Healing properties of malabaricone B and malabaricone C, against indomethacin-induced gastric ulceration and mechanism of action

The healing activity of malabaricone B and malabaricone C, the major antioxidant constituents of the spice Myristica malabarica against the indomethacin-induced gastric ulceration in mice has been studied. The histological indices revealed maximum ulceration on the 3rd day after indomethacin administration, which was effectively healed by malabaricone B, malabaricone C (each 10 mg/kg body weight/day) and omeprazole (3 mg/kg body weight/day) for 3 days. Compared to the untreated ulcerated mice, treatment with malabaricone B, malabaricone C and omeprazole reduced the ulcer indices by 60.3% (P < 0.01), 88.4% and 86.1% respectively (P < 0.001). All the test samples accelerated ulcer healing than observed in natural recovery even after 7 days. Stomach ulceration reduced the total antioxidant status of plasma by 41% (P < 0.05), which was significantly increased by malabaricone B (36%, P < 0.01), malabaricone C (61%, P < 0.001) and omeprazole (53%, P < 0.001). Compared to the ulcerated untreated mice, those treated with malabaricone B reduced the levels of thiobarbituric acid reactive substances and protein carbonyls by 17% and ∼ 34% respectively (P < 0.05), while malabaricone C and omeprazole reduced the parameters almost equally (∼ 30%, P < 0.01, and ∼ 40%, P < 0.01 respectively). Likewise, all the test samples reduced the oxidation of protein and non-protein thiols significantly (P < 0.05). The antioxidant activity of the test samples could partly account their healing capacities. However, the differential potency of them was explainable by considering their relative abilities to modulate mucin secretion, PGE2 synthesis and expression of EGF receptor and COX isoforms, malabaricone C being most effective in controlling all these factors.