scholarly journals Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPARγin a Rat Model

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Warinda Susutlertpanya ◽  
Duangporn Werawatganon ◽  
Prasong Siriviriyakul ◽  
Naruemon Klaikeaw

Nonalcoholic steatohepatitis (NASH) has become a global chronic liver disease, but no effective medicine has been proven to cure it. This study investigated the protective effects of genistein, a phytoestrogen, on NASH and examined whether it has any effect on hepatic PPARγ. Male Sprague-Dawley rats were divided into four groups: control group fed ad libitum with standard rat diet, NASH group fed ad libitum with high-fat diet to induce NASH and NASH + Gen8 group and NASH + Gen16 group fed with high-fat diet plus intragastric administration of 8 or 16 mg/kg genistein once daily. After 6 weeks, liver samples were collected to determine MDA, TNF-α, PPARγ, and histopathology. The findings were that levels of hepatic MDA and TNF-αincreased in NASH group, but 16 mg/kg genistein reduced these levels significantly. Downregulation of hepatic PPARγwas observed in NASH group, but genistein significantly upregulated the expression of PPARγin both NASH + Gen groups. The histological appearance of liver in NASH group presented pathological features of steatohepatitis which were diminished in both NASH + Gen groups. The results suggest that genistein attenuates the liver histopathology of NASH with upregulation of hepatic PPARγ, reduction of oxidative stress, and inhibition of inflammatory cytokine.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jian Li ◽  
Zezhou Liu ◽  
Mingxing Guo ◽  
Kejia Xu ◽  
Miao Jiang ◽  
...  

Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH), which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques.Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group): (i) normal control group; (ii) high-fat diet- (HFD-) induced NASH model group; and (iii) HFD berberine-treated group (i.d. 200 mg/kg). The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH.Key Findings. (i) According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii) Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM), phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE), eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine.Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH.


2017 ◽  
Vol 41 (2) ◽  
pp. 598-608 ◽  
Author(s):  
Xiangrong Cui ◽  
Chunlan Long ◽  
Jing Zhu ◽  
Jie Tian

Background: Statins can reduce reproductive damage induced by obesity or high-fat diet (HFD), but the specific regulatory mechanisms are largely unknown. Since mTOR/p70s6k sinaling promotes spermatogonia proliferation and spermatogenesis, we hypothesized that this pathway will be involved in the protective effects of statin in HFD-induced reproductive dysfunction. Methods: Male Sprague Dawley rats (3 weeks old) were randomly divided into a control group (standard diet), HFD group, and a fluvastatin group (HFD + fluvastatin at 6mg/kg, once daily by oral gavage). After 8 weeks, body weight was obtain and rats were sacrificed. Weights of the testes, gross morphology, sperm parameters, circulating levels of sex hormones, lipid levels, and tissue mTOR, p-P70s6k were measured. Another set of male rats were treated with rapamycin or vehicle. Flow cytometry was used to detect the spermatogonia marker c-kit and cell cycle. p-P70s6k expression was analyzed by Western blot. Results: HFD not only results in rat obesity but also leads to spermatogenetic damage and fluvastatin was able to partially block the effects of HFD. Fluvastatin also partially reversed the suppression of mTOR and p-p70s6k expresson. Conclusion: Our data suggest that fluvastatin has protective effects on reproductive function in obese male rats most probably through enhanced signaling of mTOR.


Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1353
Author(s):  
Ji Hyun Kim ◽  
Sanghyun Lee ◽  
Eun Ju Cho

Obesity increases risk of Alzheimer’s Disease (AD). A high fat diet (HFD) can lead to amyloidosis and amyloid beta (Aβ) accumulation, which are hallmarks of AD. In this study, protective effects of the ethyl acetate fraction of Acer okamotoanum (EAO) and isoquercitrin were evaluated on obesity and amyloidosis in the HFD- and Aβ-induced mouse model. To induce obesity and AD by HFD and Aβ, mice were provided with HFD for 10 weeks and were intracerebroventricularly injected with Aβ25–35. For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally. Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice. Additionally, EAO- and isoquercitrin-administered groups attenuated abnormal adipokines release via a decrease in leptin and an increase in adiponectin levels compared with the control group. Furthermore, HFD and Aβ-injected mice had damaged liver tissues, but EAO- and isoquercitrin-administered groups attenuated liver damage. Moreover, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice. This study indicated that EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2448
Author(s):  
Taehwan Lim ◽  
Juhee Ryu ◽  
Kiuk Lee ◽  
Sun Young Park ◽  
Keum Taek Hwang

Choline is converted to trimethylamine by gut microbiota and further oxidized to trimethylamine-N-oxide (TMAO) by hepatic flavin monooxygenases. Positive correlation between TMAO and chronic diseases has been reported. Polyphenols in black raspberry (BR), especially anthocyanins, possess various biological activities. The objective of this study was to determine the effects of BR extract on the level of choline-derived metabolites, serum lipid profile, and inflammation markers in rats fed high-fat and high-choline diets. Forty female Sprague-Dawley (SD) rats were randomly divided into four groups and fed for 8 weeks as follows: CON (AIN-93G diet), HF (high-fat diet), HFC (HF + 1.5% choline water), and HFCB (HFC + 0.6% BR extract). Serum levels of TMAO, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and cecal trimethylamine (TMA) level were significantly higher in the HFC than in the HFCB. BR extract decreased mRNA expression of pro-inflammatory genes including nuclear factor-κB (NF-κB), interleukin (IL)-1β, IL-6, and cyclooxygenase-2 (COX-2), and protein expression of NF-κB and COX-2 in liver tissue. These results suggest that consistent intake of BR extract might alleviate hypercholesterolemia and hepatic inflammation induced by excessive choline with a high-fat diet via lowering elevated levels of cecal TMA and serum TMAO in rats.


2009 ◽  
Vol 78 (4) ◽  
pp. 661-666 ◽  
Author(s):  
Emília Hijová ◽  
Anna Chmelárová ◽  
Alojz Bomba

The aim of the present study was the evaluation of possible protective effects of selected bioactive food components in experimental N,N-dimethylhydrazine (DMH)-induced colon carcinogenesis. Wistar albino rats (n = 92) were fed a high fat diet or conventional laboratory diet. Two weeks after the beginning of the trial, DMH injections were given to six groups of rats at the dose of 20 mg/kg b.w. twice weekly. The activity of bacterial enzymes in faeces and serum bile acid concentrations were determined. High fat diet, DMH injections, and their combination significantly increased the activies of β-galactosidase, β-glucuronidase, and α-glucosidase (p < 0.001) compared to the control group of rats. Treatment with the prebiotic inulin, Hyppocastani extractum siccum and Lini oleum virginale significantly decreased the activity of β-galactosidase, β-glucuronidase, and α-glucosidase (p < 0.001), as well as the bile acid concentration compared to the group at the highest risk. The protective effects of selected bioactive food components in experimentally induced colon carcinogenesis allow for their possible use in cancer prevention or treatment.


Author(s):  
Zhen-hong Xia ◽  
Wen-bo Chen ◽  
Li Shi ◽  
Xue Jiang ◽  
Ke Li ◽  
...  

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Zhixing Li ◽  
Danchun Lan ◽  
Haihua Zhang ◽  
Hongtao Zhang ◽  
Xiaozhuan Chen ◽  
...  

The aim of this work is to investigate the effect of electroacupuncture (EA) on insulin sensitivity in high-fat diet (HFD) induced insulin resistance (IR) rats and to evaluate expression of AMPK/ACC signaling components. Thirty-two male Sprague-Dawley rats were randomized into control group, HFD group, HFD+Pi (oral gavage of pioglitazone) group, and HFD+EA group. Acupuncture was subcutaneously applied to Zusanli (ST40) and Sanyinjiao (SP6). For Zusanli (ST40) and Sanyinjiao (SP6), needles were connected to an electroacupuncture (EA) apparatus. Fasting plasma glucose was measured by glucose oxidase method. Plasma fasting insulin (FINS) and adiponectin (ADP) were determined by ELISA. Triglyceride (TG) and cholesterol (TC) were determined by Gpo-pap. Proteins of adiponectin receptor 1 (adipoR1), AMP-activated Protein Kinase (AMPK), and acetyl-CoA carboxylase (ACC) were determined by Western blot, respectively. Compared with the control group, HFD group exhibits increased levels of FPG, FINS, and homeostatic model assessment of insulin resistance (HOMA-IR) and decreased level of ADP and insulin sensitivity index (ISI). These changes were reversed by both EA and pioglitazone. Proteins of adipoR1 and AMPK were decreased, while ACC were increased in HFD group compared to control group. Proteins of these molecules were restored back to normal levels upon EA and pioglitazone. EA can improve the insulin sensitivity of insulin resistance rats; the positive regulation of the AMPK/ACC pathway in the skeletal muscle may be a possible mechanism of EA in the treatment of IR.


Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 271 ◽  
Author(s):  
Zhen-Hong Xia ◽  
Wen-Bo Chen ◽  
Li Shi ◽  
Xue Jiang ◽  
Ke Li ◽  
...  

Curcumin is the main secondary metabolite of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect of curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170–190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF + STZ group), and a high-fat diet combined with curcumin and STZ group (HF + Cur + STZ group). Compared with the HF + STZ group, the HF + Cur + STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST), and aspartate transaminase (ALT) levels, as well as liver coefficients. In the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.


2015 ◽  
Vol 40 (9) ◽  
pp. 868-876 ◽  
Author(s):  
Sanne Stegen ◽  
Bram Stegen ◽  
Giancarlo Aldini ◽  
Alessandra Altomare ◽  
Luca Cannizzaro ◽  
...  

There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus β-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague–Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% β-alanine (HFba), as β-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine–4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine Nε-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1143
Author(s):  
Dewi Irawati Soeria Santoso ◽  
Nurul Paramita ◽  
Ani Retno Prijanti ◽  
Thressia Hendrawan ◽  
Swandito Wicaksono

Background: There is an increasing number of studies showing that physical activity and aerobic exercise have a positive effect on telomere length. Some studies also show that dynamics of telomere length is influenced by various environmental factors such as lifestyle and diet. However, the association between exercise and diet with telomere length is still questionable. The aim of this study was to examine the effects of aerobic physical exercise on relative telomere length changes in high fat-diet condition in rat animal models. Methods: This study was an in vivo experimental study using twelve Sprague-Dawley male white rats (12-month-old). Subjects were evenly and randomly divided into two groups (n=6): (1) high fat-diet fed control group; (2) high fat-diet fed and aerobic exercise treatment group. Aerobic exercise was conducted using animal treadmill with intensity of 20 m/min, 5 days/week. At weeks 4 and 8, relative telomere length was compared with week 0 control group, using q-RT-PCR. Results: Lengthening of relative telomere length was observed in both control and treatment groups at weeks 4 and 8, when compared to week 0 control group. The lengthening in the control group was much greater than the treatment group. Conclusions: Excessive increase of relative telomere length was seen in high fat-diet conditions. Aerobic exercise for 8 weeks suppresses excessive increase of relative telomere length in high fat-diet conditions.


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