In Vitro Antioxidant Activity, Mineral Composition, and In Silico Identification of Potential Human COX-2 Inhibitors from Azadirachta Indica: A Case Study of Rheumatoid Arthritis

Lateef Bello*, Sidiqat A Shodehinde*, Olajumoke B Ademoyegun, Bolanle Adalumo, Dorcas O Oluwafemi, Oyinkansola E Adewale, Olamide V Awelewa, Daniel O Nwankwo, Success O Olubode and Samuel A Oginni

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by synovial inflammation and joint destruction, with Cyclooxygenase-2 (COX-2) significantly contributing to its pathogenesis. Traditional management includes NSAIDs and COX-2 inhibitors, which pose gastrointestinal and cardiovascular risks. Azadirachta indica (neem), known for its anti-inflammatory properties, was studied for its antioxidant activity, mineral content, and potential COX-2 inhibitors, emphasizing its relevance to RA treatment.

Fresh leaves of neem were extracted using n-butanol and evaluated for total phenolic content (TPC), total flavonoid content (TFC), and ferric reducing antioxidant power (FRAP) using standard protocols. Mineral content was determined by atomic absorption spectroscopy, and bioactive compounds were identified using high-performance liquid chromatography (HPLC). Identified phytochemicals were subjected to in silico analyses against human COX-2.

The fraction exhibited high TPC and TFC and demonstrated strong FRAP activity. HPLC analysis identified seven polyphenolic compounds, and mineral analysis revealed the presence of essential macro- and microelements, all within FAO/WHO permissible limits. E-pharmacophore screening, molecular docking, ADMET predictions, and AutoQSAR analysis identified ferulic acid as a promising COX-2 inhibitor, with ferulic acid showing the strongest binding affinity (−6.899 kcal/mol) and favorable MM-GBSA binding free energy (−34.71 kcal/mol). 

This study demonstrates that Azadirachta indica leaf possesses significant antioxidant activity, a beneficial mineral profile, and bioactive compounds with promising COX-2 inhibitory potential. Ferulic acid stands out for its strong binding affinity, pharmacokinetic properties, and safety profile. The combined in vitro and in silico results highlight neem’s potential as a natural anti-inflammatory agent for RA, necessitating further in vivo and clinical validation.

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Published on: Jan 6, 2025 Pages: 1-11

Full Text PDF Full Text HTML DOI: 10.17352/ojor.000056
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