Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation.

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.

Modulatory Effect of Fermented Black Soybean and Adlay on Gut Microbiota Contributes to Healthy Aging.

SCOPE: Aging is a natural process characterized by a multifactorial, physical decline, and functional disability. Nevertheless, healthy aging can be achieved by following a multidirectional strategy. The current study aims to investigate the anti-aging potential of fermented black soybean and adlay (FBA). METHODS AND RESULTS: FBA supplements are incorporated into a natural aging mouse model that is designed to evaluate anti-aging effects. Results show that FBA supplementation prevents muscle loss and visceral adipose tissue accumulation. FBA can also reduce aging biomarkers (including the expression of hepatic p16INK4A and galactosidase beta-1 (GLB1). Hepatic 8-hydoxy-2'-deoxyguanosine (8-oxodG) and pro-inflammatory cytokines have been significantly reduced. Lastly, FBA supplementation improves aging-related gut microbial dysbiosis by reshaping gut microbial composition and promoting the growth of beneficial microbes such as Alistipes, Anaeroplasma, Coriobacteriaceae UCG002, and Parvibacter members in both genders of aged mice. In the functional prediction of gut microbiota, correlations to metabolic, neurodegenerative, infectious, and immune system diseases have been reduced in supplemented mice compared to aged mice. Moreover, FBA supplementation can reverse the reduced ability of microbiota in aged mice for lipid metabolism and xenobiotics biodegradation. CONCLUSIONS: The results suggest that FBA exhibits noteworthy anti-aging effects and that it can potentially be developed into a functional food for healthy aging.

Oolong tea extract alleviates weight gain in high-fat diet-induced obese rats by regulating lipid metabolism and modulating gut microbiota.

Obesity is a serious global health issue, and the societal interventions during the COVID-19 pandemic may have perturbed energy homeostasis, which affects the condition of obesity. Tea is a traditional beverage in Asia and has been shown to provide many beneficial health effects. Oolong tea is semifermented, with its chemical composition comprising features of green (unfermented) and black (fermented) tea. Although green tea has anti-obesity properties, studies on the anti-obesity ability of oolong tea are still scarce. In this study, we analyzed the chemical composition of oolong tea extract (OTE) and investigated the effects of OTE on high-fat diet-induced obese rats. OTE contained more (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, and (-)-gallocatechin-3-gallate than theaflavins and theasinensins. Rats fed with a high-fat diet (HFD) and treated with 0.5% OTE exhibited significantly reduced body weight and visceral fat weight compared with the HFD-only group. OTE also decreased adipocyte size, lipogenesis-related protein sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) protein expression and increased thermogenesis-related protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and uncoupling protein 1 (UCP1) protein expression in epididymal adipose tissue compared with the HFD group. Moreover, the OTE groups had a significantly higher abundance of Candidatus arthromitus and Hydrogenoanaerobacterium and a lower abundance of Ruminococcus1, Oscillibacter, and Odoribacter compared with the HFD group. All these results show that OTE can alleviate weight gain by regulating lipid metabolism and modulating the distribution of the gut microbiota to decrease lipid accumulation in adipose tissue.

Coleus forskohlii and Garcinia indica extracts attenuated lipid accumulation by regulating energy metabolism and modulating gut microbiota in obese mice.

Obesity is related to energy imbalance and energy metabolism. In this study, we investigated the anti-obesity effects of Garcinia indica extract (GIE), Coleus forskohlii extract (CFE), and the combinations of these two extracts in a 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. In vitro, GIE showed better effect on TG content than CFE, CFE showed better effect on glycerol released than GIE, and the combinations of GIE and CFE showed both effects compared with GIE and CFE alone. In vivo, GIE, LMIX (0.005% GIE + 0.025% CFE), and HMIX (0.01% GIE + 0.025% CFE) down-regulated adipogenesis-related transcription factors PPARγ and C/EBPα protein expression, CFE promoted lipolysis by up-regulated p-HSL and p-PKA protein expression, and four supplementations promoted fatty acid ß-oxidation by up-regulating CPT-1A and PPARα protein expression to decrease lipid accumulation in adipose tissue. Moreover, we found that CFE, LMIX and HMIX, except GIE exert increasing the abundance of Bacteroides caccae compared with HFD group. Overall, GIE, CFE, and the combinations of GIE and CFE were able to decrease body weight and adipocyte size by promoting fatty acid ß-oxidation and modulating gut microbiota in HFD-induced obese mice.

Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway.

Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.

Citrus peel extracts attenuated obesity and modulated gut microbiota in mice with high-fat diet-induced obesity.

Polymethoxyflavones (PMFs) and hydroxyl PMFs (HOPMFs) are mainly found in citrus peel and have shown anti-obesity potential in in vitro and in vivo studies. Herein, we have investigated the anti-obesity effects of two citrus peel extracts obtained via supercritical fluid extraction: PMF A, with a lower content of PMFs and HOPMFs, and PMF B, with a higher content of PMFs and HOPMFs. PMF A and PMF B were administered orally for 16 weeks to mice with high fat diet (HFD)-induced obesity. The results showed that PMF B decreased the lipid content more statistically significantly (p < 0.05) than PMF A in 3T3-L1 preadipocytes, reduced the adipocyte size, decreased the adipose tissue weight and alleviated the total body weight in the HFD mice. Both PMF A and PMF B reduced the adipocyte size in the perigonadal fat by markedly decreasing the levels of lipid droplets (LD) and perilipin 1 protein and Sterol regulatory element binding protein 1 (SREBP-1) expression. Compared to the case of the HFD group, PMF B altered the gut microbiota by increasing Prevotella and decreasing rc4-4 bacteria. The change in the composition of gut microbiota, the community of symbiotic and pathogenic microorganisms, may determine the metabolic health and be responsible for the anti-obesity mechanism. Our results indicate that the citrus peel extracts decrease lipid accumulation both in vivo and in vitro and should be considered for the management of overweight and obesity conditions.

Cellular models for the evaluation of the antiobesity effect of selected phytochemicals from food and herbs.

Dietary phytochemicals from food and herbs have been studied for their health benefits for a long time. The incidence of obesity has seen an incredible increase worldwide. Although dieting, along with increased physical activity, seems an easy method in theory to manage obesity, it is hard to apply in real life. Obesity treatment drugs and surgery are not successful or targeted for everyone and can have significant side effects. This low rate of success is the major reason that the overweight as well as the pharmaceutical industry seek alternative methods, including phytochemicals. Therefore, more and more research has focused on the role of phytochemicals to alleviate lipid accumulation or enhance energy expenditure in adipocytes. This review discusses selected phytochemicals from food and herbs and their effects on adipogenesis, lipogenesis, lipolysis, oxidation of fatty acids, and browning in 3T3-L1 preadipocytes.

Black garlic: A critical review of its production, bioactivity, and application.

Black garlic is obtained from fresh garlic (Allium sativum L.) that has been fermented for a period of time at a controlled high temperature (60-90°C) under controlled high humidity (80-90%). When compared with fresh garlic, black garlic does not release a strong offensive flavor owing to the reduced content of allicin. Enhanced bioactivity of black garlic compared with that of fresh garlic is attributed to its changes in physicochemical properties. Studies concerning the fundamental findings of black garlic, such as its production, bioactivity, and applications, have thus been conducted. Several types of black garlic products are also available in the market with a fair selling volume. In this article, we summarize the current knowledge of changes in the components, bioactivity, production, and applications of black garlic, as well as the proposed future prospects on their possible applications as a functional food product.

Protective effects of theasinensin A against carbon tetrachloride-induced liver injury in mice.

Theasinensins have been identified as a major group of unique catechin dimers mainly found in oolong tea and black tea. Among several types of theasinensins, theasinensin A (TSA), an epigallocatechin gallate (EGCG) dimer with an R-biphenyl bond, is the most abundant theasinensin prevalent in oolong tea. Previous studies have reported that TSA exhibits antioxidative, anti-inflammatory and anti-cancer activities in vitro and in vivo. However, little is known about the hepatoprotective effect of TSA. Thus, the aim of this study was to investigate the inhibitory effect of TSA on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. After intraperitoneal injection of CCl4 for eight weeks, histological lesions in the liver tissue and elevated serum levels of alanine aminotransferase and alkaline phosphatase were found in mice. Conversely, oral administration of TSA relieved CCl4-induced liver injury as well as ameliorated liver functions. Our immunohistochemical staining results revealed that collagen deposition was profoundly reduced due to supplementation with TSA. In addition, we also found that hepatic α-smooth muscle actin (α-SMA) and matrix metallopeptidase 9 (MMP-9) expression was suppressed through the inhibition of transforming growth factor ß (TGF-ß). Taken together, our current findings suggest that TSA may serve as a potent bioactive constituent from oolong tea that acts against liver fibrosis through the inhibition of hepatic stellate cell (HSC) activation.

Molecular mechanisms of the anti-obesity effect of bioactive compounds in tea and coffee.

Obesity is a serious health problem in adults and children worldwide. However, the basic strategies for the management of obesity (diet, exercise, drugs and surgery) have limitations and side effects. Therefore, many researchers have sought to identify bioactive components in food. Tea and coffee are the most frequently consumed beverages in the whole world. Their health benefits have been studied for decades, especially those of green tea. The anti-obesity effect of tea and coffee has been studied for at least ten years. The results have shown decreased lipid accumulation in cells via the regulation of the cell cycle during adipogenesis, changes in transcription factors and lipogenesis-related proteins in the adipose tissue of animal models, and decreased body weight and visceral fat in humans. Tea and coffee also influence the gut microbiota in obese animals and humans. Although the anti-obesity mechanism of tea and coffee still needs further clarification, they may have potential as a new strategy to prevent or treat obesity.

Ethanolic Extract of Agaricus blazei Fermentation Product Inhibits the Growth and Invasion of Human Hepatoma HA22T/VGH and SK-Hep-1 Cells.

Hepatoma is a leading cause of death in the world. SK-Hep-1 and HA22T/VGH cells are poorly differentiated human hepatocellular carcinoma cell lines with invasive and migratory abilities. Agaricus blazei (AB) is a mushroom with many biological effects and active ingredients, and the ethanolic extract of AB fermentation product (AB-pE) was demonstrated to inhibit the growth of hepatoma Hep3B and HepG2 cells in our previous study. In this study, we further investigated the anticancer and anti-invasive abctivities of the AB-pE. Results showed that the AB-pE inhibited the growth of SK-Hep1 and HA22T/VGH cells (with IC50 values of 26.8 and 28.7 µg/mL, respectively) and led cells toward apoptosis after 48 h of treatment. Activation of caspase-3 by AB-pE (12.5~200 µg/mL) in a dose-dependent manner was observed in both cell lines using fluorescence microscopy and flow cytometry. The apoptosis triggered by the AB-pE was regulated by the increased expression of Bax, the activation of caspase-3, caspase-9, and PARP, and the decreased expression of Bcl-2. Additionally, the AB-pE showed the potential ability to inhibit invasion of SK-Hep1 and HA22T/VGH cells according to the results of a Matrigel invasion assay. Our results suggested that the AB-pE may be a further developed for its potential against hepatoma due to its antiproliferative (via apoptosis) and anti-invasive activities in hepatoma cells.