Angiogenic and cell proliferating action of the natural diarylnonanoids, malabaricone B and malabaricone C during healing of indomethacin-induced gastric ulceration

Purpose. To evaluate the plant phenolics, malabaricone B (mal B) and malabaricone C (mal C) in healing stomach ulcer by modulating angiogenesis. Materials and Methods. Male Swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose) were treated up to 7 days with different doses of mal B or mal C. The healing capacities of the drugs and their effects on the angiogenic parameters were assessed. Results. Maximum ulceration, observed on the 3rd day after indomethacin administration was effectively healed by mal B and mal C (each 10 mg/kg, p. o. x 3 days), the latter showing equivalent potency (similar to 78% p < 0.001) as that of Omez (3 mg/kg, p. o.x3 days) and misoprostol (10 mu g/kg, p. o. x 3 days). Compared to the untreated mice, those treated with mal B or mal C respectively for 3 days increased the mucosal EGF level (139 and 178%, p < 0.001), the serum VEGF level (56%, p < 0.01 and 95%, p < 0.001) and microvessels formation (37%, p < 0.05 and 62%, p < 0.01), while reducing the serum endostatin level (37%, p < 0.05 and 61%, p < 0.01). The relative healing capacities of mal B and mal C correlated well with their respective abilities to modulate the angiogenic factors. The healing by Omez and misoprostol was not due to improved angiogenesis. Conclusions. The drugs, mal B and mal C could effectively heal indomethacin-induced stomach ulceration in mice by promoting angiogenesis.