Babaodan cures hepatic encephalopathy by decreasing ammonia levels and alleviating inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Babaodan (BBD), a famous traditional Chinese medicine used in clinic, has a strong effect on eliminating jaundice, awakening and enlightening the mind. This paper assesses the preventive and therapeutic effect of BBD on hepatic encephalopathy after liver cirrhosis (CHE) and acute liver failure (AHE) in rats and explains its possible mechanism.

METHODS: The establishment of CHE and AHE rat models: hepatic fibrosis and acute liver failure rat model established by injection of carbon tetrachloride (CCl4 ) were pretreated with BBD and then induced into hepatic encephalopathy by injection of thioacetamide (TAA). Preventive and therapeutic effect of BBD on brain dysfunction, liver injury, pathology and fibrosis were evaluated in vivo. The role of BBD in the regulation of inflammatory factors and myeloid differentiation factor 88/Toll-like receptor 4/nuclear factor kappa-B (TLR4/MyD88/NK-κ B) pathway were detected in both liver and brain in vivo. The rat BMDMs were activated by Lipopolysaccharide (LPS) and the role of BBD in regulation of inflammatory factors and NK-κ B pathway were detected in vitro.

RESULTS: In CHE rat model: the total distance and activity rate of the rats with the low dose BBD (BL), high dose BBD (BH) and Lactulose (L) groups significantly improved, and the BH group improved most obviously. BBD can effectively reduce ammonia levels. The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and total bile acid (TBA) in CHE rats after BBD intervention were significantly lower, and TP and Alb levels were significantly higher. In the liver, BBD not only inhibited the gene expression of tumor necrosis factor alpha (TNF-a), interleukini-6 (IL-6), TLR4, MyD88, and NF-κ B, but also inhibited the protein expression of TLR4, MyD88, NK-κ B and TNF-a. In the brain, BBD inhibited the gene expression of iNOS, IL-6, TNF-a, TLR-4, M yD88, and NF-κ B, as well as inhibited the protein expression of TLR4, MyD88, P65 TNF-α and ionized calcium binding adapter molecule 1 (Iba-1). In the blood, NO and TNF-α were also improved by BBD. In AHE rats model: BBD improved neurological score and blood ammonia and inhibited brain inflammatory gene expression of iNOS, TNF-α and IL-1β. BBD also improved liver function markers such as ALT, AST, TBiL, TBA, TP, Alb and inhibited inflammatory and apoptotic gene expression of genes such as TNF-α, IL-1β, IL-6, Bax, Bcl-2, caspase-9, caspase-3 and NF-κ B. In LPS-activated rat bone marrow-derived macrophages (BMDM), BBD decreased NO and TNF-α production in BMDM culture supernatant. In addition, BBD inhibited the gene expression of TNF-α, IL-1 β and IL-6 as well as the phosphorylation of P65.

CONCLUSION: BBD could prevent and cure hepatic encephalopathy derived from both chronic and acute liver diseases. Here, we found that except for the direct improvement of blood and brain ammonia level, inflammation is likely an important target of BBD to treat hepatic encephalopathy. The anti-inflammatory role of BBD may lie in its regulation of the TLR4/MyD88/NF-κ B pathways.