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The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice.

ABSTRACT: Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination.

SUBMITTER: Zhao Q

PROVIDER: S-EPMC4691119 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice.

Zhao Qun Q Yang Min M Deng Yanping Y Yu Haitao H Wang Linlin L Teng Fukang F Cho Kenka K Ma Hongmei H Wu Peng P Li Xue X Wu Wanying W Liu Xuan X Xu Feng F Jiang Baohong B Guo De-An DA

International journal of molecular sciences 20151209 12

Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down ...[more]

PMID: 26690140

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Project description:BackgroundTo observe the effect of ginsenoside Rb1, salvianolic acid B and their combination on glucolipid metabolism and structural changes of gut microbiota.MethodsEight-week-old C57BL/6J mice were fed 45% high-fat diet to induce obesity. The obese mice were randomly divided into four groups, Con group as model control, ginsenoside Rb1 (Rb1) group, salvianolic acid B (SalB) group and ginsenoside Rb1+ salvianolic acid B (Rb1SalB) group. Mice in Rb1, SalB and Rb1SalB group were treated by gavage with ginsenoside Rb1, salvianolic acid B and the combination of the two ingredients, respectively. While mice in Con group were given the same amount of sterile water. The intervention lasted 8 weeks. Body weight and fasting blood glucose were measured every 2 weeks. Oral glucose tolerance test was conducted on the 4th and 8th week of drug intervention. At the end of the experiment, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol and non-esterified fatty acid content as well as glycated hemoglobin were measured and feces were collected for 16S rDNA sequencing.ResultsBoth ginsenoside Rb1 and Rb1SalB combination decreased body weight significantly (P < 0.05). Ginsenoside Rb1, salvianolic acid B and their combination alleviated fasting blood glucose, glycated hemoglobin and blood lipid profiles effectively (P < 0.05, compared with the corresponding indicators in Con group). Oral glucose tolerance test results at the 8th week showed that glucose tolerance was significantly improved in all three treatment groups. Ginsenoside Rb1, salvianolic acid B and their combination reduced the overall diversity of gut microbiota in feces and changed the microbial composition of the obese mice. LDA effect size (LefSe) analysis revealed the key indicator taxa corresponding to the treatment.ConclusionGinsenoside Rb1, salvianolic acid B and their combination could lower blood glucose and lipid level, and improve glucose tolerance of obese mice. The above effect may be at least partially through modulation of gut microbial composition.

Project description:The present study investigated the effect and underlying mechanisms of ginsenoside Rg1 (Rg1) in attenuating subacute liver injury induced by D-galactose (D-gal) in mice. Specific Pathogen Free (SPF) male C57BL/6J mice were randomly divided into 3 groups: i) D-gal-administration group (D-gal group), where the mice were intraperitoneally administrated with D-gal (120 mg/kg/day for 42 days); ii) D-gal + Rg1 group where the mice were treated with 120 mg/kg/day D-gal for 42 days and with Rg1 at a dose of 20 mg/kg/day for 35 days. The first dose of Rg1 was administered on the 8th day of treatment with D-gal; and iii) the normal control group, where the mice were injected with an equal volume of saline for 42 days. The day following the final injections in all groups, peripheral blood was collected and serum was prepared to measure the contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBiL), advanced glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG). Liver tissue homogenates were prepared to measure the contents of malondialdehyde (MDA) and glutathione (GSH), and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Paraffin section were prepared to observe the microscopic structure of the liver. Transmission electron microscopy was used to observe the ultrastructure of hepatocytes. Frozen section were prepared and stained with senescence-associated ?-galactosidase to detect the relative optical density value of senescence-associated markers. Compared with the D-gal group, the contents of AST, ALT, TBiL, AGEs and MDA significantly decreased in the D-gal + Rg1 group, while the activities of SOD and GSH-Px markedly increased, and liver injury and degenerative alterations of hepatocytes were reduced. Administration of Rg1 induced a protective effect on D-gal-induced liver injury in mice by inhibiting the oxidative stress, reducing DNA damage and decreasing the AGE content.

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The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice.

Publications

The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice.

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