Punicalagin attenuates palmitate‐induced lipotoxicity in HepG2 cells by activating the Keap1‐Nrf2 antioxidant defense system

Pomegranate (Punica granatum Linn) is used in the prevention and treatment of metabolic syndrome in recent decades. Imbalances in lipid metabolism are profound features of metabolic disorders. In vivo and in vitro studies have shown that extracts of different pomegranate fractions (peels, flowers, juice, and seeds) regulate lipid metabolism in metabolic‐disorder‐associated diseases such as atherosclerosis, nonalcoholic fatty liver disease, and type 2 diabetes, helping to alleviate the development of diseases. Amelioration of oxidative stress and the inflammatory response is considered an important reason underlying the regulation of lipid metabolism by pomegranate extracts. Mitochondria, the major cellular site for lipid oxidation, are strongly associated with cellular oxidative and inflammatory status and are likely to be a target for pomegranate extract action. This review summarizes the main findings about the effects of different pomegranate fraction extracts on lipid metabolism in metabolic‐disorder‐associated diseases and analyses how pomegranate extracts achieve their effects. Furthermore, it also provides an important basis for the research and development of pomegranate‐related nutrients or drugs.

Section: Mechanism Analysis Of Lipid Metabolism Regulated By Pomegranatementioning

confidence: 96%

Section: Mechanism Analysis Of Lipid Metabolism Regulated By Pomegranatementioning

confidence: 98%

Section: Mechanism Analysis Of Lipid Metabolism Regulated By Pomegranatementioning

confidence: 99%

Section: Mechanism Analysis Of Lipid Metabolism Regulated By Pomegranatementioning

confidence: 99%

See 2 more Smart Citations

Beneficial Effects of Pomegranate on Lipid Metabolism in Metabolic Disorders

Hou

Zhang

et al. 2019

“…[12,13] PCG is known to regulate this signaling in several pathogenic conditions. [14,15] However, as yet, the relationship between PCGmediated activation of Nrf2/Keap1 signaling and obesity-induced inflammatory/oxidative responses has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Punicalagin, a Pomegranate‐Derived Ellagitannin, Suppresses Obesity and Obesity‐Induced Inflammatory Responses Via the Nrf2/Keap1 Signaling Pathway

Kang

Kim

Hwang

et al. 2019

Scope Punicalagin (PCG) is one of the most abundant phytochemicals found in pomegranates. The effects and mechanistic action of PCG on obesity and obesity‐induced inflammatory and oxidant responses are investigated in vitro and in vivo. Methods and results The effect of PCG on adipogenesis is examined using Oil red O staining. The effects and mechanism of action of PCG on inflammatory responses are determined in adipocyte‐conditioned medium (ACM)‐cultured macrophages, a cell‐to‐cell contact system, and a transwell system. The effects of PCG on obesity and obesity‐induced inflammatory/oxidant responses are examined in high‐fat diet (HFD)‐fed mice. PCG effectively suppresses lipid accumulation in adipocytes and adipocyte‐induced inflammatory responses in adipocyte‐macrophage co‐culture systems. Small interfering RNA (siRNA) transfection indicates that the PCG‐mediated anti‐inflammatory effect is exerted via the nuclear factor erythroid 2‐related factor 2/Kelch‐like ECH‐associated protein 1(Nrf2/Keap1) pathway. PCG administration results in a significant reduction in body and white adipose tissue (WAT) weights. PCG favorably regulates pro‐ and anti‐inflammatory cytokines, downregulating nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). Immunohistochemical (IHC) analysis demonstrates that PCG differentially modulates the distribution of complement component 3 receptor 4 subunit (CD11c) and cluster of differentiation 206 (CD206). PCG regulates the level of antioxidant and oxidant molecules by activating Nrf2/Keap1 signaling. Conclusions PCG ameliorates obesity and obesity‐induced inflammatory responses via activation of Nrf2/Keap1 signaling, suggesting that PCG has potential as an oral agent to control obesity‐mediated diseases.

Punicalagin Activates AMPK/PGC‐1α/Nrf2 Cascade in Mice: The Potential Protective Effect against Prenatal Stress

Cao

et al. 2020

ScopePrenatal stress is closely associated with poor health outcomes for offspring, yet the specific mechanisms and effective interventions remain limited.Methods and ResultsIn the present study, both male and female rat offspring exposed to prenatal restraint stress (PRS) are confirmed to have impaired spatial learning and memory, accompanied by reduced AMP‐activated protein kinase (AMPK) activity and decreased protein expression of mitochondrial biogenesis and antioxidant pathways in the hippocampus. Interestingly, a deficiency in the AMPK cascade also occurs in liver, heart, and adipose tissues, suggesting that the systemic deactivation of AMPK in the offspring is potentially attributed to increased maternal glucocorticoid levels under PRS. Punicalagin (PU), a major ellagitannin in pomegranate, is found to effectively induce mitochondrial biogenesis and phase II enzymes through activation of AMPK in both HT22 and primary hippocampal neurons, thereby inhibiting glutamate‐induced cell viability and mitochondrial membrane potential loss. Meanwhile, the activation of AMPK cascade is also confirmed in mice administrated with PU for three days.ConclusionsAltogether, these results indicate that the systemic deficiency of the AMPK cascade can be the key factor that contributes to poor outcomes of PRS, and PU may be used as an effective maternal nutritional intervention.