Inflammation is a complex biological defense system associated with a series of chronic diseases such as cancer, arthritis, diabetes, cardiovascular and neurodegenerative diseases. The extracts of pomegranate fruit and peel have been reported to possess health-beneficial properties in inflammation-associated chronic diseases. Punicalagin is considered to be the major active component of pomegranate extracts. In this review we have focused on recent studies into the therapeutic effects of punicalagin on inflammation-associated chronic diseases and the regulatory roles in NF-κB, MAPK, IL-6/JAK/STAT3 and PI3K/Akt/mTOR signaling pathways. We have concluded that punicalagin may be a promising therapeutic compound in preventing and treating inflammation-associated chronic diseases, although further clinical studies are required.

Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.

β-glucan (BG) and mulberry have received increasing attention for their benefits as natural sources of metabolic health. In the current study, we investigated the synergetic beneficial effects of BG and mulberry leaf extract (MLE) in mice fed a high-fat diet (HFD). Male C57BL6 mice were fed a HFD for twelve weeks to induce significant obesity and insulin resistance. BG and MLE were administrated orally throughout the feeding period. The administration of BG resulted in a significant reduction in body weight gain, perirenal fat mass, fasting insulin, serum lipids, serum inflammation markers, and fatty liver, showing systemic health improvement. Likewise, the administration of MLE showed benefits similar to BG, with the exception of body weight gain. In addition to the systemic benefits, the combination of BG and MLE resulted in a synergetic improvement in insulin sensitivity. Meanwhile, only the combination of BG and MLE significantly enhanced liver GST (Glutathione S-Transferase) activity and CuZn–SOD (Superoxide dismutase (Cu-Zn)) activity, resulting in a significant reduction in GSH/GSSG (Glutathione disulfide) and reactive oxygen species (ROS) levels in the liver. These results further confirm the beneficial effects of BG and MLE on metabolic disorders and show that the combination of BG and MLE has synergetic effects.

Significance: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. Recent Advances: Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. Nuclear factor erythroid 2 related factor 2 (Nrf2) is one of the important systems responding to oxidative stress and inflammation. As cells undergo stress, cysteines within Kelch-like ECH-associated protein 1 (Keap1) are oxidized or electrophilically modified, allowing Nrf2 to escape ubiquitination and be translocated from the cytoplasm to the nucleus, facilitating the initiation of the antioxidant transcriptional program. Meanwhile, a growing body of evidence points out a specific modulation of mitochondrial homeostasis by Nrf2 . After nuclear translocation, Nrf2 activates downstream genes involved in various aspects of mitochondrial homeostasis, including mitochondrial biogenesis and dynamics, mitophagy, aerobic respiration, and energy metabolism. In turn, mitochondria reciprocally activate Nrf2 by releasing reactive oxygen species and regulating antioxidant enzymes. Critical Issues: In this review, we first summarize the interactions between Nrf2 and mitochondria in the modulation of oxidative stress and inflammation to ameliorate MetS, then propose that Nrf2 and mitochondria form a mutually regulating circuit critical to maintaining homeostasis during MetS. Future Directions: Targeting the Nrf2 –mitochondrial circuit may be a promising strategy to ameliorate MetS, such as obesity, diabetes, and cardiovascular diseases.