Effects of Chinese medicinal herbs on expression of brain-derived Neurotrophic factor (BDNF) and its interaction with human breast cancer MDA-MB-231 cells and endothelial HUVECs.

BACKGROUND: Our previous study demonstrated that an up-regulation of the Brain-Derived Neurotrophic Factor (BDNF) signaling pathway is involved the mechanism causing the recurrence of triple negative breast cancer. The aim of this study is to investigate the effects of commonly used Chinese medicinal herbs on MDA-MB-231 and HUVEC cells and how they interact with BDNF. METHODS: Human TNBC MDA-MB-231 cells and human endothelial HUVEC cells were used to explore the effect of commonly used Chinese herbal medicines on cancer cells alone, on endothelial cells alone and on cancer cell/endothelial cell interactions; this was done via functional studies, including migration and invasion assays. Furthermore, Western blot analysis and real-time PCR investigations were also used to investigate migration signal transduction, invasion signal transduction, and angiogenic signal transduction in these systems. Finally, the effect of the Chinese medicinal herbs on cancer cell/endothelial cell interactions was assessed using co-culture and ELISA. RESULTS: In terms of autoregulation, BDNF up-regulated TrkB gene expression in both MDA-MB-231 and HUVEC cells. Furthermore, BDNF enhanced migration by MDA-MB-231 cells via Rac, Cdc42 and MMP, while also increasing the migration of HUVEC cells via MMP and COX-2 expression. As measured by ELISA, the Chinese herbal medicinal herbs A. membranaceus, P. lactiflora, L. chuanxiong, P. suffruticosa and L. lucidum increased BDNF secretion by MDA-MB-231 cells. Similarly, using a co-culture system with MDA-MB-231 cells, A. membranaceus and L. lucidum modulated BDNF-TrkB signaling by HUVEC cells. CONCLUSION: We conclude that BDNF plays an important role in the metastatic interaction between MDA-MB-231 and HUVEC cells. Some Chinese medicinal herbs are able to enhance the BDNF-related metastatic potential of the interaction between cancer cells and endothelial cells. These findings provide important information that should help with the development of integrated medical therapies for breast cancer patients.

[Efficacy of Zaozhu Yinchen Recipe for Treating Non-alcoholic Steatohepatitis and its Effect on Free Fatty Acid and TNF-alpha].

OBJECTIVE: To observe the efficacy of Zaozhu Yinchen Recipe (ZZYCR) on non-alcoholic steatohepatitis (NASH) patients, and to explore its effect on serum free fatty acid (FFA) and tumor necrosis factor alpha (TNF-alpha). METHODS: Totally 120 patients with NASH were randomly assigned to the treatment group (60 cases, treated with ZZYCR, one dose per day) and the control group (60 cases, treated with Silibin Meglumine Tablets, 20 mg each time, thrice per day). The therapeutic course for all was 24 weeks. Serum levels of ALT and AST activities, TC and TG levels were detected before and after treatment. Peritoneal CT was performed in all patients, and CT ratios of liver and spleen calculated. NAFLD activity score (NAS) and degree of hepatic fibrosis were assessed using pathological examinations of liver tissue, and efficacy also evaluated. Serum contents of FFA and TNF-alpha were also detected. RESULTS: Compared with before treatment in the same group, activities of ALT and AST, serum levels of TC, TG, FFA, and TNF-alpha, NAS, scores of symptoms and signs all obviously decreased, degree of hepatic fibrosis was obviously improved in the two groups (P < 0.05, P < 0.01). These changes were more obviously seen in the treatment group (P < 0.05). After 24-week treatment, the total effective rate and total clinical efficacy were 80.00% (48/60 cases) and 85.00% (51/60 cases) in the treatment group, obviously higher than those in the control group [60.00% (36/60 cases) and 73.33% (44/60 cases) respectively], with significant difference (P < 0.05, P < 0.01). CONCLUSION: ZZYCR could improve the clinical efficacy of NASH patients, and its mechanism might be associated with inhibiting serum levels of FFA and TNF-alpha.

[Mechanism of geniposide in improving free fatty acid metabolism in rats with non-alcoholic fatty liver disease].

To observe the effect of geniposide on non-alcoholic fatty liver disease (NAFLD), and discuss the mechanism of geniposide for NAFLD from the aspect of free fatty acid, forty healthy Wistar male rats were randomly divided into normal group, model group, geniposide and Xuezhikang group. The rats in normal group were fed with normal diets, and the rats in other 3 groups were given with high-fat diet for 8 weeks to induce the NAFLD models. From the week 5 to end of week 8, the rats in geniposide and Xuezhikang group were intervened with corresponding medicines. The body weight, liver wet weight, and fat weight of the rats were recorded. Visual and pathological changes in hepatic tissues were observed with HE staining. The contents of TG, FFA, FAS, AMPK, ACCase and Malonyl-CoA in hepatic tissue, contents of CHO and LDL-C in serum and activities of AST and ALT in serum were detected by using corresponding methods. The results showed that the body weight, liver wet weight, and fat weight of the rats, CHO, LDL-C, ALT and AST levels in serum, TG, FFA, FAS, ACCase and Malonyl-CoA levels in hepatic tissues of the rats in model group were significantly higher than those in normal group (P<0.01), while AMPK activity was significantly lower than that of the normal group (P<0.01), with obvious visual and pathological steatosis in hepatic tissues, and inflammatory injury occurred in model group. Compared with the model group, body weight of the rat, fat weight, levels of FFA in hepatic tissues, ALT and AST activities in serum, liver wet weight, TG, FAS, ACCase and Malonyl-CoA levels were significantly decreased in geniposide group (P<0.01), while the AMPK activity in hepatic tissues was significantly increased (P<0.05),with improvement in visual and pathological performance. Compared with the model group, liver wet weight, fat weight, TG and FFA levels in hepatic tissues, and LDL-C level in serum were significantly decreased in Xuezhikang group (P<0.05). Compared with Xuezhikang group, the body weight of rat, fat weight and FFA level in hepatic tissues were significantly lower in geniposide group (P<0.01), but with no significant difference in other aspects. These findings indicated that geniposide was highly effective in improving the pharmacological effect of NAFLD induced by high-fat diet, and the mechanism was achieved through AMPK-ACCase-Malonyl-CoA-FFA axis.

Study on effects of zhi zi (fructus gardeniae) on non-alcoholic fatty liver disease in the rat.

OBJECTIVE: To investigate the effects of Zhi Zi (Fructus Gardeniae) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet in the rat. METHODS: A rat model of NAFLD was established using a high-fat diet. Twenty one rats were randomly divided into a normal group, a model group and a Zhi Zi treatment group, 7 rats per group. Drinking water and the drug were intragastrically administrated for 5 weeks. Samples were then taken to observe pathological changes of the liver tissue (HE staining); changes in the fat metabolism pathway e. g. triglyceride (TG) and free fatty acid (FFA) content; alterations in liver function, i.e. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity; and differences in tumor necrosis factor alpha (TNF-alpha) and P-IkB protein expression in the liver tissue. RESULTS: Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group. Markers for fat metabolism, serum ALT and AST activities, and expression of TNF-alpha and P-IkB proteins in liver tissue significantly increased. Fat metabolism in the Zhi Zi group significantly reduced, as shown by a drop in marker levels. Serum ALT and AST activities, and expression of TNF-alpha, P-IkB proteins in liver tissue were also significantly decreased in this group. CONCLUSION: Zhi Zi has a very strong inhibitory action on lipidosis and inflammatory injury in the rat model of NAFLD. This mechanism may possibly be related to the inhibition of the free fatty acid metabolism pathway.