Investigation of Alpinia calcarata constituent interactions with molecular targets of rheumatoid arthritis: docking, molecular dynamics, and network approach
| Autor: | Sree Karani Kondapuram, Sanmuga Priya Ekambaram, Thamizharasi Erusappan, Mohane Selvaraj Coumar |
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| Rok vydání: | 2020 |
| Předmět: |
Phytochemicals
Syk Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Catalysis Mass Spectrometry Inorganic Chemistry Arthritis Rheumatoid chemistry.chemical_compound 0103 physical sciences Humans Syk Kinase Physical and Theoretical Chemistry Kaempferols Flavonoids 010304 chemical physics biology Traditional medicine Plant Extracts Organic Chemistry Computational Biology Janus Kinase 3 Janus Kinase 1 biology.organism_classification Molecular medicine 0104 chemical sciences Computer Science Applications Rhizome Galangin Molecular Docking Simulation Interleukin-1 Receptor-Associated Kinases Computational Theory and Mathematics chemistry Docking (molecular) Toll-Like Receptor 8 Alpinia Matrix Metalloproteinase 2 Zingiberaceae Quercetin Kaempferol Chromatography Liquid |
| Zdroj: | Journal of molecular modeling. 27(1) |
| ISSN: | 0948-5023 |
| Popis: | Rheumatoid arthritis (RA) is a systemic autoimmune disorder that commonly affects multiple joints of the body. Currently, there is no permanent cure to the disease, but it can be managed with several potent drugs that cause serious side effects on prolonged use. Traditional remedies are considered promising for the treatment of several diseases, particularly chronic conditions, because they have lower side effects compared to synthetic drugs. In folklore, the rhizome of Alpinia calcarata Roscoe (Zingiberaceae) is used as a major ingredient of herbal formulations to treat RA. Phytoconstituents reported in A. calcarata rhizomes are diterpenoids, sesquiterpenoid, flavonoids, phytosterol, and volatile oils. The present study is intended to understand the molecular-level interaction of phytoconstituents present in A. calcarata rhizomes with RA molecular targets using computational approaches. A total of 30 phytoconstituents reported from the plant were used to carry out docking with 36 known targets of RA. Based on the docking results, 4 flavonoids were found to be strongly interacting with the RA targets. Further, molecular dynamics simulation confirmed stable interaction of quercetin with 6 targets (JAK3, SYK, MMP2, TLR8, IRAK1, and JAK1), galangin with 2 targets (IRAK1 and JAK1), and kaempferol (IRAK1) with one target of RA. Moreover, the presence of these three flavonoids was confirmed in the A. calcarata rhizome extract using LC-MS analysis. The computational study suggests that flavonoids present in A. calcarata rhizome may be responsible for RA modulatory activity. Particularly, quercetin and galangin could be potential development candidates for the treatment of RA. Investigation of Alpinia calcarata constituent interactions with molecular targets of rheumatoid arthritis: docking, molecular dynamics, and network approach. |
| Databáze: | OpenAIRE |
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