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Objective: To study inhibitory effect of total flavonoids from Ampelopsis grossedentata (TF) on transplanted tumors of human hepatocellular carcinoma in nude mice, and predict that its mechanism may be related to relevant factors regulating phosphatidylinositol 3 kinase (PI3K)/protein kinases B(Akt)/p53 pathway in apoptosis. Method: The nude mice transplanted BEL-7404 hepatoma model was established and divided into model group, 5-fluorouracil (5-FU) group (1.0 g·L-1) and TF (30, 15, 7.5 g·L-1) groups. Nude mice were put to death after two weeks of administration. The tumor tissues were excised, and tumor inhibition rate (IR) and relative tumor proliferation rate (T/C) were calculated. Reverse transcription PCR(RT-PCR) was used to detect PI3K, Akt1, p53 gene(p53), Caspase-3, B cell lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) mRNA expressions, immunohistochemical method was used to detect expressions of relevant proteins PI3K, Akt1, p53, Caspase-3, Bcl-2, Bax. Result: The establishment of xenograft tumor in mice showed that TF was administered orally once per day for two consecutive weeks. IRs were 53.26%, 35.94%, and 26.74%, respectively. T/Cs were 59.74%, 69.66%, and 84.82%, respectively. RT-PCR experiments showed that compared with model group, when TF concentration was 30 g ·L-1, mRNA expressions of PI3K, Akt1, and Bcl-2 were significantly down-regulated, and mRNA expressions of tumor suppressor genes p53, Capsase-3, and Bax were significantly up-regulated. Immunohistochemical method results showed that compared with model group, at TF concentrations of 30, 15 g·L-1, all PI3K, Akt1, Bcl-2 protein expressions were significantly down-regulated, while p53, Capsase-3, Bax protein expressions were significantly increased. Conclusion: TF has an obvious anti-liver cancer activity in vivo. Its mechanism may be correlated with up-regulation of expressions of p53, Caspase-3, and activation of apoptosis PI3K/Akt/p53 pathway, thereby inhibiting Bcl-2, increasing expression of Bax, and promoting hepatocellular apoptosis.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) on insulin signaling pathway in liver tissues of central neuronal specific signal transduction and activator of transcription 5 conditional-knockout (Stat 5 NKO) mice, so as to explore its mechanism underlying improvement of insulin resistance (IR)．. METHODS: Twenty-four male Stat 5 NKO mice were randomly divided into model and EA groups (n＝12 mice/group), and 12 Stat 5 fl/fl mice were used as the normal control group. EA (2 Hz/15 Hz, 0.8－1.0 mA) was alternatively applied to ipsilateral "Zusanli" (ST 36) and "Neiting" (ST 44) for 20 min, once a day, 6 times a week for 4 weeks. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, and the values of fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by glucometer and ELISA, separately. The insulin sensitivity index (ISI) was calculated. The phosphorylation protein expressions of insulin receptor substrate 1 (IRS 1), insulin receptor β (IRβ) and protein kinases B (Akt) in the liver tissues were detected by Western blot. RESULTS: In Stat 5 NKO mice (model group), FPG level and glucose area under the curve (GAUC) of ITT and GTT were significantly increased (P0.05). Compared with the normal group, the protein expression levels of liver p-IRS 1 and p-IRβ were significantly up-regulated (P<0.001), and the p-Akt expression was significantly down-regulated (P<0.01) in the model group. Following EA treatment, the increased p-IRS 1 and p-IRβ protein expression and the decreased p-Akt expression were apparently reversed in the EA group relevant to the model group (P<0.001, P<0.01)．. CONCLUSION: EA can improve the IR induced by central neuronal Stat 5-knockout in mice, which may contribute to its effectiveness in regulating hepatic IRβ/IRS 1/Akt signaling pathway.
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This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor (TGR5), farnesoid X receptor (FXR), ursodeoxycholic acid (UDCA) and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids, we will expand the review and include sections that are most recently known (within 5-7 years) regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events.