Regulation of arginase/nitric oxide synthesis axis via cytokine balance contributes to the healing action of malabaricone B against indomethacin-induced gastric ulceration in mice

The role of the arginine-metabolism in the healing action of the Myristica malabarica phenol malabaricone B (mal B) and omeprazole against indomethacin-induced stomach ulceration in mouse was investigated. Indomethacin (18 mg kg- 1) was found to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its administration, which was associated with reduced arginase activity (30.8%, P0.01), eNOS expression, along with increased iNOS expression, total NOS activity (5.55 folds, P0.001), NO generation (2.19 folds, P0.001), and ratio of pro-/anti-inflammatory cytokines. Besides providing comparable healing as omeprazole (3 mg kg- 1 x 3 days), mal B (10 mg kg- 1 x 3 days, p. o.) shifted the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity (51.6%, P0.001), eNOS expression, and reduced iNOS expression, total NOS activity (approximately 75%, P0.001), and NO level (50.6%, P0.01). These could be attributed to a favourable anti/pro inflammatory cytokines ratio, generated by mal B. The healing by omeprazole was however, not significantly associated with those parameters.