1.Study on the improvement of Compound danshen tablets on blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats
Minghao ZHANG ; Yiying GAO ; Wenxia DONG ; Zhen WANG ; Pengkun XUE ; Weiyang MA
China Pharmacy 2022;33(7):818-824
OBJECTIVE To investigate the effect of Compound danshen tablet s o n improving the blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats. METHODS Sixty male SD rats were divided into normal group,model group ,simvastatin combined with (2S)-N-[N-(3,5-difluorophenylacetyl)-L-alanyl]-2-phenylglycine tert butyl (DAPT)group and low-dose ,medium-dose and high-dose groups of Compound danshen tablets ,with 10 rats in each group. Rats in the normal group received routine diet. The other 5 groups were intraperitoneally injected with 75% yolk emulsion 10 mL/kg, fasting and drinking freely. After 16 h,they were fed high-fat diet for 4 weeks. Simvastatin combined with DAPT group was given simvastatin 0.002 g/kg and DAPT 0.012 g/kg at the same time of modeling. The low-dose ,medium-dose and high-dose groups of Compound danshen tablets were given Compound danshen tablets 0.25,0.5 and 1 g/kg respectively at the same time of modeling , the normal group and model group were given equal volume of distilled water ,once a day ,for 4 weeks. The serum levels of total cholesterol(TC),triglyceride(TG),creatinine(Cr)and urea nitrogen (BUN)in serum were detected by biochemical method ; kidney coefficient of rats was calculated ;histopathological changes of rat kidney were observed by HE staining ,and the renal injury was scored according to the degree of renal tubular injury and glomerular sclerosis in renal cortex ;expression levels of Notch signal receptor 1(Notch 1),Notch signal ligand 1(Jagged1)and hairy division associated enhancer 1(Hes1)in kidney were detected by immunohistochemistry ;mRNA expressions of Notch 1,Jagged1 and Hes 1 in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS Compared with normal group ,the serum levels of TG , TC,Cr and BUN were increased significantly in model group (P<0.05);renal coefficient increased significantly (P<0.05); pathological changes occurred in renal tissue ,and the scores of renal tubular injury and glomerular sclerosis increased significantly (P<0.05);protein and mRNA expressions of Notch1, Jagged1, Hes1 in renal tissue were increased significantly(P<0.05). Compared with model group ,serum levels of TG ,TC,Cr and BUN ,renal coefficient ,the scores of renal tubular injury and glomerular sclerosis ,protein and mRNA expression of Notch 1,Jagged1 and Hes 1 in renal tissue were all decreased in low-dose ,medium-dose and high-dose groups of Compound danshen tablets (P<0.05),and most indexes showed a dose-dependent trend ;the degree of renal lesions was reduced. CONCLUSIONS Compound danshen tablets possess obvious hypolipidemic effect ,and can protect the renal function of hyperlipidemia model rats by down-regulating Notch 1/Jagged1 signal pathway.
2.Study on the effects and mechanism of total glucosides of paeony on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside in the treatment of eczema
Minghao ZHANG ; Zhen WANG ; Yiying GAO ; Pengkun XUE ; Weiyang MA ; Wenxia DONG ; Liya MA ; Dawei ZHANG
China Pharmacy 2023;34(4):444-449
OBJECTIVE To investigate the effects of total glucosides of paeony (TGP) on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside (TWP) in the treatment of eczema. METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2,4-dinitrofluorobenzene-acetone olive oil solution (volume ratio was 4∶1) on the abdominal area and provoking on the back and ear. Model rats were randomly divided into model group, loratadine group (0.9 mg/kg), TWP group (9.45 mg/kg), TGP group (162 mg/kg) and compatibility group (TWP 9.45 mg/kg+TGP 162 mg/kg), with 10 rats in each group. Other 10 rats were collected to set as normal group. Three days after the first sensitization, administration groups were given relevant medicine intragastrically, and normal group and model group were given constant volume of 0.1% CMC-Na solution intragastrically, once a day, for consecutive 21 d. Twenty-four hours later after the final administration, the general condition of rats in each group was observed, and the eczema area and severity index (EASI) were scored; ear swelling degree of rats was measured, and the skinhistomorphology observation and pathological score were performed; protein expressions of p38 mitogen-activated 13938427612@126.com protein kinase (p38 MAPK), phosphorylated p38 MAPK (p- MAPK) and phosphorylation level of p38 MAPK in rat skin tissue were detected; the levels of inflammatory indexes (interleukin-4, interferon- γ), liver and kidney function indexes [glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), serum creatinine (SCr) and blood urea nitrogen (BUN)] and oxidant stress indexes [total superoxide dismutase (T-SOD) and malondialdehyde (MDA)] were measured. RESULTS Compared with normal group, EASI score, ear swelling degree, pathological score, protein expressions of p38 MAPK and p-p38 MAPK, phosphorylation level of p38 MAPK, the levels of inflammatory indexes and BUN were all increased significantly in model group (P<0.05). Compared with model group, EASI scores, ear swelling degree, pathological scores, protein expressions of p38 MAPK and p-p38 MAPK, phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups (P<0.05). The levels of GPT, GOT, SCr and BUN were increased significantly in TWP group, while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly (P<0.05). The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group, while the levels of MDA were increased significantly (P<0.05). The compatibility group showed more obvious effect in improving the ear swelling degree, pathological score, p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes, and could reverse the abnormality of liver and kidney indexes caused by TWP (P<0.05). CONCLUSIONS The combination of TGP and TWP has the effects of anti-inflammatory, synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.
3.Study on intervention effect of Bushen qiangshen tablet on polycystic ovary syndrome model rats and its mechanism
Minghao ZHANG ; Yiying GAO ; Wenxia DONG ; Pengkun XUE ; Weiyang MA ; Dawei ZHANG ; Liya MA
China Pharmacy 2022;33(21):2632-2637
OBJECTIVE To study the intervention effect of Bushen qiangshen tablet on polycystic ovary syndrome (PCOS) model rats and its mechanism . METHODS Totally 50 rats were given letrozole suspension (1 mg/kg,once a day ,for consecutive 21 d) instragastrically to induce PCOS model . Model rars were randomly divided into model group ,positive control group (Ethinylestradiol and cyproterone acetate tables 0.2 mg/kg+Metformin hydrochloride tables 230 mg/kg),Bushen qiangshen tablet low-dose,medium-dose and high -dose groups (189,378,756 mg/kg),with 10 rats in each group . Another 10 healthy rats were included in normal group . Each group was given the corresponding drugs ,once a day ,for consecutive 30 d. Twenty-four hours after the last administration ,serum levels of estrogen (E2),testosterone(T),gonadotropin-releasing hormone (GnRH),follicle- stimulating hormone (FSH)and luteinizing hormone (LH)were measured . The ovary index was calculated ,and pathological changes of ovary were observed . The protein expressions of phosphoinositide 3-kinase(PI3K),phosphorylated protein kinase B (p- Akt),phosphorylated mammalian target of rapamycin (p-mTOR)and glucose transporter 4(GLUT4)in ovary were detected ,and mRNA expressions of PI 3K,Akt,mTOR and GLUT 4 in ovary were detected . RESULTS Compared with normal group ,ovarian index and ovarian cystic disease score were significantly increased in model group (P<0.05),and serum levels of T ,GnRH and LH were significantly increased (P<0.05);serum levels of FSH and E 2,protein expressions of PI 3K,p-Akt,p-mTOR and GLUT4,and mRNA expression of PI 3K,AKT,mTOR and GLUT 4 in ovarian tissue were all significantly decreased in the model group (P<0.05);in ovarian tissue ,the number of atresia follicles and non -cumulus cystic follicles increased ,and the number of granulosa cell layers decreased . Compared with model group , above indexes of Bushen qiangshen tablet medium-dose and high -dose g roups were reversed significantly 86550201。E-mail:mary868@163.com (P<0.05),and most above indexes of low -dose group were reversed significantly (P<0.05),the pathological changes of ovarian tissue were improved to varying degrees . CONCLUSIONS Bushen qiangshen tablet can regulate the secretion of sex hormones in PCOS model rats and improve ovarian cystic lesions . Its mechanism may be related to the upregulation of PI 3K/Akt/mTOR and PI 3K/Akt/GLUT4 signaling pathways .