punicalagin and Body-Weight

Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.

Topics: AMP-Activated Protein Kinases; Animals; Body Weight; Cholesterol; Diet, High-Fat; Lipid Metabolism; Lipids; Liver; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; PPAR gamma; Rats

Nowadays, medicinal plants have been widely used everywhere to provide essential care for many disorders including diabetes. Recent reports assumed that the antidiabetic activities of pomegranate aril juice (PAJ) may be ascribed to its punicalagin (PCG). Therefore, the present study evaluated and compared the antidiabetic activities of PAJ and its PCG, and monitored some mechanisms of their actions in streptozotocin-nicotinamide (STZ-NA) type 2 diabetic rats. STZ-NA diabetic rats were given, orally/daily, PAJ (100 or 300 mg/kg body weight, containing 2.6 and 7.8 mg of PCG/kg body weight, respectively), pure PCG (2.6 or 7.8 mg/kg body weight), or distilled water (vehicle) for 6 weeks. PAJ (especially at the high dose) alleviated significantly (P < 0.05-0.001) most signs of type 2 diabetes including body-weight loss, insulin resistance (IR) and hyperglycemia through decreasing serum tumor necrosis factor-α concentration and the expression of hepatic c-Jun N-terminal kinase, and increasing the skeletal muscle weight and the expression of hepatic insulin receptor substrate-1 in STZ-NA diabetic rats. Also, it decreased significantly (P < 0.001) the oxidative liver injury in STZ-NA diabetic rats through decreasing the hepatic lipid peroxidation and nitric oxide production, and improving the hepatic antioxidant defense system. Although the low dose of PCG induced some modulation in STZ-NA diabetic rats, the high dose of PCG did not show any valuable antidiabetic activity, but induced many side effects. In conclusion, PAJ was safer and more effective than pure PCG in alleviating IR and oxidative liver injury in STZ-NA diabetic rats.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Hydrolyzable Tannins; Hyperglycemia; Insulin Receptor Substrate Proteins; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Lipid Peroxidation; Liver; Male; Muscle, Skeletal; Niacinamide; Nitric Oxide; Pomegranate; Rats; Streptozocin; Tumor Necrosis Factor-alpha

The present study investigated the neuroprotective role of punicalagin, a major polyphenolic compound of pomegranate on methionine-induced brain injury. Hyperhomocysteinemia (HHcy) was induced in two months old male BALB c mice by methionine supplementation in drinking water (1 g/kg body weight) for 30 days. Punicalagin (1 mg/kg) was injected i.p every other day concurrently with methionine. Punicalagin significantly prevented the rise in the levels of homocysteine, amyloid-β and TNF-α. HHcy is associated with a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (PGx) and glutathione reductase (GR) and glutathione (GSH) levels in the brains of methionine-treated mice while these antioxidants are increased by punicalagin supplementation. The treatment with punicalagin significantly decreased oxidative stress as indicated by decreased malondialdehyde and protein carbonyl formation in the brain. Compared with methionine-treated animals, mice that treated with methionine and punicalagin remarkably displayed less apoptosis, indicated by the lower level of proapoptotic protein (Bax, caspases- 3, 9 and p53) and higher levels of antiapoptotic Bcl-2 protein than those in hyperhomocysteinemic mice. The potent bioactivity of punicalagin extends to protect neuronal DNA as evidenced by the inhibition of the increase of comet parameters compared to the methionine-treated mice. In conclusion, punicalagin protected from methionine-induced HHcy and brain damage with an ability to repress apoptosis by modulating apoptotic mediators and maintaining DNA integrity in the brain of mice.

Topics: Amyloid beta-Peptides; Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Body Weight; Brain; Caspase 3; Caspase 9; DNA Damage; Homocysteine; Hydrolyzable Tannins; Male; Methionine; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53

Punicalagin (PU) is one of the major ellagitannins found in the pomegranate (Punica granatum), which is a popular fruit with several health benefits. So far, no studies have evaluated the effects of PU on nonalcoholic fatty liver disease (NAFLD). Our work aims at studying the effect of PU-enriched pomegranate extract (PE) on high fat diet (HFD)-induced NAFLD.. PE administration at a dosage of 150 mg/kg/day significantly inhibited HFD-induced hyperlipidemia and hepatic lipid deposition. As major contributors to NAFLD, increased expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukins 1, 4, and 6 as well as augmented oxidative stress in hepatocytes followed by nuclear factor (erythroid-derived-2)-like 2 (Nrf2) activation were normalized through PE supplementation. In addition, PE treatment reduced uncoupling protein 2 (UCP2) expression, restored ATP content, suppressed mitochondrial protein oxidation, and improved mitochondrial complex activity in the liver. In contrast, mitochondrial content was not affected despite increased peroxisomal proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and elevated expression of genes related to mitochondrial beta-oxidation after PE treatment. Finally, PU was identified as the predominant active component of PE with regard to the lowering of triglyceride and cholesterol content in HepG2 cells, and both PU- and PE-protected cells from palmitate induced mitochondrial dysfunction and insulin resistance.. Our work presents the beneficial effects of PE on obesity-associated NAFLD and multiple risk factors. PU was proposed to be the major active component.. By promoting mitochondrial function, eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of NAFLD.

Topics: Animals; Body Weight; Cholesterol; Diet, High-Fat; Disease Models, Animal; Hep G2 Cells; Humans; Hydrolyzable Tannins; Inflammation; Insulin Resistance; Lipid Metabolism; Liver; Lythraceae; Male; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Plant Extracts; Rats; Sterol Regulatory Element Binding Protein 1; Triglycerides

The water-soluble ellagitanin punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (> or =2 g/L), the present study evaluated the possible toxic effect of punicalagin in Sprague-Dawley rats upon repeated oral administration of a 6% punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found in treated rats in any blood parameter analyzed (including the antioxidant enzymes gluthatione peroxidase and superoxide dismutase) with the exception of urea and triglycerides, which remained at low values throughout the experiment. Although the reason for the decrease is unclear, it could be due to the lower nutritional value of the punicalagin-enriched diet with respect to the standard rat food. Histopathological analysis of liver and kidney corroborated the absence of toxicity. In principle, the results reported here, together with the large safety margin considered, indicate the lack of toxic effect of punicalagin in rats during the 37 day period investigated. However, taking into account the high punicalagin content of pomegranate-derived foodstuffs, safety evaluation should be also carried out in humans with a lower dose and during a longer period of intake.

Topics: Animals; Antioxidants; Body Weight; Chromatography, High Pressure Liquid; Diet; Eating; Fruit; Hydrolyzable Tannins; Kidney; Liver; Lythraceae; Mass Spectrometry; Nutritive Value; Rats; Rats, Sprague-Dawley; Tannins; Tissue Distribution