Mukul S. Tambe , Shreyas R. Shinde , Akshay M. Baheti , Shuchi Nagar , Anil T. Pawar
{"title":"苦参镇痛、抗炎、抗关节炎分子机制的网络药理学及计算机模拟研究Dunal植物成份","authors":"Mukul S. Tambe , Shreyas R. Shinde , Akshay M. Baheti , Shuchi Nagar , Anil T. Pawar","doi":"10.1016/j.jaim.2024.101088","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div><em>Withania somnifera</em> (L.) Dunal, commonly known as ashwagandha, is an Ayurvedic herb belonging to the family Solanaceae.</div></div><div><h3>Objectives</h3><div>This study aims to explore the analgesic, anti-inflammatory and anti-arthritic potential of phytoconstituents of <em>Withania somnifera</em> (L.) Dunal (<em>W. somnifera</em>) by network pharmacology and <em>in-silico</em> docking studies.</div></div><div><h3>Methods</h3><div>Five major phytoconstituents, namely ashwagandhanolide, quercetin, withaferin A, withanone and withanolide A, were selected for the network pharmacology study. All five phytoconstituents were further evaluated for their binding properties using molecular docking (MD) and simulation tools. The compounds that exhibited significant binding affinities were further studied for pharmacokinetic and toxicity (ADMET) predictions.</div></div><div><h3>Results</h3><div>The network pharmacology study showed that out of the five selected constituents, withaferin A, withanolide A and quercetin can interact with various inflammation and pain-related genes. In <em>in-silico</em> studies, all five constituents were found to have significant interactions with inflammatory and nociception proteins cyclooxygenases, lipoxygenase, myeloperoxidase and cathepsin B. Further, ADMET studies predicted that all five phytoconstituents could not cross the blood-brain barrier but have high gastrointestinal absorption and bioavailability. Quercetin was predicted to have mutagenic potential and the other three constituents (withaferin A, withanone and withanolide A) were predicted to have immunotoxicity. The MD simulation studies showed that the complexes lipoxygenase_ashwagandhanolide and cathepsin B_ashwagandhanolide exhibit lower RMSD, RMSF, and higher H-bonding, indicating greater stability of ashwagandhanolide with lipoxygenase and cathepsin B.</div></div><div><h3>Conclusion</h3><div>Ashwagandhanolide, quercetin, withaferin A, withanone, and withanolide A from <em>W. somnifera</em> may show the potential for analgesic, anti-inflammatory, and anti-arthritic activities. These findings provide a foundation for future <em>in</em>-<em>vitro</em> and <em>in</em>-<em>vivo</em> studies to confirm the therapeutic efficacy of these phytoconstituents from <em>W. somnifera</em>.</div></div>","PeriodicalId":15150,"journal":{"name":"Journal of Ayurveda and Integrative Medicine","volume":"16 4","pages":"Article 101088"},"PeriodicalIF":1.7000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Network pharmacology and in-silico studies for molecular mechanisms of analgesic, anti-inflammatory and anti-arthritic effects of Withania somnifera (L.) Dunal phytoconstituents\",\"authors\":\"Mukul S. Tambe , Shreyas R. Shinde , Akshay M. Baheti , Shuchi Nagar , Anil T. Pawar\",\"doi\":\"10.1016/j.jaim.2024.101088\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div><em>Withania somnifera</em> (L.) Dunal, commonly known as ashwagandha, is an Ayurvedic herb belonging to the family Solanaceae.</div></div><div><h3>Objectives</h3><div>This study aims to explore the analgesic, anti-inflammatory and anti-arthritic potential of phytoconstituents of <em>Withania somnifera</em> (L.) Dunal (<em>W. somnifera</em>) by network pharmacology and <em>in-silico</em> docking studies.</div></div><div><h3>Methods</h3><div>Five major phytoconstituents, namely ashwagandhanolide, quercetin, withaferin A, withanone and withanolide A, were selected for the network pharmacology study. All five phytoconstituents were further evaluated for their binding properties using molecular docking (MD) and simulation tools. The compounds that exhibited significant binding affinities were further studied for pharmacokinetic and toxicity (ADMET) predictions.</div></div><div><h3>Results</h3><div>The network pharmacology study showed that out of the five selected constituents, withaferin A, withanolide A and quercetin can interact with various inflammation and pain-related genes. In <em>in-silico</em> studies, all five constituents were found to have significant interactions with inflammatory and nociception proteins cyclooxygenases, lipoxygenase, myeloperoxidase and cathepsin B. Further, ADMET studies predicted that all five phytoconstituents could not cross the blood-brain barrier but have high gastrointestinal absorption and bioavailability. Quercetin was predicted to have mutagenic potential and the other three constituents (withaferin A, withanone and withanolide A) were predicted to have immunotoxicity. The MD simulation studies showed that the complexes lipoxygenase_ashwagandhanolide and cathepsin B_ashwagandhanolide exhibit lower RMSD, RMSF, and higher H-bonding, indicating greater stability of ashwagandhanolide with lipoxygenase and cathepsin B.</div></div><div><h3>Conclusion</h3><div>Ashwagandhanolide, quercetin, withaferin A, withanone, and withanolide A from <em>W. somnifera</em> may show the potential for analgesic, anti-inflammatory, and anti-arthritic activities. 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Network pharmacology and in-silico studies for molecular mechanisms of analgesic, anti-inflammatory and anti-arthritic effects of Withania somnifera (L.) Dunal phytoconstituents
Background
Withania somnifera (L.) Dunal, commonly known as ashwagandha, is an Ayurvedic herb belonging to the family Solanaceae.
Objectives
This study aims to explore the analgesic, anti-inflammatory and anti-arthritic potential of phytoconstituents of Withania somnifera (L.) Dunal (W. somnifera) by network pharmacology and in-silico docking studies.
Methods
Five major phytoconstituents, namely ashwagandhanolide, quercetin, withaferin A, withanone and withanolide A, were selected for the network pharmacology study. All five phytoconstituents were further evaluated for their binding properties using molecular docking (MD) and simulation tools. The compounds that exhibited significant binding affinities were further studied for pharmacokinetic and toxicity (ADMET) predictions.
Results
The network pharmacology study showed that out of the five selected constituents, withaferin A, withanolide A and quercetin can interact with various inflammation and pain-related genes. In in-silico studies, all five constituents were found to have significant interactions with inflammatory and nociception proteins cyclooxygenases, lipoxygenase, myeloperoxidase and cathepsin B. Further, ADMET studies predicted that all five phytoconstituents could not cross the blood-brain barrier but have high gastrointestinal absorption and bioavailability. Quercetin was predicted to have mutagenic potential and the other three constituents (withaferin A, withanone and withanolide A) were predicted to have immunotoxicity. The MD simulation studies showed that the complexes lipoxygenase_ashwagandhanolide and cathepsin B_ashwagandhanolide exhibit lower RMSD, RMSF, and higher H-bonding, indicating greater stability of ashwagandhanolide with lipoxygenase and cathepsin B.
Conclusion
Ashwagandhanolide, quercetin, withaferin A, withanone, and withanolide A from W. somnifera may show the potential for analgesic, anti-inflammatory, and anti-arthritic activities. These findings provide a foundation for future in-vitro and in-vivo studies to confirm the therapeutic efficacy of these phytoconstituents from W. somnifera.