Hammad Ismail, Saqib Hussain Hadri, Umer Rashid, Hafiza Aqsa Ashraf, Amna Mahmood, Abdullah Tariq, Ayesha Jannat, Adeena Ansar, Sheeza Masud, Muhammad Rashid, Lyba Sarfraz, Muhammad Zeeshan Bhatti
Acer oblongifolium and its phenolic constituents, principally Gentisic acid and vanillic acid, showed analgesic, anti-inflammatory, and anxiolytic-like activity in this preclinical model, potentially mediated via modulation of pro-inflammatory cytokines.
BACKGROUND: Phenolic compounds of plant origin are promising alternatives, but the potential of Acer oblongifolium and its components has not been studied.
OBJECTIVE: To evaluate analgesic, anti-inflammatory and anxiolytic effects of Acer oblongifolium extract and four of its major phenolics, catechin, syringic acid, vanillic acid and gentisic acid-with the help of in silico, in vivo and biochemical techniques.
METHODS: HPLC was performed to investigate the phenolic content of the plant extract. The binding of known compounds with TNF α, IL-6 and IL-1β was evaluated with the help of molecular docking. In-vivo tests, including the hole board test, open field test, hot plate test, writhing assay, carrageenan induced paw edema and histamine induced edema were used to evaluate the pharmaceutical potential. ELISA was performed to measure serum and tissue IL-6, IL-1β and TNF-α levels.
RESULTS: HPLC validated the presence of four phenolic compounds, including Gentisic acid, vanillic acid, catechin and syringic acid. Gentisic acid exhibited strong hydrogen binding with TNF-α and IL-1β. The most pronounced anxiolytic-like activity was exhibited by vanillic acid which decreased immobility by 60% and freezing behavior by 62% in open field test, and enhanced the latency of hot plate by 30%. Gentisic acid prevented carrageenan induced paw swelling by 82% at 3 h and vanillic acid prevented histamine induced edema by 80%, which was better than cetirizine. ELISA indicated that both Gentisic acid and catechin were the most effective in reducing high levels of IL-1β and TNF-α levels in serum and brain tissue from 4.55 to 2.035 pg/mL.
CONCLUSION: Acer oblongifolium and its phenolic constituents, principally Gentisic acid and vanillic acid, showed analgesic, anti-inflammatory, and anxiolytic-like activity in this preclinical model, potentially mediated via modulation of pro-inflammatory cytokines.