Antioxidant, antihyperglycemic, and antihyperlipidemic properties of Chimonanthus salicifolius S. Y. Hu leaves in experimental animals: modulation of thioredoxin and glutathione systems, renal water reabsorption, and gut microbiota.

Introduction: Excessive calorie intake and physical inactivity have dramatically increased nutrient overload-associated disease, becoming a global public health issue. Chimonanthus salicifolius S. Y. Hu (CHI) is a homology plant of food and medicine in China and shows several health benefits. Methods: This work investigated the antioxidant activity, the alleviating effects, and the mechanism of action on diabetes and hyperlipidemia of CHI leaves. Results and discussion: Results showed that CHI leaves infusion displayed in vitro antioxidant activity measured by ABTS and ferric reducing antioxidant power methods. In wild-type Kunming mice, CHI leaves infusion consumption activated the hepatic antioxidant enzymes, including glutathione reductase, glutathione S-transferase, glutathione peroxidase and thioredoxin reductase as well as thioredoxin reductase 1. In alloxan-induced type 1 diabetic mice, CHI leaves infusion ameliorated diabetic symptoms, including polyuria, polydipsia, polyphagia and hyperglycemia, in a dose-dependent and time-course manners. The mechanism involved CHI leaves up-regulating renal water reabsorption associated protein - urine transporter A1-and promoting the trafficking of urine transporter A1 and aquaporin 2 to the apical plasma membrane. Despite this, in high-fat diet-induced hyperlipidemic golden hamsters, CHI leaves powder did not significantly effect on hyperlipidemia and body weight gain. This might be attributed to CHI leaves powder increasing the calorie intake. Interestingly, we found that CHI leaves extract containing a lower dose of total flavonoid than CHI leaves powder pronouncedly reduced the levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum in golden hamsters fed a high-fat diet. Furthermore, CHI leaves extract elevated the diversity of gut microbiota and the abundance of Bifidobacterium and Ruminococcaceae_UCG-014. It also decreased the abundance of Lactobacillus at the genus level in golden hamsters fed a high-fat diet. Overall, CHI leaves benefit oxidative stress prevention and metabolic syndrome amelioration in vivo.

Effectiveness of targeting the NLRP3 inflammasome by using natural polyphenols: A systematic review of implications on health effects.

Globally, inflammation and metabolic disorders pose serious public health problems and are major health concerns. It has been shown that natural polyphenols are effective in the treatment of metabolic diseases, including anti-inflammation, anti-diabetes, anti-obesity, neuron-protection, and cardio-protection. NLRP3 inflammasome, which are multiprotein complexes located within the cytosol, play an important role in the innate immune system. However, aberrant activation of the NLRP3 inflammasome were discovered as essential molecular mechanisms in triggering inflammatory processes as well as implicating it in several major metabolic diseases, such as type 2 diabetes mellitus, obesity, atherosclerosis or cardiovascular disease. Recent studies indicate that natural polyphenols can inhibit NLRP3 inflammasome activation. In this review, the progress of natural polyphenols preventing inflammation and metabolic disorders via targeting NLRP3 inflammasome is systemically summarized. From the viewpoint of interfering NLRP3 inflammasome activation, the health effects of natural polyphenols are explained. Recent advances in other beneficial effects, clinical trials, and nano-delivery systems for targeting NLRP3 inflammasome are also reviewed. NLRP3 inflammasome is targeted by natural polyphenols to exert multiple health effects, which broadens the understanding of polyphenol mechanisms and provides valuable guidance to new researchers in this field.

N-Acetyl-l-cysteine Enhances the Effect of Selenium Nanoparticles on Cancer Cytotoxicity by Increasing the Production of Selenium-Induced Reactive Oxygen Species.

Peritoneal carcinomatosis (PC) has an extremely poor prognosis, which leads to a significantly decreased overall survival in patients with peritoneal implantation of cancer cells. Administration of sodium selenite by intraperitoneal injection is highly effective in inhibiting PC. Our previous study found that selenium nanoparticles (SeNPs) have higher redox activity and safety than sodium selenite. In the present study, we examined the therapeutic effect of SeNPs on PC and elucidated the potential mechanism. Our results revealed that intraperitoneal delivery of SeNPs to cancer cells in the peritoneal cavity of mice at a tolerable dose was beneficial for prolonging the survival time of mice, even better than the optimal dose of cisplatin. The underlying mechanism involved in SeNP-induced reactive oxygen species (ROS) production caused protein degradation and apoptotic response in cancer cells. Interestingly, N-acetyl-l-cysteine (NAC), recognized as a ROS scavenger, without reducing the efficacy of SeNPs, enhanced ROS production and cytotoxicity. The effect of NAC was associated with the following mechanisms: (1) the thiol groups in NAC can increase the biosynthesis of endogenous glutathione (GSH), thus increasing the production of SeNP-induced ROS and cytotoxicity and (2) redox cycling of SeNPs was directly driven by thiol groups in NAC to produce ROS. Moreover, NAC, without increasing the systematic toxicity of SeNPs, decreased SeNP-induced lethality in healthy mice. Overall, we demonstrated that SeNPs exert a potential cytotoxicity effect by inducing ROS production in cancer cells; NAC effectively heightens the property of SeNPs in vitro and in vivo.

A mouse model of subacute liver failure with ascites induced by step-wise increased doses of (-)-epigallocatechin-3-gallate.

Acute liver failure is divided into hyperacute, acute and subacute liver failure. Ascites is a common complication of subacute liver failure. Although animal models of acute liver failure have been established, the study of the pathogenesis of subacute liver failure with ascites complication is hampered by the lack of experimental animal model. The present study aimed at providing a mouse model of subacute liver failure with ascites complication. Kunming mice were intraperitoneally injected with (-)-epigallocatechin-3-gallate (EGCG), a redox-active polyphenol from green tea, for 32 consecutive days with step-wise increased dosage. The EGCG treatment resulted in liver failure as evidenced by extensive hepatocyte necrosis observed histologically along with significant elevation of serum alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin levels as well as significant reduction of serum albumin. Liver fibrosis was not observed by Masson staining and fibrosis-associated proteins were not increased. The mortality was less than 12% and the survival mice developed noticeable ascites. Hepatic thioredoxin and glutathione systems were activated by the EGCG. These adaptive responses might render most mice tolerable to the EGCG treatment. The EGCG treatment significantly up-regulated renal urea transporter A1 and promoted its trafficking to apical membrane. These alterations, known to increase water reabsorption, may be responsible, at least in part, for the formation of the ascites. Overall, the mice treated with gradually elevated doses of EGCG exhibits some of the features observed in patients with subacute liver failure, especially ascites. This mouse model is a useful tool for investigating the pathogenesis of subacute liver failure with ascites complication.

[Pyramiding of 3-resistant-gene to improve rice blast resistance of a restorer line, Fuhui 673].

To improve the blast resistance of elite rice restorer line Fuhui 673, 3 blast resistance genes Pi-1, Pi-9 and Pi-kh were introduced into Fuhui 673 from a good-quality restorer line Jinhui 1059 through 3 successive backcrosses followed by one selfing using the technique of marker-assisted selection. Ten near-isogenic lines (NILs) of Fuhui 673 carrying the 3 introduced resistance genes were created. Genotype analysis using 68 SSR markers evenly distributed in the genome indicated that 92.96%-98.59% of the NILs' genetic background had been recovered to Fuhui 673. Both indoor and field resistance tests indicated that the NILs and their hybrids with sterile line Yixiang A were all resistant to rice blast, with resistance levels significantly higher than those of controls Fuhui 673 and hybrid Yiyou 673 (Yixiang A  Fuhui 673). In addition, among the 10 hybrids between the NILs and Yixiang A, 2 showed significantly higher yield than and 4 displayed similar yield to that of control Yiyou 673, suggesting that most of the NILs retained the elite characteristics of Fuhui 673. Two new hybrid rice cultivars Liangyou 7283 and Jintaiyou 683 from NIL Line 9 showed high yield, good resistance to blast and moderate growth period in regional trial, suggesting that the NIL Line 9 has a good prospect for application.

Three-dimensional reduced graphene oxide aerogel modified electrode for the sensitive quercetin sensing and its application.

Quercetin belongs to flavonoid drug that has favorable properties such as antiviral, anticancer, anti-allergic and anti-tumor. Therefore a sensitive method is highly required for quercetin determination. In this paper, a three-dimensional reduced graphene oxide aerogel (3D-rGA) with excellent porous framework was synthesized via one-step hydrothermal technique. The characteristics and performances of 3D-rGA were checked by SEM, TEM, BET, XRD, Raman, FT-IR, XPS and electrochemical methods, which exhibited good properties including unique porous structure, large surface area and excellent conductivity. 3D-rGA was further used as the modifier on carbon ionic liquid electrode (CILE) to construct a modified electrode, which was applied to sensitive and selective determination of quercetin. Electrochemical responses of quercetin were accelerated with a pair of symmetrical cyclic voltammetric peaks in good shape appeared and the electrochemical parameters were calculated. The sensitive oxidation response of quercetin from differential pulse voltammetry was verified. Under the selected conditions, electroanalysis of quercetin was established by plotting the oxidation peak currents against quercetin concentrations with linear regression analysis. A wider linear range from 0.1 µmol/L to 100.0 µmol/L was obtained with a detection limit of 0.065 µmol/L (3S0/S). This as-explored approach could be successfully utilized for quercetin detection in Ginkgo tablets.

Synergistic toxicity of epigallocatechin-3-gallate and diethyldithiocarbamate, a lethal encounter involving redox-active copper.

Dithiocarbamates (DTC) are widely used in agricultural, industrial and therapeutic domains. There are ample opportunities for human exposure to DTC. Green tea extracts, with epigallocatechin-3-gallate (EGCG) being the most abundant constituent, have been used as dietary supplements for body weight reduction. Our hypothesis is that DTC can act as a copper ionophore to increase hepatic levels of redox-active copper which promotes EGCG auto-oxidation to produce oxidative stress and toxicity. The results of the present study in a mouse model is consistent with this hypothesis, showing that co-administration of EGCG and diethyldithiocarbamate - a metabolite of disulfiram (a drug for alcohol aversion therapy), both at tolerable levels, caused lethality. The liver was the major organ site of toxicity. The co-administration drastically increased lipid peroxidation, DNA damage and cell apoptosis as well as caused deleterious transcriptional responses including basal and Nrf2 antioxidant systems in the liver. The results suggest that exposure to DTC reduces toxic threshold of dietary polyphenols from green tea and possibly other plants, and vice versa. This novel hypothesis is important to human health, and the dose-response relationship of this synergistic toxicity needs to be further characterized.

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice.

Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system. In selenium-optimal mice, EGCG increased hepatic activities of thioredoxin reductase, glutathione reductase and glutaredoxin. These effects of EGCG appeared to be not due to overt pro-oxidant action because melatonin, a powerful antioxidant, did not influence the increase. However, in selenium-deficient mice, with low basal levels of thioredoxin reductase 1, the same dose of EGCG did not elevate the above-mentioned enzymes; intriguingly EGCG in turn activated hepatic Nrf2 response, leading to increased heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 protein levels and thioredoxin activity. Overall, the present work reveals that EGCG is a robust inducer of the Nrf2 system only in selenium-deficient conditions. Under normal physiological conditions, in selenium-optimal mice, thioredoxin and glutathione systems serve as the first line defense systems against the stress induced by high doses of EGCG, sparing the activation of the Nrf2 system.

Certain (-)-epigallocatechin-3-gallate (EGCG) auto-oxidation products (EAOPs) retain the cytotoxic activities of EGCG.

(-)-Epigallocatechin-3-gallate (EGCG) from green tea has anti-cancer effect. The cytotoxic actions of EGCG are associated with its auto-oxidation, leading to the production of hydrogen peroxide and formation of numerous EGCG auto-oxidation products (EAOPs), the structures and bioactivities of them remain largely unclear. In the present study, we compared several fundamental properties of EGCG and EAOPs, which were prepared using 5mg/mL EGCG dissolved in 200mM phosphate buffered saline (pH 8.0 at 37°C) and normal oxygen partial pressure for different periods of time. Despite the complete disappearance of EGCG after the 4-h auto-oxidation, 4-h EAOPs gained an enhanced capacity to deplete cysteine thiol groups, and retained the cytotoxic effects of EGCG as well as the capacity to produce hydrogen peroxide and inhibit thioredoxin reductase, a putative target for cancer prevention and treatment. The results indicate that certain EAOPs possess equivalent cytotoxic activities to EGCG, while exhibiting simultaneously enhanced capacity for cysteine depletion. These results imply that EGCG and EAOPs formed extracellularly function in concert to exhibit cytotoxic effects, which previously have been ascribed to EGCG alone.