Food & Function
·
2022
·Vol. 13
·期 5
·2618-2630
·
IF 6.317
Xin Hao,Jiahong Xie,Yuting Li,Wei Chen
Anthocyanins are natural products that display diverse bioactivities but are limited in their applications by low stability and bioavailability. Acylated anthocyanins are found to possess higher stability, while their bioactivities are still obscure. In this study, acetylation of pelargonidin-3-O-glucoside (Pg3G) was catalyzed by Candida antarctica lipase B (CALB) for the first time, with a conversion rate up to 88.77% over 48 h. The acetylated product was identified as pelargonidin-3-O-(6′′-acetyl)-glucoside and its properties were detected. Notably, acetylated Pg3G (Ace Pg3G) possessed better thermostability and lipophilicity than Pg3G, indicating a longer retention time at physiological pH and facilitating penetration into the lipophilic medium as well as the cell membrane. Most importantly, Ace Pg3G exerted better alleviation effects against H2O2-induced oxidative hepatic damage than parent Pg3G via activating the Nrf2/ARE signaling pathway and upregulating the expressions of the downstream phase II detoxification enzymes GCLC and HO-1, thereby reversing redox imbalance and enhancing cell survival. Overall, our research unveiled the better health benefits of Ace Pg3G and also provided new insights about the applications of acetylated anthocyanins in food, cosmetic, and pharmaceutical products.
研究领域:
食品科学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
·
IF 4.679
Hang Qu,Shuang Liu,Cuilin Cheng,Haitian Zhao,Xin Gao,Zhenyu Wang,Juanjuan Yi
Previously, we obtained a purified polysaccharide (PNP40c-1) from Pinus koraiensis pine nut and reported its protective effect on carbon tetrachloride (CCl 4 )-induced liver injury in vitro . The object of this study is to investigate its hepatoprotective activity in vivo and elucidate the mechanism underlying the hepatoprotection . PNP40c-1 effectively prevented the accumulation of serum liver injury biomarkers including alanine aminotransferase , aspartate aminotransferase, alkaline phpsphatase and total bilirubin stimulated by CCl 4 . The pathological changes in PNP40c-1-treated mice livers were also markedly ameliorated. Results showed that PNP40c-1 suppressed the production of reactive oxygen species (ROS) and lipid peroxidation, upregulated Nrf2/ARE pathway and enhanced the antioxidant capacity of hepatocytes. Furthermore, the reaction between Nrf2 and ARE promoted the generation of Mkp1 , which inhibited the activation of JNK induced by CCl 4 , and suppressed hepatocytes apoptosis by regulating the protein expression of Bax, cleaved-Caspase-3 and Bcl2, exerting hepatoprotective activity. Taken together, upregulation of Nrf2/ARE pathway and suppression of JNK activation via Nrf2/ARE/Mkp1/JNK signaling pathways are the main mechanisms underlying the hepatoprotective effect of PNP40c-1 against CCl 4 -induced mice liver injury. These results indicated that PNP40c-1 has potential to serve as a hepatoprotective agent against chemical induced hepatotoxicity.
研究领域:
药理学
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毒理学
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生物化学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2021
·
IF 4.315
Hao Huang,Xielan Kuang,Xiaobo Zhu,Hao Cheng,Yuxiu Zou,Han Du,Han Tang,Linbin Zhou,Jingshu Zeng,Huijun Liu,Jianhua Yan,Chongde Long,Huangxuan Shen
Retinal ischemia-reperfusion (I/R) often results in intractable visual impairments, where blood retinal barrier (BRB) homeostasis mediated by retinal pigment epithelium (RPE) and retinal microvascular endothelium (RME) is crucial. However, strategies targeting the BRB are limited. Thus, we investigated the inconclusive effect of lycopene (LYC) in retinal protection under I/R. LYC elevated cellular viability and reversed oxidative stress in aRPE-19 cells/hRME cells under I/R conditions based on oxygen-glucose deprivation (OGD) in vitro . Molecular analysis showed that LYC promoted NRF2 expression and enhanced the downstream factors of the KEAP1/NRF2/ARE pathway: LYC increased the activities of antioxidants, including SOD and CAT , whereas it enhanced the mRNA expression of HO-1 ( ho-1 ) and NQO-1 ( nqo-1 ). The activation resulted in restrained ROS and MDA. On the other hand, LYC ameliorated the damage to retinal function and morphology in a mouse I/R model, which was established by unilateral ligation of the left pterygopalatine artery/external carotid artery and reperfusion . LYC promoted the expression of NRF2 in both the neural retina and the RPE choroid in vivo . This evidence revealed the potential of LYC in retinal protection under I/R, uncovering the pharmacological effect of the KEAP1/NRF2/ARE pathway in BRB targeting. The study generates new insights into scientific practices in retinal research.
研究领域:
眼科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Fuqiang Liang,Yajing Fang,Weiwei Cao,Zhuo Zhang,Siyi Pan,Xiaoyun Xu
The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
研究领域:
药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Wang Kaiping,Yang Linlin,Zhou Jing,Pan Xianglin,He Zihao,Liu Junxi,Zhang Yu
The alleviation of oxidative stress is considered an effective treatment for acetaminophen (APAP)-induced acute liver injury (AILI). However, it remains unknow whether the potential antioxidant Smilax china L. polysaccharide (SCLP) protects against AILI. In this study, in vitro and in vivo experiments were conducted to verify the hepatoprotective effect of SCLP against AILI and explore the potential mechanism. We found that SCLP relieved liver histopathological changes; reversed the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and reactive oxygen species (ROS); reversed the change in liver myeloperoxidase (MPO) activity; and enhanced liver antioxidant (GSH, GSH-Px, and t-SOD) levels in APAP-treated mice, thereby significantly reducing APAP-induced liver toxicity. SCLP rescued the cell viability and alleviated oxidative stress in H2O2-treated mouse AML12 (Alpha mouse liver 12) hepatocytes. The results of the mechanistic studies showed that SCLP upregulated nuclear factor E2 related factor (Nrf2) expression, promoted Nrf2 nuclear translocation, and enhanced the ability of Nrf2 to bind antioxidant response elements (AREs). Furthermore, SCLP activated Nrf2-ARE pathway, thus upregulating the expression of oxidative stress-related proteins heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1(NQO-1) and glutamic acid cysteine ligase catalytic subunit (GCLC). In conclusion, this study confirmed the close correlation between liver protection by SCLP upon exposure to APAP and activated of the Nrf2-ARE pathway. These findings suggest that SCLP is an attractive therapeutic candidate drug for the treatment of AILI.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 4
·3043-3052
·
IF 4.171
Wenli Yan,Guimei Lin,Rong Zhang,Zhen Liang,Wenjuan Wu
Two novel effective antioxidative tripeptides GWY and QWY were designed based on 3D-QSAR models. Their activities were confirmed by an improved TEAC assay. The experimental results showed that GWY and QWY possessed good antioxidant activity, equaling 3.32 mM TE and 2.97 mM TE respectively. This indicated that 3D-QSAR models possessed significant predictive capacity for drug design. In addition, molecular docking and molecular dynamics simulation were applied to reveal the potential molecular mechanism of antioxidant peptides. The result showed that GWY and QWY could enhance the stability of Keap1 by interacting with the key residues Arg415, Arg483, Arg380 and Ser555 in the active sites. Interestingly, the key residues were exactly the binding site of Nrf2 in the active pocket of Keap1. Thus, GWY and QWY could compete with Nrf2 for binding to Keap1. This demonstrated that the new tripeptides might have the ability to activate the signaling pathway Keap1–Nrf2–ARE and improve the antioxidant defense system of the body as well.
研究领域:
生物化学
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药物设计
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Mengdi Zhang,Jindong Gao,Md. F. Kulyar,Wanhe Luo,Guodong Zhang,Xiaoqi Yang,Tianguang Zhang,Haihang Gao,Yuxuan Peng,Jiabin Zhang,Muhammad Altaf,Samah Attia Algharib,Donghai Zhou,Jianzhong He
Acute renal failure is a common clinical disease in canines, affecting antioxidant levels and decreasing the body's resistance. This study aims to explore the therapeutic mechanism of Nano-selenium in acute renal failure. The histopathological and imaging changes of kidney tissue were observed with the gene and protein expression levels of Keap1, Nrf2, HO-1, and NQO1 in the kidney. According to our findings, adding nano-selenium can effectively reduce the concentration of CRE and BUN in blood and kidney tissues. It increased the activity of GSH-PX and SOD by an effective reduction of MDA. Through pathological and imaging observations, it was found that adding nano-selenium could improve the kidney tissue structure of acute renal failure. The results of the RT-qPCR experiment showed that after the addition of nano-selenium, the mRNA expression of the Keap1 gene decreased significantly. In contrast, the mRNA expression of the Nrf2, HO-1, and NQO1 genes increased significantly. The experimental results were further verified by western blot and immunohistochemical analysis. Hence, the nano-selenium intervention improved kidney function and increased antioxidant levels in canines suffering from acute renal failure with the involvement of the Keap1-Nrf2/ARE signaling pathway.
研究领域:
兽医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2021
·
IF 7.086
Lei Liu,Huan Wang,Meng Xu,Tian-Xiu Qiu,Jiong Chen
Azoxystrobin (AZ) has entered aquatic ecosystems and produced serious damages to fish associated with potentially increasing the susceptibility to pathogens . This study characterized the defense abilities of fish by exposed to AZ on challenging with the infection of spring viraemia of carp virus (SVCV). The results showed that SVCV replication increased significantly in EPC cells and zebrafish that were exposed to up to 50 μg/L of AZ at 3, 5, 7, and 14 d. Intracellular biochemical assays indicated that AZ at 5 and 50 μg/L inhibited the activation of Nrf2-ARE pathway including a decrease in Nrf2 expression, Nrf2 phosphorylation, HO-1 content, and three antioxidant activities. While no significant difference in ERK1/2 and JNK MAPKs in zebrafish was observed, P38 phosphorylation was significantly decreased at 7 and 14 d, and the changes in MAPKs were more evident in EPC cells previously exposed to AZ at 7 d. These results revealed that AZ initially induced low phosphorylation of MAPKs, triggering the attenuation of Nrf2 phosphorylation to weaken Nrf2 translocation into the nucleus in a longer exposure period (more than 5 d). The data in the cells and fish also showed that antioxidant activities were decreased to some extent at 5–7 d for the cells and 7–14 d for the fish. Furthermore, interferon-related factors were decreased in AZ-exposed zebrafish, explaining the reason that fish can't resist the virus infection. Overall, the present study provided a new adverse threat of AZ by amplifying the viral outbreak to endanger ecological safety in aquatic environment.
研究领域:
环境科学
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鱼类病理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2016
·
IF 3.522
Linling Que,Liu He,Chenshu Yu,Wencheng Yin,Liwen Ma,Baoshan Cao,Siwang Yu
Myelosuppression is the most common dose-limiting adverse effect of chemotherapies. In the present study, we investigated the involvement of nuclear erythroid 2-related factor 2 (Nrf2) in cyclophosphamide-induced myelosuppression in mice, and evaluated the potential of activating Nrf2 signaling as a preventive strategy. The whole blood from Nrf2 −/− mice exhibited decreased antioxidant capacities, while the bone marrow cells, peripheral blood mononuclear cells and granulocytes from Nrf2 −/− mice were more susceptible to acrolein-induced cytotoxicity than those from wild type mice. Single dosage of cyclophosphamide induced significantly severer acute myelosuppression in Nrf2 −/− mice than in wild type mice. Furthermore, Nrf2 −/− mice exhibited greater loss of peripheral blood nucleated cells and recovered slower from myelosuppression nadir upon multiple consecutive dosages of cyclophosphamide than wild type mice did. This was accompanied with decreased antioxidant and detoxifying gene expressions and impaired colony formation ability of Nrf2 −/− bone marrow cells. More importantly, activation of Nrf2 signaling by CDDO-Me significantly alleviated cyclophosphamide-induced myelosuppression, while this alleviation was diminished in Nrf2 −/− mice. In conclusion, the present study shows that Nrf2 plays a protective role in cyclophosphamide-induced myelosuppression and activation of Nrf2 is a promising strategy to prevent or treat chemotherapy-induced myelosuppression.
研究领域:
药理学
·
肿瘤学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 20
·12086
·
IF 6.208
Jiaojiao Zhang,Shaozhen Wu,Qingqing Wang,Qinjie Yuan,Yane Li,Patricia Reboredo-Rodríguez,Alfonso Varela-López,Zhiping He,Fenghua Wu,Hao Hu,Xingquan Liu
Pecan (Carya cathayensis) is an important economic crop, and its hydrolyzed peptides have been evidenced to reduce the effect of oxidative stress due to their antioxidant capacity. Hence, the protocols of ultrafiltration and gel filtration chromatography were established to obtain bioactive peptides from by-products ofC. cathayensis(pecan cake). As measured by DPPH/ABTS radical scavenging, the peptides with less molecular weight (MW) possess higher antioxidant capacity. PCPH-III (MW < 3 kDa) presented higher radical scavenging capacity than PCPH-II (3 kDa < MW < 10 kDa) and PCPH-I (MW > 10 kDa) measured by DPPH (IC50: 111.0 μg/ mL) and measured by ABTs (IC50: 402.9 μg/mL). The secondary structure and amino acid composition varied by their MW, in which PCPH-II contained more α-helices (26.71%) and β-sheets (36.96%), PCPH-III contained higher ratios of β-turns (36.87%), while the composition of different secondary of PCPH-I was even 25 ± 5.76%. The variation trend of α-helix and random experienced slightly varied from PCPH-I to PCPH-II, while significantly decreased from PCPH-II to PCPH-III. The increasing antioxidant capacity is followed by the content of proline, and PCPH-III had the highest composition (8.03%). With regard to the six peptides identified by LC-MS/MS, two of them (VYGYADK and VLFSNY) showed stronger antioxidant capacity than others. In silico molecular docking demonstrated their combining abilities with a transcription factor Kelch-like ECH-associated protein 1 (Keap1) and speculated that they inhibit oxidative stress through activating the Keap1-Nrf2-ARE pathway. Meanwhile, increased activity of SOD and CAT—antioxidant markers—were found in H2O2-induced cells. The residue of tyrosine was demonstrated to contribute the most antioxidant capacity of VYGYADK and its position affected less. This study provided a novel peptide screening and by-product utilization process that can be applied in natural product developments.Keywords:Chinese pecan by-products;antioxidant peptides;proline content;molecular docking;Keap1-Nrf2-ARE pathway
研究领域:
食品科学
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生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Yongming Wu,Jing Huang,Mi Deng,Yuanxiang Jin,Huilin Yang,Yu Liu,Qinyan Cao,Jan A. Mennigen,Wenqing Tu
6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a Chinese PFOS alternative, has recently been identified in the aquatic environment at concentrations similar to or higher than perfluorooctane sulfonate (PFOS). Although previous studies have shown that F-53B can trigger oxidative stress in fish, the underlying molecular mechanism is still largely unknown. In this study, zebrafish embryos were exposed to various concentrations of F-53B (0, 0.5, 20 and 200 μg/L) for 5 d to investigate oxidative stress responses and possible molecular mechanisms of action. Our results showed that F-53B accumulated in a concentration-dependent manner in zebrafish larvae. The contents of malondialdehyde (MDA) and reduced glutathione (GSH), as well as the activities, mRNA and protein levels of most of antioxidant enzyme genes involved in the phosphatidylinositol 3-kinase (PI3K)/Akt/Nrf2-ARE pathway were significantly reduced. Further in silico study indicated that F-53B binds tightly to PI3K, which may be related to the inhibition of Nrf2-regulated antioxidant functions by F-53B as a PI3K inhibitor. Combining in vivo and in silico studies, we elucidated the effects of F-53B on antioxidant system of zebrafish through the PI3K/Akt/Nrf2-ARE pathway, which increases our understanding of the molecular mechanism of F-53B on antioxidant responses in fish.
研究领域:
环境科学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Life-Basel
·
2022
·Vol. 12
·期 9
·1436
·
IF 3.251
Ce Chen,Mingyue He,Xueting Li,Lidong Yu,Yi Liu,Yan Yang,Li Li,Jianbo Jia,Bingsheng Li
The Nrf2/ARE signaling pathway is a cell survival response pathway in response to environmental stresses. The Nrf2/ARE signaling pathway can be activated by stimulating cysteine residues at different positions in the Keap1. However, the epigenetic mechanisms of the Nrf2/ARE pathway under different stimuli are still poorly understood. In this study, we found that both hydrogen peroxide (H2O2) and Diethyl Maleate (DEM) activated the Nrf2/ARE signaling pathway at 120 hpf in zebrafish. H2O2regulated the demethylation of themaftpromoter by inhibiting the expression of methyltransferase. This promotes the mRNA expression of the Nrf2 binding factormaft, thereby promoting the downstream antioxidant genes. The methylation of the Nrf2/ARE signaling pathway was not significantly regulated by DEM. However, under oxidative stress, the methyltransferase inhibitors (decitabine and azacitidine) demethylated the promoter region ofmaft. It activated the expression of themaft, further improving the Nrf2/ARE signal pathway. At last, antioxidant target genes were activated. It was shown that H2O2and DEM cooperated with methyltransferase inhibitors, providing an important reference for the treatment of oxidative stress-related diseases and breaking new ground for the study of the mechanism of methyltransferase inhibitors in the process of tumor chemotherapy.Keywords:zebrafish;Nrf2/ARE signaling pathway;oxidative stress;methylation regulation
研究领域:
分子生物学
·
毒理学
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表观遗传学
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发育生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）