Varsha S Honmore1, Amit D Kandhare2, Parag P Kadam2, Vijay M Khedkar3, Arun D Natu1, Supada R Rojatkar4, Subhash L Bodhankar5. 1. Post Graduate and Research Center, Department of Chemistry, MES Abasaheb Garware College, Pune, Maharashtra, India. 2. Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India. 3. Department of Pharmaceutical Chemistry, SVKM's Institute of Pharmacy, Survey No. 499, Plot No, 03, Mumbai - Agra National Highway, Maharashtra 424001, India. 4. R&D Centre in Pharmaceutical Sciences and Applied Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India. 5. Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India. Electronic address: subhash.bodhankar@bharatividyapeeth.edu.
Abstract
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 (MEAO) 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-α. 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-3-one (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-α). 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-α with high affinity and specificity.
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 (MEAO) 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-α. 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-3-one (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-α). 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-α with high affinity and specificity.