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The neuroprotective role of celastrol on hippocampus in diabetic rats by inflammation restraint, insulin signaling adjustment, Aß reduction and synaptic plasticity alternation.
Zhou, Qiaofeng; Guo, Xiying; Chen, Tu; Liu, Yumin; Ji, Huimin; Sun, Yixuan; Yang, Xiaosong; Ouyang, Changhan; Liu, Xiufen; Lei, Min.
Afiliação
  • Zhou Q; Hubei Key Laboratory of Diabetes And Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
  • Guo X; Hubei Key Laboratory of Diabetes And Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
  • Chen T; Xianning Public Inspection and Testing Center, Xianning 437100, China.
  • Liu Y; Wuhan Huake Reproductive Specialist Hospital, Wuhan 430000, China.
  • Ji H; Hubei Key Laboratory of Diabetes And Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
  • Sun Y; Hubei Key Laboratory of Diabetes And Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
  • Yang X; Hubei Key Laboratory of Diabetes And Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
  • Ouyang C; School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
  • Liu X; Hubei Key Laboratory of Diabetes And Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China. Electronic address: lxiufen2023@126.com.
  • Lei M; Hubei Key Laboratory of Diabetes And Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China. Electronic address: leimin.a0502@aliyun.com.
Biomed Pharmacother ; 179: 117397, 2024 Oct.
Article em En | MEDLINE | ID: mdl-39232386
ABSTRACT
Celastrol, the primary constituent of Tripterygium wilfordii, has demonstrated neuroprotective properties in rats with dementia by reducing inflammation. A high-fat diet and streptozotocin injection were utilized to establish a diabetic rat model, which was then employed to investigate the possible protective effect of celastrol against the development of diabetes-induced learning and memory deficits. Afterwards, the experimental animals received a dose of celastrol by gavage (4 mg/kg/d). An animal study showed that celastrol enhanced insulin sensitivity and glucose tolerance in diabetic rats. In the Morris water maze test, rats with diabetes performed poorly in terms of spatial learning and memory; treatment with celastrol improved these outcomes. Additionally, administration of celastrol downregulated the expression of inflammatory-related proteins (NF-κB, IKKα, TNF-α, IL-1ß, and IL-6) and greatly reduced the generation of Aß in the diabetic hippocampus tissue. Moreover, the insulin signaling pathway-related proteins PI3K, AKT, and GSK-3ß were significantly upregulated in diabetic rats after celastrol was administered. Also, celastrol prevented damage to the brain structures and increased the synthesis of synaptic proteins like PSD-95 and SYT1. In conclusion, celastrol exerts a neuroprotective effect by modulating the insulin signaling system and reducing inflammatory responses, which helps to ameliorate the cognitive impairment associated with diabetes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triterpenos / Transdução de Sinais / Peptídeos beta-Amiloides / Fármacos Neuroprotetores / Diabetes Mellitus Experimental / Triterpenos Pentacíclicos / Hipocampo / Inflamação / Insulina / Plasticidade Neuronal Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2024 Tipo de documento: Article País de publicação: França
Texto completo
Adicionar na Minha BVS
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triterpenos / Transdução de Sinais / Peptídeos beta-Amiloides / Fármacos Neuroprotetores / Diabetes Mellitus Experimental / Triterpenos Pentacíclicos / Hipocampo / Inflamação / Insulina / Plasticidade Neuronal Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2024 Tipo de documento: Article País de publicação: França