Formononetin protects against concanavalin-A-induced autoimmune hepatitis in mice through its anti-apoptotic and anti-inflammatory properties.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that seriously threatens the health of humans globally. Formononetin (FMN) is a natural herb extract with multiple biological functions. In this study, an experimental model of AIH was established in mice through the use of concanavalin A (ConA). To investigate the effects of FMN on ConA-induced hepatitis, the mice were pretreated with 50 or 100 mg/kg body mass of FMN. The results show that FMN alleviated ConA-induced liver injury of mice in a dose-dependent manner. Moreover, pretreatment with FMN inhibited the apoptosis of hepatocytes in the ConA-treated mice through downregulating the expression of pro-apoptotic proteins (Bax, cleaved caspase 9, and cleaved caspase 3) and upregulating the expression of anti-apoptotic protein (Bcl-2). It was also found that the levels of proinflammatory cytokines were greatly reduced in the serum and liver tissues of mice pretreated with FMN. Further studies showed that FMN reduced the level of phosphorylated nuclear factor kappa B (p-NF-κB) p65 and enhanced the level of IκBα (inhibitor of NF-κB), suggesting that FMN inhibits the activation of the NF-κB signaling pathway. In addition, FMN inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Therefore, FMN could be a promising agent for the treatment of AIH.

[Clinical research of refractory ascites of cirrhosis treated with acupoint-penetrating needling technique of acupuncture and enema with tuihuang mixture].

OBJECTIVE: To observe the effects on liver function, portal hemodynamics, plasma nitric oxide (NO), intestinal endotoxin (ETM) and interferon γ (IFN-γ) treated with acupoint-penetrating needling technique of acupuncture and enema with tuihuang mixture in the patients with refractory ascites of cirrhosis. METHODS: A total of 120 patients with refractory ascites of cirrhosis were divided randomly into an observation group and a control group, 60 cases in each one. In the control group, the routine western medicine treatment was applied in combination with enema with tuihuang mixture. In the observation group, on the base of the treatment as the control group, acupoint-penetrating needling technique of acupuncture was added, Zhongwan (CV12) penetrated toward Shuifen (CV9), CV9 toward Qihai (CV6), CV6 toward Guanyuan (CV4) and CV4 toward Zhongji (CV3) respectively. The duration of treatment was 60 days in both groups. The clinical therapeutic effect was analyzed in the patients of both groups. Before and after treatment, the changes in body mass, abdominal circumference, 24 h urine output/week, maximum depth of dark area of ascites, liver function indicators, portal vein hemodynamics, plasma NO, ETM and IFN-γ were observed in the patients of the two groups. RESULTS: The total effective rate was 81.03% (47/58) in the observation group, higher than 63.16% (36/57) in the control group (P<0.05). After treatment, in the self-comparison of each group, the levels of body mass, abdominal circumference, the maximum depth of the dark area of ascites, the main portal vein diameter (Dpv), maximum blood flow velocity (Vmax) and venous blood flow (Q) were all lower than those before treatment (P<0.05), 24 h urine output/week was higher than that before treatment (P<0.05), and every indicator of liver function was improved (P<0.05). After treatment, the values of body mass, abdominal circumference, the maximum depth of the dark area of ascites, Dpv, Vmax and Q in the observation group were all lower than those in the control group (P<0.05), 24 h urine output/week was higher than that in the control group (P<0.05), and the improvement in every indicator of liver function was larger than that in the control group (P<0.05). The levels of plasma NO and ETM after treatment were all lower than those before treatment in both two groups (P<0.05), and the level of IFN-γ was higher than that before treatment (P<0.05). After treatment, the levels of NO and ETM in the observation group were lower than those of the control group and the level of IFN-γ was higher than that in the control group (P<0.05). CONCLUSION: The combined therapy of acupoint-penetrating needling technique of acupuncture and enema with tuihuang mixture effectively improves the effective rate on refractory ascites of cirrhosis, which is related to the decrease of endotoxin and the improvements of portal hemodynamics and cellular immune function.