Phycocyanin attenuates skeletal muscle damage and fatigue via modulation of Nrf2 and IRS-1/AKT/mTOR pathway in exercise-induced oxidative stress in rats.

Prolonged strenuous exercise induces oxidative stress, leading to oxidative damage, skeletal muscle fatigue, and reduced exercise performance. The body compensates for oxidative stress through antioxidant actions, while related enzymes alone may not overcome excessive oxidative stress during prolonged strenuous exercise. Phycocyanin is an important antioxidant supplement derived from blue-green algae, which may be helpful in this type of situation. This study determined the effects of phycocyanin on exercise performance from prolonged strenuous exercise. Forty Sprague Dawley male rats were divided into 5 groups (n = 8 /group); Control group (C), Exercise group (E), and Exercise with supplement groups receiving low dose (Phycocyanin = 100 mg/kg BW; ELP) and high dose (Phycocyanin = 200 mg/kg BW; EHP) or vitamin C (Vitamin C = 200 mg/kg BW; VC). Phycocyanin was found to decrease oxidative damage markers, muscle fatigue, and muscle atrophy through the activated AKT/mTOR pathway. This was also found to have greater increases in antioxidants via Nrf2 signaling and increases ATP synthesis, GLUT4 transporters, and insulin signaling due to increased IRS-1/AKT signaling. In conclusion, phycocyanin was found to reduce oxidative damage and muscle atrophy, including an increase in insulin signaling in skeletal muscles leading to increased exercise performance in rats.

Wax apple (Syzygium samarangense) fruit extract ameliorates endothelial dysfunction and liver damage in high cholesterol diet-fed rats.

Background and aim: Wax apple fruit (Syzygium samarangense) is one of the most popular tropical fruit in Asia, and contains several essential nutrients. Therefore, this study explored the effects of the wax apple fruit extract on a high-cholesterol diet-induced vascular endothelial dysfunction and fatty liver in rats. Experimental procedure: Male Sprague Dawley rats were fed a diet with 1.5% cholesterol (HCD) for 8 weeks, and were given wax apple fruit extract (50 and 100 mg/kg/day) orally for the last 4 weeks. After 8 weeks, blood sample, thoracic aorta, and liver were collected and processed for biochemical and histological analysis. Additionally, vascular endothelial function and the protein expression of oxidative stress markers in aortae were evaluated. Results and conclusion: Wax apple reduced serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), but increased high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, the liver levels of TG and TC were reduced in wax apple-treated hypercholesterolemic rats. Histological studies revealed that wax apple ameliorated HCD-induced morphologic changes of aortic and liver tissues of rats. In aortic tissues, the impaired endothelium-dependent responses to acetylcholine, the reduced nitric oxide (NO) contents, the elevated endothelin (ET)-1 contents, and the increased expression of NADPH oxidase subunit p47phox and 4-hydroxynonenal in HCD-fed rats were reversed by wax apple treatment. These results suggest that oral administration of wax apple improves vascular dysfunction and damage in hypercholesterolemic rats possibly through increasing NO bioavailability, decreasing ET-1 levels and reducing oxidative stress. Furthermore, wax apple ameliorates the HCD-induced fatty liver in rats.

Naringin Ameliorates Skeletal Muscle Atrophy and Improves Insulin Resistance in High-Fat-Diet-Induced Insulin Resistance in Obese Rats.

Obesity causes progressive lipid accumulation and insulin resistance within muscle cells and affects skeletal muscle fibres and muscle mass that demonstrates atrophy and dysfunction. This study investigated the effects of naringin on the metabolic processes of skeletal muscle in obese rats. Male Sprague Dawley rats were divided into five groups: the control group with normal diet and the obese groups, which were induced with a high-fat diet (HFD) for the first 4 weeks and then treated with 40 mg/kg of simvastatin and 50 and 100 mg/kg of naringin from week 4 to 8. The naringin-treated group showed reduced body weight, biochemical parameters, and the mRNA expressions of protein degradation. Moreover, increased levels of antioxidant enzymes, glycogen, glucose uptake, the expression of the insulin receptor substrate 1 (IRS-1), the glucose transporter type 4 (GLUT4), and the mRNA expressions of protein synthesis led to improved muscle mass in the naringin-treated groups. The in vitro part showed the inhibitory effects of naringin on digestive enzymes related to lipid and glucose homeostasis. This study demonstrates the potential benefits of naringin as a supplement for treating muscle abnormalities in obese rats by modulating the antioxidative status, regulating protein metabolism, and improved insulin resistance in skeletal muscle of HFD-induced insulin resistance in obese rats.

Effects of curcumin and γ-oryzanol solid dispersion on the brain of middle-aged rats.

Oxidative stress is one of the major factors that contributes to brain deterioration in the elderly. Oxidation causes molecular alterations, structural damage, and brain dysfunction, which includes cognitive impairment. Memory loss can begin in middle-aged individuals, so prevention of brain deterioration before aging is important. Several studies have reported that curcumin and γ-oryzanol exhibits anti-oxidant and anti-inflammatory properties. However, curcumin and γ-oryzanol exhibit low aqueous solubility. Thus, a solid dispersion technique was used to prepare curcumin and γ-oryzanol to enhance their solubility and stability. This study aims to evaluate the effects and mechanisms of γ-oryzanol solid dispersion (GOSD) and curcumin solid dispersion (CURSD) on learning and memory in six groups of male rats (n=5/group). Group one was the adult control consisting of 6-week old male rats, and the remaining five groups consisted of 42-week (middle-aged) male rats. The groups were labeled as the control group, the GO group (GOSD 10 mg/kg·BW), the Cur group (CURSD 50 mg/kg·BW), the GO-LCur group (GOSD 10 mg/kg·BW plus CURSD 25 mg/kg·BW), and the GO-HCur group (GOSD 10 mg/kg·BW plus CURSD 50 mg/kg·BW). Substances were administrated by oral gavage once daily for 42 consecutive days. The GO-HCur group exhibited significantly increased learning and memory performance in a Morris water maze and in reacting to a spontaneous tendency novel object test. The rats also exhibited decreased levels of lipid peroxidation, increased superoxide dismutase levels, glutathione peroxidase levels, catalase activity, and enhanced c-Fos expression both in the hippocampus and prefrontal cortex. The results indicated that GOSD 10 mg/kg plus CURSD 50 mg/kg was able to enhance learning and memory performance in the middle-aged rats.

Hibiscus sabdariffa extract improves hepatic steatosis, partially through IRS-1/Akt and Nrf2 signaling pathways in rats fed a high fat diet.

Non-alcoholic fatty liver disease (NAFLD) has become a major world-wide health problem and is characterized by lipid accumulation in the liver induced by high fat diet (HFD) consumption. It is usually associated with inflammation, oxidative stress, and insulin resistance. Roselle extract (Hibiscus sabdariffa) is an herb which is used in traditional medicine. However, further study is necessary to represent the mechanism of NAFLD and find new preventive strategies. This study aims to investigate the protective effects of roselle extract on NAFLD rat models. Male Sprague-Dawley rats (n = 35) were divided into 5 groups, control, HFD, HFD + Simvastatin (HFD + SIM), HFD + 250 mg/kg BW, and HFD + 500 mg/kg BW of roselle extract (HFD + R250 and HFD + R500, respectively). The results showed that roselle extract reduced hepatic lipid contents, de novo lipogenesis enzymes, microsomal triglyceride transfer protein, inflammatory cytokines, malondialdehyde, and increased antioxidant properties, transporter related with lipoprotein uptake, and insulin signal proteins. Comparing to SIM, the HFD + R500 group exhibited the greater benefit in terms of anti-hepatic steatosis, antioxidant properties, and an ability to improve insulin resistance. This study demonstrates that roselle extract improved antioxidant properties and attenuated hepatic steatosis, liver inflammation, oxidative stress, and insulin resistance in HFD-induced NAFLD in rats, which could be used for NAFLD prevention.

Papaya improves non-alcoholic fatty liver disease in obese rats by attenuating oxidative stress, inflammation and lipogenic gene expression.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a global health issue that is correlated with obesity and oxidative stress. AIM: To evaluate the anti-NAFLD effect of papaya in high fat diet induced obesity in rats. METHODS: Four-week-old male Sprague-Dawley rats were divided into four groups after 1 wk of acclimatization: Group 1 was the rats fed a normal diet (C); group 2 was the rats fed a high fat diet (HFD); group 3 was the rats fed a HFD with 0.5 mL of papaya juice/100 g body weight (HFL), and group 4 was the rats fed a HFD with 1 mL of papaya juice/100 g body weight (HFH) for 12 wk. At the end of the treatment, blood and tissue samples were collected for biochemical analyses and histological assessment. RESULTS: The results of the HFH group showed significantly reduced body weight (HFH vs HFD, P < 0.01), decreased NAFLD score (HFH vs HFD, P < 0.05), and reduced hepatic total cholesterol (HFL vs HFD, P < 0.01; HFH vs HFD, P < 0.001), hepatic triglyceride (HFH vs HFD, P < 0.05), malondialdehyde (HFL, HFH vs HFD, P < 0.001), tumour necrosis factor-α (HFH vs HFD, P < 0.05) and interleukin-6 (HFH vs HFD, P < 0.05) when compared to the HFD group. However, the liver weight showed no significant difference among the groups. The activities of catalase and superoxide dismutase significantly increased in HFH when compared with the HFD group (P < 0.05 and P < 0.001, respectively). The suppression of transcriptional factors of hepatic lipogenesis, including sterol regulatory element-binding protein 1c and fatty acid synthase, were observed in the papaya treated group (HFH vs HFD, P < 0.05). These beneficial effects of papaya against HFD-induced NAFLD are through lowering hepatic lipid accumulation, suppressing the lipogenic pathway, improving the balance of antioxidant status, and lowering systemic inflammation. CONCLUSION: These current results provide experimental-based evidence suggesting papaya is an efficacious medicinal fruit for use in the prevention or treatment of NAFLD.

Hibiscus sabdariffa L. calyx extract prevents the adipogenesis of 3T3-L1 adipocytes, and obesity-related insulin resistance in high-fat diet-induced obese rats.

Roselle (Hibiscus sabdariffa) is reported to be beneficial in treating obesity which can develop into a range of metabolic disorders. The molecular mechanisms by which roselle extract works to prevent obesity-related insulin resistance remains poorly understood. We hypothesized that the roselle extract can decrease lipid accumulation and improve insulin resistance by downregulating adipogenesis. The aim of this study is to investigate the protective effect of roselle extract on the mechanism of adipogenesis and prevent complications of the obesity-related insulin resistance in high-fat diet-induced obese rats for 8 weeks. Male Sprague Dawley rats were divided into 4 groups: control (C), high-fat diet (HFD), high-fat diet supplemented with 250 mg/kg BW of roselle (R250), and high-fat diet supplemented with 500 mg/kg BW of roselle (R500). The results demonstrated that roselle had the potential to reduce body weight, food intake, lipid profiles, inflammatory cytokines, lipid peroxidation, serum leptin, insulin and duodenal glucose absorption, while significantly increased glucose uptake of adipose tissue and muscle when compared to the HFD group. Roselle can prevent lipid accumulation by suppressing differentiation of 3T3-L1 adipocyte by downregulating the adipogenic gene expression. The results of this study demonstrated that the molecular mechanism underlying the protective effect of roselle, could be an alternative approach for obesity-related insulin resistance prevention.

Anti-obesity effect of Carica papaya in high-fat diet fed rats.

The present study evaluated the anti-obesity properties of papaya in high-fat (HF) diet fed rats. In the in vitro portion of the present study, the effects of papaya juice on pancreatic lipase enzyme activity was assessed, and it was shown that papaya exhibited an inhibitory effect on these enzymes. In the in vivo portion of the study, papaya was found to reduce the expression levels of markers of obesity, inflammation and oxidative stress in rats. Obesity was induced in 28 male Sprague Dawley rats by feeding them a HF diet for 12 weeks. The anti-obesity effects of papaya was evaluated by feeding papaya juice orally in with two experimental doses: 0.5 ml (HFL) and 1.0 ml (HFH) per 100 g of body weight. The HF diet resulted in significant increases in the body weight, serum triglyceride, serum total cholesterol and serum low-density lipoprotein cholesterol levels, as well as a decrease in serum high-density lipoprotein cholesterol levels. The HF diet also induced adipocyte hypertrophy, lipid accumulation and increased malondialdehyde levels. Papaya reversed all of these changes and significantly increased serum superoxide dismutase and decreased serum cytokine (interleukin-6) levels. The protein expression of levels PPARγ in the HF group was significantly increased compared with the other groups, but was decreased significantly in the HFH group. Histological observations of epididymal adipose tissue provided evidence for the lipid-lowering effects of papaya. The results of the present study demonstrate that papaya has the potential to reduce the risk of obesity associated with adiposity, anti-inflammation and anti-oxidation.

Ginger Extract and [6]-Gingerol Inhibit Contraction of Rat Entire Small Intestine.

This study aims to investigate the effect of oral administration and the direct action of ginger extract or [6]-gingerol on small intestinal contractility. The direct effect of 10 minutes preincubation of ginger ethanolic extract (10, 100 and 300 µg/mL) or [6]-gingerol (1, 30, and 100 µM) on 0.01 to 30 µM ACh-induced contractions of all parts of the small intestine isolated from normal rats was investigated using the organ bath technique. For in vivo study, the rats were orally administered with extract (10, 20, and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d) for 7 days, followed by determining the contractile responses to ACh of rat isolated duodenum, jejunum, and ileum and their histology were assessed. Direct application of the extract or [6]-gingerol attenuated ACh-induced contractions in each small intestinal segment, Emax was reduced by 40% to 80%, while EC50 increased 3- to 8-fold from control. Similarly, in the in vivo study ACh-induced contractions were reduced in all parts of the small intestine isolated from rats orally treated with ginger extract (20 and 100 mg/kg/d) or [6]-gingerol (2 mg/kg/d). Emax decreased 15% to 30%, while EC50 increased 1- to 3-fold compared to control. No discernable changes in the histology of intestinal segments were detectable. Thus, the results support the clinical application of ginger for disorders of gastrointestinal motility.

Naringin ameliorates endothelial dysfunction in fructose-fed rats.

High fructose consumption is associated with metabolic disorders including hyperglycemia and dyslipidemia, in addition to endothelial dysfunction. Naringin, a flavonoid present in citrus fruit, has been reported to exhibit lipid lowering, antioxidant, and cardiovascular protective properties. Therefore, the present study investigated the effect of naringin on fructose-induced endothelial dysfunction in rats and its underlying mechanisms. Male Sprague-Dawley rats were given 10% fructose in drinking water for 12 weeks, whereas control rats were fed drinking water alone. Naringin (100 mg/kg) was orally administered to fructose fed rats during the last 4 weeks of the study. Following 12 weeks, blood samples were collected for measurement of blood glucose, serum lipid profile and total nitrate/nitrite (NOx). Vascular function was assessed by isometric tension recording. Aortic expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and nitrotyrosine were evaluated by western blot analysis. Fructose feeding induced increased levels of blood glucose, total cholesterol, triglyceride, and low density lipoprotein. In rat aortae, fructose reduced acethycholine-induced vasorelaxation, without affecting sodium nitroprusside-induced vasorelaxation. Treatment of fructose-fed rats with naringin restored fructose-induced metabolic alterations and endothelial dysfunction. Fructose-fed rats also exhibited decreased serum NOx level, reduced eNOS and p-eNOS protein expression, and enhanced nitrotyrosine expression in aortae. These alterations were improved by naringin treatment. The results of the present study suggested that naringin treatment preserves endothelium-dependent relaxation in aortae from fructose fed rats. This effect is primarily mediated through an enhanced NO bioavailability via increased eNOS activity and decreased NO inactivated to peroxynitrite in aortae.

Comparative effects of piperine and simvastatin in fat accumulation and antioxidative status in high fat-induced hyperlipidemic rats.

The present study investigated the comparative effects of piperine (PIP) - the active ingredient of black and long peppers - and simvastatin (SIM) on hepatic steatosis in hyperlipidemic rats. Male Wistar rats were fed a cholesterol mixture daily by intragastric gavage for 8 weeks. Piperine was given by oral gavage 8 h after cholesterol feeding. The animals were divided into 4 groups: control, high fat (HF), high fat plus 40 mg PIP/kg, and high fat plus 2 mg SIM/kg. At the end of the treatment, liver cholesterol, triglyceride, thiobaribituric reacting substances, superoxide dismutase (SOD), serum aminotransferase (AST), and alanine transferase (ALT) were measured. The result demonstrated that PIP and SIM significantly reduced the accumulation of cholesterol, triglyceride, and lipid peroxidation in the liver, while elevation of SOD was observed. The activities of AST and ALT significantly decreased in PIP when compared with the HF group. Our in vitro study of pancreatic lipase also showed the inhibitory effect of PIP higher than 30% at 5 mmol/L. These results demonstrate that PIP has beneficial effects in the treatment and (or) prevention of fat accumulation in the liver and that this mechanism is due to the inhibition of pancreatic lipase and the improvement of oxidative status.

Protein kinase C isotypes in signal transduction for the 1,25D3-MARRS receptor (ERp57/PDIA3) in steroid hormone-stimulated phosphate uptake.

We undertook studies to determine which isotype(s) of protein kinase C (PKC) is/are activated by ligand binding to the 1,25D(3)-MARRS receptor (ERp57/PDIA3) and subsequent stimulation of phosphate uptake. Isolated intestinal epithelial cells from vitamin D-replete chicks were exposed to 1,25(OH)(2)D(3) for 1, 3, or 5min, thoroughly chilled, homogenized, and P(2) fractions (20,000xg post-nuclear pellet) prepared. Western analyses with anti-pan PKC revealed steroid-stimulated redistribution to P(2) membranes 1min after hormone. Using this time point, cells were treated with vehicle, 130-, 300- or 650-pM hormone. Western blots with anti-PKCalpha exhibited redistribution to membranes in a biphasic dose-response curve: slightly stimulated at the lowest dose, maximal at 300pM 1,25(OH)(2)D(3), and equivalent to control levels at the highest dose, paralleling hormone-mediated phosphate uptake. Westerns with anti PKCbeta also revealed hormone-mediated differences, while those with anti PKCgamma did not. RNAi studies were then performed with siRNA against PKCalpha or PKCbeta. Untransfected cells treated with hormone for 7min exhibited enhanced (32)P uptake relative to vehicle controls. Cells transfected with either active siRNA revealed decreased (32)P uptake in both controls (relative to untransfected controls), and hormone treated cells. However, control and transfected cells treated with hormone had equivalent levels of uptake. Western blot analyses confirmed decreased immunoreactivity in transfected cells. Chemical PKCalpha (safingol) and PKCbeta ([3-(1-(3-Imidazol-1-ylpropyl)-1H-indol-3-yl)-4-anilino-1H-pyrrole-2,5-dione] blockers also confirmed the results from siRNA and demonstrated decreased (32)P uptake in cells treated with 1,25(OH)(2)D(3) plus blockers in comparison with cells treated with 1,25(OH)(2)D(3) alone. Thus, PKCalpha and PKCbeta are both involved in steroid-stimulated phosphate uptake.