Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, wa...

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Main Authors: Kazuo Sugimoto, Jia Liu, MingXuan Li, YueBo Song, Chi Zhang, ZhiGuang Zhai, Ying Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.701886/full
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author Kazuo Sugimoto
Kazuo Sugimoto
Jia Liu
Jia Liu
MingXuan Li
YueBo Song
Chi Zhang
Chi Zhang
ZhiGuang Zhai
ZhiGuang Zhai
Ying Gao
Ying Gao
author_facet Kazuo Sugimoto
Kazuo Sugimoto
Jia Liu
Jia Liu
MingXuan Li
YueBo Song
Chi Zhang
Chi Zhang
ZhiGuang Zhai
ZhiGuang Zhai
Ying Gao
Ying Gao
author_sort Kazuo Sugimoto
collection DOAJ
description Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2–related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer.Objective: We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS.Methods: Transgenic SOD1-G93A mice were intraperitoneally injected with SFI (40 ml/kg) three times a week from 87 days of age. Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed.Results: SFI treatment efficiently postponed the disease onset (p = 0.022) and extended the overall survival (p = 0.038) of the SOD1-G93A mice. Moreover, SFI significantly reduced motor neuron loss (p < 0.001) and astrocytic activation (p < 0.05) in the motor cortex of the brain of SOD1-G93A mice at 130 days of age. The protective effects of SFI in the SOD1-G93A mice were associated with decreasing the level of malondialdehyde (p < 0.05) and increasing the levels of superoxide dismutase (p < 0.05), Nrf2 (p < 0.05), heme oxygenase-1 (p < 0.05), and glutathione S-transferase (p < 0.05) in the SOD1-G93A mice.Conclusion: The SFI treatment efficiently extended the overall survival and improved the pathological manifestations of the brain via alleviating the OS injury and activating the Nrf2 pathway in the animal model of ALS, which made SFI a potentially promising candidate for ALS treatment.
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spelling doaj.art-d547034609764b12bd21b45b7d6165112022-12-21T19:14:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-10-011210.3389/fphar.2021.701886701886Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral SclerosisKazuo Sugimoto0Kazuo Sugimoto1Jia Liu2Jia Liu3MingXuan Li4YueBo Song5Chi Zhang6Chi Zhang7ZhiGuang Zhai8ZhiGuang Zhai9Ying Gao10Ying Gao11Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaInstitute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaInstitute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaInstitute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, ChinaInstitute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaBeijing University of Chinese Medicine Third Affiliated Hospital, Beijing, ChinaDepartment of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaInstitute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, ChinaBackground: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2–related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer.Objective: We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS.Methods: Transgenic SOD1-G93A mice were intraperitoneally injected with SFI (40 ml/kg) three times a week from 87 days of age. Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed.Results: SFI treatment efficiently postponed the disease onset (p = 0.022) and extended the overall survival (p = 0.038) of the SOD1-G93A mice. Moreover, SFI significantly reduced motor neuron loss (p < 0.001) and astrocytic activation (p < 0.05) in the motor cortex of the brain of SOD1-G93A mice at 130 days of age. The protective effects of SFI in the SOD1-G93A mice were associated with decreasing the level of malondialdehyde (p < 0.05) and increasing the levels of superoxide dismutase (p < 0.05), Nrf2 (p < 0.05), heme oxygenase-1 (p < 0.05), and glutathione S-transferase (p < 0.05) in the SOD1-G93A mice.Conclusion: The SFI treatment efficiently extended the overall survival and improved the pathological manifestations of the brain via alleviating the OS injury and activating the Nrf2 pathway in the animal model of ALS, which made SFI a potentially promising candidate for ALS treatment.https://www.frontiersin.org/articles/10.3389/fphar.2021.701886/fullShenqi Fuzheng Injectionamyotrophic lateral sclerosisneurodegenerationneuroprotective effectoxidative stressNrf2 pathway
spellingShingle Kazuo Sugimoto
Kazuo Sugimoto
Jia Liu
Jia Liu
MingXuan Li
YueBo Song
Chi Zhang
Chi Zhang
ZhiGuang Zhai
ZhiGuang Zhai
Ying Gao
Ying Gao
Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
Frontiers in Pharmacology
Shenqi Fuzheng Injection
amyotrophic lateral sclerosis
neurodegeneration
neuroprotective effect
oxidative stress
Nrf2 pathway
title Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
title_full Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
title_fullStr Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
title_full_unstemmed Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
title_short Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
title_sort neuroprotective effects of shenqi fuzheng injection in a transgenic sod1 g93a mouse model of amyotrophic lateral sclerosis
topic Shenqi Fuzheng Injection
amyotrophic lateral sclerosis
neurodegeneration
neuroprotective effect
oxidative stress
Nrf2 pathway
url https://www.frontiersin.org/articles/10.3389/fphar.2021.701886/full
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