Intervention of total saponins of Panax japonicas on non-alcoholic steatohepatitis in mice by regulating miR-199/SIRTl/MFN2 / 中国药理学通报

Aim To discuss the effect of miR-199/ SIRT1/MFN2 signaling pathway on the progression of NASH and its related mechanisms.Methods 45 BALB/e mice were randomly divided into normal group, high fat diet(HFD) group, total saponins of panax japonicas ( TSPJ ) low-dose group ( 15 mg • kg-1) and TSPJ high-dose group (45 mg • kg"1 ).Normal group was given normal diet, while HFD group, TSPJ low-dose and high-dose groups were given high-fat diet.The mice were intragastrioally given 15 and 45 mg 'kg"1 TSPJ (dissolved in saline) daily in TSPJ low-dose and high-dose groups, while those in other groups were intragastric ally given the same a- mount of saline daily.After seven months, they were sacrificed for serum collection and hepatic tissue col¬lection.Results HE staining showed that liver lipido¬sis and inflammation were obvious in HFD group.while liver lipidosis anrl inflammation were alleviated in TSPJ group.MFN2 and SIRT1 levels significantly de¬creased.TNF-a, 1L-1 p , SREBP, ChREBP levels sig¬nificantly increased in HFD group.After treated with TSPJ, SIRT1 and MFN2 levels were significantly up- regulated , while TNF-a, IL-ip, ChREBP and SREBP levels were significantly down-regulated.The Immuno¬fluorescence results showed that the fluorescence inten¬sity of MFN2 and SIR 11 increased in TSPJ low-dose and high-dose groups.At mRNA level, miR-199 had a negative regulatory relationship with SIRT1.Conclu¬sions TSPJ can alleviate NASH induced by high fat diet through miR-199/SIRTl/MFN2 signaling path¬way.

A mathematical model for quality evaluation of total saponins of Panax japonicas based on hypolipidemic activity / 中草药·英文版

Objective: The chemical finger printing-based methods for evaluating TCMs quality can report partial of TCMs quality without linking to effective constituents. In this study, a mathematical model was established for the quality evaluation of total saponins of Panax japonicus (TSPJ), a folk medicine in China and Japan for treating diseases, through coupling the dynamic changes of chemical constitutions with corresponding activities. Methods: High-performance liquid chromatography (HPLC) fingerprints were applied to establish the chromatographic database of TSPJ. The associated hypolipidemic activity database was determined by TG assay using HepG2 cell model. Correlation analyses of two databases were performed by partial least squares (PLS) for calculating regression coefficients, and the interval value of YZL value (the ratio of positive and negative peak-to-peak area coefficient) closely related to hypolipidemic activity was refined by the formula of Norminv function to value the quality of TSPJ. Results: In this study, the chromatographic data of 16 common peaks were obtained from 20 batches of TSPJ. After the estimate by this mathematical evaluation model, seven peaks were positively correlated with hypolipidemic activity, and nine peaks were negatively correlated with hypolipidemic activity. When the YZL value was less than 0.7861, the quality of sample was inferior, while YZL value was more than 6.6992, and the quality of samples was superior. The quality of another ten batches of TSPJ was further assessed to verify this method. Conclusion: These results indicated that the established model could be usefully applied to evaluate the quality of TSPJ in the hypolipidemic activity.

Protective mechanism of saponins of Panax Japonicus on high-fat diet induced reproductive dysfunction in mice / 中国药理学通报

Aim To investigate the effects of saponins of Panax japonicus (SPJ) on high-fat diet induced reproductive dysfunction in mice and its underlying mechanisms. Methods Sperm viability and sperm count were assessed using hemocytometer and eosin Y staining under light microscope. Testicular morphology was evaluated by HE staining. Germ cell apoptosis was detected by deoxyribonucleotide terminal transferasemediated (TUNEL). The relative protein expression levels of p-NF-κB, TNF-α and IL-1β were detected by Western blot. The numbers of testicular macrophages were assessed by immunofluorescence. Results Compared with high-fat model group, SPJ significantly reduced the body mass of mice, significantly increased the weight and index of testis and epididymis, elevated sperm viability and sperm count, improved the morphology of seminiferous tubules, and reduced germ cell the apoptosis. In addition, SPJ markedly decreased the relative protein expression levels of p-NF-κB, TNF-α and IL-1β, and reduced the numbers of testicular macrophages. Conclusions SPJ significantly improves high-fat diet induced reproductive dysfunction in male mice, and its mechanism may be related to the reduction of macrophage infiltration and inhibition of NF-ΚB pathway-mediated testicular inflammation.

Protective effects of total saponins of Panax japonicas on non-alcoholic fatty liver disease through regulating expression of miR-199-5p / 中国中药杂志

To research the effection and probable mechanism for the total saponins of Panax japonicas(TPSJ) in mice on non-alcoholic fatty liver disease. Forty SPF male Kunming mice were randomily divided into four group:control group,NAFLD group, low-dose TPSJ treated group,high-dose TPSJ treated group. High-fatty and high-frutose-diet was applied to eatablish NAFLD model，and TPSJ (100 and 200 mg·kg⁻¹) in feeding were given for the TPSJ groups for 4 weeks. To collect the serum with liver and the ALT and TC of serum were monitored after 4 weeks. The hepatic histopathologic structure was observed by haematoxylin-eosin (HE) staining, RT-PCR and RT-qPCR was applied for the detection of miR-199-5p，VEGFa，HGF，c-Met and protein expression level was detected bv laser confocal microscope.Compared with control group, the level of serum ALT and TC in the model group was higher,the liver of the model group showed that hepatocytes display obvious lipid deposition. Then TPSJ treated showed that markedly improved histopathologic changes, decreased fatty deposition. In the meantime,the expression level of miR-199-5p was significantly decreased, thus the expression of HGF and c-Met were significantly increased. TPSJ play a role of prevention on fatty liver, the machanism maybe by blocking miR-199-5p targeted to c-Met signaling pathways in NAFLD.

Effects and mechanism research of total saponins of Panax japonicas improving lipid metabolism in HepG2 cells based on computer aided drug design / 中草药

Objective To research the effects of total saponins of Panax japonicas (TSPJ) improving lipid metabolism in HepG2 cells, and to predict and verify TPSJ possible targets based on computer aided drug design. Methods HepG2 cells fatty degeneration model was induced with palmitic-acid (PA). The HepG2 cells were divided into five groups: the control group, the model group, the high-dose group (50 mg/L), the middle-dose group (25 mg/L), and the low-dose group (12.5 mg/L). The cells of five groups were cultured continuously for 24 h. The intracellular lipid accumulation was qualitative and quantitative detected by Oil red and Nile red staining. The content of triglyceride (TG) was detected by detection kit. TPSJ possible targets were predicted by computer. The expressions of related proteins were detected by immunofluorescence. Results The lipid accumulation model of HepG2 cells was successfully established for 24 h with the 100 μmol/L concentration of PA. TSPJ can significantly improve the lipid accumulation (P < 0.01), and decrease the content of triglyceride (TG) of HepG2 cells. The possible target of TSPJ may be estrogen-related receptors based on computer aided drug design. Compared with the control group, the expression levels of estrogen receptor β (ERβ) protein in model group were decreased. Compared with the model group, the expression level of ERβ protein in high-, middle-, and low-dose group were upregulated. Conclusion TSPJ can significantly improve the lipid metabolism of HepG2 cells, and the target of TSPJ might be ERβ.