1.Prevention Effect of Danlou Pills on Atherosclerosis through PI3K/AKT Signal Pathways in Rabbit Atherosclerosis Model
He WANG ; Minghua LUO ; Xiaojun SHEN ; Jinhong XIE ; Yushan CHEN ; Chunying SI ; Liang LI ; Huaimin GUAN
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(6):1194-1197
This study was aimed to investigate the effect ofDanlou pills on prevent atherosclerosis from hypercholesterolemia rabbit and its relationship with inflammatory factors as well as PI3K/AKT signal pathways. A total of 24 Japanese male white rabbits were randomly divided into the control group (CL), model group (M) and Danlou group (DL), with 8 in each group. Normal diet was given to CL rabbits. High-fat diet was given to rabbits in other groups to establish the atherosclerosis model. Danlou pills (0.5 g·kg-1·d-1) were also given to DL rabbits. Rabbits were sacrificed after 9-week medication. The contents of blood lipid, TNF-α and IL-6 were detected. HE staining was used in the observation of histological changes in the aorta. Western blot was used to observe PI3K and p-AKT expression in the aorta. The results showed that compared with CL, the contents of TG, TC, LDL, IL-6 and TNF-α were significantly increased in M (P < 0.01); PI3K and p-AKT expression in the aorta were significantly decreased (P < 0.01). Compared with M, blood lipid, IL-6 and TNF-α were significantly reduced in DL (P < 0.05, orP < 0.01); PI3K and p-AKT expression were significantly increased (P < 0.01). It was concluded thatDanlou pills had prevention effects on atherosclerosis through reducing blood lipid and inflammatory factors. The action mechanism maybe related to the activation of PI3K/AKT signal pathways.
2.Berberine regulates polarization of macrophages:a mechanistic study based on PI3K/Akt1 signaling pathway
Yushan CHEN ; Tingting WANG ; Zhonghua MENG ; Shasha SHANG ; Junmeng ZHENG ; Yonghua ZONG ; Chunying SI ; Yazhou LIANG ; Huaimin GUAN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(6):694-698
Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P<0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)%,(0.82±0.03)%,(0.71±0.02)%,(0.62±0.03)%and(0.53±0.02)%vs(1.01±0.01)%,P<0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P<0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P<0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P<0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.
3.Inhibitory effect and mechanism of epigallocatechin-3-gaUate on autogenous vein graft stenosis in rat models
ZHANG Yi ; GU Jun ; LIU Linbo ; LIAO Zhijie ; ZHANG Hongwei ; YANG Peng ; FAN Kangjun ; LIANG Huaimin ; XIAO Zhenghua ; HU Jia
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2017;24(10):791-790
Objective To investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on restenosis of the vein graft. Methods Totally 90 Sprague-Dawley rats were randomly divided a the control group, a vein graft group and an EGCG+vein graft group. At week 1, 2 and 4, the intimal and tunica thickness of the venous graft wall was evaluated by hematoxylin-eosin staining, and the expression of Ki-67 was assessed by immunohistochemistry analysis, and then the expression of hairy and enhancer of split-1 (HES1) was measured by Western blot assay. Results At week 2, the intimal thickness (46.76±4.89 μm vs. 8.93±0.82 μm, 46.76±4.89 μm vs. 34.24±3.57 μm), tunica thickness (47.28±4.37 vs. 16.33±1.52 μm, 47.28±4.37 vs. 36.27±3.29 μm), positive cell rate of Ki-67 (21.59%±2.29% vs. 1.12%±0.22%, 21.59%±2.29%vs. 15.38%±1.30%), expression of HES1 respectively increased in the experimental group than those in the control group and the EGCG+vein graft group (P<0.05, respectively). At week 4, the intimal thickness (66.38±6.23 μm vs. 8.29±0.79 μm, 66.38±6.23 μm vs. 48.39±4.23 μm), tunica thickness (63.27±6.18 μm vs. 15.29±1.49 μm, 63.27±6.18 μm vs. 44.63±4.49 μm), positive cell rate of Ki-67 (33.19%±3.03% vs. 1.09%±0.19%, 33.19%±3.03% vs. 24.37%±2.73%), expression of HES1 increased in the experimental group than those in the control group and EGCG+vein graft group (P<0.05, respectively). Conclusion EGCG may inhibite restenosis of vein graft by inhibiting Notch signal pathway.