Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling

Notoginsenoside R1 (NGR1), the primary bioactive compound found in Panax notoginseng, is believed to have antihypertrophic and antiapoptotic properties, and has long been used to prevent and treat cardiovascular diseases. However, its potential role in prevention of diabetic cardiomyopathy remains u...

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Autores principales:	Fawang Du, Huiling Huang, Yalin Cao, Yan Ran, Qiang Wu, Baolin Chen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	notoginsenoside R1 high glucose-induced cell injury AMPK Nrf2 apoptosis diabetic cardiomyopathy Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bd18bca154084a7680786ca8aa424c7e
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spelling	oai:doaj.org-article:bd18bca154084a7680786ca8aa424c7e2021-12-02T00:33:14ZNotoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling2296-634X10.3389/fcell.2021.791643https://doaj.org/article/bd18bca154084a7680786ca8aa424c7e2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.791643/fullhttps://doaj.org/toc/2296-634XNotoginsenoside R1 (NGR1), the primary bioactive compound found in Panax notoginseng, is believed to have antihypertrophic and antiapoptotic properties, and has long been used to prevent and treat cardiovascular diseases. However, its potential role in prevention of diabetic cardiomyopathy remains unclear. The present study aimed to investigate the mechanism of NGR1 action in high glucose-induced cell injury. H9c2 cardiomyocytes were cultured in a high-glucose medium as an in-vitro model, and apoptotic cells were visualized using TUNEL staining. Expression of Nrf2 and HO-1 was measured using Western blotting or reverse transcription-quantitative PCR (RT-qPCR). The Nrf2 small interfering (si) RNA was transfected into cardiomyocytes using Opti-MEM containing Lipofectamine® RNAiMAX. NGR1 protected H9c2 cardiomyocytes from cell death, apoptosis and hypertrophy induced by high glucose concentration. Expression of auricular natriuretic peptide and brain natriuretic peptide was remarkably reduced in NGR1-treated H9C2 cells. Western blot analysis showed that high glucose concentration markedly inhibited AMPK, Nrf2 and HO-1, and this could be reversed by NGR1 treatment. However, the cardioprotective effect of NGR1 was attenuated by compound C, which reverses Nrf2 and HO-1 expression levels, suggesting that AMPK upregulates Nrf2 and HO-1 gene expression, protein synthesis and secretion. Transfection of H9C2 cells with Nrf2 siRNA markedly reduced the cardioprotective effect of NGR1 via reduced expression of HO-1. These results indicated that NGR1 attenuated high glucose-induced cell injury via AMPK/Nrf2 signaling and its downstream target, the HO-1 pathway. We conclude that the cardioprotective effects of NGR1 result from upregulation of AMPK/Nrf2 signaling and HO-1 expression in cardiomyocytes. Our findings suggest that NGR1 treatment might provide a novel therapy for diabetic cardiomyopathy.Fawang DuHuiling HuangYalin CaoYan RanQiang WuBaolin ChenFrontiers Media S.A.articlenotoginsenoside R1high glucose-induced cell injuryAMPKNrf2apoptosisdiabetic cardiomyopathyBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	notoginsenoside R1 high glucose-induced cell injury AMPK Nrf2 apoptosis diabetic cardiomyopathy Biology (General) QH301-705.5
spellingShingle	notoginsenoside R1 high glucose-induced cell injury AMPK Nrf2 apoptosis diabetic cardiomyopathy Biology (General) QH301-705.5 Fawang Du Huiling Huang Yalin Cao Yan Ran Qiang Wu Baolin Chen Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling
description	Notoginsenoside R1 (NGR1), the primary bioactive compound found in Panax notoginseng, is believed to have antihypertrophic and antiapoptotic properties, and has long been used to prevent and treat cardiovascular diseases. However, its potential role in prevention of diabetic cardiomyopathy remains unclear. The present study aimed to investigate the mechanism of NGR1 action in high glucose-induced cell injury. H9c2 cardiomyocytes were cultured in a high-glucose medium as an in-vitro model, and apoptotic cells were visualized using TUNEL staining. Expression of Nrf2 and HO-1 was measured using Western blotting or reverse transcription-quantitative PCR (RT-qPCR). The Nrf2 small interfering (si) RNA was transfected into cardiomyocytes using Opti-MEM containing Lipofectamine® RNAiMAX. NGR1 protected H9c2 cardiomyocytes from cell death, apoptosis and hypertrophy induced by high glucose concentration. Expression of auricular natriuretic peptide and brain natriuretic peptide was remarkably reduced in NGR1-treated H9C2 cells. Western blot analysis showed that high glucose concentration markedly inhibited AMPK, Nrf2 and HO-1, and this could be reversed by NGR1 treatment. However, the cardioprotective effect of NGR1 was attenuated by compound C, which reverses Nrf2 and HO-1 expression levels, suggesting that AMPK upregulates Nrf2 and HO-1 gene expression, protein synthesis and secretion. Transfection of H9C2 cells with Nrf2 siRNA markedly reduced the cardioprotective effect of NGR1 via reduced expression of HO-1. These results indicated that NGR1 attenuated high glucose-induced cell injury via AMPK/Nrf2 signaling and its downstream target, the HO-1 pathway. We conclude that the cardioprotective effects of NGR1 result from upregulation of AMPK/Nrf2 signaling and HO-1 expression in cardiomyocytes. Our findings suggest that NGR1 treatment might provide a novel therapy for diabetic cardiomyopathy.
format	article
author	Fawang Du Huiling Huang Yalin Cao Yan Ran Qiang Wu Baolin Chen
author_facet	Fawang Du Huiling Huang Yalin Cao Yan Ran Qiang Wu Baolin Chen
author_sort	Fawang Du
title	Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling
title_short	Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling
title_full	Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling
title_fullStr	Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling
title_full_unstemmed	Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling
title_sort	notoginsenoside r1 protects against high glucose-induced cell injury through ampk/nrf2 and downstream ho-1 signaling
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/bd18bca154084a7680786ca8aa424c7e
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Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling

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