Jing Zhang , Zhen Peng , Dong Cheng , Wenhuan Yao , Hui Li , Qi Zhang , Ruisen Guo , Kunyan Li , Longrui Zou , Jia-Sheng Wang , Qiang Jia , Tianliang Zhang , Jun Zhou
{"title":"麦角多糖通过激活NRF-2/GPX和AhR/STAT3信号通路减轻黄曲霉毒素B1对肝脏的毒性。","authors":"Jing Zhang , Zhen Peng , Dong Cheng , Wenhuan Yao , Hui Li , Qi Zhang , Ruisen Guo , Kunyan Li , Longrui Zou , Jia-Sheng Wang , Qiang Jia , Tianliang Zhang , Jun Zhou","doi":"10.1016/j.toxicon.2024.108117","DOIUrl":null,"url":null,"abstract":"<div><div>Aflatoxin B<sub>1</sub> (AFB<sub>1</sub>) can induce serious liver toxicity in human. While completely avoiding AFB<sub>1</sub> exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of <em>Lepidium meyenii</em> (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB<sub>1</sub>. A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2–1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25–100 μg/mL which successfully alleviated cobalt-caused cell apoptosis by ∼20%. In terms of anti-AFB<sub>1</sub> hepatoxicity function, MPs 0.4–1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-κB p65, secretion of cytokines such as IL-6 and TNF-α in AFB<sub>1</sub>-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB<sub>1</sub>-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB<sub>1</sub>. Our findings not only add to the current understanding on the toxicity mechanism of AFB<sub>1</sub>, but also provide references to the development of dietary intervention strategy using MPs.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108117"},"PeriodicalIF":2.6000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lepidium meyenii (Maca) polysaccharides mitigate liver toxicity of aflatoxin B1 through activation of NRF-2/GPX and AhR/STAT3 signaling pathways\",\"authors\":\"Jing Zhang , Zhen Peng , Dong Cheng , Wenhuan Yao , Hui Li , Qi Zhang , Ruisen Guo , Kunyan Li , Longrui Zou , Jia-Sheng Wang , Qiang Jia , Tianliang Zhang , Jun Zhou\",\"doi\":\"10.1016/j.toxicon.2024.108117\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Aflatoxin B<sub>1</sub> (AFB<sub>1</sub>) can induce serious liver toxicity in human. While completely avoiding AFB<sub>1</sub> exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of <em>Lepidium meyenii</em> (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB<sub>1</sub>. A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2–1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25–100 μg/mL which successfully alleviated cobalt-caused cell apoptosis by ∼20%. In terms of anti-AFB<sub>1</sub> hepatoxicity function, MPs 0.4–1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-κB p65, secretion of cytokines such as IL-6 and TNF-α in AFB<sub>1</sub>-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB<sub>1</sub>-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB<sub>1</sub>. Our findings not only add to the current understanding on the toxicity mechanism of AFB<sub>1</sub>, but also provide references to the development of dietary intervention strategy using MPs.</div></div>\",\"PeriodicalId\":23289,\"journal\":{\"name\":\"Toxicon\",\"volume\":\"250 \",\"pages\":\"Article 108117\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicon\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0041010124006895\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicon","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041010124006895","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Lepidium meyenii (Maca) polysaccharides mitigate liver toxicity of aflatoxin B1 through activation of NRF-2/GPX and AhR/STAT3 signaling pathways
Aflatoxin B1 (AFB1) can induce serious liver toxicity in human. While completely avoiding AFB1 exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of Lepidium meyenii (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB1. A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2–1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25–100 μg/mL which successfully alleviated cobalt-caused cell apoptosis by ∼20%. In terms of anti-AFB1 hepatoxicity function, MPs 0.4–1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-κB p65, secretion of cytokines such as IL-6 and TNF-α in AFB1-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB1-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB1. Our findings not only add to the current understanding on the toxicity mechanism of AFB1, but also provide references to the development of dietary intervention strategy using MPs.
期刊介绍:
Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee.
Toxicon''s "aims and scope" are to publish:
-articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms
-papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins
-molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins
-clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained.
-material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems.
-articles on the translational application of toxins, for example as drugs and insecticides
-epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged.
-articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon.
-review articles on problems related to toxinology.
To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.