Antispasmodic and Anti-inflammatory Effects of Kratom Leaf Extract on Acetic Acid-induced Ulcerative Colitis in Mice.

Abstract

BACKGROUND/AIM: Ulcerative colitis (UC) is colonic inflammation associated with increased production of pro-inflammatory cytokines, oxidative stress, and disturbances of immune responses. Mitragynine is the most abundant active alkaloid in(kratom) and may have anti-inflammatory, antioxidant, and antispasmodic properties. In this study, we investigated the palliative effects of mitragynine in kratom leaf extract on the symptoms of UC. MATERIALS AND METHODS: Mice were divided into six groups (n=9): control; colitis; colitis plus syrup with kratom extract containing 5, 10, or 20 mg/kg mitragynine; and a positive control group treated with 4 mg/kg loperamide. The treatments were orally administered for 5 days after colitis was induced by transrectal administration of 5% acetic acid. RESULTS: The results showed that syrup with 10 and 20 mg/kg mitragynine significantly alleviated colonic tissue damage caused by acetic acid-induced colitis. Furthermore, the disease activity index, colonic weight, colonic lesions, and levels of malondialdehyde and inflammatory cytokines (tumor necrosis factor-α and interleukin-1β) decreased in these groups in comparison with the colitis-only group. With regard to antispasmodic activity, kratom extract significantly increased colonic smooth muscle relaxation by acting on μ-opioid receptor signaling and inhibited induced muscular contraction in mice with colitis. Moreover, kratom extract attenuated nitric oxide levels and enhanced the phagocytic activity of mouse peritoneal macrophages. CONCLUSION: Kratom leaf extract, which contains mitragynine, alleviated acetic acid-induced colitis in mice by modulating immune responses and by its anti-inflammatory, antioxidative, and antispasmodic effects. Therefore, kratom leaves may be an effective therapeutic candidate for subsequent development as a multitarget drug for UC.