Regulatory Effect of Gandou Decoction on Wnt/β-catenin Signaling Pathway in Liver of Wilson Model Copper-loaded Rats / 中国实验方剂学杂志

Objective: To investigate the regulatory effect of Gandou decoction (GDD) on Wnt/β-catenin signaling pathway in hepatic tissue of Wilson disease model copper-loaded rats and its potential mechanism. Method: One hundred and fifteen SD rats were randomly divided into the normal group (n=20) and modeling group. Modeling group was given copper sulfate feed (1 g·kg-1·d-1) and 0.185%copper sulfate solution (0.02 mL·g-1·d-1) for 12 weeks after one week's adaptive feeding, so as to build the copper loaded rats model. After modeling, 95 model rats were randomly divided into model group (n=45), which were fed by modeling method for continuously four weeks; GDD group and penicillamine (PCA) group (n=25 per group). GDD group and PCA group were given GDD(0.4 g·kg-1·d-1) and PCA (0.09 g·kg-1·d-1) by gavage for four weeks. The hepatic tissues of rats in each group were removed after final medication for further research:inductively coupled plasma-atomic emission spectrometry(ICP-AES) was used to detect the content of Cu element in rat livers. Htoxylin eosin(HE) staining was used to detect the pathological changes of rat liver. Immunohistochemistry was used to detect expression of oxidative stress. Western blot was used to detect protein expressions in Wnt/β-catenin of rat livers. Result: Compared with model group, content of Cu element in GDD group was less (PPPβ-catenin, p-glycogen synthase kinase-3β(p-GSK3β),cellular myelocytomatosis oncogene (c-Myc) in GDD and PCA group increased, while p-β-catenin, Dishevelled3, GSK3β protein expressions reduced (PConclusion: GDD can relieve liver damage by promoting excessive copper discharge. GDD decoction can promote the compensatory self-healing of the injured liver tissue by activating Wnt/β-catenin signaling pathway in the hepatic tissue of Wilson disease model copper-loaded rats, so as to reduce the therapeutic effect of hepatocellular injury induced by high copper.

Research Progress of Therapeutic Mechanism of Gandou Decoction in Treatment of Wilson's Disease / 中国实验方剂学杂志

Wilson disease (WD) is a treatable neurological inherited disorder characterized by copper metabolism impairment. Metal chelating drugs, such as penicillamine, have been used to treat WD for decades, is exposuring its limitations of effect and utilize sphere. Genetic therapy was considered as the most potential way of curing WD, is still can only be achieved in the laboratory, which have massive problems to solve before its clinical utilization. Based on this, we started to research the curative mechanism of traditional Chinese medicine(TCM) donated by national natural science fund project funding, found that TCM formula Gandou decoction regulate the metabolic disorders caused by liver cells and neurons apoptosis, autophagy, such as programmed cell death,from the molecular pathways of copper metabolism, Wnt/β-catenin pathway and mitogen-activated protein kmase(MAPK) pathways regulating liver damage such as cell signaling pathways, extracellular signal-regulated kinase(ERK) pathway and liver kinase B1(LKB1)/adenosine monophosphate activated protein kinase(AMPK) pathway and the cell signaling pathway of neuronal damage. The above experimental results were verified by TX mice, a reliable WD animal models. This paper aimed to systematically review the research of GDD therapeutic mechanisms from the sight of programmed cell death, including aptosis and autophagy, and provided theoretical for formula optimization. In addition, we elaborated some assumptions and feasible advice for the further research of GDD therapeutic mechanism.

Effect of Gandou Decoction IV combined with short-term decoppering therapy with sodium dimercapto-sulphonate on serum indexes of hepatic fibrosis in patients with Wilson' s disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Gandou Decoction IV (GDIV) on serum indexes of hepatic fibrosis and liver function in patients with Wilson's disease (WD).</p><p><b>METHODS</b>Sixty-one WD patients were assigned to two groups, 30 patients in the sodium dimercaptosulphonate (DMPS) group and 31 patients in the GD IV group. Both groups received 8 courses of DMPS treatment with 6 days as one course, and the GD IV group was given GD IV additionally. Serum indexes of liver function were examined, serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by double antibody sandwish ABC enzyme-linked immunosorbent assay (ELISA), and serum hyaluronic (HA), laminin (LN), procollagen III (PC III) and collagen type IV (C-IV) were determined by radioimmunoassay (RIA).</p><p><b>RESULTS</b>After treatment, all indexes of hepatic fibrosis and liver function had no significant change in the DMPS group, while in the GD IV group, the serum TIMP-1 level markedly decreased (P <0.05), the ratio of MMP-1/TIMP-1 significantly increased (P <0.01), and serum indexes of liver function markedly decreased (P < 0.05), but the changes in serum levels of HA, LN and PCIII, as well as in serum MMP-1 and C-IV were insignificant (P> 0.05), though they showed a trend of decreasing or increasing, respectively.</p><p><b>CONCLUSION</b>Short-term decopper-ing treatment with DMPS alone has no significant effect on hepatic function and serum fibrosis indexes in WD patients, while combined with GD IV, it can improve liver function and display an anti-fibrosis effect through inhibiting the serum TIMP-1 level and increasing the ratio of MMP-1/TIMP-1.</p>

Effect of gandou tablet I on neurological electrophysiology in patients of hepatolenticular degeneration / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the influence of Gandou Tablet I (GD I) on neurologic electrophysiology in patients of hepatolenticular degeneration (HLD).</p><p><b>METHODS</b>Vigilance-controlled electroencephalogram (VEEG), electromyogram (EMG) and brain-stem auditory evoked potential (BAEP) in 32 cases of HLD were examined before GD I treatment, and reexamined after 4 weeks of treatment in those with abnormal neurologic electrophysiology.</p><p><b>RESULTS</b>At the same time of clinical symptom improvement after treatment, the abnormal VEEG, EMG and BAEP also improved with the effective rate of 71.43%, 70% and 66.67% respectively, their constitutional ratio were different insignificantly, P > 0.05. The peak latency (PL) of III, V waves and interpeak latency (IPL) of I-III, III-V and I-V waves in patients before treatment were all greatly prolonged, compared with those in the healthy control group (P < 0.05 or 0.01), the IPL of III-V and I-V waves were markedly improved after treatment.</p><p><b>CONCLUSION</b>Neurologic electrophysiologic examination was valuable for complementary diagnosis and therapeutic effect evaluation of HLD. GD I could improve the abnormal neurologic electrophysiologic parameters.</p>