{"title":"Morin通过TrkB/Akt途径对糖尿病介导的神经细胞氧化应激和凋亡的神经保护作用","authors":"R. L. Shyma, S. Mini","doi":"10.1080/15376516.2022.2065225","DOIUrl":null,"url":null,"abstract":"Abstract Long-term diabetes mellitus results in neuronal damage by increased intracellular glucose leading to oxidative stress. This condition is known as diabetic encephalopathy. Morin is a bioflavonoid, has significant antidiabetic, antioxidant and anti-inflammatory activities. The present study investigated whether the antioxidant properties of morin has beneficial effects on structural brain damage, neuronal apoptosis and dysregulation of TrkB/Akt signaling associated with diabetes. Adult male Sprague Dawley rats were induced diabetes by an intraperitoneal injection of 40 mg/kg of streptozotocin and kept untreated for 30 days to induce DE. Cognitive performance was assessed using the Morris water maze test followed by morin and metformin administration at the doses of 50 and 100 mg/kg, respectively, for 60 days. After 60 days of treatment, animals were subjected to the behavioral test and sacrificed to collect blood and brain and checked biochemical parameters. The treatment with morin could significantly reduce the escape latency time in Morris water maze test, blood glucose level, HbA1c, toxicity markers, lipid peroxidation products and protein carbonyl content, downregulated the expression of Bax, Caspase - 3 and Cytochrome C and upregulated Bcl-2, Bcl-XL, Akt, BDNF and TrkB expressions. Besides, enhanced the activities of antioxidant enzymes, and plasma insulin level. Histomorphological observations also confirmed the protective effect of morin on neuronal degeneration. Morin 50 mg once daily for 60 days was the most effective dose with a significant reduction in diabetes mediated complications in the brain associated with neuronal apoptosis and dysregulation of TrkB/Akt signaling.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Neuroprotective effect of Morin via TrkB/Akt pathway against diabetes mediated oxidative stress and apoptosis in neuronal cells\",\"authors\":\"R. L. Shyma, S. Mini\",\"doi\":\"10.1080/15376516.2022.2065225\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract Long-term diabetes mellitus results in neuronal damage by increased intracellular glucose leading to oxidative stress. This condition is known as diabetic encephalopathy. Morin is a bioflavonoid, has significant antidiabetic, antioxidant and anti-inflammatory activities. The present study investigated whether the antioxidant properties of morin has beneficial effects on structural brain damage, neuronal apoptosis and dysregulation of TrkB/Akt signaling associated with diabetes. Adult male Sprague Dawley rats were induced diabetes by an intraperitoneal injection of 40 mg/kg of streptozotocin and kept untreated for 30 days to induce DE. Cognitive performance was assessed using the Morris water maze test followed by morin and metformin administration at the doses of 50 and 100 mg/kg, respectively, for 60 days. After 60 days of treatment, animals were subjected to the behavioral test and sacrificed to collect blood and brain and checked biochemical parameters. The treatment with morin could significantly reduce the escape latency time in Morris water maze test, blood glucose level, HbA1c, toxicity markers, lipid peroxidation products and protein carbonyl content, downregulated the expression of Bax, Caspase - 3 and Cytochrome C and upregulated Bcl-2, Bcl-XL, Akt, BDNF and TrkB expressions. Besides, enhanced the activities of antioxidant enzymes, and plasma insulin level. Histomorphological observations also confirmed the protective effect of morin on neuronal degeneration. Morin 50 mg once daily for 60 days was the most effective dose with a significant reduction in diabetes mediated complications in the brain associated with neuronal apoptosis and dysregulation of TrkB/Akt signaling.\",\"PeriodicalId\":49117,\"journal\":{\"name\":\"Toxicology Mechanisms and Methods\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2022-04-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology Mechanisms and Methods\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/15376516.2022.2065225\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology Mechanisms and Methods","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15376516.2022.2065225","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Neuroprotective effect of Morin via TrkB/Akt pathway against diabetes mediated oxidative stress and apoptosis in neuronal cells
Abstract Long-term diabetes mellitus results in neuronal damage by increased intracellular glucose leading to oxidative stress. This condition is known as diabetic encephalopathy. Morin is a bioflavonoid, has significant antidiabetic, antioxidant and anti-inflammatory activities. The present study investigated whether the antioxidant properties of morin has beneficial effects on structural brain damage, neuronal apoptosis and dysregulation of TrkB/Akt signaling associated with diabetes. Adult male Sprague Dawley rats were induced diabetes by an intraperitoneal injection of 40 mg/kg of streptozotocin and kept untreated for 30 days to induce DE. Cognitive performance was assessed using the Morris water maze test followed by morin and metformin administration at the doses of 50 and 100 mg/kg, respectively, for 60 days. After 60 days of treatment, animals were subjected to the behavioral test and sacrificed to collect blood and brain and checked biochemical parameters. The treatment with morin could significantly reduce the escape latency time in Morris water maze test, blood glucose level, HbA1c, toxicity markers, lipid peroxidation products and protein carbonyl content, downregulated the expression of Bax, Caspase - 3 and Cytochrome C and upregulated Bcl-2, Bcl-XL, Akt, BDNF and TrkB expressions. Besides, enhanced the activities of antioxidant enzymes, and plasma insulin level. Histomorphological observations also confirmed the protective effect of morin on neuronal degeneration. Morin 50 mg once daily for 60 days was the most effective dose with a significant reduction in diabetes mediated complications in the brain associated with neuronal apoptosis and dysregulation of TrkB/Akt signaling.
期刊介绍:
Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy.
Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including:
In vivo studies with standard and alternative species
In vitro studies and alternative methodologies
Molecular, biochemical, and cellular techniques
Pharmacokinetics and pharmacodynamics
Mathematical modeling and computer programs
Forensic analyses
Risk assessment
Data collection and analysis.