Evaluation of In vitro anti-inflammatory activity and In-silico pharmacokinetics and molecular docking study of Horsfieldia iryaghedhi

Abstract

Background: Phytochemicals are still a valuable source to develop clinically important drugs in treating chronic and acute diseases. Inflammation is a response to an injurious stimulus of the body and novel therapeutic agents are needed to alleviate the condition with minimum side effects. Aims and Objectives: To investigate in vitro anti-inflammatory activity of methanol and aqueous leaf, bark, and combination extracts of plant Horsfieldia iryaghedhi by heat-induced egg albumin denaturation method and to analyze the phytochemicals of Horsfieldia iryaghedhi for their anti-inflammatory potential against cyclooxygenase- 2 (COX-2) using molecular docking. Methodology: Matured and fully expanded fresh leaves and barks of H. iryaghedhi were collected, and the extractions were obtained cold maceration using 99.9% methanol and distilled water as solvents. A concentration series was then developed, and the anti-inflammatory activity was evaluated against Diclofenac sodium as the positive control, using the heat-induced egg albumin denaturation method. Further, selected phytochemicals were tested against COX-2 enzyme (PDB ID: 5IKR) using site-specific molecular docking with autodock vina and the binding energies and pharmacokinetic and toxicity parameters were evaluated. Results: The methanol and aqueous extracts have shown a moderate to strong concentration-dependent anti-inflammatory activity with reference to standard Diclofenac sodium (IC50 116.4 μg/ml) and Methanol bark extract exhibited potent anti-inflammatory activity compared to other extracts (IC50 293 μg/ml). Further, Methanol and aqueous extracts showed a statistically significant correlation between concentration and percentage inhibition (p<0.05, R2 ≈1). The molecular docking results suggest that the phytochemicals available on the plant have possible COX-2 inhibitory activity and the compounds selected (Methyl 2,4-dihydroxy-6-methylbenzoate and N, N-Dimethyl-5-methoxy tryptamine) even got favourable toxicity and pharmacokinetic parameters confirming their drugability. Conclusion: Methanol bark extract of Horsfieldia iryaghedhi have marked in vitro anti-inflammatory activity. The results indicate a solid possibility of lead discovery of anti- inflammatory agents from the bark and leaves of Horsfieldia iryaghedhi. However, further molecular dynamics studies and in vivo tests may be required to confirm the findings.