N Sai Supra Siddhu1, Ajay Guru2, Rajappan Chandra Satish Kumar3, Bader O Almutairi4, Mikhlid H Almutairi4, Annie Juliet5, Thangavel Mahalingam Vijayakumar6, Jesu Arockiaraj7. 1. Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, 603 203, Kattankulathur, Chennai, Tamil Nadu, India. 2. Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, 603203, Kattankulathur, Chennai, Tamil Nadu, India. 3. Interdisciplinary Institute of Indian System of Medicine, SRM Institute of Science and Technology, 603 203, Kattankulathur, Chennai, Tamil Nadu, India. 4. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia. 5. Institute for Cellular and Molecular Biology, The University of Texas at Austin, University Station A4800, 78712, Austin, Texas, USA. 6. Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, 603 203, Kattankulathur, Chennai, Tamil Nadu, India. vijaypractice@yahoo.com. 7. Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, 603203, Kattankulathur, Chennai, Tamil Nadu, India. jesuaraj@hotmail.com.
Abstract
BACKGROUND: Boswellia serrate is an ancient and highly valued ayurvedic herb. Its extracts have been used in medicine for centuries to treat a wide variety of chronic inflammatory diseases. However, the mechanism by which B. serrata hydro alcoholic extract inhibited pro-inflammatory cytokines in zebrafish (Danio rerio) larvae with LPS-induced inflammation remained unknown. METHODS: LC-MS analysis was used to investigate the extract's phytochemical components. To determine the toxicity of B. serrata extract, cytotoxicity and embryo toxicity tests were performed. The in-vivo zebrafish larvae model was used to evaluate the antioxidant and anti-inflammatory activity of B. serrata extract. RESULTS: According to an in silico study using molecular docking and ADMET, the compounds acetyl-11-keto-boswellic and 11-keto-beta-boswellic acid present in the extract had higher binding affinity for the inflammatory specific receptor, and it is predicted to be an orally active molecule. In both in-vitro L6 cells and in-vivo zebrafish larvae, 160 µg/mL concentration of extract caused a high rate of lethality. The extract was found to have a protective effect against LPS-induced inflammation at concentrations ranged between 10 and 80 µg/mL. In zebrafish larvae, 80 µg/mL of treatment significantly lowered the level of intracellular ROS, apoptosis, lipid peroxidation, and nitric oxide. Similarly, zebrafish larvae treated with B. serrata extract (80 µg/mL) showed an increased anti-inflammatory activity by lowering inflammatory specific gene expression (iNOS, TNF-α, COX-2, and IL-1). CONCLUSIONS: Overall, our findings suggest that B. serrata can act as a potent redox scavenger against LPS-induced inflammation in zebrafish larvae and an inhibitor of specific inflammatory genes.
BACKGROUND: Boswellia serrate is an ancient and highly valued ayurvedic herb. Its extracts have been used in medicine for centuries to treat a wide variety of chronic inflammatory diseases. However, the mechanism by which B. serrata hydro alcoholic extract inhibited pro-inflammatory cytokines in zebrafish (Danio rerio) larvae with LPS-induced inflammation remained unknown. METHODS: LC-MS analysis was used to investigate the extract's phytochemical components. To determine the toxicity of B. serrata extract, cytotoxicity and embryo toxicity tests were performed. The in-vivo zebrafish larvae model was used to evaluate the antioxidant and anti-inflammatory activity of B. serrata extract. RESULTS: According to an in silico study using molecular docking and ADMET, the compounds acetyl-11-keto-boswellic and 11-keto-beta-boswellic acid present in the extract had higher binding affinity for the inflammatory specific receptor, and it is predicted to be an orally active molecule. In both in-vitro L6 cells and in-vivo zebrafish larvae, 160 µg/mL concentration of extract caused a high rate of lethality. The extract was found to have a protective effect against LPS-induced inflammation at concentrations ranged between 10 and 80 µg/mL. In zebrafish larvae, 80 µg/mL of treatment significantly lowered the level of intracellular ROS, apoptosis, lipid peroxidation, and nitric oxide. Similarly, zebrafish larvae treated with B. serrata extract (80 µg/mL) showed an increased anti-inflammatory activity by lowering inflammatory specific gene expression (iNOS, TNF-α, COX-2, and IL-1). CONCLUSIONS: Overall, our findings suggest that B. serrata can act as a potent redox scavenger against LPS-induced inflammation in zebrafish larvae and an inhibitor of specific inflammatory genes.
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