Anti-arthritic potential of linalool: in vitro, in vivo, and in silico mechanistic insights for safer therapeutic applications

Abstract

Linalool (LIN), a monoterpene alcohol from lavender and coriander essential oils, is known for its anti-inflammatory and analgesic properties. However, its potential in arthritis management, combining in vitro, in vivo, and in silico studies; pharmacokinetics; and toxicity management, remains unexplored. This study investigated LIN's anti-arthritis activity through various approaches: in vitro (egg albumin test), in vivo (terpene oil, formaldehyde-induced, and Freund's complete adjuvant (FCA)-induced models), and in silico analyses. In the in vivo study, LIN (25, 50, and 75 mg/kg, p.o.) and the combination of LIN-50 with indomethacin (INDO, 10 mg/kg, p.o.) were evaluated. LIN-75 significantly reduced paw licking, inhibited paw edema in the terpene oil and formaldehyde-induced models, and showed significant inhibition in the FCA-induced arthritis model. The combination therapy of LIN-50 + INDO-10 demonstrated enhanced anti-arthritis activity compared to individual treatments. In the in vitro egg albumin test, LIN-75 exhibited the highest membrane-stabilizing activity, and its combination with INDO-10 resulted in a synergistic effect. In silico studies revealed significant binding affinities of LIN with COX-1, COX-2, and TNF-α (-5.5, -5.1, and -5.0 kcal/mol, respectively), suggesting its potential mechanism of action. Additionally, LIN showed favorable pharmacokinetics with lower toxicity than INDO. In conclusion, LIN exhibited dose-dependent anti-arthritic effects across various models, highlighting its potential as a therapeutic agent for rheumatoid arthritis (RA). Its efficacy suggests promising clinical relevance, warranting further research on its pharmacokinetics, toxicity management, and clinical applicability to fully establish its therapeutic benefits.

Keywords: In vivo; Indomethacin; Molecular docking; Pharmacokinetics; Rheumatoid arthritis.