Abstract
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.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease and the most frequent motor neuron disorder in adults, characterized by progressive loss of the upper and lower motor neurons (MNs) in the motor cortex, brainstem, and anterior horn of the spinal cord, which leads to weakness and atrophy of voluntary muscles (Kiernan et al, 2011; Guttenplan et al, 2020; Oggiano et al, 2021)
Six mice in each group were randomly selected for the survival experiment, which was conducted to determine the effects of Shenqi Fuzheng Injection (SFI) on motor functions and survival of the mice, and 12 mice in each group were used for pathological and nuclear factor-E2-related factor (Nrf2) pathway-related assessments, which were performed to determine the effects of SFI on pathological manifestations and investigate the mechanisms mediating the action of SFI
Regarding the motor function evaluated by the rotarod test (RT), the rotating rod maintaining duration of mice in both the SOD1+SFI group and SOD1+saline groups dropped sharply from 115 days of age
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease and the most frequent motor neuron disorder in adults, characterized by progressive loss of the upper and lower motor neurons (MNs) in the motor cortex, brainstem, and anterior horn of the spinal cord, which leads to weakness and atrophy of voluntary muscles (Kiernan et al, 2011; Guttenplan et al, 2020; Oggiano et al, 2021). A series of antioxidants with the ability of Nrf pathway activation, such as curcumin, resveratrol, and sulforaphane, were proven to delay disease progression in the murine model of ALS (Duan et al, 2010; Jiang et al, 2011; Mancuso et al, 2014). Dimethyl Fumarate, a well-known Nrf pathway activator, was used in a clinical trial for sporadic ALS treatment and observed to preserve the MN function and stabilize the respiratory function of patients through inducing Nrf activity (Vucic et al, 2020). 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
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