ANTIOXIDANTS & REDOX SIGNALING
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2026
·
IF 6.8
Jiaxue Tian,Huimin Wang,Huimin Liu,Wenlu Xu,Mengting Xiao,Xuemei Qin,Xiaojie Liu
Aims:Depression is a prevalent mood disorder with significant suffering and heightened suicide risk. Accumulating evidence points to oxidative stress and impaired energy metabolism of the brain as key contributors to the pathogenesis of depression. Astragaloside IV (AIV) has been demonstrated to alleviate neurological damage. The capacity of AIV for antioxidation has also been gradually discovered. Yet, it still just scratches the surface of the antidepression mechanisms of AIV. Our aim was to explore a novel mechanism of action of AIV from the perspectives of redox homeostasis and energy metabolism via the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) axis.Results:AIV ameliorated anxiety and cognitive dysfunction in rats with depression-like behaviors. Furthermore, we illustrated that AIV reversed redox dyshomeostasis of rats with depression-like behaviors in terms of decreasing the level of malondialdehyde while increasing the abundances of catalase, superoxide dismutase, and glutathione peroxidase. In addition, AIV significantly increased the levels of indicators of energy metabolism that were interrupted by depression. Furthermore, in vitro, AIV significantly increased the levels of indicators related to the Nrf2/Keap1 signaling pathway in corticosterone-induced PC12 cells.Innovation:For the first time, it demonstrates that AIV alleviates depression by modulating the ROS/Nrf2/Keap1 axis and restoring hippocampal energy metabolism in a chronic unpredictable mild stress model.Conclusion:The current findings not only offer novel insights into antidepressant-like effects of AIV through the ROS/Nrf2/Keap1 axis but also provide a foundation for enhancing clinical efficiency and enriching drug selection. Antioxid. Redox Signal. 00, 000–000.
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DOI
PubMed
高影响因子
Nature Communications
·
2021
·Vol. 12
·期 1
·1-14
·
IF 14.919
Weng Qinjie,Sun Heng,Fang Chunyan,Xia Fan,Liao Hongwei,Lee Jiyoung,Wang Jincheng,Xie An,Ren Jiafeng,Guo Xia,Li Fangyuan,Yang Bo,Ling Daishun
Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H + that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients.
研究领域:
纳米技术
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药理学
·
肿瘤学
·
肾脏生理学
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高影响因子
JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING
·
2026
·
IF 2
Jing Zhu,Mengmeng Gao,Hao Ling,Phar Ku Ngwe,Chengxiang Guo,Yinan Hu,Jicang Wang
This study investigated the protective effects of naringenin (Nar) against lead (Pb)-induced testicular injury in rats, focusing on the Nrf2/Keap1 antioxidant pathway and PINK1/Parkin-mediated mitophagy. To this end, male SD rats were exposed to Pb (60 mg/kg) and co-treated with Nar (50 mg/kg) for 8 consecutive weeks, followed by assessments via biochemical detection, oxidative stress (OS) evaluation, hematological examination, histopathological observation, qPCR, WB, and IHC analyses. Pb exposure caused hematological disturbances, reduced serum LH and T levels, and OS imbalance (lower GSH, SOD, CAT; higher MDA), aggravating testicular damage. Meanwhile, it suppressed the Nrf2/NQO1 pathway, elevated Keap1, impaired autophagy (elevated p62, declined LC3‑II/LC3‑I ratio), and induced aberrant accumulation of PINK1/Parkin. Co-treatment with Nar mitigated these alterations, ameliorating testicular injury, restoring redox homeostasis and serum reproductive hormone levels, and normalizing key molecular expressions in both pathways. In conclusion, Nar alleviates Pb-induced rat testicular damage by reactivating the Nrf2/Keap1 axis to suppress OS, and by restoring autophagic flux to facilitate PINK1/Parkin-mediated clearance of damaged mitochondria.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 14
·6666
·
IF 4.9
Siqi Zhang,Fei Tang,Zhe Zhou,Linhui Li,Yang Tang,Kaiwen Fu,Yang Tan,Ling Li
Liver fibrosis remains a critical health concern with limited therapeutic options. Kaempferol (Kae) is a natural flavonoid widely present in natural plants, yet its role in modulating gut–liver axis interactions during fibrosis is unexplored. This study investigates the hepatoprotective effects of Kae on alleviating carbon tetrachloride (CCl4)-induced liver fibrosis, and its underlying mechanisms, focusing on oxidative stress, gut microbiota, and short-chain fatty acids (SCFAs), are revealed. A mouse model of hepatic fibrosis was built by the subcutaneous injection of CCl4. Meanwhile, Kae was administered by gavage at doses of 25, 50, and 100 mg/kg body weight. Serum biomarkers, liver histopathology, oxidative damage markers, and nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase 1 (HO-1) signaling were analyzed. AML12 hepatocytes were pretreated with Kae or SCFAs (acetate, propionate, butyrate) before H2O2-induced oxidative injury. The changes in gut microbiota and the levels of SCFAs were assessed via 16S rRNA sequencing and GC-MS, respectively. Kae effectively alleviated the destruction of the liver morphology and tissue structure, reduced the infiltration of inflammatory cells, collagen deposition in the liver, and the expression of fibrotic factors, and downregulated the oxidative stress level in the liver of mice with liver fibrosis by activating the Nrf2/Keap1/HO-1 pathway (p< 0.05 or 0.01). In vitro, Kae significantly mitigated H2O2-induced cytotoxicity and oxidative damage (p< 0.05 or 0.01). Furthermore, Kae restored gut microbiota diversity, increased beneficial genera (e.g.,Lactobacillus), and elevated both intestinal and hepatic SCFA levels (p< 0.01). The discrepant SCFA pretreatment similarly protected AML12 cells by activating Nrf2 signaling (p< 0.05 or 0.01). Our research suggests that Kae could inhibit CCl4-induced liver fibrosis by restoring the levels of intestinal metabolite SCFAs to reduce oxidative damage.
研究领域:
药理学
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肝脏病学
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微生物学
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生物化学
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分子生物学
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营养科学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Meng Chen,Yonglu Li,Xin Yu,Yaxuan Wang,Wen Chen,Xiang Ye,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Tetrastigma hemsleyanum Diels et Gilg, a rare herbal plant native to China, possesses high medicinal value. More researches have focused on the flavones in the tubers of Tetrastigma hemsleyanum whereas polysaccharides attract few attentions. In this study, a purified polysaccharide (TTP-1) with the average molecular weights of 478.33 kDa was extracted from Tetrastigma hemsleyanum and conducted multiple analysis to identify its structural information. In vitro , TTP-1 could suppress the inflammation, cytotoxicity, genotoxicity, mitochondrial dysfunction and oxidative damage induced by LPS in RAW264.7 cells. Meanwhile, TTP-1 could attenuate inflammation via COX-2, iNOS, MAPKs pathways and ameliorate oxidative damage through Nrf2-Keap1, Sirt1-FoxO1 pathways in RAW264.7 cells. In vivo , the inflammation induced by LPS triggered the suppression of survival ratio and growing development, as well as the restrain of athletic ability in Caenorhabditis elegans . The treatment of TTP-1 reversed the situation induced by LPS. In a word, TTP-1 could ameliorate LPS-induced inflammation both in vitro and in vivo .
研究领域:
药理学
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免疫学
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分子生物学
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高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 4
·e13602
·
IF 2.72
Yang Yue,Mengting Wang,Zhangping Feng,Yanyun Zhu,Jianchu Chen
Rice protein hydrolysates (RPH) prepared by enzymatic hydrolysis have plenty of bioactive functions. Herein, we investigated the antiaging effect of RPH on Drosophila melanogaster (fruit fly) and its mechanisms. According to the results, fruit flies reared on 0.2% and 3.2% RP-supplement diet prolonged their average lifespan, 50% survival days, and the maximum lifespan, together with increasing superoxide dismutase, manganese superoxide dismutase, and catalase activity compared to those reared on basal diet. Further studies showed the lifespan extending effect of RPH was regulated by the cooperation with the intrinsic stress protection system (Nrf2/Keap1), age-related signaling pathway (TOR, S6K) and the expression of longevity genes (methuselah). In conclusion, the lifespan extending effect of RPH makes it possible to be applied in food and healthcare industry. Practical applications In previous studies, rice protein hydrolysates (RPH) have been found to have strong antioxidant properties. But so far, most researches focused on the preparation, identification and in vitro antioxidant experiments of RPH, and there is still a lack of researches on its effect on the antioxidant system of fruit flies and the antiaging of fruit flies. This report showed that RPH enhanced the antioxidant system and prolonged the lifespan of Drosophila, which might help us rationally use rice peptides in functional foods.
研究领域:
衰老研究
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营养科学
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生物化学
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PubMed
高影响因子
Food Bioscience
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2025
·
IF 5.9
Cheng Ning,Cailing He,Ling Yan,Changhong Liu,Aijin Ma,Lei Zheng
The research aimed to investigate the underlying anti-inflammatory and antioxidative mechanisms of walnut-derived peptides in BV-2 microglia with H 2 O 2 -induced injury, and to further assess their neuroprotective properties against cognitive impairments caused by lipopolysaccharide (LPS) in mice. The findings indicated that both walnut-derived peptides NPFD and LDAF significantly inhibited ROS production in H 2 O 2 -injured BV-2 microglia and attenuated oxidative stress in BV-2 microglial cells via the Nrf2/keap1 signaling pathway. In addition, LDAF showed greater improvement in inflammatory than NPFD in H 2 O 2 -injured BV-2 microglia. Meanwhile, The MWM demonstrated that LDAF had the potential to mitigate memory impairments caused by LPS through normalizing the brain's inflammatory responses and reducing oxidative stress. And LDAF treatment improved neuronal cell morphology in the hippocampal region of mouse brain tissue and increased the number of Nissl bodies in neurons of injured mice. These results showed that LDAF was able to improve spatial cognitive ability in mice by reducing inflammation and oxidative stress.
研究领域:
神经生物学
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分子药理学
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免疫调节
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氧化应激
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神经退行性疾病
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营养干预
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信号转导
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高影响因子
Antioxidants
·
2026
·Vol. 15
·期 9
·1207
·
IF 8.2
Kaiwen You,Yixuan Li,Wanqing Zhong,Jie Yu,Yamei Wu,Yuqi Guo,Haoyang Liu,Haiping Xie,Kai Yuan,Yihong Chen,Lei Wang
Due to the hypoxic environment caused by global warming and intensive aquaculture process, fish are susceptible to oxidative damage and death.Eucommia ulmoidesextract (EUE) has demonstrated antioxidant and anti-inflammatory properties. However, whether EUE can mitigate hypoxia-induced negative effects remains uninvestigated in fish. This study investigated the effect of 0 and 1.0 g/kg EUE on acute hypoxia-induced damage in largemouth bass and its potential mechanisms. The results showed that EUE alleviated the deterioration of plasma activities (ALT and AST) induced by acute hypoxic stress, decreased the number of macrophages and increased the total number of blood cells. EUE was effective in reducing the level of apoptosis and the content of ROS, Ca2+, and NO in blood cells. Additionally, EUE alleviated liver tissue injury caused by acute hypoxic stress, which could be associated with increased total antioxidant capacity and antioxidant enzyme activities (SOD, CAT and GSH-Px). Furthermore, EUE up-regulated the expression levels ofNrf2andCAT, activatedXBP1andIREexpression and down-regulatedGRP78expression, relieving the endoplasmic reticulum (ER) stress response. The down-regulation ofCaspase3andCaspase9is evidence that EUE inhibited apoptosis in acute hypoxic stress. In summary, EUE reduced oxidative damage, ER stress, and apoptosis caused by hypoxic stress via the Nrf2/Keap1 signaling pathway in largemouth bass. This study presents a part of the theoretical foundation for the EUE to resist damage caused by hypoxic stress, thereby establishing a basis for sustainable development in aquaculture.
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高影响因子
Probiotics and Antimicrobial Proteins
·
2022
·Vol. 14
·期 4
·741-750
·
IF 5.265
Gao Xiaoxi,Zhang Yuhong,Mu Guangqing,Xu Yunpeng,Wang Xinmiao,Tuo Yanfeng,Qian Fang
The aim of the present study was to investigate the in vitro antioxidant potential of Bacillus coagulans T242. B. coagulans T242 showed better antioxidant activities, including the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging ability, lipid peroxidation inhibiting ability and reducing ability, than those exerted by Lactobacillus rhamnosus GG (LGG). B. coagulans T242 positively regulated the expression of the nuclear factor erythroid 2-relatedfactor 2/Kelch-like ECH-associated protein-1 (Nrf2/Keap1) pathway-related proteins (Nrf2, Keap1, heine oxygenase-1 (HO-1)); increased antioxidant enzymes (glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD)); reduced the content of malondialdehyde (MDA) level; decreased the expression of inflammatory-related cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α); and thus increased the survival rate in 2,2′-azobis (2-methylpropionamidine) dihydrochloride (AAPH)-damaged HT-29 cells. This study proved that B. coagulans T242 exerted antioxidative effects by quenching oxygen free radicals and activating the Nrf2 signaling pathway in HT-29 cells.
研究领域:
微生物学
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细胞生物学
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药理学
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分子生物学
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PubMed
高影响因子
Food Frontiers
·
2023
·
IF 9.9
Pengde Lu,Jinfen Chen,Ying Chen,Xingping Quan,Jiayue Liu,Yan Han,Yiyang Li,Li Yang,Jian-Bo Wan,Yonghua Zhao
Ulcerative colitis (UC) is a digestive disease with a high incidence and is difficult to be cured due to its complex etiology. It has evidenced that intestinal barrier dysfunction plays a predominant role in UC. 20( S )-protopanaxadiol saponins (PDS) isolated from Panax notoginseng possess anti-inflammatory and antioxidative activities, suggesting its potential of treating UC. Herein, the therapeutic effects of PDS against UC and underlying mechanisms in the aspect of intestinal barrier dysfunction were investigated in vivo and in vitro. The results showed PDS had protective effects against dextran sulfate sodium–induced colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening, and histological lesions. Additionally, PDS reduced the colonic activity of myeloperoxidase and the cytokine levels of TNF-α, IL-6, and IL-1β, decreased MDA production, and elevated colonic activities of SOD and GSH-Px in the colitis mice. The expressions of proteins related to tight junction (TJ), including ZO-1, claudin-5, occludin, caveolin-1 (Cav-1), and Nrf2 were downregulated, whereas that of Keap1 was upregulated after colitis induction. These changes were reversed by PDS. Cav-1 expression was downregulated in lipopolysaccharides (LPS)- and H 2 O 2 -induced HCT116 cells, and the expressions of ZO-1, claudin-5, and occludin were suppressed in HCT116 cells stimulated by LPS and H 2 O 2 combined with Cav-1 small interfering RNA transfection, which were ameliorated by PDS, suggesting PDS targeted Cav-1 against intestinal barrier damage. Collectively, PDS alleviates inflammatory injury and oxidative stress by regulating the Nrf2/Keap1 pathway, contributing to targeting Cav-1 against intestinal epithelial TJ proteins loss. It suggests PDS might be a promising therapeutic natural product for UC treatment.
研究领域:
药理学
·
胃肠病学
·
免疫学
·
分子生物学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Chao Xin,Shuang Liu,Hang Qu,Zhenyu Wang
Chemical liver injury threatens seriously human health, along with the shortage of efficiency and low-toxicity drugs. Herein, the novel oral nanocomplexes composed of deoxycholic acid-grafted chitosan and oleanolic acid were constructed to reverse the CCl 4 -induced acute liver damage in mice. Results indicated core-shell nanocomplexes, maintained by the hydrophobic interaction between deoxycholic acid and oleanolic acid, could be dissociated in the intestine. Notably, the nanocomplexes possessed superior hepatoprotective effect in vivo , possibly due to the synergistic effect between grafted chitosan and oleanolic acid. Mechanism investigations suggested that nanocomplexes reversed CCl 4 -induced liver injury through improving hepatic antioxidant capacity via NrF2/Keap1 pathway and regulating inflammation response via NF-κB signaling pathway. The novel oral nanocomplexes represent an effective strategy for chemical liver injury therapy.
研究领域:
药学
·
毒理学
·
药理学
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PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Changxing Liu,Yawei Sun,Dengju Li,Fan Wang,Haojue Wang,Senbo An,Shui Sun
Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.
研究领域:
生物材料
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组织工程
·
骨科
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）