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@#In order to explore the therapeutic effects and preliminary mechanism of gypenosides (GP) on hypercholesterolemia, as well as the protective effect on liver injury induced by high-dose simvastatin and high cholesterol diet (HCD), the hypercholesterolemia model of golden hamster was established by high cholesterol diet. The experimental animals were divided into blank group, model group, GP low and high dose groups (60 mg/kg, 120 mg/kg), simvastatin group (10 mg/kg), and GP high dose combined with simvastatin group (120 mg/kg + 10 mg/kg).The efficacy was investigated through dynamic monitoring serum cholesterol and liver function related indexes after drug treatment of 14 and 23 days. The results showed that GP could significantly reduce the levels of serum low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), increase the level of serum high density lipoprotein cholesterol (HDL-C), and reduce the secretion of PCSK9. It is suggested that GP has a good therapeutic effect on HCD diet-induced hypercholesterolemia hamsters, which may be related to its inhibition of PCSK9 secretion. In addition, GP can significantly ameliorate liver damage caused by HCD diet and high-dose simvastatin. These findings provide a scientific basis and useful reference for the combination of GP and statins to reduce toxicity and increase efficacy.
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@#To investigate the hypolipidemic effects of gypenosides granules and its combination with lipitor, a model of hyperlipidaemia C57BL/6J mice was established by high-fat diet feeding for 4 weeks. The mice were randomly divided into blank group, model group, lipitor group(10 mg/kg of lipitor), low dose group(90 mg/kg of gypenosides granules), medium dose group(120 mg/kg of gypenosides granules), high dose group(180 mg/kg of gypenosides granules)and the combination group(180 mg/kg of gypenosides granules and 10 mg/kg of lipitor). After 4 weeks of continuous administration, the contents of serum lipid indexes, serum ALT, AST and apolipoprotein B(ApoB)were measured. The liver tissues of mice were observed by H&E staining. The expression levels of key factors involved in hepatic cholesterol metabolism were observed by RT-PCR and Western blot methods, such as adenosine triphosphate combined box transporter A1(ABCA1), liver X receptor(LXRα), cholesterol 7 alpha hydroxylase(CYP7A1)and type BΙ scavenger receptor(SR-BΙ). The results revealed that gypenosides granules significantly decreased the mice body weight, total abdominal fat area and the level of serum total cholesterol(TC). The combination group showed a more significant reduction in TC level than the other administration groups. Moreover, gypenosides granules treatment remarkably increased the protein expression of ABCA1 and up-regulated the mRNA expression of ABCA1, CYP7A1 and SR-BI. The above results suggest that gypenosides granules can significantly reduce blood lipid contents, and the combination therapy with lipitor show better the lipid-lowering effect. Meanwhile, gypenosides granules can decrease the level of serum transaminase. Preliminary exploration suggests the lipid-lowering mechanism of gypenosides granules may be involved in cholesterol reversal to regulate the level of TC.
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@#In order to investigate the therapeutic effects of scutellarein on acute pharyngitis, 60 rats were randomly divided into five groups: blank group, model group, low-dose scutellarein group, high-dose scutellarein group and positive drug group. HE staining, blood-cell-analyzer, IL-6, IL-1β and TNF-α ELISA kit were used to study the effects of scutellarein on acute pharyngitis in pharyngeal tissue morphology, the counts of white blood cells and neutrophil and the serum concentrations of TNF-α, IL-1β and IL-6. Meanwhile, forty mice were randomly divided into four groups: blank group, low-dose scutellarein group, high-dose scutellarein group and positive drug group. Then, hot plate and writhing test of mice were carried out to study the analgesic effects of scutellarein. Results showed that, compared to the model group, scutellarein improved the physical status of acute pharyngitis rats, reduced the number of white blood cells significantly(P< 0. 05)and decreased the number of neutrophils and the levels of TNF-α, IL-1β and IL-6 in rats serum significantly(P< 0. 01). Meanwhile, scutellarein dramatically improved the pain threshold in hot plate test and decreased the number of writhing mice(P< 0. 01). It can be concluded that scutellarein can be used to treat acute pharyngitis with its anti-inflammatory and analgesic effect.
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@#In order to explore the effect and its mechanism of paeoniflorin on PD-L1, a PD-L1 high expression cell model was established in interferon gamma(IFN-γ)-induced HepG2 cells. The cytotoxicity of paeoniflorin was detected by MTT assay. Flow cytometry, ELISA and RT-PCR were performed to detect protein and mRNA levels of PD-L1 regulated by paeoniflorin. In HepG2 cells and Jurkat T cell co-culture system, the expression of IL-2 was detected by ELISA. Besides, T cell proliferation was evaluated by CCK-8 method, and the protein expression levels of PD-L1, JAK and STAT3 after drug treatment were determined by Western blot. These results indicated that paeoniflorin could significantly down-regulate the levels of PD-L1 protein and mRNA. In addition, it increased the number of T cells and the concentration of IL-2 in the co-culture system. Furthermore, paeoniflorin could significantly inhibit the protein expression of JAK and STAT3. Au the above experimental data indicated that paeoniflorin could down-regulate the expression of PD-L1, and its mechanism might be related to the JAK/STAT3 pathway.
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@#To investigate the antipyretic effects and potential mechanism of Isodon eriocalyx ethanol extracts, the SD rats was injected by dry yeast subcutaneously to establish the model of fever. Experimental groups were divided into blank, model, positive drug paracetamol(150 mg/kg), low doses(200 mg/kg), high doses(800 mg/kg)of ethanol extracts of I. eriocalyx, rosmarinic acid(150 mg/kg), cirsimaritin(150 mg/kg)and maoecrystal D(150 mg/kg). After 4 hours of model establishment, the drugs were administered orally to each group; the blood and tissue samples were then collected 8 hours affer model establishment. Rectal temperature was detected to evaluate the antipyretic effects. The levels of tumor necrosis factor(TNF-α), arginine vasopressin(AVP), cyclic adenosine monophosphate(cAMP)and prostraglandin E2(PGE2)were measured to explore the potential mechanism. Results showed that the inoreased rectal temperature in rats was ameliorated by ethanol extracts of I. eriocalyx. Moreover, administration of ethanol extracts of I. eriocalyx could reduce the serum TNF-α levels and increase AVP levels in rats, decrease the levels of cAMP and PGE2 in hypothalamus and promote AVP secretion in ventral septal area of rats. However, there were no dramatic changes about rectal temperature and biochemical indicators mentioned above after administration of rosmarinic acid, cirsimaritin and maoecrystal D, respectively. In conclusion, ethanol extracts of I. eriocalyx exerted antipyretic effects on fever rats induced by yeast, which is probably due to the suppression of the secretion of TNF-α, cAMP and PGE2 and promotion of the excretion of AVP. However, the material basis of the antipyretic mechanism of this plant still remains to be further explored.
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To investigate the therapeutic effects of triterpenoids from Cyclocarya paliurus on non-alcoholic fatty liver disease (NAFLD),the model of NAFLD in HepG2 cells was induced by free fatty acids (FFAs). Cytotoxicity of the triterpenoids from C. paliurus was determined by MTT method,and the effects of triterpenoids without cytotoxicity on intracellular triglyceride (TG)and superoxide dismutase (SOD)were detected by the kits. Data indicated that compound 4 [2α,3α,23-trihydroxy-12,20 (30)-dien-28-ursolic acid,TUA]had hypolipidemic and antioxidant activities. After being treated with TUA and FFAs for 24 h,the intracellular lipid content was observed using Oil Red O staining,and intracellular TG,malondialdehyde (MDA ),SOD and reactive oxygen species (ROS)levels were determined by the assay kits. The protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase-1 (HO-1 )and NAD (P)H quinone oxidoreductase 1 (NQO-1 )were measured by Western blot. The results showed that TUA significantly increased SOD activity,and decreased intracellular TG, ROS and MDA levels in FFAs-induced HepG2 cells. Moreover,TUA dramatically improved Nrf2,NQO-1 ,and HO-1 expression. However,the dramatic increase in TG,ROS,MDA levels and the reduction in SOD,NQO-1 and HO-1 expression following Nrf2 inhibitor brusatol treatment were observed. In conclusion,these results suggest that TUA has the therapeutic effect on NAFLD which may be associated with Nrf2 activation.
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@#The purpose of this study was to investigate the hypoglycemic effect and the safety of medicinal formula composed of Cyclocarya paliurus and Mulberry leaves. An experimental diabetic rat model was established by high energy diet plus small dosage of auoxan(ALX). At the same time, each group rats were given distilled water(blank and model), metformin(Met), Cyclocarya paliurus aqueous extract(CP), Mulberry leaves aqueous extract(ML)and the different proportions of aqueous extract mixtures of Cyclocarya paliurus and Mulberry leaves(CM1, CM2 and CM3), respectively. Fasting blood glucose(FBG), OGTT, TC, TG, LDL-C, HDL-C, insulin and liver and kidney function related index were gauged to evaluate the hypoglycemic effect and the safety of samples. The results showed that FBG level of the rats in CM1, CM2 and CM3 groups decreased 21. 64%, 16% and 12. 55%, respectively, comparing with that of model group. Moreover, FBG, glucose tolerance and pancreatic tissue morphology were remarkably improved in CM1 group. TC and LDL-C levels of rats in ML and CM3 groups decreased significantly compared with the those of Model group(P< 0. 05), which showed ML and CM3 were beneficial to regulate the blood lipid level in diabetic rats. Furthermore, all the administration groups had no adverse effect on liver function index. The down regulation of kidney function index of CP, ML, CM1, CM2 and CM3 groups comparing with model group indicated that Cyclocarya paliurus and Mulberry leaves could alleviate the injury of liver and kidney. Our results demonstrated that the medicinal formula composed of Cyclocarya paliurus and Mulberry leaves were favorable to reduce blood glucose and can regulate lipid metabolism without liver and kidney toxicity.
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@#To investigate the effect and possible mechanisms of triterpenic acid-enriched fraction from Cyclocarya paliurus(TAE)on glucagon secretion in insulin-resistance pancreatic α cells, the model of insulin resistance in αTC1-6 cells was induced by long term exposure to high glucose. Experimental groups were divided as follow: control(5. 5 mmol/L glucose), model(25 mmol/L), TAE(1, 5, 10 μg/mL), and TAE(10 μg/mL)plus wortmannin(10 nmol/L)group. The supernatant and lysate of treated cells were collected to determine glucagon secretion by ELISA kit. The mRNA and protein abundance of IRS-1, PI3K and Akt were measured by qPCR and Western blot analysis. Results showed that TAE could not only significantly reduce glucagon secretion induce by high glucose in a dose-dependent manner, but also remarkably increased the mRNA and protein abundance of IRS-1, PI3K and Akt in αTC1-6 cells. However, these effects of TAE were reversed by PI3K inhibitor wortmannin. In conclusion, it suggested that TAE could improve the insulin resistance induced by high glucose in pancreatic α cells which may be related with the activation of IRS-1/PI3K/Akt signaling pathway.
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To investigate the hypoglycemic effects of ethyl acetate extract of Alismatis Rhizoma (AREEA) on type 2 diabetes mellitus,the model of type 2 diabetic rats was induced by high-fat diet feeding for 4 weeks and then intraperitoneal injection of a low dose of streptozotoin (STZ).Rats without the above-mentioned treatment were selected as the normal control group.The diabetic rats were randomly divided into 5 groups:the model control group,low doses (20 mg/kg),medium doses (50 mg/kg),high doses (100 mg/kg) of AREEA groups and positive control-metformin group (100 mg/kg).After four weeks,oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed,respectively.12 hours after the last administration,the levels of serum glucose,glycated hemoglobin(HbA1 c),insulin (Ins),total cholesterol (TC),triglyceride (TG),high density lipoprotein (HDL-C),low density lipoprotein (LDL-C),superoxide dismutase (SOD),malondialdehyde (MDA),glutathione (GSH-Px),tumor necrosis factor-or (TNF-α),interleukin-6 (IL-6),insulin-mediated tyrosine of IRS-1 and Akt phosphorylation in adipose tissue were determined.In addition,the pathological changes of pancreas were examined.After administration for 4 weeks,all doses of AREEA significantly reduced the fasting blood glucose of type 2 diabetic rats (P ＜0.05).In the high doses group of AREEA,the levels of GLU,HbA1c,TC,TG,MDA,TNF-α and IL-6 in serum were decreased significantly,and the levels of SOD and GSH-Px were increased (P ＜ 0.05).These results suggest that AREEA has the therapeutic effect on type 2 diabetes-related symptoms by metabolic regulation of glucose and lipids.
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@#The research of triterpenoids on hypoglycemic and anti-diabetic activities have made great progress. Findings indicated that triterpenoids could reduce blood glucose via different mechanisms, including increasing insulin secretion, enhancing insulin sensitivity, promoting glucose uptake by activation of AMP-activated protein kinase(AMPK), decreasing glycogenolysis and gluconeogenesis, and inhibiting protein tyrosine phosphates 1B(PTP1B), α-glycosidase, aldose reductase(AR)and dipeptidyl peptidase-4(DPP-4). This article reviews the hypoglycemic effects and mechanisms of triterpenoids, providing the reference for further research and development of triterpenoids.
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Complement receptor of the immunoglobulin superfamily ( CRIg) can regulate immune reactions via T cells and cy-tokines and is involved in various diseases .The effect of CRIg on the pathogenesis of immunological liver injury , intestinal ischemia-reperfusion injury , type Ⅰdiabetes mellitus , experimental autoimmune uveoretinitis , and rheumatoid arthritis etc .in animal models of disease are reviewed in this article .