Preclinical Evaluation of UNIM-H and UNIM-R Polyherbal Formulations for the Management of Experimental Arthritis

Arthritis is a chronic inflammatory disorder characterized by persistent inflammation, joint damage, and dysregulated inflammatory pathways, necessitating safer and effective therapeutic approaches. This study evaluated the safety, chemical profile, and antiarthritic potential of two polyherbal formulations, UNIM-H for oral administration and UNIM-R for topical application. UNIM-H was investigated through acute and 28-day toxicity, cytotoxicity, carrageenan-induced paw oedema, cotton pellet-induced granuloma, and complete Freund’s adjuvant (CFA)-induced arthritis models, whereas UNIM-R was assessed for dermal safety, irritation, cytotoxicity, and antiarthritic efficacy. HPTLC profiling confirmed characteristic chemical markers in UNIM-H, including aloe-emodin, colchicine, guggulsterone-Z, and quercetin, while UNIM-R contained 1,8-cineole, benzoic acid, sesamol, and quercetin, supporting chemical standardization of both formulations. UNIM-H demonstrated strong in vitro antioxidant and anti-inflammatory activities, with IC₅₀ values of 0.0352 and 2.078 mg/mL, respectively. In vivo, UNIM-H at 200 and 400 mg/kg and the topical UNIM-R formulation produced significant reductions in paw oedema and inflammatory mediators, including TNF-α, IL-1β, IL-02, IFN-γ, and PGE₂, along with modulation of the anti-inflammatory cytokine IL-10. Histopathological and radiographic findings further supported the antiarthritic effects of both formulations, with responses comparable to those observed with the respective reference drugs, indomethacin (3 mg/kg) for UNIM-H and diclofenac gel for UNIM-R.  Molecular assessment further demonstrated changes in MMP-9 gene expression and COX-2 and LOX protein expression, indicating modulation of key inflammatory and joint-destructive pathways. Overall, UNIM-H and UNIM-R demonstrated promising complementary oral and topical antiarthritic activity, with favorable safety profiles and defined chemical-marker characteristics, supporting their further preclinical development.