scholarly journals Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

2015 ◽  
Vol 35 (5) ◽  
pp. 1744-1755 ◽  
Author(s):  
Xin Liu ◽  
Chun-Yu Guo ◽  
Xiao-Juan Ma ◽  
Cai-Feng Wu ◽  
Ying Zhang ◽  
...  

Aims: Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA) is similar to the 17ß-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation. Methods: Subjects for this study were 120 apoE-/- female mice and 20 C57/BL female mice. The apoE-/- mice were ovariectomized (OVX) and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR) group. The OVX apoE-/- mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD) group which was fed a high fat diet only, E2 group were given estrogen (E2) 0.13mg/kg/d; E2+ICI group were given E2:0.13mg/kg/d and ICI182780:65mg/kg/m; TLD group (TanIIA low dose) were given TanIIA: 30mg/kg/d; THD group (TanIIA high dose) were given TanIIA:60mg/kg/d; and TLD+ICI group were given TanIIA 30mg/kg/d and ICI182780 65mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE) and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), nuclear factor kappa (NF-κB), soluble intercellular cell adhesion molecule-1 (sICAM-1), activating protein-1 (AP-1), E-selectin and 17ß-estradiol in serum. Results: Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL) and SOD in serum. Tanshinone IIA also suppressed the expression of p-ERK1/2. Tanshinone IIA had no effect of level of serum 17ß-estradiol levels. All of the effects of Tanshinone IIA were similar to estrogen and were inhibited by the estrogen receptor antagonist ICI182780. Conclusion: Tanshinone IIA may play an anti-inflammatory and anti-oxidative stress role in OVX atherosclerotic apoE-/- mice by activating the estrogen receptor through the ERK signaling pathway. Therefore, Tanshinone IIA, as a phytoestrogen, could be used for estrogen replacement therapy for cardiovascular disease of postmenopausal women.

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
O. B. Ibitoye ◽  
U. M. Ghali ◽  
J. B. Adekunle ◽  
J. N. Uwazie ◽  
T. O. Ajiboye

Dioscoreophyllum cumminsii (Stapf) Diels leaves are widely used in the treatment of diabetes, obesity, and cardiovascular related complications in Nigeria. This study investigates the anti-inflammatory and antiobesity effect of aqueous extract of Dioscoreophyllum cumminsii leaves in high-fat diet- (HFD-) induced obese rats. HFD-fed rats were given 100, 200, and 400 mgkg−1 body weight of aqueous extract of Dioscoreophyllum cumminsii leaves for 4 weeks starting from 9th week of HFD treatment. D. cumminsii leaves aqueous extract reversed HFD-mediated decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase. Moreover, HFD-mediated elevation in the levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl, and DNA fragmentation in rats liver was lowered. HFD-mediated alterations in serum total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were significantly reversed by the extract. The treatment of HFD-fed rats reduced the levels of insulin, leptin, protein carbonyl, fragmented DNA, and tumour necrosis factor-α and interleukin- (IL-) 6 and IL- 8 and increased the adiponectin level. This study showed that aqueous extract of Dioscoreophyllum cumminsii leaves has potential antiobesity and anti-inflammatory effects through modulation of obesity-induced inflammation, oxidative stress, and obesity-related disorder in HFD-induced obese rats.


2019 ◽  
Vol 10 (2) ◽  
pp. 1181-1184
Author(s):  
Satheesh Naik K ◽  
Gurushanthaiah M ◽  
Nagesh Raju G ◽  
Lokanadham S ◽  
Seshadri Reddy V

Eclipta Alba has been used in traditional and folklore medicine to treat Hyperlipidemia and hepatic disorders. The present study was aimed to investigate the Antihyperlipidemic and hepatoprotective potentials of Eclipta Alba in high-fat diet -induced Albino rats and to determine the underlying mechanism.  A total of 30 adult albino rats of Wistar strain weighing 165–215 g were utilized. Animals were treated with high-fat diet for 8 weeks followed by post-treatment of E. Alba for 1 week, 2 weeks, and 3 weeks, respectively. After 12 h of fasting on the last day of the experiment, serum blood samples were collected in EDTA vials and processed for biochemical analysis.  A significant decrease in levels of total cholesterol and triglycerides was noted on animals treated with E. alba compared to high-fat diet animals. Treatment of hypercholesterolemic rats with E. Alba showed a marked decrease of serum low-density lipoprotein (LDL) and very LDL cholesterol concentrations compared to the hypercholesterolemic rats. High-fat diet feeding worsened the levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase enzymes, whereas the same markers were significantly improved by supplementation with E. alba compared to the normal group.  E. alba acts as an antihyperlipidemic agent in hyperlipidemic conditions and helps for better health.


2018 ◽  
Vol 19 (12) ◽  
pp. 3903 ◽  
Author(s):  
Xiaofei Zhu ◽  
Jingyi Yang ◽  
Wenjuan Zhu ◽  
Xiaoxiao Yin ◽  
Beibei Yang ◽  
...  

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1—a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 748 ◽  
Author(s):  
Tzu-Hsuan Ou ◽  
Yu-Tang Tung ◽  
Ting-Hsuan Yang ◽  
Yi-Wen Chien

The aim of this study was to investigate the effect of melatonin on hepatic lipid metabolism in hamsters with high-fat diet (HFD)-induced dyslipidemia. Male Syrian hamsters were kept on either a chow control (C) or HFD for four weeks. After four weeks, animals fed the HFD were further randomly assigned to four groups: high-fat only (P), melatonin low-dosage (L), medium-dosage (M), and high-dosage (H) groups. The L, M, and H groups, respectively, received 10, 20, and 50 mg/kg/day of a melatonin solution, while the P and C groups received the ethanol vehicle. After eight weeks of the intervention, results showed that a low dose of melatonin significantly reduced HFD-induced hepatic cholesterol and triglycerides; decreased plasma cholesterol, triglycerides, and low-density lipoprotein cholesterol; and increased plasma high-density lipoprotein cholesterol (p < 0.05). In addition, melatonin markedly decreased activities of the hepatic lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) (p < 0.05), and elevated the relative hepatic carnitine palmitoyltransferase-1α expression in hamsters with HFD-induced hyperlipidemia. Consequently, melatonin reduced activities of the hepatic lipogenic enzymes, ACC and FAS. In summary, chronic melatonin administration improved HFD-induced dyslipidemia and hepatic lipid accumulation in Syrian hamsters with HFD-induced dyslipidemia, which might have occurred through inhibiting the lipogenesis pathway.


2019 ◽  
Vol 97 (7) ◽  
pp. 611-622 ◽  
Author(s):  
Mohammed M. Heikal ◽  
Ahmed A. Shaaban ◽  
Wagdi F. Elkashef ◽  
Tarek M. Ibrahim

Febuxostat, a highly potent xanthine oxidase inhibitor with an antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. The aim of this study was to test the potential antioxidant and anti-inflammatory effects of febuxostat and (or) stopping a high-fat diet on the biochemical parameters in rabbits with hyperlipidemia induced by a high-fat diet. Male New Zealand rabbits were distributed into 3 groups: a normal control group fed standard chow for 12 weeks and 2 other groups fed a high-fat diet with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks, one high-fat diet group received 0.5% carboxymethyl cellulose, whereas the other group was treated with febuxostat (2 mg/kg per day p.o.). Febuxostat significantly lowered low-density lipoprotein cholesterol (“bad” cholesterol) compared to the untreated group (high-fat diet group). Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, proinflammatory cytokines, and enhancing antioxidant enzyme activity. Stopping the hyperlipidemic diet in the high-fat diet group did not show improvement. These findings indicate the antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping a hyperlipidemic diet without treatment is not sufficient once injury has occurred.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Bilal A. Zargar ◽  
Mubashir H. Masoodi ◽  
Bahar Ahmed ◽  
Showkat A. Ganie

The present study was intended to evaluate the effects of Paeonia emodi rhizome extracts on serum triglycerides (TGs), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), atherogenic index (AI), superoxide dismutase (SOD), and glutathione peroxidase (GPx). The plant was extensively examined for its in vitro antioxidant activity, and the preliminary phytochemical screening was carried out using standard protocols. Male Wistar rats were induced with hyperlipidemia using high-fat diet and were treated orally with hydroalcoholic and aqueous extracts at the dose of 200 mg/kg bw for 30 days. TGs, TC, LDL-c, and AI were significantly reduced while HDL-c, SOD, and GPx levels rose to a considerable extent. After subjecting to acute toxicity testing, the extracts were found to be safe. The observations suggest antihyperlipidemic and antioxidant potential of P. emodi in high-fat diet induced hyperlipidemic/oxidative stressed rats.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Liang Liu ◽  
Chao Gao ◽  
Ping Yao ◽  
Zhiyong Gong

A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved.


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