Protective Effect Of Punicalagin Research Articles

Punicalagin Inhibits Palmitate Acid-induced Lipoapoptosis through Inhibition of ER Stress, and Activation of SIRT1/Autophagy in HepG2 Cells

Lipid metabolism balance plays a vital role in maintaining normal levels of sterols, triglycerides, and free fatty acids (FFA). Inhibiting FFA-induced lipotoxicity is considered a highly potential treatment for non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism diseases. Punicalagin (PU), a pomegranate-derived polyphenol, has been found to effectively regulate lipid metabolism and prevent fatty liver, cardiovascular and other chronic diseases caused by lipid metabolism disorders. In the present study, we found that PU protects HepG2 cells from palmitic acid (PA)-induced lipapoptosis. Silent information regulator 1 (SIRT1) plays a key role in protecting against lipapoptosis in HepG2 cells. Knockdown of SIRT1 significantly diminished the protective effect of PU. Besides, PU could be able to reactivate weakened autophagy and inhibit PA-induced ER stress. Our findings supported that PU can effectively attenuate FFA-induced lipotoxicity via activating SIRT1/autophagy and inhibiting ER stress.

Protective effect of punicalagin, the main polyphenol compound of pomegranate, against acrylamide-induced neurotoxicity and hepatotoxicity in rats.

Acrylamide (ACR) is widely used in industries. Oxidative stress and apoptosis pathways are important mechanisms behind ACR-induced hepatotoxicity and neurotoxicity. Regarding to antioxidant and antiapoptotic properties of punicalagin (PUN), the protective effect of this agent on ACR-induced toxicity in rat was evaluated. Rats were divided into seven groups: control, ACR (50 mg/kg/day, i.p.), PUN (10, 20, and 40 mg/kg/day, i.p.) plus ACR, vitamin E (200 mg/kg, i.p.) plus ACR, and PUN groups. After 11 days, the gait score test was evaluated. Then, the animals were sacrificed and the malondialdehyde (MDA) and glutathione (GSH) contents were determined in the brain and liver tissues. Apoptosis-involved factors and myelin basic protein (MBP) were determined by western blotting. Severe movement disorder, MDA enhancement, and GSH reduction in the brain and liver tissues were observed in ACR-treated animals. The Bax/Bcl2 ratio and caspase-3 levels were enhanced in the tested tissues. ACR elevated the level of aspartate aminotransferases and decreased serum protein and albumin concentration. PUN recovered movement disorders, changed the level of markers which are important in oxidative stress and reduced apoptosis. Also, PUN increased the MBP level which was reduced due to ACR toxicity. PUN can protect against ACR-induced toxicity through antioxidant and antiapoptotic properties.

Protective Effects of Punicalagin on Osteoporosis by Inhibiting Osteoclastogenesis and Inflammation via the NF-κB and MAPK Pathways

Postmenopausal osteoporosis is a worldwide disease characterized by reduced bone mineral density and increased fracture risk. Inflammatory bone loss due to excessive osteoclast bone resorption is significant in the pathogenesis and development of osteoporosis. Punicalagin (PUN) is a pomegranate fruit derivative and has potential anti-inflammatory effects. However, the effect of PUN on osteoporotic bone loss has yet to be clarified. In this study, we investigated the effect of PUN on RANKL-induced osteoclast formation and bone resorption in vitro, as well as its potential therapeutic effect on ovariectomized-induced bone loss in vivo. PUN was demonstrated to suppress osteoclast formation and bone resorptive function dose-dependently, while osteoclast-specific genes were also downregulated by PUN. In vivo micro-CT and histopathological staining showed that the OVX procedure led to significant bone loss characterized by decreased bone parameters and increased osteoclast numbers, while PUN treatment dramatically prevented these changes. Furthermore, PUN treatment effectively inhibited proinflammatory cytokine expression in vitro. Mechanistically, PUN maintained bone mass via suppressing nuclear factor κB (NF-κB) and mitogen‐activated protein kinase (MAPK) signaling pathway activation. Collectively, our observations provide evidence that PUN is a potential candidate for the treatment of osteoporosis.

Metabolic Alterations and the Protective Effect of Punicalagin Against Glutamate-Induced Oxidative Toxicity in HT22 Cells.

Oxidative stress is involved in many neurological diseases, including Alzheimer's disease. Punicalagin (PC) is a hydrolysable polyphenol derived from Punica granatum and a potent antioxidant. In this study, the neuroprotective effect of PC on glutamate-induced oxidative stress was evaluated in the mouse hippocampal cell line, HT22. PC treatment protected HT22 cells from glutamate-induced cell death in a concentration-dependent manner, potentially attenuated glutamate-induced intracellular reactive oxygen species (ROS) and restored the mitochondrial membrane depolarization. Metabolic alterations after glutamate-induced oxidative stress and the protective effect of PC were evaluated with HPLC and GC-MS profiling methods with multivariate statistical analyses. Alterations in ten metabolites were identified, including amino acids, aspartic acid, asparagine, threonine, anserine, cysteine, tryptophan, lysine, as well as fatty acids palmitic acid, stearic acid, and palmitoleic acid. Metabolic pathway analysis revealed the involvement of multiple affected pathways, such as cysteine and methionine metabolism, tryptophan metabolism, alanine, aspartate, and glutamate and fatty acid oxidation. These results clearly demonstrate that PC is a promising therapeutic agent for oxidative stress-associated diseases.