Oryzanol Ameliorates DSS-Stimulated Gut Barrier Damage via Targeting the Gut Microbiota Accompanied by the TLR4/NF-κB/NLRP3 Cascade Response In Vivo.

Inflammatory bowel disease (IBD) is a global chronic disease with a long duration and repeated relapse. Currently, there is still a lack of effective approaches to prevent IBD. Food-derived oryzanol (ORY) possesses extensive biological activities, such as ameliorating bowel diseases, antioxidation, and antiobesity. However, the mechanism of ORY in preventing colitis remains unclear. The present research aims to explore the potential mechanism of ORY in dextran sulfate sodium (DSS)-stimulated colitis in a rat model. The results showed that the symptoms of colitis were significantly improved with the administration of ORY. Mechanismly, the expression levels of Zonula occludens-1 (ZO-1), Claudin-1, Occludin, MUC2, and TFF3 were elevated through ORY treatment, suggesting that oral ORY relieved the degree of gut barrier damage of colitis rats. Meanwhile, 16S sequencing results found that ORY supplementation increased the abundances of Alloprevotella, Roseburia, Treponema, Muribaculaceae, and Ruminococcus, which are associated with the synthesis of short-chain fatty acids (SCFAs). Moreover, GC-MS results confirmed that ORY supplementation reversed the DSS-induced reduction of acetic acid, butyric acid, and total acid. Further research indicated that ORY intervention downregulated the TLR4/NF-κB/NLRP3 pathway, which is closely linked to the expression of proinflammatory cytokines and colon injury. Taken together, ORY ameliorates DSS-stimulated gut barrier damage and inflammatory responses via the gut microbiota-TLR4/NF-κB/NLRP3 signaling axis.

Efficient Preparation of Black Tea Extract (BTE) with the High Content of Theaflavin Mono- and Digallates and the Protective Effects of BTE on CCl4-Induced Rat Liver and Renal Injury.

Theaflavins (TFs), formed by the dimerization of green tea catechins during "fermentation" to prepare black tea, possess antioxidant and anti-inflammatory effects. Reported efficacious effects of black tea (∼2% of TFs) or related products come from catechins unless TFs are assayed. The present study aimed to target the preparation of black tea extract (BTE) enriched with theaflavin mono- and digallates majorly from dry tea leaves in aqueous media versus traditional fermentation of fresh leaves. We further investigated the protective function of the produced BTE on rat liver and kidney injury induced by CCl4 and its underlying molecular mechanisms. The results showed that BTE suppressed the activation level of hepatic stellate cells (HSCs), and the secretion of collagen was induced by CCl4. The relative expression levels of TGF-ß, p-ERK1/ERK1, p-ERK2/ERK2, p-Smad1/Smad1, and p-Smad2/Smad2 were reduced to 56, 68, 56, 44, and 32%, respectively, compared with those of CCl4-treated rats. Therefore, BTE enriched with TFs prevented rat hepatic fibrosis through the TGF-ß/Smad/ERK signaling pathway and kidney injury by inhibiting the expression of TGF-ß and proinflammatory cytokines in rats. We predict the broad application of TFs and related products because of their strong antioxidant and inhibitory effects on chronic inflammation.

Protective effects of trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-glucopyranoside on liver fibrosis and renal injury induced by CCl4via down-regulating p-ERK1/2 and p-Smad1/2.

Both as a food and an herbal plant, Polygonum multiflorum (PM) has long been used in food and prescriptions for several centuries in Southeast Asia. trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-glucopyranoside (trans-THSG) is one of the major compounds derived from PM and has been reported to exhibit multiple biological activities such as antioxidation and anti-obesity activities among others. The current study was aimed at investigating the effects of trans-THSG on liver fibrosis and renal injury in a carbon tetrachloride (CCl4) induced rodent model via oral feeding. Research results have demonstrated that administration of trans-THSG (100 and 300 mg kg-1) significantly ameliorated liver fibrosis, manifested by reduced expression of desmin and α-smooth muscle actin (α-SMA) plus collagen deposition. Specifically, treatment with trans-THSG effectively decreased the levels of transforming growth factor-ß (TGF-ß) and reduced the phosphorylation of Smad1/2 (p-Smad1/2) and extracellular signal-regulated kinases 1/2 (p-ERK1/2). Furthermore, we found that trans-THSG significantly down-regulated CCl4-induced excessive collagen secretion and increased the levels of desmin, MMP2 and MMP9 in rat liver tissues, suggesting that trans-THSG prevents liver fibrosis by attenuating the activation of hepatic stellate cells (HSCs) through the inhibition of Smad and ERK signaling pathways. Hence, the present findings demonstrate that trans-THSG is an effective antifibrotic agent in protecting liver from CCl4-induced toxicity.

Supercritical fluid CO2 extraction of three polymethoxyflavones from Citri reticulatae pericarpium and subsequent preparative separation by continuous high-speed counter-current chromatography.

Polymethoxyflavones (PMFs) are widely found in Citri Reticulatae Pericarpium (CRP) and have been investigated with a broad spectrum of biological activities as well as health promoting properties. However, separation of the PMFs from a complex sample, especially preparative separation of these PMFs with high purity, remains challenging. In the present study, an efficient method based on supercritical fluid extraction (SFE) and continuous high-speed counter-current chromatography (HSCCC) has been developed for extracting and preparative purification PMFs from CRP. Various experimental conditions were investigated to optimize the SFE and HSCCC processes. Under these optimized conditions, crude extract of CRP (extract I) was obtained with a maximum contents of nobiletin, 3,5,6,7,8,3',4'-heptamethoxyflavone and tangeretin. Further extraction of crude extract I was carried out to obtain crude extract II, which was further isolated and purified by HSCCC. It was worth mentioned that continuous injection HSCCC process were realized without lost of separation efficiency, which allowed for multiple purification cycles and therefore saved a lot of labor and time. Furthermore, high-performance liquid chromatography (HPLC) was employed to analyze the fractions separated by HSCCC, which revealed that the purities of the three PMFs were all above 98%. The structures of the three PMFs were identified by LC-MS and 1H NMR spectroscopy.

Simultaneous separation of six pure polymethoxyflavones from sweet orange peel extract by high performance counter current chromatography.

Successful isolation of polymethoxyflavones (PMFs) from citrus peels has led to numerous evaluations of PMFs in a broad spectrum of biological activities, such as inhibition of chronic inflammation, cancer prevention and anti-atherogenic properties. Recent reports associated with the health promoting properties of PMFs in citrus fruits have dramatically increased. However, the limiting factor in animal and human study of PMFs is still the supply of pure PMFs, such as tangeretin, nobiletin, sinensetin and 3,5,6,7,3',4'-hexamethoxyflavone. Herein, we introduce the newly developed efficient separation method using high-performance counter-current chromatography (HPCCC) in isolating multiple pure single PMFs simultaneously in one cycle process. With the smallest preparation loop on the semi-preparative HPCCC instrument, the optimized solvent system of hexanes/ethyl acetate/methanol/water resulted in the isolation of pure sinensetin, tangeretin, nobiletin, 3,5,6,7,3',4'-hexamethoxyflavone, 5,6,7,4'-tetramethoxyflavone and 3,5,6,7,8,3',4'-heptamethoxyflavone directly from crude sweet orange peel extract in one cycle of separation process by HPCCC in the mode of reverse phase. The purity of each of the six isolated PMFs is greater than 96.6% analyzed by high-performance liquid chromatography and proton nuclear magnetic resonance. Scale-up and high purity of individual PMFs can be separated by using a large separation loop in preparative HPCCC model. The renovated HPCCC methodology can be practically used in natural product isolation and consequent biological property evaluation.

Green Tea Catechins Effectively Altered Hepatic Fibrogenesis in Rats by Inhibiting ERK and Smad1/2 Phosphorylation.

Polyphenols derived from green tea have been reported to have a wide range of profound functions. Tea catechins, including epicatechin, epigallocatechin (EGC), epicatechin-3- O-gallate (ECG), and epigallocatechin-3- O-gallate (EGCG), are considered as the major bioactive polyphenols in tea. The present study was designed to elucidate the potential antifibrogenic role of three abundant tea catechins (ECG, EGC, and EGCG) in a CCl4-induced fibrotic rat and their underlying molecular mechanisms. Tea catechins, especially groups of ECG, EGC, and EGCG, effectively induced several beneficial alterations of liver injury markers, oxidative status, and liver histology. Furthermore, catechins ameliorated liver fibrosis, as evidenced by the reduced expression of desmin, α-smooth muscle actin, transforming growth factor ß (TGF-ß), and downstream ERK1/2 and Smad1/2 phosphorylation. The most significant inhibitory effect on those proteins was observed in ECG (300 mg/kg) and EGCG (300 mg/kg) groups. In addition, catechins conferred their protective role by downregulating the proinflammation cytokines TGF-ß, tumor necrosis factor α, and interleukin 17. It is postulated that tea catechins, particularly ECG and EGCG, are potential therapeutic candidates in antifibrotic therapy.

Anti-fibrotic activity of polyphenol-enriched sugarcane extract in rats via inhibition of p38 and JNK phosphorylation.

Sugarcane (Saccharum officinarum L.), which is one of the most important sources of sugar, is also rich in polyphenolic compounds. In this study, polyphenols from sugarcane were extracted, and the dominant component was characterized quantitatively via HPLC to be (-)-epicatechin. Fibrosis occurs in many organs and is associated with severe tissue damage. Liver fibrosis is the excessive accumulation of extracellular matrix proteins and advanced liver fibrosis, resulting in cirrhosis, liver failure and portal hypertension. Thus, the prevention and treatment of liver fibrosis is urgent. Therefore, we further investigated the protective effect of sugarcane polyphenol extract (SPE) on carbon tetrachloride-induced liver fibrosis in rats and observed that SPE (20 or 50 mg kg-1) improved the serum GOT (glutamic oxaloacetic transferase) and GPT (glutamic pyruvate transaminase) levels and decreased the expression of α-smooth muscle actin (α-SMA) in liver tissues. The mechanistic study showed that in transforming growth factor ß1(TGF-ß1)-induced hepatic stellate cells (HSCs), SPE attenuated the phosphorylation of p38 and JNK1/2 and down-regulated the expression of α-SMA. Collectively, SPE mitigated carbon tetrachloride-induced liver fibrosis in rats and its mechanism may be related to the p38 and JNK signalling pathways.

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.

Combination of citrus polymethoxyflavones, green tea polyphenols, and Lychee extracts suppresses obesity and hepatic steatosis in high-fat diet induced obese mice.

SCOPE: SlimTrym® is a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract, and lychee extract. We investigated the effect of dietary SlimTrym® on diet-induced obesity and associated non-alcoholic fatty liver disease (NAFLD) in mice. METHODS AND RESULTS: Male C57BL/6 mice were fed a normal diet (ND), high fat diet (HFD) or HFD containing 0.1% or 0.5% SlimTrym® for 16 weeks. Dietary SlimTrym® significantly reduced weight gain and relative perigonadal, retroperitoneal, mesenteric fat weight as well as the size of adipocyte in HFD-fed mice. SlimTrym® supplementation also effectively diminished hepatic steatosis and the serum levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), triacylglycerol (TG), and total cholesterol (TCHO). Down-regulation of peroxisome proliferator-activated receptor (PPAR)γ, sterol regulatory element-binding protein (SREBP)-1, and the activation of AMP-activated protein kinase (AMPK) signaling by SlimTrym® in both adipose tissue and liver may be responsible for the observed anti-obesity effects. CONCLUSION: SlimTrym® supplementation potentially diminished diet-induced obesity and hepatic steatosis via regulating AMPK signaling and molecules involved in lipid metabolism.

Momordica charantia: a popular health-promoting vegetable with multifunctionality.

Products derived from edible medicinal plants have been used for centuries to prevent, treat, and even cure multiple diseases. Momordica charantia L., widely cultivated around the world, is a typical one bred for vegetables and medicinal usage. All parts of M. charantia possess important medicinal properties, including antidiabetic, anticancer, hypotensive, anti-obesity, antimicrobial, antihyperlipidemic, antioxidant, anti-inflammatory, immuno-modulatory, anthelmintic, neuro-protective, as well as hepato-protective properties both in vitro and in vivo. This review summarizes the active components and medicinal properties of M. charantia, especially the activities and mechanisms of its anti-diabetic and anti-cancer properties. The anti-diabetic properties involve inhibiting intestinal α-glucosidase and glucose transport, protecting islet ß-cells, enhancing insulin secretion, increasing hepatic glucose disposal, decreasing gluconeogenesis, and even ameliorating insulin resistance. Moreover, the expressions of PPARs could also be activated and up-regulated. Meanwhile, its anticancer properties are mostly due to apoptosis, cell cycle arrest, and expression of serum factors associated with immunity. In this review, we aim to provide an overview of M. charantia and its benefits for development as a functional food.

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.

Antifungal activity of Momordica charantia seed extracts toward the pathogenic fungus Fusarium solani L.

Momordica charantia L., a vegetable crop with high nutritional value, has been used as an antimutagenic, antihelminthic, anticancer, antifertility, and antidiabetic agent in traditional folk medicine. In this study, the antifungal activity of M. charantia seed extract toward Fusarium solani L. was evaluated. Results showed that M. charantia seed extract effectively inhibited the mycelial growth of F. solani, with a 50% inhibitory rate (IC50) value of 108.934 µg/mL. Further analysis with optical microscopy and fluorescence microscopy revealed that the seed extract led to deformation of cells with irregular budding, loss of integrity of cell wall, as well as disruption of the fungal cell membrane. In addition, genomic DNA was also severely affected, as small DNA fragments shorter than 50 bp appeared on agarose gel. These findings implied that M. charantia seed extract containing α-momorcharin, a typical ribosome-inactivating protein, could be an effective agent in the control of fungal pathogens, and such natural products would represent a sustainable alternative to the use of synthetic fungicides.