Guanxin Danshen Formulation improved the effect of mesenchymal stem cells transplantation for the treatment of myocardial infarction probably via enhancing the engraftment.

Although intravenous injection is the most convenient and feasible approach for mesenchymal stem cells (MSCs) delivery, the proportion of donor stem cells in the target myocardium after transplantation is small. It is believed that TCM enhances the effect of stem cell therapy by improving the hostile microenvironment and promoting the migration and survival of stem cells. Guanxin Danshen (GXDS) formulation is one of the main prescriptions for clinical treatment of ischemic heart diseases in China. The purpose of this study was to evaluate the effects of GXDS formulation administration combined with MSCs transplantation on cardiac function improvement, apoptosis, angiogenesis and survival of transplanted cells in an acute model of acute myocardial infarction (MI). After being labeled with GFP, MSCs were transplanted via intravenous injection. Meanwhile, GXDS dripping pills were given by intragastric administration for 4 weeks from 2 days before MI. Echocardiography showed moderate improvement in cardiac function after administration of GXDS formulation or intravenous transplantation of MSCs. However, GXDS formulation combined with MSCs transplantation significantly improved cardiac function after MI. The myocardial infarct size in rats treated with MSCs was similar to that in rats treated with GXDS formulation. However, GXDS formulation combined with MSCs transplantation significantly reduced infarction area. In addition, GXDS formulation combined with MSCs transplantation not only decreased cell apoptosis according to the TUNEL staining, but also enhanced angiogenesis in the peri-infarction and infarction area. Interestingly, the use of GXDS formulation increased the number of injected MSCs in the infarct area. Furthermore, GXDS formulation combined with MSCs transplantation increased SDF-1 levels in the infarcted area, but did not affect the expression of YAP. Our study provided a more feasible and accessible strategy to enhance the migration of stem cells after intravenous injection by oral administration of GXDS formulation. The combination of GXDS formulation and stem cell therapy has practical significance and application prospects in the treatment of ischemic cardiomyopathy such as MI.

[Effect of lycopene on oxidative stress and behavioral deficits in rotenone induced model of Parkinson's disease].

OBJECTIVE: To investigate the neuroprotective potential of lycopene on oxidative stress and neurobehavioral abnormalities in rotenone induced Parkinson' disease (PD). METHODS: Forty adult C57BL/6 mice were randomly divided into four groups (n = 10): control, lycopene (10 mg/kg body weight, orally), rotenone (3 mg/kg bw, intraperitoneally) and rotenone plus lycopene, which were sacrificed for 5 weeks. The spectrophotometry was used to determine the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and the content of malondialdehyde (MDA) in substantia nigra and right striatum. At the same time, the number of tyrosine hydroxylase (TH), alpha-synuclein (alpha-SYN) and microtubule-associated protein 3 light chain (LC3-B) positive neurons were estimated by immunohistochemistry. We also examined neurobehavioral abnormalities by WT-200 water maze. RESULTS: Rotenone administration increased the MDA levels and significantly decreased the activities of SOD, GSH-Px and CAT. However, lycopene administration to the rotenone treated animals increased the activities of SOD, GSH-Px and CAT when compared to rotenone treated animals in substantia nigra and right striatum. The cognitive and motor deficits in rotenone administered animals, which were reversed on lycopene treatment. Along with this, the number of TH decreased, alpha-SYN increased and LC3-B positive neurons increased in rotenone administered animals, which were reversed on lycopene treatment. CONCLUSION: Collectively, these observations provide an evidence for beneficial effect of lycopene supplementation in rotenone-induced PD and suggest therapeutic potential in neurodegenerative diseases involving accentuated oxidative stress.

[Zinc supplementation effects on alcoholic liver disease and the molecular mechanism].

OBJECTIVE: To examine dietary zinc supplementation could alleviate the damage of alcoholic liver disease and the relationship with the expression of hepatocyte nuclear factor 4alpha (HNF-4alpha). METHODS: 40 adult C57 BL/6 mice were randomly divided into four groups (n = 10): control, zinc, ethanol and zinc plus ethanol, which were sacrificed after fed four different diets for 6 months. Zinc sulfate was added in the drinking water of the Zinc and Zinc Plus Ethanol group and the content was 75 mg/L. Liver regeneration was assessed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA), and the expression of HNF-4alpha was determined by RT-PCR and Western blot. And as to assess the status of oxidative stress of the mice, malondialdehyde (MDA) and superoxide dismutase (SOD) were detected. RESULTS: Compared with the control group, the expression level of HNF-4alpha decreased significantly in the ethanol group (P < 0.05), and the content of MDA increased significantly in this group, while the content of SOD declined significantly (P < 0.05). Compared with the ethanol group, the number of PCNA-positive hepatocytes increased significantly, and the expression level of HNF-4alpha also increased in the zinc plus ethanol group (P < 0.05), and the content of SOD increased in this group, while MDA decreased significantly (P < 0.05). CONCLUSION: Long term ethanol exposure can lead to oxidoreduction imbalances which can be reversed by zinc supplementation. We suppose that zinc-enhanced liver regeneration is associated with an increase in HNF-4alpha, suggesting that dietary zinc supplementation may have beneficial effects in alcoholic liver disease.

[Effects of α-lipoic acid and vitamin C on oxidative stress in rat exposed to chronic arsenic toxicity].

OBJECTIVE: To explore arsenic-induced oxidative stress and the protective efficacy of α-lipoic acid and vitamin c. METHODS: 50 male SD rats were randomly divided into 5 groups. Ten rats (the control group) were exposed to deionized water for 6 weeks, and the others were alone exposed to sodium arsenite (50 mg/L water) for 6 weeks, at the same time, three group rats were administered intragastrically (i.g.) with α-lipoic acid 10 mg×kg(-1)×d(-1) and vitamin C 25 mg×kg(-1)×d(-1) either alone or in combination. At the end of experiment, blood was drawn from abdominal aorta, and then the blood, brain and liver of rats were used for biochemical assays, including blood glutathione (GSH), δ-aminolevulinic acid dehydratase (δ-ALAD ), reactive oxygen species (ROS) and oxidized glutathione (GSSG) level. At the same time, the super oxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, catalase (CAT) activity, ATPase activity of brain and liver were determined. The caspase activity of brain were also determined. RESULTS: There were a significant increase in ROS level (P < 0.05), but a significant decrease in δ-ALAD activity (P < 0.01) in the chronic arsenic toxicity model group compared with the control group. These alterations were marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite in rat (P < 0.05). At the same time, there was a significant increase in the ROS and TBARS level of the brain and liver (P < 0.05), and caspase activity of the brain (P < 0.05), while there was a significant decrease in antioxidant enzymes and ATPase activity on arsenite exposure in rats (P < 0.05). These alterations were also marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite in rat (P < 0.05). CONCLUSIONS: Arsenite-induced oxidative stress can be significantly protected by co-administration of α-lipoic acid and vitamin C individually, but the best effects could be observed with combined administration of two antioxidants during arsenite exposure in animals. The dietary intervention of or supplementation with natural dietary nutrients is possible to prevent the effects of arsenic in populations of risk.