scholarly journals Ficus thonningii Stem Bark Extracts Prevent High Fructose Diet Induced Increased Plasma Triglyceride Concentration, Hepatic Steatosis and Inflammation in Growing Sprague-Dawley Rats

Author(s):  
Eliton Chivandi ◽  
Yvonne Mhosva ◽  
Trevor Nyakudya ◽  
Pilani Nkomozepi

BACKGROUND: Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activities. We investigated the potential of methanolic F. thonningii stem-bark extracts (MEFT) to protect growing Sprague-Dawley (SD) against high-fructose diet-induced metabolic derangements (MD) in a model mimicking children fed obesogenic diets. METHODS: Eighty (40 males; 40 females) 21-days old SD rat pups were randomly allocat-ed to and administered, for 8 weeks, five treatment regimens: 1 - standard rat chow (SC) + water (PW), 2 - SC + 20% (w/v) fructose solution (FS), 3 - SC + FS + fenofibrate at 100 mg/kg bwt/day, 4 - SC + FS + low dose MEFT (LD; 50 mg/kg bwt/day) and 5 - SC + FS + high dose MEFT (HD; 500 mg/kg bwt/day). Body weight, glucose load tolerance, fasting blood glucose and triglyceride, plasma insulin concentration, sensitivity to insulin, liver mass and fat content, steatosis and inflammation were determined. RESULTS: Fructose had no effect on the rats’ growth, glucose and insulin concentration, glucose tolerance and insulin sensitivity (P>0.05) but increased triglycerides in females; in-duced hepatic microsteatosis and inflammation in both sexes but macrosteatosis in females (P<0.05). In females, MEFT prevented fructose-induced plasma triglyceride increase. Low dose MEFT increased liver lipid content in females (P<0.05). The MEFT protected the rats against hepatic steatosis and inflammation but fenofibrate protected against hepatic mi-crosteatosis. CONCLUSION: MEFT can be used as prophylaxis against dietary fructose-induced ele-ments of MD but caution must be taken as low dose MEFT increases hepatic lipid accretion in females predisposing to fatty liver disease.

Author(s):  
Masiline Mapfumo ◽  
Busisani W. Lembede ◽  
Ashwell R. Ndhlala ◽  
Eliton Chivandi

AbstractBackgroundMoringa oleifera seed has anti-diabetic and anti-obesogenic properties. This study interrogated the effect of crude hydroethanolic M. oleifera seed extract on the blood markers of metabolic syndrome (MetS) in high-fructose diet fed growing Sprague-Dawley rats.MethodsSixty 21-day old female and male Sprague-Dawley rat pups were randomly allocated to and administered one of the following treatment regimens daily for twelve weeks: group I – plain drinking water (PW)+plain gelatine cube (PC), group II – 20% (w/v) fructose solution (FS)+PC, group III – FS+100 mg/kg body mass fenofibrate in gelatine cube (FN), group IV – FS+low dose (50 mg/kg body mass) of M. oleifera in gelatine cube (LMol) and group V – FS+high dose (500 mg/kg body mass) of M. oleifera in gelatine cube (HMol). The rats in each treatment regimen had ad libitum access to a standard rat chow. After the 12-week trial, the rats were subjected to an oral glucose tolerance test and then euthanised 48 h later. Blood was collected. Plasma triglyceride, cholesterol and insulin concentration were determined. HOMA-IR was then computed.ResultsThe high-fructose diet increased (p<0.05) plasma insulin concentration and HOMA-IR in female rats only. It increased plasma triglyceride concentration in both female and male rats and plasma cholesterol concentration in male rats only. The crude hydroethanolic M. oleifera seed extract prevented the high-fructose diet-induced metabolic derangements in male and female rats.ConclusionCrude hydroethanolic M. oleifera seed extract can potentially be used as a prophylactic intervention for diet-induced MetS in children.


2013 ◽  
Vol 305 (2) ◽  
pp. E293-E304 ◽  
Author(s):  
Masateru Ushio ◽  
Yoshihiko Nishio ◽  
Osamu Sekine ◽  
Yoshio Nagai ◽  
Yasuhiro Maeno ◽  
...  

Nonalcoholic fatty liver disease is the most frequent liver disease. Ezetimibe, an inhibitor of intestinal cholesterol absorption, has been reported to ameliorate hepatic steatosis in human and animal models. To explore how ezetimibe reduces hepatic steatosis, we investigated the effects of ezetimibe on the expression of lipogenic enzymes and intestinal lipid metabolism in mice fed a high-fat or a high-fructose diet. CBA/JN mice were fed a high-fat diet or a high-fructose diet for 8 wk with or without ezetimibe. High-fat diet induced hepatic steatosis accompanied by hyperinsulinemia. Treatment with ezetimibe reduced hepatic steatosis, insulin levels, and glucose production from pyruvate in mice fed the high-fat diet, suggesting a reduction of insulin resistance in the liver. In the intestinal analysis, ezetimibe reduced the expression of fatty acid transfer protein-4 and apoB-48 in mice fed the high-fat diet. However, treatment with ezetimibe did not prevent hepatic steatosis, hyperinsulinemia, and intestinal apoB-48 expression in mice fed the high-fructose diet. Ezetimibe decreased liver X receptor-α binding to the sterol regulatory element-binding protein-1c promoter but not expression of carbohydrate response element-binding protein and fatty acid synthase in mice fed the high-fructose diet, suggesting that ezetimibe did not reduce hepatic lipogenesis induced by the high-fructose diet. Elevation of hepatic and intestinal lipogenesis in mice fed a high-fructose diet may partly explain the differences in the effect of ezetimibe.


2021 ◽  
Vol 17 ◽  
Author(s):  
Yuxian Lin ◽  
Faxin Sun ◽  
Jinlai Liu ◽  
Qinghua Weng ◽  
Lijun Jin ◽  
...  

Background: To mitigate diabetes and its complications in cardiovascular diseases, the antidiabetic agent glimepiride is usually administered with ferulic acid concomitantly in clinics. However, both drugs are prone to be metabolized partly by CYP2C9, thus they have the potential drug-drug interaction affecting the safety and efficacy. Objective: This project aimed to evaluate the pharmacokinetic (PK) effects of ferulic acid (FA) on glimepiride (GLM) and its metabolite hydroxy glimepiride (OH-GLM) in plasma by using the HPLC-MS/MS method. Methods: Healthy male Sprague Dawley (SD) rats were randomly divided into three groups. They received intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC), low-dose FA (20 mg•kg-1), and high-dose FA (40 mg•kg-1) for 8 days, respectively. Rats were given 0.5% sodium CMC or FA on the last day and then uniformly given 1.0 mg•kg-1 glimepiride by gavage. Blood samples were obtained from retro-orbital plexus at the time points of 0.167, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. Plasma samples were analyzed for GLM and its metabolite OH-GLM on an HPLC-MS/MS system. Results: No statistically significant difference was found in the effect of low-dose FA on the pharmacokinetics of GLM. High-dose FA significantly decreased Cmax of GLM by 30.05% and CLz/F of OH-GLM by 47.45%. It also increased Tmax and t1/2z of GLM by 95.87% and 140.00%. Conclusion: Low-dose FA did not alter GLM metabolism, while high-dose treatment of FA caused pharmacokinetics interaction with GLM in rats.


2015 ◽  
Vol 57 (3) ◽  
pp. 244-253 ◽  
Author(s):  
Tetsuya Sujishi ◽  
Shinya Fukunishi ◽  
Masaaki Ii ◽  
Ken Nakamura ◽  
Keisuke Yokohama ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Wai-Teng Wong ◽  
Maznah Ismail ◽  
Eusni Rahayu Mohd Tohit ◽  
Rasedee Abdullah ◽  
Yi-Da Zhang

Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities.Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats.Ex vivoplatelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified.Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg).Results. Low dose 100 mg/kg of RBE inhibited aggregation by42.32±4.31% and this was comparable with the effect of 30 mg/kg aspirin,43.91±5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2was attenuated while prostacyclin level increased upon RBE treatment.Conclusions. RBE reducedex vivoADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms.


1997 ◽  
Vol 272 (3) ◽  
pp. E352-E358 ◽  
Author(s):  
N. Porksen ◽  
M. A. Hussain ◽  
T. L. Bianda ◽  
B. Nyholm ◽  
J. S. Christiansen ◽  
...  

Insulin-like growth factor I (IGF-I) shares structural and functional features with insulin, affects carbohydrate metabolism, and inhibits insulin secretion. Insulin secretion is pulsatile, and it is regulated by changing frequency and/or mass of secretory bursts. To examine the mechanism of IGF-I's inhibition of insulin secretion, eight healthy volunteers were studied three times. During glucose infusion (2.5 mg x kg(-1) x min(-1)) blood was sampled minutely at time 75-200 min for triplicate insulin concentration measurements by enzyme-linked immunosorbent assay (ELISA; coefficient of variation 2.1%). Time 125 min infusion of saline, low-dose IGF-I (0.025 microg x kg(-1) x min(-1)) or high-dose IGF-I (0.15 microg x kg(-1) x min(-1)) was commenced and continued until 200 min. Data were compared before (75-125 min) vs. during infusion (150-200 min). Insulin concentration time series were deconvolved, using validated pulse-detection criteria, to assess insulin secretory burst mass and frequency. During saline infusion no time effect occurred. After IGF-I infusion, serum C-peptide decreased (582 +/- 85 vs. 481 +/- 82 pM, low-dose IGF-I, P < 0.05; 539 +/- 84 vs. 427 +/- 69 pM, high-dose IGF-I, P < 0.01). Total insulin secretion rates decreased by 17 and 21%, respectively, via specific inhibition of the insulin secretory burst mass (31 +/- 8 vs. 20 +/- 4 pmol/ml, low-dose IGF-I, P = 0.06; 22 +/- 4 vs. 17 +/- 3 pmol/ml, high-dose IGF-I, P < 0.05), whereas the frequency was not affected (10.5 +/- 1.3 vs. 10.7 +/- 1.3 pulses/h, low-dose IGF-I, P = 0.85; 8.7 +/- 1.0 vs. 11.1 +/- 1.2 min/pulse, high-dose IGF-I, P = 0.15). We conclude that IGF-I inhibits pulsatile insulin secretion by specific inhibition of mass but not frequency of secretory bursts.


2020 ◽  
Vol 11 ◽  
Author(s):  
Mikhaïl A. Van Herck ◽  
Luisa Vonghia ◽  
Wilhelmus J. Kwanten ◽  
Thomas Vanwolleghem ◽  
Didier G. Ebo ◽  
...  

2016 ◽  
Vol 9 (1) ◽  
pp. 17-24
Author(s):  
Shamaya L. Whitby ◽  
Daniel A. Hunter ◽  
Wilson Yau ◽  
Elizabeth W. Howerth ◽  
Worlanyo E. Gato

Abstract Adipocyte dysfunction may be a critical link between obesity and insulin resistance as a result of abnormal fat storage and mobilization. Adipocytes uniquely secrete adipokines and cytokines, such as leptin and TNFα, wich promote insulin sensitivity. Previously we reported insulin-signaling related altered gene expression in animals exposed to 2-Aminoanthracene (2AA). 2AA is an aminosubstituted polycyclic aromatic hydrocarbon used in manufacturing dyes, chemicals, inks, resins, and polyurethanes. The objective of this study was to examine the inflammation related effects of 2AA exposure from gestation to postnatal period on dams that ingested 2AA. To examine 2AA effects, pregnant dams were assigned into dose regimens of 2AA. Dams were fed 2AA contaminated diet during the period of gestation and postpartum. The expression of key gene transcripts reported to be important in mediating inflammatory processes was examined via quantitative RT-PCR. Histologic examination of adipose tissue (AT) was also carried out to understand the anatomy of AT due to 2AA exposure during gestation and two weeks postpartum. Examination of the adipose tissue for microscopic changes revealed no alterations between control and low-dose animals. However, AT of the high-dose animals was infiltrated by increased numbers of CD68+mononuclear cells (macrophages) and small numbers of eosinophils and mast cells, consistent with inflammation. In addition, analysis of the mRNA expression of cytokines and adipokines demonstrated the importance of inflammation in AT dysfunction. For instance, TNFα, LEPTIN and IL-6 transcripts were relatively more expressed in the low dose animals than in the high dose and control rats. At the protein level, however, high amounts of cytokines were noted. The effects of 2AA on pregnant dams appear to be more pronounced in the high dose group than in the low dose group, possibly indicating increased susceptibility of rat offspring within this group to elicit a diabetic-type response.


2018 ◽  
Vol 52 ◽  
pp. 45-53 ◽  
Author(s):  
Katsutaka Oishi ◽  
Tatsuya Konishi ◽  
Chiaki Hashimoto ◽  
Saori Yamamoto ◽  
Yoshinori Takahashi ◽  
...  

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