Protection against Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Neferine, A Natural Product from Nelumbo nucifera Gaertn

Ulcerative colitis (UC) is a long-lasting inflammatory disease of the colon. Epidemiological studies showed that the
prevalence and incidence of UC are increasing worldwide in recent years. Neferine is a natural alkaloid isolated from Nelumbo nucifera Gaertn that exerts a variety of biological activities. This study was designed to evaluate the protective effect of neferine on dextran sulfate sodium (DSS)-induced experimental UC in mice.

In this experimental study, 4% DSS was used to induce a mice model of UC. Neferine (5 and
10 mg/kg) was administered by intraperitoneal injection (ip). Clinical symptoms and disease activity index (DAI) scores
were recorded and calculated. Pathological changes of colon tissues were detected by Hematoxylin and Eosin (H&E)
staining. The levels of inflammatory mediators were detected by ELISA kits. Western blotting and immunohistochemical
analysis were used for the evaluation of protein expressions.

Neferine treatment significantly alleviated DSS-induced UC by inhibiting weight loss, decreasing DAI scores,
and alleviating the pathological changes in colon tissues. Furthermore, neferine significantly decreased serum levels
of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 and
increased serum levels of anti-inflammatory cytokine IL-10. The increased myeloperoxidase (MPO) activity and nitric
oxide (NO) in colon tissues were also inhibited. In addition, neferine significantly down-regulated inducible NO synthase
(iNOS), cyclooxygenase-2 (COX-2), and intercellular cell adhesion molecule-1 (ICAM-1) expression in colon tissues.

These results provided evidence that neferine could protect against DSS-induced UC symptoms in an
experimental mice model. This effect might be mediated through inhibition of inflammation.