Babao Dan improves neurocognitive function by inhibiting inflammation in clinical minimal hepatic encephalopathy.

BACKGROUND AND PURPOSE: Inflammation has been considered a precipitating event that contributes to neurocognitive dysfunction in minimal hepatic encephalopathy (MHE). Inhibition TLR-4 related inflammation can effectively improve neurocognitive dysfunction of MHE. Our previous study showed that Babao Dan (BBD) effectively inhibited inflammation and ameliorated neurocognitive function in rats with acute hepatic encephalopathy (HE) and chronic HE. The mechanism may lie in the regulation of TLR4 signaling pathway. Therefore, this study aimed to evaluate the role of BBD in the treatment of MHE patients with cirrhosis and to elucidate the underlying mechanism by which BBD regulated TLR4 pathway to alleviate inflammation. METHODS: A randomized controlled trial (n = 62) was conducted to evaluate the clinical efficacy between BBD plus lactulose (n = 31) and lactulose alone (n = 31) in MHE patients by testing neurocognitive function (NCT-A and DST), blood ammonia, liver function (ALT, AST and TBIL) and blood inflammation (IL-1ß, IL-6 and TNF-α). Afterward, we detected NO, inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and the phosphorylation of P65, JNK, ERK as well as P38 in LPS-activated rat primary bone marrow-derived macrophages (BMDMs), peritoneal macrophages (PMs), and mouse primary BMDMs/PMs/microglia/astrocytes, to investigate the underlying mechanism of BBD inhibiting inflammation through TLR4 pathway. Also, the survival rate of mice, liver function (ALT, AST), blood inflammation (IL-1ß, IL-6 and TNF-α), inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and histopathological changes in the liver, brain and lung were measured to assess the anti-inflammatory effect of BBD on neurocognitive function in endotoxin shock/endotoxemia mice. RESULTS: BBD combined with lactulose significantly ameliorated neurocognitive function by decreasing NCT-A (p＜0.001) and increasing DST (p＜0.001); inhibited systemic inflammation by decreasing IL-1ß (p＜0.001), IL-6(p＜0.001) and TNF-α (p＜0.001); reduced ammonia level (p = 0.005), and improved liver function by decreasing ALT(p = 0.043), AST(p = 0.003) and TBIL (p = 0.026) in MHE patients. Furthermore, BBD inhibited gene and protein expression of IL-1ß, IL-6 and TNF-α as well as NO in rat primary BMDMs/PMs, and mouse primary BMDMs/PMs/microglia/astrocytes in a dose-dependent manner. BBD inhibited the activation of mouse primary BMDMs/PMs/microglia/astrocytes by regulating TLR4 pathway involving the phosphorylation of P65, JNK, ERK and P38. Also, BBD reduced the mortality of mice with endotoxin shock/endotoxemia; serum levels of ALT, AST, IL-1ß, IL-6 and TNF-α; gene expression of IL-1ß, IL-6 and TNF-α in the liver, brain and lung, and tissue damage in the liver and lung. CONCLUSION: Our study provided for the first time clinical and experimental evidence supporting the use of BBD in MHE, and revealed that BBD could play a crucial role in targeting and regulating TLR4 inflammatory pathway to improve neurocognitive function in MHE patients.

Therapeutic mechanism of Yin-Chén-Hao decoction in hepatic diseases.

Yin-Chén-Hao decoction (YCHD) is a traditional Chinese medicine formula composed of capillaris (Artemisia capillaris), gardenia (Gardenia jasminoides), and rhubarb (Rheum rhabarbarum) that is used for the treatment of damp-heat jaundice. In modern clinics, YCHD is mostly used for hepatic diseases. This review summarizes the biological activities of YCHD and its medical applications. The main active compounds of YCHD are chlorogenic acid, rhein, geniposide, emodin, and scoparone. The pharmacological actions of YCHD include inhibition of hepatic steatosis, apoptosis, necrosis, anti-inflammation, and immune regulation. YCHD could be developed as a new therapeutic strategy for the treatment of hepatic diseases.

Research Progress on the Antitumor Effects of Rhein: Literature Review.

BACKGROUND: Rhein (1,8-dihydroxy-3-carboxyanthraquinone) is a monomer of anthraquinone derivatives mainly found in Polygonaceae plants such as Rhubarb, and Cuspidatum, widely used in the traditional Chinese medicine with many pharmacological activities, such as antitumor, anti-inflammatory and antifibrotic effects, and regulation of glucose and lipid metabolism. OBJECTIVE: To conclude the role of Rhein in cancer control and its mechanisms for its futher deep research and potential clinical application. METHOD: All kinds of reports previously related to Rhein from PubMed datebase were collected, integrated and analyzed. RESULTS: Rhein could control many cancer cells by regulating their proliferation and apoptosis, invasion and migration, especially intrinsic and extrinsic apoptosis pathways induced by Rhein plays the core role in cancer control. For good inhibitory role in NF-κB pathway, the Ras/Raf/MEK (MAPK)/ERK and PTEN/PI3K/AKT/mTOR pathways are other two key pathways regulated by Rhein with its role in antiphosphorylation of ERK, PI3K and AKT to control many cancers' development which frequently dysregulated in cancer, involved in the activation, proliferation, invasion, and migration of cancer cells. CONCLUSION: Rhein is a potential cancer treatment agent.