Diospyros malabarica (Desr.) Kostel fruits extract attenuated acute and chronic inflammation through modulation of the expression of pro- and anti-inflammatory biomarkers in rat models

Rheumatoid arthritis is a chronic inflammatory disorder of polyarticular tissues, characterised by progressive synovitis. Its prolonged treatment imparts a huge burden on the healthcare system and results in toxicity, which necessitates the search for safe, efficacious and cost-effective therapies. Diospyros malabarica (Desr.) Kostel is traditionally used for anti-inflammatory purposes; however, to the best of our knowledge, there is no detailed study reporting the in vivo anti-inflammatory potential of this plant. Therefore, in the current study, the methanol extract of D. malabarica (Desr.) Kostel fruit (mDMF) was evaluated for its antioxidant, anti-inflammatory and anti-arthritic potentials, along with its underlying mechanisms. The antioxidant activity was evaluated by DPPH assay. Total phenolic and flavonoid contents were estimated via colorimetric and high-performance liquid chromatography (HPLC) methods. Different doses (250, 500 and 750 mg/kg) of mDMF were used to evaluate the anti-inflammatory and anti-arthritis actions in acute inflammatory (carrageenan and histamine-induced paw oedema) and Freund's complete adjuvant (FCA)-induced arthritis rat models. Levels of various pro- and anti-inflammatory biomarkers were estimated using ELISA and RT-PCR techniques. Paw samples were used for different histopathological and radiographic studies. Qualitative phytochemical and HPLC analyses indicated the presence of various polyphenolic compounds in mDMF, which exhibited marked antioxidant activity in the DPPH assay. mDMF showed time-dependent anti-inflammatory and anti-arthritic effects in in vivo models. ELISA assay data showed significant (p