Xiaochaihu Decoction attenuates the vicious circle between the oxidative stress and the ALP inactivation through LPS-catecholamines interactions in gut, liver and brain during CCI(4)+ethanol-induced mouse HCC

BACKGROUND: Xiaochaihu Decoction (XCHD) prevents hepatocarcinogenesis in association with inhibition of oxidative stress. However, alkaline phosphatase (ALP) activity, lipopolysaccharides (LPS)-catecholamines (CA) interactions in gut, liver and brain may play an important role in the status of oxidative stress. This study was to assess whether XCHD attenuates the vicious circle between oxidative stress and ALP inactivation through LPS-CA interactions. METHODS: Hepatocellular carcinoma group (HCC) were induced by CCI(4) + ethanol; HCC with Liver Depression and Spleen Deficiency (HCC + LDSD) were induced by squeezing tails (30 min/day), solitary breeding and intermittent fasting on the basis of HCC; XCHD was administered after 4 weeks of the HCC + LDSD. The degree of tissue injury were studied using a scoring system, and brain weights were measured. Peroxynitrite (ONOO(−)), malondialdehyde (MDA), 4-hydroxy-3-methoxymandelic acid (VMA, CA metabolites), lipopolysaccharide-phosphate (LPS-P), ALP activity (ALP-A) and Concanavalin A (ConA)-binding rate of ALP (ALP-C) were determined by colorimetric method and lectin (ConA) affinity precipitation method. RESULTS: More injuries and ONOO(−), MDA, VMA, LPS-P, ALP-C were increased, ALP-A were decreased in the gut, liver and brain of HCC group, the most in HCC + LDSD group, after treatment with XCHD, all of which were improved. A positive association found between gut-liver-brain injury and ONOO(−), MDA, VMA, LPS-P, ALP-C, between ONOO(−), MDA, VMA, LPS-P and ALP-C in the gut, liver and brain, and a negative association found between gut-liver-brain injury and ALP-A, between ALP-A and ONOO(−), MDA, VMA, LPS-P, ALP-C in the gut, liver and brain. CONCLUSIONS: XCHD can attenuates the vicious circle between the oxidative stress, nitrosative stress, N-glycan deficiency and inactivation of ALP through LPS-CA interactions in gut, liver and brain.