Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1-JNK Signaling Pathway.

Lycopene has been proven to alleviate nonalcoholic steatohepatitis (NASH), but the precise mechanisms are inadequately elucidated. In this study, we found a previously unknown regulatory effect of lycopene on the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway in both in vivo and in vitro models. Lycopene supplementation (3 and 6 mg/kg/day) exhibited a significant reduction in lipid accumulation, inflammation, and fibrosis of the liver in mice fed with a high-fat/high-cholesterol diet or a methionine-choline-deficient diet. RNA sequencing uncovered that the mitogen-activated protein kinases signaling pathway, which is closely associated with inflammation and endoplasmic reticulum (ER) stress, was significantly downregulated by lycopene. Furthermore, we found lycopene ameliorated ER swelling and decreased the expression levels of ER stress markers (i.e., immunoglobulin heavy chain binding protein, C/EBP homologous protein, and X-box binding protein 1s). Especially, the inositol-requiring enzyme 1α involved in the ASK1 phosphorylation was inhibited by lycopene, resulting in the decline of the subsequent c-Jun N-terminal kinase (JNK) signaling cascade. ASK1 inhibitor DQOP-1 eliminated the lycopene-induced inhibition of the ASK1-JNK pathway in oleic acid and palmitic acid-induced HepG2 cells. Molecular docking further indicated hydrophobic interactions between lycopene and ASK1. Collectively, our research indicates that lycopene can alleviate ER stress and attenuate inflammation cascades and lipid accumulation by inhibiting the ASK1-JNK pathway.

A Review of Healthy Dietary Choices for Cardiovascular Disease: From Individual Nutrients and Foods to Dietary Patterns.

Cardiovascular disease (CVD) remains the first cause of mortality globally. Diet plays a fundamental role in cardiovascular health and is closely linked to the development of CVD. Numerous human studies have provided evidence on the relationship between diet and CVD. By discussing the available findings on the dietary components that potentially influence CVD progression and prevention, this review attempted to provide the current state of evidence on healthy dietary choices for CVD. We focus on the effects of individual macronutrients, whole food products, and dietary patterns on the risks of CVD, and the data from population-based trials, observational studies, and meta-analyses are summarized. Unhealthy dietary habits, such as high intake of saturated fatty acids, sugar-sweetened beverages, red meat, and processed meat as well as high salt intake are associated with the increased risk of CVD. Conversely, increased consumption of plant-based components such as dietary fiber, nuts, fruits, and vegetables is shown to be effective in reducing CVD risk factors. The Mediterranean diet appears to be one of the most evidence-based dietary patterns beneficial for CVD prevention. However, there is still great debate regarding whether the supplementation of vitamins and minerals confers cardioprotective benefits. This review provides new insights into the role of dietary factors that are harmful or protective in CVD, which can be adopted for improved cardiovascular health.

Barley Leaf Ameliorates Citrobacter-rodentium-Induced Colitis through Arginine Enrichment.

Inflammatory bowel disease (IBD) has become a global public health challenge. Our previous study showed that barley leaf (BL) significantly reduces Citrobacter-rodentium (CR)-induced colitis, but its mechanism remains elusive. Thus, in this study, we used non-targeted metabolomics techniques to search for potentially effective metabolites. Our results demonstrated that dietary supplementation with BL significantly enriched arginine and that arginine intervention significantly ameliorated CR-induced colitis symptoms such as reduced body weight, shortened colon, wrinkled cecum, and swollen colon wall in mice; in addition, arginine intervention dramatically ameliorated CR-induced histopathological damage to the colon. The gut microbial diversity analysis showed that arginine intervention significantly decreased the relative abundance of CR and significantly increased the relative abundance of Akkermansia, Blautia, Enterorhabdus, and Lachnospiraceae, which modified the CR-induced intestinal flora disorder. Notably, arginine showed a dose-dependent effect on the improvement of colitis caused by CR.

Purinergic ATP triggers moxibustion-induced local anti-nociceptive effect on inflammatory pain model.

Purinergic signalling adenosine and its A1 receptors have been demonstrated to get involved in the mechanism of acupuncture (needling therapy) analgesia. However, whether purinergic signalling would be responsible for the local analgesic effect of moxibustion therapy, the predominant member in acupuncture family procedures also could trigger analgesic effect on pain diseases, it still remains unclear. In this study, we applied moxibustion to generate analgesic effect on complete Freund's adjuvant (CFA)-induced inflammatory pain rats and detected the purine released from moxibustioned-acupoint by high-performance liquid chromatography (HPLC) approach. Intramuscular injection of ARL67156 into the acupoint Zusanli (ST36) to inhibit the breakdown of ATP showed the analgesic effect of moxibustion was increased while intramuscular injection of ATPase to speed up ATP hydrolysis caused a reduced moxibustion-induced analgesia. These data implied that purinergic ATP at the location of ST36 acupoint is a potentially beneficial factor for moxibustion-induced analgesia.

Dietary Barley Leaf Mitigates Tumorigenesis in Experimental Colitis-Associated Colorectal Cancer.

Dietary barley (Hordeum vulgare L.) leaf (BL) is a popular functional food known to have potential health benefits; however, the effect of BL in colorectal cancer prevention has not been examined. Here, we examined the role of BL on the prevention of colorectal carcinogenesis and defined the mechanism involved. BL supplementation could protect against weight loss, mitigate tumor formation, and diminish histologic damage in mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). Moreover, BL suppressed colonic expression of inflammatory enzymes, while improving the mucosal barrier dysfunctions. The elevated levels of cell proliferation markers and the increased expression of genes involved in ß-catenin signaling were also reduced by BL. In addition, analyses of microbiota revealed that BL prevented AOM/DSS-induced gut microbiota dysbiosis by promoting the enrichment of Bifidobacterium. Overall, these data suggest that BL is a promising dietary agent for preventing colitis-associated colorectal cancer.

Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota.

Supplementation of dietary fiber has been proved to be an effective strategy to prevent and relieve inflammatory bowel disease (IBD) through gut microbiota modulation. However, more attention has been paid to the efficacy of soluble dietary fiber than that of insoluble dietary fiber (IDF). In the present study, we investigated whether IDF from barley leaf (BLIDF) can inhibit gut inflammation via modulating the intestinal microbiota in DSS-induced colitis mice. The mice were fed 1.52% BLIDF-supplemented diet for 28 days. Results demonstrated that feeding BLIDF markedly mitigated DSS-induced acute colitis symptoms and down-regulated IL-6, TNF-α, and IL-1ß levels in the colon and serum of colitis mice. BLIDF supplementation effectively reduced the abundance of Akkermansia and increased the abundance of Parasutterella, Erysipelatoclostridium, and Alistipes. Importantly, the anti-colitis effects of BLIDF were abolished when the intestinal microbiota was depleted by antibiotics. Furthermore, the targeted microbiota-derived metabolites analysis suggested that BLIDF feeding can reverse the DSS-induced decline of short-chain fatty acids and secondary bile acids in mice feces. Finally, BLIDF supplementation elevated the expression of occludin and mucin2, and decreased the expression of claudin-1 in colons of DSS-treated mice. Overall, our observations suggest that BLIDF exerts anti-inflammatory effects via modulating the intestinal microbiota composition and increasing the production of microbiota-derived metabolites.

Gut microbiota-derived inosine from dietary barley leaf supplementation attenuates colitis through PPARγ signaling activation.

BACKGROUND: Ulcerative colitis is a type of chronic inflammatory bowel disease closely associated with gut microbiota dysbiosis and intestinal homeostasis dysregulation. Barley leaf (BL) has a long history of use in Traditional Chinese Medicine with potential health-promoting effects on intestinal functions. However, its mechanism of action is not yet clear. Here, we explore the potential modulating roles of gut microbial metabolites of BL to protect against colitis and elucidate the underlying molecular mechanisms. RESULTS: Using 16S rRNA gene-based microbiota analysis, we first found that dietary supplementation of BL ameliorated dextran sulfate sodium (DSS)-induced gut microbiota dysbiosis. The mechanisms by which BL protected against DSS-induced colitis were resulted from improved intestinal mucosal barrier functions via the activation of peroxisome proliferator-activated receptor (PPAR)γ signaling. In addition, metabolomic profiling analysis showed that the gut microbiota modulated BL-induced metabolic reprograming in the colonic tissues particularly by the enhancement of glycolysis process. Notably, dietary BL supplementation resulted in the enrichment of microbiota-derived purine metabolite inosine, which could activate PPARγ signaling in human colon epithelial cells. Furthermore, exogenous treatment of inosine reproduced similar protective effects as BL to protect against DSS-induced colitis through improving adenosine 2A receptor (A2AR)/PPARγ-dependent mucosal barrier functions. CONCLUSIONS: Overall, our findings suggest that the gut microbiota-inosine-A2AR/PPARγ axis plays an important role in the maintenance of intestinal homeostasis, which may represent a novel approach for colitis prevention via manipulation of the gut microbial purine metabolite. Video Abstract.

Beneficial effects of ginger on prevention of obesity through modulation of gut microbiota in mice.

PURPOSE: Recent evidence has demonstrated that the gut microbiota plays a critical role in the treatment of obesity and other metabolic dysfunctions. Ginger (Zingiber officinale Roscoe), one of the most commonly used spices and dietary supplements, has been shown to exert beneficial effects against obesity and related disorders. However, to date, the mechanisms linking these effects to the gut microbiota remain unclear. This study aims to investigate the relationship between the gut microbiota and the metabolic adaptations resulting from ginger supplementation in mice. METHODS: Four groups of mice were fed a normal chow diet (NCD) or a high-fat diet (HFD) with or without ginger supplementation for 16 weeks. Lipid profiles, proinflammatory cytokines, glucose tolerance, microbiota composition and short-chain fatty acid (SCFA) concentrations were analyzed at the end of the experiment. In addition, microbiota-depleted mice were transplanted with the fecal microbiota of mice fed a HFD or mice fed a HFD along with ginger supplementation. Glucose tolerance and microbiota composition were assessed after a 8-week fecal microbiota transplantation (FMT). RESULTS: We observed marked decreases in body weight, liver steatosis, and low-grade inflammation as well as amelioration of insulin resistance in the HFD-fed mice treated with ginger. Furthermore, ginger supplementation modulated the gut microbiota composition and increased species belonging to the Bifidobacterium genus and SCFA-producing bacteria (Alloprevotella and Allobaculum), along with increases in fecal SCFA concentrations. The FMT experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral ginger-feeding experiment. CONCLUSIONS: This study suggests that modulation of the gut microbiota as a result of ginger supplementation has a therapeutic effect on obesity in mice.

Ginger prevents obesity through regulation of energy metabolism and activation of browning in high-fat diet-induced obese mice.

Numerous natural herbs have been proven as safe anti-obesity resources. Ginger, one of the most widely consumed spices, has shown beneficial effects against obesity and related metabolic disorders. The present study aimed to examine whether the antiobesity effect of ginger is associated with energy metabolism. Mice were maintained on either a normal control diet or a high-fat diet (HFD) with or without 500 mg/kg (w/w) ginger supplementation. After 16 weeks, ginger supplementation alleviated the HFD-induced increases in body weight, fat accumulation, and levels of serum glucose, triglyceride and cholesterol. Indirect calorimetry showed that ginger administration significantly increased the respiratory exchange ratio (RER) and heat production in both diet models. Furthermore, ginger administration corrected the HFD-induced changes in concentrations of intermediates in glycolysis and the TCA cycle. Moreover, ginger enhanced brown adipose tissue function and activated white adipose tissue browning by altering the gene expression and protein levels of some brown and beige adipocyte-selective markers. Additionally, stimulation of the browning program by ginger may be partly regulated by the sirtuin-1 (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway. Taken together, these results indicate that dietary ginger prevents body weight gain by remodeling whole-body energy metabolism and inducing browning of white adipose tissue (WAT). Thus, ginger is an edible plant that plays a role in the therapeutic treatment of obesity and related disorders.