scholarly journals Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifan Zhang ◽  
Jie Ding ◽  
Yiru Wang ◽  
Xiaoteng Feng ◽  
Min Du ◽  
...  

Guanxinkang decoction (GXK), a traditional Chinese medicinal drug, is used to treat cardiovascular disease. The aim of the study was to investigate the effects of GXK on inflammation in LDLR−/− mice and RAW264.7 cells. Fed with high fat diet for 12 weeks, the mice were randomly divided into six groups, then administered with oral 0.9% saline or GXK (7.24, 14.48, and 28.96 g/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL or ox-LDL plus different concentrations of GXK (1.25, 2.5, and 5 μg/ml), or ox-LDL plus GXK plus MAPKs activators. Serum lipid profiles and inflammatory cytokines were detected by ELISA, gene expression by RT-qPCR, plaque sizes by Oil Red O, α-SMA, caspase 3, NF-κB p65 and TNF-α production by immunofluorescence staining, and protein expression by Western Blot. The phagocytic ability of cells was determined by neutral red uptake assay. Efferocytosis-related proteins (AML, MERTK, TYRO3 and MFGE8) and MAPKs pathways were detected by Western Blot. Compared to mice fed with high fat diet, the mice with GXK showed lower cholesterol, triglyceride, low-density lipoprotein cholesterol, IL-1β, IL-6, and TNF-α, smaller plaque sizes, higher α-SMA, and lower caspase 3 and NF-κB p65 in aortic roots. RAW264.7 cells treated with ox-LDL plus GXK had lower IL-1β, IL-6, and TNF-α. GXK also increased the phagocytic ability of cells. High levels of AML, MERTK, TYRO3 and MFGE8, and decreased levels of iNOS, VCAM-1, LOX-1 and MCP-1, and phosphorylation of ERK1/2, JNK, p38, and NF-κB were detected in GXK-treated group. MAPKs activators reversed the effects of GXK in repressing inflammation and promoting phagocytosis. These results suggested that GXK could attenuate atherosclerosis and resolve inflammation via efferocytosis and MAPKs signaling pathways in LDLR−/− mice and RAW264.7 cells.

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dandan Sheng ◽  
Shanmin Zhao ◽  
Lu Gao ◽  
Huifei Zheng ◽  
Wenting Liu ◽  
...  

Abstract Background Babaodan (BBD), a traditional Chinese medicine, has been shown to have protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effects of BBD on obesity-induced NAFLD. Methods C57BL/6 J mice were fed with normal diet, high fat diet (HFD) or HFD + BBD for 8 weeks. Weights of all mice were recorded every 3 days. At the end of the experiments, the level of livers, kidneys and adipose tissues of each animal was weighed. Blood serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) cholesterol, low density lipoprotein cholesterol (LDL-C), glucose and leptin were detected with appropriate test kits. Haematoxylin–eosin (HE), Masson trichrome and Oil Red O staining of the liver were performed. We applied immunohistochemical analysis to investigate the expression of TNF-α, IL-6 and leptin in liver tissue. The expression of genes related lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and ß-oxidation (CPT-1 and PPARα) in liver and adipose tissues was determined by RT-PCR. The expression of AMPK and p-AMPK was determined by western blot analysis. Results We found the weight of bodies and tissues (retroperitoneal fat pads, kidneys and livers) of mice fed with HFD + BBD were significantly lower than that of HFD-fed mice. And liver injury induced by HFD was relieved in mice treated with BBD, accompanied with significant reduction were observed in serum ALT/AST activities and alleviated pathological damage. The levels of glucose, TG, TC, HDL-C and LDL-C in the liver or serum were significantly decreased on HFD + BBD group compared with HFD group. Furthermore, BBD treatment reduced the level of TNF-α and IL-6 induced by HFD. The level of leptin in the liver and serum were reduced in mice fed with HFD + BBD than that of HFD-fed mice. Several lipid synthesis genes (SREBP1-c, ACC, SCD-1, LXRα and CD36) were down-regulated and that of ß-oxidation (CPT-1 and PPARα) up-regulated in HFD + BBD group compared with HFD group. In addition, BBD increased the expression of p-AMPK compared with untreated HFD group, which suggested BBD improved the activation of AMPK pathway. Conclusion In summary, our results indicate that BBD has potential applications in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism via activation of AMPK signaling.


2018 ◽  
Vol 16 ◽  
pp. 205873921877271
Author(s):  
Zhiqian Wang ◽  
Xuejun Jiang

This research was carried out to investigate the effects of flavonoids ingredient from Polygonum capitatum (FPC) on blood lipid levels, vascular inflammation, and oxidative stress in high-fat diet (HFD) rats, as well as their mechanism of action. Rats fed with HFD for 6 weeks obviously displayed hyperlipidemia ( P < 0.01). Treatment with FPC at 90 and 180 mg/kg body weight significantly increased serum apolipoprotein A (ApoA) and high-density lipoprotein-cholesterol (HDL-C) levels and decreased serum apolipoprotein B (ApoB), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels of hyperlipidemia rats. FPC also improved the serum superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and decreased serum malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels. Meanwhile, the result of reverse transcription polymerase chain reaction (RT-PCR) manifested that FPC upregulated the messenger RNA (mRNA) expression of low-density lipoprotein receptor (LDLR) and peroxisome proliferator–activated receptor α (PPARα) and downregulated the mRNA expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), acetyl CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP-1C) in the hepatic. These results demonstrated that FPC exerted anti-atherosclerosis effect in hyperlipidemia rats by regulating blood lipid metabolism, improving antioxidant ability, and modulating a proinflammatory profile and the expression levels of genes referred to lipogenesis and lipid oxidation, which might be attributed to flavonoid ingredients such as luteolin-7-O-glucoside, rutin, and quercitrin.


Author(s):  
IRAM NAZISH ◽  
FAIZA SHAIKH ◽  
GAURANG SAWANT

Objective: To evaluate anti-obesity effect of aqueous P. nigrum extract in a murine model of high-fat diet (HFD) induced obesity. Methods: Male Wistar rats were fed with a high-fat diet (HFD) (20g/day/rat) for a period of 50 d to induce obesity. Aqueous P. nigrum extract (20 mg/kg) administered orally to high-fat diet (HFD) fed rats from 8th day to 50th day (total 42 d). The parameters like gain in body weight, serum lipids, insulin and leptin were measured. Results: The rats treated with extract showed a significant reduction in body weight gain, serum insulin, leptin, lipids as compared to rats fed with only a high-fat diet (HFD). In addition, the extract-treated group showed a considerable rise in high-density lipoprotein (HDL-C) level (29.61±7.68 mg/dl) as compared to the control group (23.23±9.69 mg/dl). Conclusion: The results indicate that aqueous P. nigrum extract possess the potential to reduce obesity markers in a high-fat diet (HFD) fed rats.


2019 ◽  
Vol 7 (7) ◽  
pp. 194 ◽  
Author(s):  
Kai Zhu ◽  
Fang Tan ◽  
Jianfei Mu ◽  
Ruokun Yi ◽  
Xianrong Zhou ◽  
...  

Sichuan pickle is a traditional fermented food in China which is produced by the spontaneous fermentation of Chinese cabbage. In this study, the anti-obesity effects of a new lactic acid bacterium (Lactobacillus fermentum CQPC05, LF-CQPC05) isolated from Sichuan pickles were assessed in vivo. An obese animal model was established in mice by inducing obesity with high-fat diet. Both serum and tissues were collected from the mice, and then subjected to qPCR and Western blot analyses. The results showed that LF-CQPC05 could decrease the values of hepatosomatic, epididymal fat, and perirenal fat indices that were induced by a high-fat diet in mice. Moreover, LF-CQPC05 reduced the levels of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), and increased the level of high-density lipoprotein cholesterol (HDL-C) in both serum samples and liver tissues of obese mice fed with a high-fat diet. Pathological observations demonstrated that LF-CQPC05 could alleviate the obesity-induced pathological changes in the liver tissue of mice, and reduce the degree of adipocyte enlargement. The results of qPCR and Western blot analyses further indicated that LF-CQPC05 upregulated the mRNA and protein expression levels of lipoprotein lipase (LPL), PPAR-α: peroxisome proliferator-activated receptor-alpha (PPAR-α), (cholesterol 7 alpha-hydroxylase) CYP7A1, and carnitine palmitoyltransferase 1 (CPT1A), and downregulated the expression levels of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and CCAAT enhancer-binding protein alpha (C/EBP-α) in both liver tissue and epididymal adipose tissue. Taken altogether, this study reveals that LF-CQPC05 can effectively inhibit high-fat diet-induced obesity. Its anti-obesity effect is comparable to that of l-carnitine, and is superior to that of Lactobacillus delbrueckii subsp. bulgaricus, a common strain used in the dairy industry. Therefore, LF-CQPC05 is a high-quality microbial strain with probiotic potential.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wojciech Dworzański ◽  
Iwona Sembratowicz ◽  
Ewelina Cholewińska ◽  
Krzysztof Tutaj ◽  
Bartosz Fotschki ◽  
...  

The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.


2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.


Author(s):  
Sihoon Park ◽  
Jae-Joon Lee ◽  
Hye-Won Shin ◽  
Sunyoon Jung ◽  
Jung-Heun Ha

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.


2009 ◽  
Vol 7 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Haifeng Zhang ◽  
Yuxiu He ◽  
Pak Kwong Chung ◽  
Tom K. Tong ◽  
Frank H. Fu ◽  
...  

2004 ◽  
Vol 91 (5) ◽  
pp. 715-723 ◽  
Author(s):  
Yajun Cheng ◽  
Lena Ohlsson ◽  
Rui-Dong Duan

Dietary fibre and fat affect colonic tumourigenesis and inflammation. Sphingomyelin metabolism may have implications for the pathogenesis of colonic tumours and ulcerative colitis. The present study examined the effects of psyllium and fat on the enzymes responsible for sphingomyelin metabolism and apoptosis in the colon. Mice were fed control, psyllium-containing (100 g/kg), high-fat (313 g/kg, 53 % energy as fat) or high-fat plus psyllium diets for 4 weeks. The activities of acid, neutral and alkaline sphingomyelinase (SMase), neutral ceramidase, and caspase 3, 8 and 9 in colonic mucosa were determined. The expressions of alkaline SMase and caspase 3 were examined. The psyllium-containing diet was found to increase significantly the activities of alkaline SMase and caspase 3 and decreased those of acid SMase and neutral ceramidase. The high-fat diet had opposite effects on these enzymes and attenuated the effects of psyllium. Western blotting showed that psyllium increased and high-fat decreased the levels of alkaline SMase and caspase 3 in colonic mucosa. The change in caspase 3 activity was positively correlated with that of alkaline SMase and negatively with acid SMase. No similar changes of acid and alkaline phosphatase activities in the colon or acid and neutral SMase activity in the liver were identified. In conclusion, colonic sphingomyelin metabolism and apoptosis were affected by psyllium and fat in an opposite manner. The results may have implications for colorectal tumourigenesis and inflammation.


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