The Toxicology Of Total Saponins From Physalis Alkekengi L. Calyx And The Anti-Hyperlipidemia Activities

In this study, total saponins from Physalis alkekengi L. var. francheti (Mast.) Makino (TSP) was choosed as tested material. Firstly, the acute and subacute toxicology of the TSP were studied, on the basis of this, the anti-hyperlipidemia effects of TSP were investigated by modeling a rat hyperlipidemia model which induced by high-fat diet, and some indexes such as high-density lipoprotein cholesterol (HDL-C) level, triglycerides (TG) level, low density lipoprotein cholesterol (LDL-C) level, total cholesterol (TC) level and so on were tested for evaluating the hypolipidemic effects of the TSP. Meanwhile, the hypolipidemic effects of TSP on blood lipid-related genes expressions were also carried out to explore the possible mechanism of hypolipidemic effects of the TSP.The main results are as follows:1. Data of acute toxicology experiments showed that, the LDso of TSP on mice was more than 21.50 g/kg ·bw, which showed non-toxic according to the acute toxicity (LD50) dose classification standard. Meanwhile, the highest dosage of TSP (21.50 g/kg) showed inhibition effect on the body weight gain.2. Subacute toxicology test showed that, compared to the control group, the body weight gain, the total food intake, food utilization were significant or highly significant (P<0.05 or P<0.01) in the high dosage group (4.3 g/kg); in aspect of the organ index, cerebral index of high dose group (4.3 g/kg) showed significantly or very significant change(P<0.05 or P<0.01) compared to the control group; hematology results show that the number of white blood cells (WBC), hematocrit (HCT), mean platelet volume (MPV) and platelet ratio (P-LCR) of high-dosage male group (4.3 g/kg) were significantly higher (P<0.05 or P <0.01), whereas only the number of white blood cells (WBC) was significantly higher (P<0.05 or P<0.01) in high-dosage female group; when considering the blood indicators, aspartate aminotransferase GOT activity in male mice for each dosage group had significantly the lower (P<0.01), the significantly or very significantly reduce of GPT activities only occurs in the low and medium dose groups of male mice (P< 0.05 or P<0.01). Organ pathology slice also verified the micro-toxicity of high dosage group on rat livers.3. The effect of TSP on Lipid-lowering were as followed:(1) Compared with the control group, TSP with high and medium dosage (200 mg/kg,500 mg/kg) and drug group could significantly or very significantly lower (P<0.05 or P<0.01) the body weight, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) levels and increase high-density lipoprotein cholesterol (HDL-C) levels in hyperlipidemia mice. Besides, there was no significant difference (P>0.05) between high dosage group and drug group.(2) Pathology slices showed that, hepatic steatosis and damaged liver tissue could be repaired when treated with TSP or drug.4. The effect of TSP on hyperlipidemia related gene expressions in mice were as followed:(1) Compared with the control group, different concentrations of TSP (80 mg/kg,200 mg/kg, and 500 mg/kg) could reduce the expressions of liver and adipose tissues FAS and LPL mRNA, significantly (P <0.05 or P<0.01). But, there existed a certain degree of organizational differences.(2) Compared with the control group, different concentrations of TSP (80 mg/kg,200 mg/kg, and 500 mg/kg) could increase the TGH mRNA expressions of liver and adipose tissues, but only middle and high dosages (200 mg/kg,500 mg/kg) showed some differences (P<0.01). What’s more, the regulation effect of TSP on TGH mRNA expressions in adipose tissues was stronger.(3) In liver tissues, different concentrations of TSP (80 mg/kg,200 mg/kg,500 mg/kg) could significantly reduce the expressions of HMG-CoA mRNA, significantly or highly significantly (P<0.05 or P<0.01), and the inhibitory effects of TSP with 200 mg/kg,500 mg/kg were comparable to the drug used. However, the effects of TSP on LDLR mRNA expressions were totally opposite.(4) In adipose tissues, different concentrations of TSP (80 mg/kg, 200 mg/kg, and 500 mg/kg) could increase the expressions of HSL mRNA and C/EBPa mRNA, significantly (P<0.05 or P<0.01). The promoted effects of TSP with 200 mg/kg,500 mg/kg were comparable to the drug used.In summary, TSP was non-toxic natural products, and could effectively reduce blood lipid levels of hyperlipidemic mice. TSP could also protect the liver and adipose tissues in mice, regulate the expressions hyperlipidemic metabolism-related genes. It could be concluded that TSP could possess anti-hypolipidemic effects.