Diarylheptanoid, a constituent isolated from methanol extract of Alpinia officinarum attenuates TNF-α level in Freund's complete adjuvant-induced arthritis in rats

Ethnopharmacological relevance: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease that affects the worldwide population. Alpinia officinarum Hance (Zingiberaceae), rhizomes are widely used ethnobotanically as an anti-inflammatory, analgesic, and antioxidant agent in traditional medicine. Aim: To investigate the efficacy and possible mechanism of isolated phytoconstituent from the methanol extract of A. officinarum (MEAD) rhizomes against Freund's complete adjuvant (FCA)-induced arthritis in rats. Furthermore, molecular docking was performed to study the binding mode of this compound into the active site of TNF-alpha. Materials and methods: Diarylheptanoid was isolated from MEAO, well characterized (HPTLC, 1H NMR, 13C NMR, and ESI-MS) and evaluated for its antiarthritic activity in female Wistar rats (170-200 g). Diarylheptanoid (5, 10 and 20 mg/kg, p.o.) was administered starting from day 12. Various behavioral, biochemical, molecular and histopathology parameters were evaluated. Molecular docking study was performed using Glide module integrated into Schrodinger molecular modeling software. Results: The structure and molecular weight of the isolated compound (diarylheptanoid) were confirmed by 1D and mass spectral data and characterized as 1-phenyl-5-hydroxy-7- (4"-hydroxy-3"-methoxyphenyl) heptane-3one (i.e., 5-HPH) with molecular formula C20H24O4. Administration of 5-HPH (10 and 20 mg/kg) significantly inhibited (p < 0.05) FCA induced increases in paw volume, joint diameter, thermal hyperalgesia and tactile allodynia. It also significantly decreased oxido-inflammatory markers (SOD, GSH, MDA, and TNF-alpha). FCA induced a histological alteration in ankle joint also attenuated by 5-HPH. Its Glide docking score was found to be 9.702 with binding energy (Glide energy) of 37.033 kcal/mol. Conclusion: 5-HPH may exhibit its anti-arthritic potential via inhibition of elevated oxido-inflammatory markers thus restoring the elevated hyperalgesia, allodynia and reducing destruction in synovial membrane and cartilage. Therefore, 5-HPH is a potential moiety bearing antioxidant and with anti-inflammatory properties to inhibit FCA-induced arthritis in rats. The results of the present investigation should enable the design of potent small-molecule inhibitors that inactivate TNF-alpha with high affinity and specificity.