Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

Abstract

Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5% glucose solution (vehicle). The blank group (n = 10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-κB p65, TNF-α, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that oxymatrine improves intestinal barrier function via NF-κB-mediated signaling pathway and may be used as a new protecting agent for cirrhosis-associated intestinal mucosal damage.

Gastroprotective and anti‐ulcer effects of oxymatrine against several gastric ulcer models in rats: Possible roles of antioxidant, antiinflammatory, and prosurvival mechanisms

“…In the present study, we first showed that OXY could decrease gastric mucosa damage in ethanol, indomethacin, and stress‐induced ulceration models, as evidenced by macroscopic assessment of ulcer lesions and pathologic evaluation. In previous studies, Wen et al () demonstrated that OXY improves intestinal epithelial barrier function in CCl 4 ‐induced cirrhotic rats by improving intestinal mucosal atrophic, fractured performance and decreasing inflammatory cells infiltrated into lamina propria and muscular layers. Moreover, Zheng et al () concluded that OXY improves histological damage of colonic mucosa in dextran sulfate sodium‐induced colitis of rats.…”

Efficacy of oxymatrine for treatment and relapse suppression of severe plaque psoriasis: results from a single-blinded randomized controlled clinical trial

“…Nuclear factor‐κB (NF‐κB) is an essential transcription factor involved in the pathogenesis of psoriasis. Oxymatrine has been shown to increase the phosphorylation of the inhibitor of κB‐α in the cytosol, prevent the nuclear translocation of NF‐κB, or reduce the expression level of NF‐kB p65, resulting in the inhibition of NF‐κB activation . Therefore, oxymatrine may ameliorate psoriasis via the inhibition of NF‐kB activation.…”

“…Oxymatrine has been shown to increase the phosphorylation of the inhibitor of jB-a in the cytosol, prevent the nuclear translocation of NF-jB, or reduce the expression level of NF-kB p65, resulting in the inhibition of NF-jB activation. [43][44][45] Therefore, oxymatrine may ameliorate psoriasis via the inhibition of NF-kB activation. However, further studies using skin cells or related immune cells involved in the inflammatory process of psoriasis are needed to verify the underlying mechanism(s) of the effects of oxymatrine.…”

Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats

“…Its anti-oxidative activity has been useful in the treatment of liver fibrosis, viral hepatitis, skin diseases, and autoimmune disease [8]. Recently, oxymatrine has been extensively studied for its protective effects against heart injuries induced by isoproterenol [9], myocardial ischemia [10, 11], hypertension [12], aldosterone [13], septic shock [14], and arrhythmias [15].…”