Abstract
BackgroundOverproduction of free radicals and decreased antioxidant capacity are well-known risk factors for inflammatory bowel diseases. Gymnema sylvestre (GS) leaves extract is distinguished for its anti-diabetic, antioxidant and anti-inflammatory properties. Present study is designed to evaluate the preventative activities of GS against acetic acid (AA)-induced ulcerative colitis in Wistar rats.MethodsExperimentally ulcerative colitis (UC) was induced by AA in animals pretreated with three different doses of GS leaves extract (50, 100, 200 mg/kg/day) and a single dose of mesalazine (MES, 300 mg/kg/day) for seven days. Twenty four hours later, animals were sacrificed and the colonic tissues were collected. Colonic mucus content was determined using Alcian blue dye binding technique. Levels of thiobarbituric acid reactive substances (TBARS), total glutathione sulfhydryl group (T-GSH) and non-protein sulfhydryl group (NPSH) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were estimated in colon tissues. Colonic nucleic acids (DNA and RNA) and total protein (TP) concentrations were also determined. Levels of pro-inflammatory cytokines including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) as well as prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated in colonic tissues. The histopathological changes of the colonic tissues were also observed.ResultsIn AA administered group TBARS levels were increased, while colonic mucus content, T-GSH and NP-SH, SOD and CAT were reduced in colon. Pretreatment with GS inhibited TBARS elevation as well as mucus content, T-GSH and NP-SH reduction. Enzymatic activities of SOD and CAT were brought back to their normal levels in GS pretreated group. A significant reduction in DNA, RNA and TP levels was seen following AA administration and this inhibition was significantly eliminated by GS treatment. GS pretreatment also inhibited AA-induced elevation of pro-inflammatory cytokines, PGE2 and NO levels in colon. The apparent UC protection was further confirmed by the histopathological screening.ConclusionThe GS leaves extract showed significant amelioration of experimentally induced colitis, which may be attributed to its anti-inflammatory and antioxidant property.
Highlights
Overproduction of free radicals and decreased antioxidant capacity are well-known risk factors for inflammatory bowel diseases
Studies demonstrated that oxidative injury resulting from free radicals overproduction such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) in patients with colitis can lead to adverse effects such as lipid peroxidation (LPO) of the cellular membrane and attack on tissue proteins and nucleic acids [10]
In seven days pretreatment with different doses of Gymnema sylvestre (GS) groups showed marked reduction in mean colon weights compared to acetic acid (AA) group (Figure 1-A)
Summary
Overproduction of free radicals and decreased antioxidant capacity are well-known risk factors for inflammatory bowel diseases. Inflammatory changes associated with UC are limited to the mucosa and typically affects the rectum but often extends to involve the whole colon [3,4] Both excessive inflammation and oxidative stress play a pivotal role in the pathogenesis of UC [5,6]. The pathophysiology of UC as an inflammatory disease mainly characterized by migration of neutrophils, basophils and other leukocytes to the mucosa membranes and the superficial ulcers [7] This process leads to release of inflammatory mediators such as cytokines and arachidonic acid metabolites, as well as free radicals resulting in oxidative damage to the colonic tissue [8,9]. Management of UC using therapies with limited toxicity is a severe challenge
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