scholarly journals Effect of Compound Chuanxiong Capsule on Inflammatory Reaction and PI3K/Akt/NF-κB Signaling Pathway in Atherosclerosis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Qunfu Kang ◽  
Weihong Liu ◽  
Hongxu Liu ◽  
Mingxue Zhou

Compound Chuanxiong Capsule (CCC), a Chinese herbal compound, can exhibit antiatherosclerotic effect; however, its mechanism is still unclear. This study is designed to study the mechanism of CCC on atherosclerosis in the ApoE-knockout (ApoE−/−) mice fed with a high-fat diet. After 6 weeks of high-fat feeding, 40 ApoE−/−mice were randomized (n=10) and treated with lipitor, high-dose or low-dose CCC, or distilled water (ApoE−/−group) for 7 weeks. The blood lipids in serum and the plaque areas of the mice were measured and the mRNA expressions of phosphatidylinositol-3-kinases (PI3K), Akt, nuclear factor-kappa B (NF-κB), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) of the aortae were determined. The data showed that CCC can significantly decrease the levels of blood lipids, atherosclerosis index, and plaque areas and increase collagen proportion in plaques as compared with the untreated mice (p<0.05,p<0.01). In addition, CCC can significantly reduce the mRNA expressions of PI3K, Akt, NF-κB, IL-6, and TNF-αin the mice fed with a high-fat diet (p<0.001). Thus, we concluded that CCC can inhibit inflammatory reaction in the ApoE−/−mice fed with a high-fat diet. This mechanism may be attributed to regulating PI3K/Akt/NF-κB signaling pathway.

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Han ◽  
Hua-Qin Tong ◽  
Song-Yi Cheng ◽  
Li Yang ◽  
Han-Yu Chen ◽  
...  

Endothelial injury plays an important role in atherosclerosis (AS). Kangshuanyihao formula uses therapeutic principles from Chinese medicine to supplement Qi, thereby promoting blood circulation, and remove blood stasis. The mechanism by which the formula inhibits endothelial injury was examined in a rat model of 1,25-dihydroxyvitamin D3 (VD3) intraperitoneal injection and high-fat-induced endothelial injury. Rats were randomly divided into the model, high-dose, middle-dose, low-dose, positive drug (rosuvastatin), and combination (positive drug + middle-dose) groups; 10 Sprague-Dawley rats served as the blank group. The aortic endothelium was stained with hematoxylin and eosin and the levels of blood lipids and inflammation markers (mRNA and protein) were measured. Endothelial injury, lipid levels, and inflammation were increased in the model. Kangshuanyihao formula reduced endothelial injury, improved lipid levels, and downregulated inflammation, as shown by significant reduction of the protein levels of SIRT1, TLR4, and NF-κB and mRNA levels of SIRT1, TLR4, NF-κB, IL-1β, IL-6, and IL-12. Thus, we conclude that Kangshuanyihao formula can inhibit the inflammatory reaction in the rat model of high-fat-induced endothelial injury after intraperitoneal injection of VD3. This mechanism may be attributed to regulating the SIRT1/TLR4/NF-κB signaling pathway.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zhang ◽  
Pan Ren ◽  
Qunfu Kang ◽  
Weihong Liu ◽  
Sinai Li ◽  
...  

Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high-fat diet, 30 ApoE−/−mice were randomized (n=10) and treated with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and insulin levels were measured. The expressions of PAQR3, Insig-1, SCAP, SREBP-1c, IRS-1, PI3K, Akt, and mTORC-1 in the adipose tissues were determined. The results showed that TMP could significantly decrease blood lipids levels, insulin, and corrected plaque area of the ApoE−/−mice as compared to the untreated mice (P<0.05,P<0.01). Moreover, TMP could significantly downregulate the expressions of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P<0.01). Thus, TMP may ameliorate lipid metabolism disorder and As by downregulating PAQR3 and inhibiting SCAP/SREBP-1c signaling pathway. In addition, PI3K/Akt/mTORC1 signaling pathway may be involved in this process.


2021 ◽  
Author(s):  
Tianmin Wu ◽  
Xuanbin Huang ◽  
Jinshui Chen ◽  
Wenjuan Xue ◽  
Liufang Fan ◽  
...  

Abstract BackgroundTo investigate the effect of Ruanmailing oral liquid on atherosclerosis and TGF-β1/SMAD4 signaling pathway in ApoE knockout mice induced by high-fat diet. MethodsForty ApoE-/- mice were randomly divided into 5 groups, and mice fed with standard diets were the control group. ApoE-/- mice high-fat diet induced atherosclerotic phenotype. After grouping and treatment, they were divided into high-fat feeding model group, low-dose and high-dose of Ruanmailing groups (1.75, 4.55 ml/kg/d), Lipitor Group (3.0 mg/kg/d). After 12 weeks of administration, blood was collected from the mice orbit to determine the levels of TC, TG, LDL-C, and HDL-C, and the pathological changes of thoracic aorta atherosclerosis were observed. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of serum TGF-β1, and RT-PCR and Western Blot were used to detect the expression of SMAD4 and GATA2 in the thoracic aorta of ApoE-/- mice in each group. ResultsCompared with the high-fat model group, the serum lipids level of each administration group were reduced (P<0.01 or P<0.05), and the ratio of plaque area to luminal area (W/L) was significantly reduced (P<0.05), and pathological examination indicated atherosclerotic lesions in thoracic aorta of ApoE-/- mice were alleviated, and the high-dose Ruanmailing group had the most significant anti-atherosclerotic effect. ConclusionsRuanmailing oral liquid has an anti-atherosclerotic effect, and its mechanism may be related to the intervention of GATA2 in the TGF-β1/SMAD4 signaling pathway to reduce the differentiation and proliferation of arterial smooth muscle cells.


2016 ◽  
Vol 19 (4) ◽  
pp. 404-409 ◽  
Author(s):  
Wei-Wei Ma ◽  
Bing-Jie Ding ◽  
Li-Jing Wang ◽  
Yi Shao ◽  
Rong Xiao

2018 ◽  
Vol 119 (10) ◽  
pp. 1102-1110 ◽  
Author(s):  
Xuejuan Xia ◽  
Guannan Li ◽  
Jiaxin Song ◽  
Jiong Zheng ◽  
Jianquan Kan

AbstractWhole-grain highland hull-less barley (WHLB) contains high amounts of bioactive compounds that potentially exhibit cholesterol-lowering effects. This study investigated the hypocholesterolaemic effect of WHLB. A total of seventy-two male Sprague–Dawley rats were divided into four groups and were fed with the normal control diet, high-fat diet (HFD) and HFD containing low or high dose (10 or 48·95 %) of WHLB. High dose of WHLB significantly decreased the organ indexes of liver and abdominal fat and lipid levels of plasma and liver in HFD rats. The lipid regulation effect of WHLB, which was reconfirmed through hepatocyte morphologic observation, was accompanied by a large excretion of bile acids in the small intestinal contents and the faeces. Real-time PCR analyses, which were further reconfirmed through Western blot analyses, revealed that a high dose of WHLB significantly enhanced the hepatic expressions of AMP-activated protein kinase α, cholesterol 7α-hydroxylase, LDL receptor, liver X receptor, and PPARα and decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It also enhanced the ileal expression of farnesoid X receptor and resulted in the decrease of expression of apical sodium-dependent bile acid transporter. WHLB exhibited hypocholesterolaemic effects mainly by inhibiting cholesterol synthesis, cholesterol accumulation in peripheral tissue, and bile acid reabsorption and by stimulating bile acid synthesis.


2020 ◽  
Author(s):  
Xiaoling Wu ◽  
Xinyu Zou ◽  
Mi Zhang ◽  
Haiqiang Hu ◽  
Xueliang Wei ◽  
...  

Abstract Background: Osteocalcin (OCN), as an energy-regulating hormone, involves in preventing nonalcoholic steatohepatitis. Laying hens have been used as an animal model for investigating liver function and related metabolic disordersas that the synthesis of fat in laying hens is much faster than in mammals with limited adipose tissue. The aim of this study was to investigate the effects of OCN on fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Methods: Thirty 68-week-old White Plymouth laying hens were randomly assigned into conventional single-bird cages, and the cages were randomly allocated into one of three treatments: normal diet (ND + vehicle , ND+V), high-fat diet (HFD + vehicle, HFD+V), and HFD + OCN (3 μg/bird, 1 time/2 days, i.m.) for 40 days. At experimental day 30, oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were performed. At the end of experiment, the hens were euthanized followed blood collection. The plasma aspartate transaminase (AST), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automatic biochemistry analyzer. Pathological changes in the liver were examined under both light and transmission electron microscopes. The plasma inflammatory factors including interleukin-1 (IL-1), IL-6, and tumor Necrosis Factor-alpha (TNF-α) were analyzed by ELISA, and the gene expressions of these inflammatory factors in the liver were analyzed by Real-time PCR. And oxidative stress was evaluated using Malondialdehyde (MDA) and Glutathione peroxidase (GSH-Px) assay kits. Results: The results showed HFD hens had more severe liver haemorrhage and fibrosis than ND hens. The ultra-microstructural examination showed that hepatocytes of HFD hens appeared necrotic pyknosis associated with great intracellular electron, mitochondrial swelling, shrunk nucleus and absence of autolysosomes. OCN mitigated these pathological changes by improved HFD hens’ insulin resistance via alleviating the glucose intolerence and improving insulin sensitivity; inhibited HFD-induced oxidative stress as evidenced by decreased liver concentrations of MDA but increased GSH-Px; and reduced the inflammatory reaction with reducing blood IL-6 and TNF-α concentrations and mRNA expressions. Conclusion: These results suggest a high-fat diet promotes the FLHS development in aged hens, while OCN prevents the FLHS process through inhibiting insulin resistance, inflammatory reaction, oxidative stress and fibrosis, and acting autophagy.


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