Aqueous Ethanol Fruit Extract of Xylopia aethiopica and Xylopic Acid Exhibit Anti-inflammatory Activity Through Inhibition of the Arachidonic Acid Pathway

Abstract

In the form of a decoction, X. aethiopica is traditionally employed in the treatment of bronchitis, asthma, arthritis and rheumatism in Ghana, Nigeria and Cameroon. This study establishes the inhibitory effect of X. aethiopica and its principal constituent, xylopic acid, on the arachidonic acid pathway of inflammation. Hydrogen sulphide is endogenously produced in mammalian tissues from the enzymatic activity of cystathionine β-synthase and cystathionine γ-lyase on L-cysteine. Its involvement in the local and systemic inflammatory process has been documented in animal models. Recent studies have identified its activation of phospholipase A₂ as the mechanism involved in its anti-inflammatory role. We henceforth conducted this study to investigate the inhibitory role of X. aethiopica and its principal constituent xylopic acid on hydrogen sulphide-induced inflammation and eventual effect on the activation of phospholipase A₂. Sodium hydrogen sulphide (NaHS) was injected into the mouse hind paw and oedema was monitored for 60 min. Paws were examined by the histological method. X. aethiopica extract (30, 100, 300 mg kg^-1) suppressed the mean maximal swelling attained at 15 min to 42.58±1.66%, 42.58±1.66% and 34.91±2.39%, respectively compared to the mean inflamed control response of 61.51±3.90%. The total paw swellings induced over the 1 h were also significantly suppressed by 31.82±5.28%, 36.19±6.01%, and 31.65±5.16%, respectively. The xylopic acid (10, 30, 100 mg kg^-1) suppressed the mean maximal swelling attained at 15 min to 41.75±1.24%, 40.26±1.68% and 38.26±2.52%, respectively relative to the control response while the total paw swelling was significantly suppressed by 34.08±4.49%, 38.19±4.50% and 43.40±5.09% respectively relative to the inflamed control response. Histologically, there was a significant (P < 0.0001) reduction in cytoplasmic vacuolation, inflammation, cellular degeneration, loss of tissue organisation and necrotic tissues with administration of X. aethiopica extract and xylopic acid in the inflamed paws of the mice. This study establishes that X. aethiopica extract, and xylopic acid mediate their anti-inflammatory actions in part through inhibition of hydrogen sulphide-induced inflammation and subsequently has an inhibitory role on phospholipase A₂ activation.