Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

Protective effect of hot-water and ethanol-aqueous extracts from Anneslea fragrans against acetaminophen-induced acute liver injury in mice.

Anneslea fragrans Wall. (AF) is an important medicinal and edible plant in China. The principal objectives of this study are to explore the hepatoprotective effect of ethanol-aqueous (AFE) and hot-water (AFW) extracts in vitro and in vivo. UPLC-ESI-MS/MS analysis showed that AFW and AFE are rich in dihydrochalcones. Both AFW and AFE significantly up-regulated the expressions of SOD, CAT and GSH, reduced the MDA content in acetaminophen (APAP)-induced HepG2 cells, and suppressed the expressions of NO, TNF-α, IL-1ß, and IL-6 in LPS-induced RAW246.7 cells. In APAP-induced mice, AFW and AFE administration significantly decreased the plasma levels of AST and ALT, and improved liver tissue damage, the collagen deposition and fibrosis formation. Moreover, AFW and AFE decreased the MDA and ROS accumulations via activating Nrf2 pathway to increase the hepatic GSH contents and activities of SOD, CAT, HO-1, and NQO-1, reduced the levels of NO, TNF-α, IL-1ß, and IL-6 by suppressing the JNK/p38/ERK/NF-κB pathways, and alleviated apoptosis via regulating Bcl-2, Bax, caspase-3/9 protein expressions. This study provides a new sight that AFW and AFE may have a potential natural resource for the treatment of liver injury.

E Se tea extract ameliorates CCl4 induced liver fibrosis via regulating Nrf2/NF-κB/TGF-ß1/Smad pathway.

BACKGROUND: Liver fibrosis is a crucial progress to deteriorate liver disease. E Se tea (ES) is an ethnic herbal tea in China that has various biological activities for human beings. However, the traditional application on the treatment of liver disease is not studied. PURPOSE: This study is firstly performed to explore the chemical constituents of ES extract together with its anti-hepatic fibrosis effect and potential mechanism on CCl4 treated mice. STUDY DESIGN AND METHODS: The chemical constituents of ethanol-aqueous extract from ES (ESE) were analyzed by UPLC-ESI-MS/MS. The anti-hepatic fibrosis effect of ESE was determined by measuring ALT and AST activities, antioxidative indexes, inflammatory cytokines and collagen protein levels on CCl4 treated mice. Moreover, H&E, Masson staining and immunohistochemical analysis were performed for evaluating the protective effect of ESE on histopathological changes of liver tissues. RESULTS: UHPLCHRESI-MS/MS analysis showed that the ESE was rich in flavonoids such as phlorizin, phloretin, quercetin and hyperoside. ESE could significantly reduce the plasma AST and ALT activities. The cytokines (IL-6, TNF-α, IL-1ß) expressions were inhibited after ESE administration via suppressing NF-κB pathway. In addition, ESE could decrease MDA accumulation for alleviating CCl4 induced liver oxidative stress via regulating Nrf2 pathway to promote the expressions of antioxidant enzymes (SOD, HO-1, CAT and NQO1). Moreover, ESE could inhibit the expressions of TGF-ß1, Smad2, α-SMA, and collagens Ⅰ and III proteins, thereby effectively alleviate the liver fibrosis. CONCLUSION: This study demonstrated that ESE could alleviate liver fibrosis through enhancing antioxidant and anti-inflammatory abilities by Nrf2/NF-κB pathway and reducing deposition of liver fibrosis via suppressing TGF-ß/Smad pathway.

Protective effect of Anneslea fragrans ethanolic extract against CCl4-induced liver injury by inhibiting inflammatory response, oxidative stress and apoptosis.

Anneslea Fragrans Wall. (AF) is a medicinal and edible plant distributed in China. Its leaves and barks are generally used for the treatments of diarrhea, fever, and liver diseases. While its ethnopharmacological application against liver diseases has not been fully studied. This study was aimed to evaluate the hepatoprotective effect of ethanolic extract from A. fragrans (AFE) on CCl4 induced liver injury in mice. The results showed that AFE could effectively reduce plasma activities of ALT and AST, increase antioxidant enzymes activities (SOD and CAT) and GSH level, and decrease MDA content in CCl4 induced mice. AFE effectively decreased the expressions of inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2 and iNOS), cell apoptosis-related proteins (Bax, caspase-3 and caspase-9) and increased Bcl-2 protein expression via inhibiting MAPK/ERK pathway. Additionally, TUNEL staining, Masson and Sirius red staining, immunohistochemical analyses revealed that AFE could inhibit the CCl4-induced hepatic fibrosis formation via reducing depositions of α-SMA, collagen I and collagen III proteins. Conclusively, the present study demonstrated that AFE had an hepatoprotective effect by suppressing MAPK/ERK pathway to inhibit oxidative stress, inflammatory response and apoptosis in CCl4-induced liver injury mice, suggesting that AFE might be served as a hepatoprotective ingredient in the prevention and treatment of liver injury.

Effect of ultra-high pressure pretreatment on the phenolic profiles, antioxidative activity and cytoprotective capacity of different phenolic fractions from Que Zui tea.

This study aims to explore whether ultra-high pressure (UHP) pre-treatment strengthened the bioaccessibility and bioactivities of the free (QF), esterified (QE) and insoluble-bound phenolics (QIB) from Que Zui tea (QT). The results revealed that the extraction yields, the total phenolic (TPC) and total flavonoid contents (TFC) of three phenolic fractions from QT were markedly increased after ultra-high pressure (UHP) processing (p < 0.05). A total of 19 and 20 compounds were characterized and quantified in non- and UHP-treated QT, respectively, including the content of 6'-O-caffeoylarbutin (11775.68 and 13248.87 µg/g of dry extract) was highest in QF, the content of caffeic acid was highest in QE (2131.58 and 7362.99 µg/g of dry extract) and QIB (9151.89 and 10930.82 µg/g of dry extract). QF, QE and QIB from QT after UHP processing had better antioxidant, ROS scavenging, and anti-apoptosis effects. The possible mechanism of cytoprotective effect was related to Keap1-Nrf2 pathway.

Rice Protein Exerts Endogenous Antioxidant Capacity via Methionine Sulfoxide Reductase and the Nrf2 Antioxidant System Independent of Age.

The major aim of this study was to investigate the effect of rice protein (RP) on the activation of endogenous antioxidant defense in growing and adult rats. After 2 weeks, RP activated nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) by suppressing Kelch-like ECH-associated protein 1 (Keap1) and Cullin 3 (Cul3) in growing and adult rats. Compared with casein, the upregulation of antioxidant responsive element (ARE)-driven antioxidant expression levels (glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modulatory subunit, glutathione synthase, glutathione reductase, glutathione S-transferase, glutathione peroxidase, catalase, superoxide dismutase, heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1) were found in RP groups. Also, RP upregulated methionine sulfoxide reductase (MsrA, MsrB2, and MsrB3) expression levels in growing and adult rats. As a result, RP enhanced endogenous antioxidative capacities to reduce hepatic accumulations of malondialdehyde, protein carbonyl, and reactive oxygen species. This study demonstrates that RP exerts the endogenous antioxidant capacity in growing and adult rats, which is due to stimulating Msr antioxidant expression and activating Nrf2-ARE pathway. Results suggest that the antioxidant activity induced by RP is independent of age.

l-Arginine induces antioxidant response to prevent oxidative stress via stimulation of glutathione synthesis and activation of Nrf2 pathway.

Arginine is a conditionally essential amino acid. To elucidate the influence of l-arginine on the activation of endogenous antioxidant defence, male Wistar rats were orally administered daily with l-arginine at different levels of 25, 50, 100 mg/100 g body weight. After 7 and 14 days feeding, the antioxidative capacities and glutathione (GSH) contents in the plasma and in the liver were uniformly enhanced with the increasing consumption of l-arginine, whereas the oxidative stress was effectively suppressed by l-arginine treatment. After 14 days feeding, the mRNA levels and protein expressions of Keap1 and Cul3 were gradually reduced by increasing l-arginine intake, resulting that the nuclear factor Nrf2 was activated. Upon activation of Nrf2, the expressions of antioxidant responsive element (ARE)-dependent genes and proteins (GCLC, GCLM, GS, GR, GST, GPx, CAT, SOD, NQO1, HO-1) were up-regulated by l-arginine feeding, indicating an upward trend in antioxidant capacity uniformly with the increasing consumption of l-arginine. The present study demonstrates that the supplementation of l-arginine stimulates GSH synthesis and activates Nrf2 pathway, leading to the up-regulation of ARE-driven antioxidant expressions via Nrf2-Keap1 pathway. Results suggest the availability of l-arginine is a critical factor to suppress oxidative stress and induce an endogenous antioxidant response.