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Nrf2/Keap1通路
FOOD RESEARCH INTERNATIONAL · 2024 · IF 7

Selenium nanoparticles modified with Ophiocordyceps gracilis polysaccharides: Enhancing stability, bioavailability, and anti-inflammatory efficacy

Xinya Qi,Lingling Tong,Hui Lian,Zilei Chen,Linhui Yang,Yang Wu,Suxing Jin,Dongsheng Guo

Here, a high molecular weight polysaccharide preparation from Ophiocordyceps gracilis was utilized as a stabilizer and dispersant to create nanocomposites based on selenium nanoparticles (GSP-1a-SeNPs). The NPs showed the highest stability at a selenium/polysaccharide mass ratio of 1:1, with no significant change after 28 days of storage at 4 ℃. The NPs exhibited a symmetrical spheroid structure with an average diameter of 85.4 nm. Next, the anti-inflammatory properties and mechanisms of the GSP-1a-SeNPs were examined in LPS-induced RAW264.7 cells, which efficiently internalized the NPs. In the anti-inflammatory assays, GSP-1a-SeNPs significantly reduced the production of pro-inflammatory cytokines, including TNF-α and IL-6, and lowered ROS levels by activating the Nrf2-Keap1 pathway. This pathway regulates selenoprotein expression, thereby balancing the immune microenvironment of RAW264.7 cells and mitigating inflammation. These results suggest that GSP-1a-SeNPs could serve as potential therapeutic agents or adjuvants for treating LPS-induced inflammation.

CAS / MDL: 64-17-5 67-68-5
研究领域: 药理学 · 纳米医学 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2016 ·Vol. 7 ·期 11 ·4683-4692 · IF 2.686

Genistein promotes the metabolic transformation of acetaminophen to glucuronic acid in human L-O2, HepG2 and Hep3b cells via the Nrf2/Keap1 pathway

Fan Yuan-jing,Wei Wei,Luo Jian-ping,Jin Yu-xia,Dai Zi-ling

This study aimed to explore the effects of genistein on regulating the activation of UGTs via the Nrf2/Keap1 pathway and to elucidate the underlying mechanisms of detoxification and hepatic protection. Experiments monitoring genistein-induced protection against acetaminophen-induced cell damage were performed in L-02, HepG2 and Hep3b cells. The results of the MTT, AST, ALT, LDH, GSH and GSSG assays showed that genistein evidently protected the cells from acetaminophen-induced injury in a dose-dependent manner. The control cells were treated with 10 mM acetaminophen without genistein to compare with the effects of the combination of acetaminophen and genistein on the expression of UGT1A1, 1A6 and 1A9, Nrf2 and Keap1 mRNAs, as well as the expression of Nrf2 and Keap1 proteins, which were tested by western blotting. The results showed that the expression of the Nrf2 mRNA and protein increased; in contrast, the expression levels of the Keap1 mRNA and protein were obviously reduced by genistein in a dose-dependent manner. Meanwhile, the expression of the UGT mRNA was increased, and UGT1A9 exhibited the highest expression among the three UGTs. Accordingly, the residual acetaminophen content was obviously reduced and acetaminophen glucuronidation increased after 24 hours of treatment with genistein in a dose-dependent manner.

CAS / MDL: 103-90-2
研究领域: 药理学 · 毒理学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Foods · 2025 ·Vol. 14 ·期 10 ·1707 · IF 5.1

Antioxidant Peptides from the Fruit Source of the Oil Crop Litsea cubeba Ameliorate FFA-Induced Oxidative Stress Injury: Based on Nrf2/Keap1 Pathway and Molecular Dynamics Simulations

Li Li,Ying Hu,Yu-Mei Wang,Xiao-Xue Wu,Si-Tong Lin,Hang Li,Ji Zhang,Guo-Rong Fan,Zong-De Wang,Bin Wang,Shang-Xing Chen

In this study, we systematically investigated the mechanisms of the antioxidation and anti-lipid accumulation effects of antioxidant peptides fromLitsea cubebaon a free fatty acid (FFA)-induced NAFLD model of HepG2 cells. The NAFLD cell model was constructed by inducing the HepG2 hepatocellular carcinoma cell line with 0.5 mmol/L FFAs, and AQRDAGLL, QEGPFVR, and DVPPPRGPL were given to the culture to study their lipid-lowering and antioxidant activities on NAFLD cells. The lipid-lowering activities of the three antioxidant peptides were evaluated by Oil Red O staining and TG and TC content assays, and the results showed that all three peptides had strong ameliorating effects on FFA-induced lipid accumulation in NAFLD cells. The intracellular antioxidant protease (CAT, GSH, and SOD) activity levels and lipid peroxidation (MDA) content were measured and intracellular ROS levels were detected. The results showed that after intervention with the antioxidant peptides, the intracellular ROS levels in the NAFLD model cells were significantly reduced, the SOD and CAT activities were increased, the GSH content was elevated, and the MDA content was reduced, which indicated that AQRDAGLL, QEGPFVR, and DVPPPRGPL were able to inhibit the oxidative stress of the cells effectively and to achieve the effect of intervening in NAFLD. JC-1 fluorescence staining experiments showed that the mitochondrial membrane potential function of NAFLD cells was restored under the effect of the antioxidant peptides. Molecular dynamics simulations revealed that the main driving force between QEGPFVR and Keap1 protein was van der Waals forces, ΔG = −62.11 kcal/mol, which indicated that QEGPFVR was capable of spontaneously binding to Keap1 protein.

CAS / MDL: 112-80-1 57-10-3
研究领域: 生物化学 · 分子生物学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TISSUE & CELL · 2023 · IF 2.6

Engeletin alleviates erastin-induced oxidative stress and protects against ferroptosis via Nrf2/Keap1 pathway in bone marrow mesenchymal stem cells

Lei Huang,Mengxuan Bian,Shunyi Lu,Jiayi Wang,Jieqin Yu,Libo Jiang,Jian Zhang

Ferroptosis is a novel form of cell death, which is a unique modality of cell death and closely associated with iron concentrations, generation of reactive oxygen species (ROS), and accumulation of the lipid reactive oxygen species. In the present study, the anti-ferroptosis effects of Engeletin was studied in erastin-induced bone marrow mesenchymal stem cells (BMSCs). After treatment with Engeletin, cell viability was determined by CCK-8 assay. The production of ROS, malonaldehyde (MDA), Superoxide dismutase (SOD) activities and glutathione peroxidase (GSH) were detected by using commercially-available kits. Ferroptosis-related proteins (GPX4, SLC7A11, TFR1, FPN1, Nrf2, Keap1) were evaluated by Western blotting. Osteogenic capacity was evaluated by ALP staining and ARS staining. The expression of osteogenic-related proteins (OPN, Runx2, OCN) were evaluated by Western blotting and changes in mRNA (ALP, BMP-2, COL-1, Osterix) were evaluated by RT-PCR. Consistent improvements in angiogenesis are observed with Engeletin in the presence of erastin. Engeletin significantly alleviated erastin-induced oxidative damage and protected against ferroptosis in BMSCs. Ferroptosis was inhibited by Engeletin, leading to decreasing reducing accumulation of ROS and lipid peroxidation products. Moreover, Engeletin promoted osteogenic differentiation in BMSCs and angiogenesis in human umbilical vein endothelial cells (HUVECs). Taken together, these findings indicate that Engeletin can protect BMSCs from erastin-induced ferroptosis through the Nrf2/Keap1 antioxidant pathway and identify Engeletin as a novel ferroptosis inhibitor, suggesting that Engeletin may promote resistance to ferroptosis and enable osteogenic function of BMSCs.

CAS / MDL: 30525-89-4
研究领域: 细胞生物学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 19 ·14721 · IF 5.6

A Neutral Polysaccharide from Spores of Ophiocordyceps gracilis Regulates Oxidative Stress via NRF2/FNIP1 Pathway

Yue Wang,Shixiang Wei,Hui Lian,Lingling Tong,Linhui Yang,Bo Ren,Dongsheng Guo,He Huang

Ophiocordyceps gracilis(O. gracilis) is a parasitic fungus used in traditional Chinese medicine and functional foods. In this study, a neutral heteropolysaccharide (GSP-1a) was isolated from spores ofO. gracilis, and its structure and antioxidant capacities were investigated. GSP-1a was found to have a molecular weight of 72.8 kDa and primarily consisted of mannose (42.28%), galactose (35.7%), and glucose (22.02%). The backbone of GSP-1a was composed of various sugar residues, including →6)-α-D-Manp-(1→, →2,6)-α-D-Manp-(1→, →2,4,6)-α-D-Manp-(1→, →6)-α-D-Glcp-(1→, and →3,6)-α-D-Glcp-(1→, with some branches consisting of →6)-α-D-Manp-(1→ and α-D-Gal-(1→. In vitro, antioxidant activity assays demonstrated that GSP-1a exhibited scavenging effects on hydroxyl radical (•OH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS•+), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•). Moreover, GSP-1a was found to alleviate H2O2-induced oxidative stress in HepG2 cells by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing the activities of superoxide dismutase (SOD). Furthermore, GSP-1a upregulated the mRNA expression of antioxidant enzymes such asHo-1,Gclm, andNqo1, and regulated the NRF2/KEAP1 and FNIP1/FEM1B pathways. The findings elucidated the structural types of GSP-1a and provided a reliable theoretical basis for its usage as a natural antioxidant in functional foods or medicine.Keywords:Ophiocordyceps gracilis;spores;polysaccharide;structural characterization;antioxidant activity

研究领域: 药理学 · 生物化学 · 分子生物学 · 传统中药
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY · 2023 · IF 4.7

Ferulic acid alleviates carp brain damage and growth inhibition caused by avermectin by modulating the Nrf2/Keap1 and NF-κB signaling pathways

Guanglu Wang,Jiajia Guo,Yeyun Ma,Yue Xin,Xiaomeng Ji,Ying Sun,Jian Zhang,Jingquan Dong

The increasing concern over environmental pollution caused by the pesticide avermectin used in aquaculture has attracted significant attention. The use of avermectin, a neurotoxic pesticide, in aquatic environments leads to toxic effects on non-target organisms, particularly causing harm to fish. The phenolic compound ferulic acid possesses excellent anti-inflammatory and antioxidant capabilities. This study was conducted by establishing a chronic exposure experiment to avermectin, proposes the use of ferulic acid as a dietary additive to protect the carp brain from damage caused by exposure to avermectin. Furthermore, it investigates the anti-inflammatory and antioxidant effects of ferulic acid in the carp brain under chronic exposure to avermectin. The experimental results demonstrate that ferulic acid can alleviate brain tissue inflammation and oxidative stress by modulating the Nrf2/Keap1 and NF-κB signaling pathways . It protects the carp brain from chronic avermectin-induced damage, preserves the integrity of the carp blood-brain barrier, enhances the levels of feeding factors, and thereby alleviates carp growth inhibition. These findings provide new therapeutic strategies and a theoretical foundation for the sustainable development of carp aquaculture.

CAS / MDL: 65195-55-3 1135-24-6
研究领域: 水产养殖 · 毒理学 · 药理学 · 神经科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Physiology · 2025 · IF 3.4

The multi-protective role of dietary betaine in largemouth bass (Micropterus salmoides): coordinating antioxidant, inflammatory, and metabolic homeostasis under high-fat diet stress

Yi-Jia Liu,Jian Guo,Chang-Da Li,Si-Yin Han,Lu Cai

Introduction Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous fish. Betaine, a natural methyl donor, has shown potential as a functional feed additive, but its comprehensive protective mechanisms under HF stress remain to be fully elucidated. Methods Juvenile largemouth bass (Micropterus salmoides) were fed one of four isonitrogenous diets for 8 weeks: a normal-fat control (Control), a high-fat diet (HF), and two high-fat diets supplemented with 0.5% (HFB0.5) or 1.0% (HFB1) betaine. Growth performance, digestive enzyme activities, serum biochemical parameters, hepatic antioxidant capacity, and the expression of genes related to antioxidant defense, lipid metabolism, and inflammation were analyzed. Results The HF group exhibited significantly impaired growth, digestive function, and antioxidant capacity, along with elevated lipid peroxidation, dyslipidemia, and pro-inflammatory cytokine expression. Betaine supplementation restored growth performance and feed efficiency to control levels, ameliorated digestive enzyme activities (particularly enhancing lipase), and activated the hepatic Nrf2-Keap1 pathway, upregulating antioxidant genes (nrf2, sod1, cat, gpx, ho-1, gr) and enhancing enzyme activities. Betaine also improved serum lipid profiles, upregulated genes related to fatty acid oxidation (pparα, cpt-1) and lipolysis (lpl, hsl), suppressed lipogenic genes (srebp-1, fas), and rebalanced inflammatory cytokines by reducing tnf-α and il-1β while increasing tgf-β1 and il-10. Discussion Dietary betaine effectively counteracts HF-induced metabolic stress in M. salmoides through coordinated multi-pathway regulation. It enhances antioxidant defense, reprograms hepatic lipid metabolism toward catabolism, and restores inflammatory homeostasis. These findings underscore betaine’s role as a multi-functional feed additive capable of mitigating HF-related metabolic disorders and promoting overall health in carnivorous fish aquaculture.

CAS / MDL: 107-43-7
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Probiotics and Antimicrobial Proteins · 2022 ·Vol. 14 ·期 4 ·741-750 · IF 5.265

Protecting Effect of Bacillus coagulans T242 on HT-29 Cells Against AAPH-Induced Oxidative Damage

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.

CAS / MDL: 61-73-4 76-03-9
研究领域: 微生物学 · 细胞生物学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Frontiers · 2023 · IF 9.9

20(S)-Protopanaxadiol saponins isolated from Panax notoginseng target caveolin-1 against intestinal barrier dysfunction by alleviating inflammatory injury and oxidative stress in experimental murine colitis

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
✓ 已验证 DOI 高影响因子
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Journal of Inflammation Research · 2025 · IF 4.1

Subchronic Chlorpyrifos Exposure Induces Thyroid Follicular Cell Pyroptosis to Exacerbate Thyroid Toxicity by Modulating Nrf2/Keap1/NF-κB Pathway in Male Mice

Bingyan Gu,Yuying Chen,Huifang Xu,Kunyu Zhan,Keying Zhu,Huan Luo,Yanqun Huang,Hanbing Zeng,Wenbiao Zheng,Kun Tian,Hongfeng Ruan

Purpose Chlorpyrifos (CPF), a widely used organophosphate pesticide in agriculture, particularly in China, has raised significant environmental and health concerns due to its persistence and bioaccumulation. While CPF-induced toxicity in multiple organ systems has been documented, its long-term impact on thyroid homeostasis and the underlying mechanisms remain poorly understood. This study aimed to investigate the subchronic effects of CPF on thyroid function and elucidate the underlying mechanisms of CPF-induced thyroid toxicity.Methods The study utilized 4-week-old male C57BL/6J mice as experimental subjects. These mice were exposed to CPF via intragastric gavage at doses of 3 or 6 mg/kg for a duration of 8 weeks. Throughout the study period, various parameters were assessed, including body weight, serum antioxidant capacity, thyroid endocrine function and structure, apoptosis markers, inflammatory cytokines, and relevant molecular pathways.Results The study revealed that CPF exposure resulted in significant systemic toxicity, manifested through reduced body weight and impaired serum antioxidant capacity. Examination of thyroid-specific effects showed disrupted thyroid endocrine function and structure, accompanied by increased apoptosis and elevated inflammatory cytokines. At the molecular level, CPF significantly stimulated thyroid follicle cell pyroptosis by upregulating the expression of Nlrp3, Caspase-1, and Gsdmd. Further mechanistic analysis demonstrated that CPF activated thyroid follicular cell pyroptosis by modulating the Nrf2/Keap1 antioxidative pathway and enhancing phosphorylation of p65 via NF-κB signaling.Conclusion This comprehensive investigation provides novel insights into the mechanisms of CPF-induced thyroid toxicity. The findings demonstrate that CPF exposure compromises thyroid homeostasis through the induction of follicular cell pyroptosis and modulation of the Nrf2/Keap1/NF-κB signaling axis, highlighting the potential health risks associated with CPF exposure and its impact on thyroid function.

CAS / MDL: 2921-88-2
研究领域: 毒理学 · 内分泌学 · 分子生物学 · 环境卫生 · 药理学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

The novel nanocomplexes containing deoxycholic acid-grafted chitosan and oleanolic acid displays the hepatoprotective effect against CCl4-induced liver injury in vivo

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.

CAS / MDL: 56-23-5 67-68-5
研究领域: 药学 · 毒理学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2023 · IF 4.3

Silybin mitigates chronic Avermectin exposure-induced intestinal damage and growth inhibition in carp

Guanglu Wang,Yue Xin,Kaixin Ping,Xuhui Xu,Ying Sun,Xing Li,Xinying Guan,Jingquan Dong

Avermectins, as a new type of environmental pollutant, have received significant attention in recent years. Previous research has shown that acute exposure to avermectins can induce oxidative stress and inflammation in non-target fish species, such as carp. Flavonoid lignans, particularly Silybin, have demonstrated promising biological activities, including regulation of non-alcoholic fatty liver and cerebral ischemia-reperfusion injury. This study aims to investigate the impact of dietary supplementation with Silybin on the intestinal damage in carp caused by chronic exposure to avermectins and to improve the health status and production of carp in aquaculture. Silybin was used as a dietary supplement by adding it to the experimental feed, and an animal experimental model was utilized to assess its effects on oxidative stress, inflammation, and cell apoptosis in carp intestine. Additionally, intestinal barrier integrity, digestive capacity, and fish growth were evaluated. The results indicated that dietary supplementation with Silybin effectively alleviated the oxidative stress induced by chronic exposure to avermectins in carp intestine. Furthermore, Silybin improved intestinal barrier integrity and digestive capacity by modulating the Nrf2/Keap1 pathway. This study demonstrates that dietary supplementation with Silybin can effectively mitigate the intestinal damage caused by chronic exposure to avermectins in carp, providing a sustainable solution for the aquaculture industry to enhance the overall health and production of cultured fish. The research expands our understanding of avermectin environmental pollution and offers a potential remediation approach.

研究领域: 水产养殖 · 环境毒理学 · 药理学 · 鱼类生理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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