Alpha-lipoic acid attenuates trinitrobenzene sulfonic acid-induced ulcerative colitis in mice

Ulcerative colitis (UC), characterized by inflammation, oxidative stress, and increased intestinal epithelial cell apoptosis, is an immunologically mediated chronic intestinal disorder. The present study was aimed at investigating the protective effects of alpha-lipoic acid (ALA) against trinitrobenzene sulfonic acid (TNBS)-induced UC and the underlying mechanism. ALA of 80 mg/kg bw/day was administered by gastric gavage to mice for 7 days after TNBS-induced UC. Our data indicated that ALA effectively facilitated recovery of pathologic changes in the colon, as evidenced by a significant increase of body weight, decrease of colon mass index and histopathological score. Furthermore, ALA significantly inhibited TNBS-induced apoptosis, which partly due to up-regulation of Bcl-2 expression, reduction of Bax expression and caspase-3, caspase-9 activity. ALA reduced malondialdehyde (MDA), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) levels, and restored superoxide dismutase (SOD) activity and glutathione (GSH) content in colon tissues from TNBS-challenged mice. Additionally, phosphorylation of extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38) in colon tissues were significantly inhibited by ALA treatment. In summary, we demonstrate that ALA has protective properties against TNBS-induced UC through anti-apoptosis, anti-oxidant actions, and mitogen-activated protein kinase (MAPK) signaling pathway. Our present findings suggest a therapeutic potential of ALA in UC.