ABSTRACT
There are presently no miracle drugs for non-alcoholic fatty liver disease (NAFLD). This study investigates the synergistic effect of Silibinin combined with Pu-erh tea extract (PTE) against NAFLD and explores the suggested mechanism of action. Ob/ob mice were fed a high fat diet along with the oral administration of Silibinin (86 mg per kg per day), PTE (250 mg per kg per day) or their combination for 6 weeks. Their lean littermates who were fed with standard chow diet were used as the control group. The blood biochemical index and histopathological evaluation were analyzed. The expression of genes involved in the lipogenesis pathway and cholesterol metabolism were evaluated. When compared with that of the NAFLD group, the body weight and blood lipid of the mice from the PTE group or combination group were significantly reduced. To some degree, fat metabolism and the inflammatory response were ameliorated by Silibinin and PTE used alone or in combination. It was notable that the combination group had a stronger efficacy in adjusting fat metabolism and inhibiting oxidative stress than that of Silibinin or PTE used alone. Silibinin and PTE inhibited fat synthesis by regulating the mRNA expression of CRTC2, SREBP-1c, and SCD-1. Moreover, the cholesterol homeostasis was improved in the treatment groups via regulating the mRNA expression of ABCA1 and ApoB100. The improvement of the combination group was superior to each drug used alone. In conclusion, Silibinin in combination with PTE can prevent NAFLD with greater potential than Silibinin or PTE used alone and may be a new therapeutic strategy.
Subject(s)
Camellia sinensis/chemistry , Non-alcoholic Fatty Liver Disease/prevention & control , Plant Extracts/administration & dosage , Silymarin/administration & dosage , Animals , Disease Models, Animal , Humans , Lipid Metabolism/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Oxidative Stress/drug effects , Silybin , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Tea/chemistry , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Ischemic stroke is one of the most common causes of death and disability that is induced by ischemia reperfusion (IR). Granulocyte adherence has been proven to be a principal cause of IR. Salvianolic acid A (Sal A) is one of the major active components of Danshen, a Chinese herbal medicine used for the treatment of cardiovascular and cerebrovascular diseases, such as ischemic stroke. Some experimental studies have shown the strong cerebral protection effect of Sal A. However, little information is available about the effect of Sal A on granulocyte adherence to brain micro-vascular endothelial cells (BMEC). Therefore, the aim of the present study was to investigate the effect of Sal A on the leukocyte adhesion rate and the intercellular cell adhesion molecule-1 (ICAM-1) expression in BMEC injured by hypoxia/reoxygenation (H/R), using a rheometer, qRT-PCR, and flow cytometry (FCM). The results of the adhesion rate gathered by the rheometer showed that Sal A could remarkably inhibit the adherence of granulocytes on BMEC in the case of H/R injury. Moreover, PCR and FCM results showed that Sal A could decrease the expression of ICAM-1 on BMEC on the gene and protein levels. In conclusion, the study demonstrated that the inhibition of granulocyte adherence is one of the targets of Sal A in the treatment of ischemic stroke. Meanwhile, Sal A inhibits of granulocyte adherence by decreasing the expression of ICAM-1 in BMEC.
