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Calcarea carbonica treatment rescues lipopolysaccharide-induced inflammatory response in human mononuclear cells via downregulation of inducible cyclooxygenase pathway

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Journal of Integrative Medicine 2020年第5期18卷 441-449页

作者： Swatantra Kumar vimal kmaurya Debadatta Nayak Anil Khurana Raj KManchanda Srinivasulu Gadugu Madan LBBhatt Shailendra K.Saxena Centre for Advanced Research Faculy of MedicineKing George's Medical UniversityLucknow 226003India Central Council for Research in Homoeopathty.Ministry of Ayush.Janakpuri.New Delhi 10058 India Deparment of Medicine Jaisoorya and Potti Sreeramulu Government Medical Cllege.Hyderabad 500013India

Objective: Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low ***: THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration(CC_(50)) and 50% effective concentration(EC_(50)). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide(NO) and tumor necrosis factor-a(TNF-a) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2(COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking ***: The CC_(50) and EC_(50) of C. carbonica were found to be 43.26 and 11.99 mg/mL, respectively. The cell survival assay showed a 1.192-fold(P = 0.0129), 1.443-fold(P = 0.0009) and 1.605-fold(P = 0.0004)increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds(P = 0.0001), 2.181 folds(P = 0.0001) and 2.071 folds(P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNFa levels by 1.395 folds(P = 0.0013), 1.541 folds(P = 0.0005) and 1.550 folds(P = 0.0005) at 24, 48 and72 h, respectively. In addition, a 1.193-fold reduction(P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in active site of ***: C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-a level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine

关键词： Inflammation Calcarea carbonica Cyclooxygenase-2 Nitric oxide Tumor necrosis factor-a Anti-inflammatory

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