The Journal of Phytopharmacology 2024; 13(2):143-153 ;   DOI:10.31254/phyto.2024.13208

Research Article

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

HKK Rajapaksha¹ , MN Fernando² , NRM Nelumdeniya² , AWMKK Bandara³ , ARN Silva⁴

HKK Rajapaksha,MN Fernando,NRM Nelumdeniya,AWMKK Bandara,ARN Silva

1. Department of Basic Sciences, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Werahera, Sri Lanka
2. Department of Pharmacy, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Sri Lanka
3. Department of Basic Sciences, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Sri Lanka
4. Department of Basic Sciences, Faculty of Allied Health Sciences, General Sir John Kotelawala Defence University, Weraera, Sri Lanka

*Author to whom correspondence should be addressed.

Received: 16th February, 2024 / Accepted: 24th April, 2024 / Published : 30th April, 2024

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.

Keywords

Horsfieldia iryaghedhi, Anti-inflammatory, Egg albumin denaturation, Cyclooxygenase- 2 (COX-2), Molecular docking

---