. Some studies suggest that gymnemic acids, triterpene glucosides, and saponins may be responsible for this plant's impact on blood glucose regulation. This study aimed to evaluate the effects of Gymnema sylvestre aqueous extract (AEGS) on rat model of IR.</div></div><div><h3>Methods</h3><div>IR was induced in male Wistar rats aged between 5 and 6 weeks by a high sucrose diet during 20 weeks then an intraperitoneal injection of dexamethasone (4mg/kg) once daily during 7 consecutive days. IR rats were divided into 5 groups of 5 animals each and received orally the different treatments as follows: a negative IR control group (NC-IR) received distilled water (10mL/kg), a positive IR control group (PC-IR) received metformin (200mg/kg), three experimental groups received AEGS (50, 100 and 200 mg/kg respectively). The different treatments were administered for 14 days. At the end of treatment, animals were sacrificed after urine collection; serum and homogenates from liver kidney and pancreas were prepared for biochemical analysis and histology.</div></div><div><h3>Results</h3><div>Compared to NC-IR, AEGS at all doses tested significantly reduced IR. It is the same for glucose, creatinine, direct bilirubin, serum transaminase total proteins and uric acid. The histopathological study revealed that AEGS restored tissues injuries induced by dexamethasone combined with high-sucrose diet, thus justifying its empirical use.</div></div><div><h3>Discussion</h3><div>The results obtained in this study suggest that AEGS have hypoglycemic, hepatoprotective and nephroprotective properties.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100642"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290876","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}

{"title":"Network pharmacology-based toxicity, molecular docking, and molecular dynamics analysis of phytoconstituents from roots of Nerium indicum L","authors":"Veerkumar P. Japti ,&nbsp;Mrityunjaya B. Patil ,&nbsp;Banappa S. Unger ,&nbsp;Shamanand P. Mallapur ,&nbsp;Akshay Shamnewadi ,&nbsp;Vishal S. Patil ,&nbsp;Sathgowda Patil ,&nbsp;Anand V. Desai","doi":"10.1016/j.prmcm.2025.100640","DOIUrl":"10.1016/j.prmcm.2025.100640","url":null,"abstract":"<div><h3>Background</h3><div>Herbal medicine plays a vital role in healthcare, but safety concerns arise due to potential toxicity risks. <em>Nerium indicum</em> (夹竹桃, jiā zhú táo) is used in Chinese herbal medicine for its therapeutic effects, yet it contains toxic cardiac glycosides. This study investigates its toxicity mechanisms using systems biology tools to support safer applications through comprehensive risk-benefit evaluation and detoxification strategies.</div></div><div><h3>Methods</h3><div>Computational analyses were performed to predict drug-likeness, toxicity, LD₅₀, and blood-brain barrier (BBB) penetration. Key toxicity-related genes were identified using SwissTargetPrediction and GeneCards. Gene Ontology (GO) and pathway enrichment analyses further explored toxicity mechanisms, while molecular docking and dynamics simulations assessed interactions between core targets, Prostaglandin-endoperoxide synthase 2 (PTGS2) and Mitogen-Activated Protein Kinase 1 (MAPK1), offering deeper insights into toxicity modulation.</div></div><div><h3>Results</h3><div>Computational analyses identified oleandrin, and odoroside A as highly toxic, with significant cardiotoxic and hepatotoxic risks. Network analysis revealed PTGS2 and MAPK1 as key toxicity regulators, mediating pathways linked to inflammation and cellular stress. Molecular docking showed Oleandrin exhibiting the strongest binding affinities with PTGS2 (-8.5 kcal/mol) and MAPK1 (-9.2 kcal/mol), while molecular dynamics simulations confirmed its stable interactions, suggesting a critical role in toxicity modulation.</div></div><div><h3>Conclusion</h3><div>This study highlights Oleandrin and related compounds as major toxicity contributors in <em>N. indicum</em>, emphasizing their impact on cardiac, hepatic, and neurological pathways. The findings underscore the need for cautious therapeutic use and potential detoxification strategies for safer applications.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100640"},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263754","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}

{"title":"Unveiling polyphyllin's role in neuroprotection: A pharmacological perspective","authors":"Md Sadique Hussain ,&nbsp;Amita Joshi Rana ,&nbsp;Mudasir Maqbool ,&nbsp;Nasreen Sulthana ,&nbsp;Ayesha Sultana ,&nbsp;Sumel Ashique ,&nbsp;Yumna Khan ,&nbsp;Prasanna Srinivasan Ramalingam ,&nbsp;Sushil S. Burle ,&nbsp;Vikas Jakhmola ,&nbsp;Gaurav Gupta","doi":"10.1016/j.prmcm.2025.100641","DOIUrl":"10.1016/j.prmcm.2025.100641","url":null,"abstract":"<div><h3>Introduction</h3><div>Polyphyllins are bioactive steroidal saponins predominantly derived from <em>Paris polyphylla</em> (Chinese: Chonglou, 重楼), an herb long employed in Traditional Chinese Medicine (TCM) for detoxification, inflammation control, and pain relief, commonly administered as decoctions or powdered <strong>Rhizoma Paridis</strong>. Beyond these traditional uses, growing evidence supports their neuroprotective efficacy, especially in the context of neurodegenerative diseases (NDs), where inflammation, oxidative stress, and dysregulated cell death are central to disease progression.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted up to March 2025. Out of 423 initially retrieved articles, 143 were included based on relevance to neuroprotective mechanisms, pharmacokinetics, and translational potential. Reviews, non-English articles, and studies not focused on brain-related mechanisms were excluded.</div></div><div><h3>Results</h3><div>Polyphyllins demonstrate potent neuroprotective activities through anti-inflammatory, antioxidant, and autophagy-modulating mechanisms. PP-II interrupts the KEAP1-NRF2 interaction, activating antioxidant gene expression, while PP-I induces mitophagy via the PINK1-Parkin pathway. PP-VII modulates neuroinflammation through activation of the cGAS-STING axis. These actions collectively protect neurons, preserve mitochondrial function, and reduce pathological cascades associated with NDs. However, poor solubility and limited blood-brain barrier permeability remain key translational barriers.</div></div><div><h3>Discussion</h3><div>The promising therapeutic effects of polyphyllins in ND models align with their historical use in TCM. Advances in nanomedicine, including lipid nanoparticles and carbon dots; have improved polyphyllin delivery to the central nervous system. Nevertheless, the absence of clinical trials and the need for safety profiling require resolution before clinical adoption. Future investigations should prioritize optimized drug formulations and validation in human models to bridge preclinical evidence with therapeutic applications.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100641"},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271432","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}

{"title":"LC-MS profiling and multi-target mechanistic insights of Hibiscus rosa-sinensis in diabetes: Network pharmacology, molecular docking, MD simulation, PCA, and in-vitro α-amylase inhibition","authors":"Shankar Thapa ,&nbsp;Sharvendra Nath Maurya ,&nbsp;Kavya Manjunath ,&nbsp;Ammar A․Razzak Mahmood ,&nbsp;Kalpana Devi ,&nbsp;Shithin Ann Varghese ,&nbsp;Ashish Lamsal ,&nbsp;Binaya Tamang ,&nbsp;Mahalakshmi Suresha Biradar","doi":"10.1016/j.prmcm.2025.100636","DOIUrl":"10.1016/j.prmcm.2025.100636","url":null,"abstract":"<div><h3>Background</h3><div><em>Hibiscus rosa-sinensis</em> Linn. (Zhū Jǐn Huā), known in Traditional Chinese Medicine (TCM) as Dà Hóng Huā, has been widely used for its cooling, detoxifying, and anti-inflammatory properties. It is a medicinal plant traditionally used for managing diabetes, yet its multi-target mechanisms remain largely unexplored. This study aimed to investigate the anti-diabetic potential of <em>H. rosa-sinensis</em> through LC-MS-based phytochemical profiling, network pharmacology, molecular docking, molecular dynamics (MD) simulations, principal component analysis (PCA), and <em>in vitro</em> α-amylase inhibition assay.</div></div><div><h3>Methods</h3><div>LC-MS analysis was performed to identify bioactive compounds present in the methanolic extract of <em>H. rosa-sinensis</em>. Identified compounds were subjected to network pharmacology analysis to predict potential diabetes-related protein targets. Key compound-target interactions were evaluated using molecular docking (AutoDock Vina v1.2.0), followed by 100 ns MD simulations to assess structural stability and binding dynamics. PCA and free energy landscape (FEL) analyses were conducted to examine conformational behaviour. Finally, <em>in vitro</em> α-amylase inhibition was tested to validate the hypoglycaemic potential.</div></div><div><h3>Results</h3><div>Quercetin demonstrated strong binding affinities with PTK2 (–8.2 kcal/mol), SRC (–9.2 kcal/mol), and α-amylase (–8.9 kcal/mol), suggesting its multi-target action in diabetes. MD simulation confirmed the structural stability of all three complexes over 100 ns, supported by consistent RMSD and favourable interaction profiles. The PCA and FEL analyses showed minimal conformational fluctuations and energetically favourable states. The <em>in vitro</em> α-amylase inhibition assay further validated the antidiabetic potential, with an IC₅₀ value of 107.75 µg/mL for the <em>H. rosa-sinensis</em> flower extract.</div></div><div><h3>Conclusion</h3><div>This integrative study provides strong evidence for the multi-target antidiabetic potential of <em>Hibiscus rosa-sinensis</em>, primarily attributed to quercetin and its derivatives. The findings highlight stable interactions with key diabetic targets and demonstrate significant α-amylase inhibition, supporting the traditional use of <em>H. rosa-sinensis</em> as a complementary therapy for diabetes management.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100636"},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271433","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}