scholarly journals Metabolomics Profiling to Investigate the Pharmacologic Mechanisms of Berberine for the Treatment of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

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 24 (02) ◽  
pp. 216-220
Author(s):  
Faizania Shabbir ◽  
M. Mazhar Hussain ◽  
Tausif Ahmed Rajput ◽  
Alamgir Khan

Objectives: To observe the effect of obesity and subsequent atorvastatinadministration on MPV in high fat diet induced obese male and female Sprague Dawley rats.Study Design: Randomized control trial (RCT). Setting: Department of Physiology, Army MedicalCollege, Rawalpindi. Animal procurement and blood sampling was done at National Instituteof Health (NIH), Islamabad and biochemical assays were performed at Centre for Research inExperimental and Applied Medicine (CREAM), Army Medical College, Rawalpindi. Period: Thestudy was completed in 12 months. Material and Methods: Ninety healthy Sprague Dawley(male and female) rats were purchased and divided randomly into three equal groups. Ratsin normal control group (Group I) were given normal chow diet for three weeks. Rats in obesecontrol group (Group II) were given high fat diet for three weeks. Rats in obese treated group(Group III) were administered atorvastatin for three weeks in a dose of 10 mg/kg/day orally bygavage method after obesity induction. Terminal sampling was done at the end of the studyby intra-cardiac puncture. MPV is a part of blood complete picture that was analysed by KX 21Sysmex Hematology Analyzer. Results: High fat diet induced obesity resulted in a significant(p < 0.05) increase in MPV. The MPV was significantly (p < 0.05) decreased after atorvastatinadministration. The result was comparable for both genders. Conclusions: Obesity increasesMPV and hence the risk of adverse cardiovascular outcome. Atorvastatin apart from its knownlipid lowering effect, decreases MPV and can play a beneficial role in decreasing cardiovascularmorbidity and mortality. 


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.


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.


Author(s):  
Sara Ameen Nafeer ◽  
Munaf Zalzala

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, which characterized by steatosis, inflammation, and fibrosis. The aim of this designed study is to evaluate the ability of guggulsterone to prevent high fat diet induced steatohepatitis in mice. Five groups of male mice were selected and treated as the following: group I, mice had free access to standard commercial diet and considered as control group, group II, mice were fed a specially formulated high-fat diet for 12 weeks to induce non-alcoholic liver disease, while groups III, IV and V the mice were administered high fat diet containing guggulsterone at 500, 1000 and 2000 ppm concentration respectively for 12 weeks. Maintaining mice on fat rich diet only resulted in inducing the metabolic and histological NAFLD associated. While the treatment with guggulsterone significantly improves the evaluated markers. These results demonstrate guggulsterone may be useful in preventing the development of steatohepatitis.


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.


2012 ◽  
Vol 90 (11) ◽  
pp. 1535-1543 ◽  
Author(s):  
Abdel-Aziz M. Hussein ◽  
Nashwa Barakat ◽  
Amira Awadalla ◽  
Ahmed A. Shokeir

The objective of this study was to investigate the effects of erythropoietin (EPO) on systemic and renal hemodynamics in a rat model of renal ischemic/reperfusion (I/R) injury. We used 30 male Sprague–Dawley rats distributed among the following 3 groups (10 rats per group): (i) the sham-operated group, (ii) the control group (I/R injury only), and (iii) the EPO-treated group (I/R injury with 1500 U EPO·(kg body mass)–1 on day 0, and 500 U·kg–1 on days 2 and 4 after ischemia). Renal function, arterial blood pressure (ABP), renal plasma flow (RPF), renal blood flow (RBF), and renal vascular resistance (RVR) were measured on days 1, 2, and 7 after ischemia. The expression of endothelial NO synthase (eNOS) and histopathology of kidney were evaluated on day 7. The contractility of aortic strips was recorded from the different groups. The results show that renal function and histopathology were significantly improved after treatment with EPO. Compared with the control group, the EPO-treated group showed a significant increase in RPF, RBF, haematocrite, ABP, eNOS expression, and a decrease in RVR (p < 0.05).The response of aortic strips to the relaxant effect of acetylcholine was improved in the EPO-treated group. In conclusion, treatment with EPO improves renal function and renal haemodynamics in renal I/R injury, and causes significant rise of ABP and haematocrite value.


2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Najla Gooda Sahib Jambocus ◽  
Nazamid Saari ◽  
Amin Ismail ◽  
Alfi Khatib ◽  
Mohamad Fawzi Mahomoodally ◽  
...  

The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract ofMorinda citrifoliaL. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a1H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon 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.


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