Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment

Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recen...

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Autores principales: Zheng, Yanfang, Zhou, Xian, Wang, Chenxiang, Zhang, Jialin, Chang, Dennis, Liu, Wenjing, Zhu, MingXing, Zhuang, Shuting, Shi, Hong, Wang, Xiaoning, Chen, Yong, Cheng, Zaixing, Lin, Yanxiang, Nan, Lihong, Sun, Yibin, Min, Li, Liu, Jin, Chen, Jianyu, Zhang, Jieping, Huang, Mingqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309808/
https://www.ncbi.nlm.nih.gov/pubmed/35899118
http://dx.doi.org/10.3389/fphar.2022.890444
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author Zheng, Yanfang
Zhou, Xian
Wang, Chenxiang
Zhang, Jialin
Chang, Dennis
Liu, Wenjing
Zhu, MingXing
Zhuang, Shuting
Shi, Hong
Wang, Xiaoning
Chen, Yong
Cheng, Zaixing
Lin, Yanxiang
Nan, Lihong
Sun, Yibin
Min, Li
Liu, Jin
Chen, Jianyu
Zhang, Jieping
Huang, Mingqing
author_facet Zheng, Yanfang
Zhou, Xian
Wang, Chenxiang
Zhang, Jialin
Chang, Dennis
Liu, Wenjing
Zhu, MingXing
Zhuang, Shuting
Shi, Hong
Wang, Xiaoning
Chen, Yong
Cheng, Zaixing
Lin, Yanxiang
Nan, Lihong
Sun, Yibin
Min, Li
Liu, Jin
Chen, Jianyu
Zhang, Jieping
Huang, Mingqing
author_sort Zheng, Yanfang
collection PubMed
description Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recent evidence has demonstrated that the gut microbiome plays an important role in DCI by modulating cognitive function through the gut–brain crosstalk. The bioactive compound tanshinone IIA (TAN) has shown to improve cognitive and memory function in diabetes mellitus models, though the pharmacological actions are not fully understood. This study aims to investigate the effect and underlying mechanism of TAN in attenuating DCI in relation to regulating the gut microbiome. Metagenomic sequencing analyses were performed on a group of control rats, rats with diabetes induced by a high-fat/high-glucose diet (HFD) and streptozotocin (STZ) (model group) and TAN-treated diabetic rats (TAN group). Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neurological biomarkers. The fasting blood glucose (FBG) level was monitored throughout the experiments. The levels of serum lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level. The morphology of the colon barrier was observed by histopathological staining. Our study confirmed that TAN reduced the FBG level and improved the cognitive and memory function against HFD- and STZ-induced diabetes. TAN protected the endothelial tight junction in the hippocampus and colon, regulated neuronal biomarkers, and lowered the serum levels of LPS and TNF-α. TAN corrected the reduced abundance of Bacteroidetes in diabetic rats. At the species level, TAN regulated the abundance of B. dorei, Lachnoclostridium sp. YL32 and Clostridiodes difficile. TAN modulated the lipid metabolism and biosynthesis of fatty acids in related pathways as the main functional components. TAN significantly restored the reduced levels of isobutyric acid and butyric acid. Our results supported the use of TAN as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome regulation.
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spelling pubmed-93098082022-07-26 Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment Zheng, Yanfang Zhou, Xian Wang, Chenxiang Zhang, Jialin Chang, Dennis Liu, Wenjing Zhu, MingXing Zhuang, Shuting Shi, Hong Wang, Xiaoning Chen, Yong Cheng, Zaixing Lin, Yanxiang Nan, Lihong Sun, Yibin Min, Li Liu, Jin Chen, Jianyu Zhang, Jieping Huang, Mingqing Front Pharmacol Pharmacology Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recent evidence has demonstrated that the gut microbiome plays an important role in DCI by modulating cognitive function through the gut–brain crosstalk. The bioactive compound tanshinone IIA (TAN) has shown to improve cognitive and memory function in diabetes mellitus models, though the pharmacological actions are not fully understood. This study aims to investigate the effect and underlying mechanism of TAN in attenuating DCI in relation to regulating the gut microbiome. Metagenomic sequencing analyses were performed on a group of control rats, rats with diabetes induced by a high-fat/high-glucose diet (HFD) and streptozotocin (STZ) (model group) and TAN-treated diabetic rats (TAN group). Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neurological biomarkers. The fasting blood glucose (FBG) level was monitored throughout the experiments. The levels of serum lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level. The morphology of the colon barrier was observed by histopathological staining. Our study confirmed that TAN reduced the FBG level and improved the cognitive and memory function against HFD- and STZ-induced diabetes. TAN protected the endothelial tight junction in the hippocampus and colon, regulated neuronal biomarkers, and lowered the serum levels of LPS and TNF-α. TAN corrected the reduced abundance of Bacteroidetes in diabetic rats. At the species level, TAN regulated the abundance of B. dorei, Lachnoclostridium sp. YL32 and Clostridiodes difficile. TAN modulated the lipid metabolism and biosynthesis of fatty acids in related pathways as the main functional components. TAN significantly restored the reduced levels of isobutyric acid and butyric acid. Our results supported the use of TAN as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome regulation. Frontiers Media S.A. 2022-07-11 /pmc/articles/PMC9309808/ /pubmed/35899118 http://dx.doi.org/10.3389/fphar.2022.890444 Text en Copyright © 2022 Zheng, Zhou, Wang, Zhang, Chang, Liu, Zhu, Zhuang, Shi, Wang, Chen, Cheng, Lin, Nan, Sun, Min, Liu, Chen, Zhang and Huang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zheng, Yanfang
Zhou, Xian
Wang, Chenxiang
Zhang, Jialin
Chang, Dennis
Liu, Wenjing
Zhu, MingXing
Zhuang, Shuting
Shi, Hong
Wang, Xiaoning
Chen, Yong
Cheng, Zaixing
Lin, Yanxiang
Nan, Lihong
Sun, Yibin
Min, Li
Liu, Jin
Chen, Jianyu
Zhang, Jieping
Huang, Mingqing
Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment
title Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment
title_full Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment
title_fullStr Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment
title_full_unstemmed Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment
title_short Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment
title_sort effect of tanshinone iia on gut microbiome in diabetes-induced cognitive impairment
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309808/
https://www.ncbi.nlm.nih.gov/pubmed/35899118
http://dx.doi.org/10.3389/fphar.2022.890444
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