Anti-inflammatory Effects of a Novel Herbal Extract in the Muscle and Spinal Cord of an Amyotrophic Lateral Sclerosis Animal Model.

Sun Hwa Lee,Mudan Cai,Eun Jin Yang

doi:10.3389/fnins.2021.743705

Sun Hwa Lee, Mudan Cai + Show 1 more

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https://doi.org/10.3389/fnins.2021.743705

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Abstract

Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by motor neuron loss and muscle atrophy. There is no prominent treatment for ALS as the pathogenic process in the skeletal muscle and spinal cord is complex and multifactorial. Therefore, we investigated the effects of a herbal formula on the multi-target effects in the skeletal muscle and spinal cord in hSOD1G93A transgenic mice. We prepared a herbal extract (HE) from Glycyrrhiza uralensis, Atractylodes macrocephala Koidzumi, Panax ginseng, and Astragalus membranaceus. Control and HE-treated mice underwent rotarod and footprint tests. We also performed immunohistochemical and Western blotting analyses to assess expression of inflammation-related and oxidative stress-related proteins in the muscle and spinal cord tissues. We found that the HE increased motor activity and reduced motor neuron loss in hSOD1G93A mice. In addition, the HE significantly reduced the levels of inflammatory proteins and oxidative stress-related proteins in the skeletal muscles and spinal cord of hSOD1G93A mice. Furthermore, we demonstrated that the HE regulated autophagy function and augmented neuromuscular junction in the muscle of hSOD1G93A mice. Based on these results, we propose that the HE formula may be a potential therapeutic strategy for multi-target treatment in complex and multifactorial pathological diseases.

Highlights

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive degeneration and death of the motor neurons and muscle paralysis
The body weight and muscle weight of the mice were significantly reduced by 1.1- and 1.7-fold (p < 0.05, p < 0.001), respectively, in the transgenic mice (Tg) group compared with the non-transgenic mice (nTg) group (Figure 1A)
There was no change in the body weight of mice in the TgHE group, the muscle weights of tibialis anterior (TA) and GC of mice in the Tg-herbal extract (HE) group were significantly increased by 1.3- and 1.2-fold, respectively, compared with those of mice in the Tg group (Figure 1A)

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive degeneration and death of the motor neurons and muscle paralysis. Ten percent of patients with ALS are known to have familial ALS that is caused by genetic mutations in genes, such as SOD1 and C9ORF72. Despite several attempts to find effective therapy, only two drugs are permitted for the treatment of ALS—riluzole reduces excessive glutamate excitotoxicity and edaravone reduces oxidative stress. Even these show only a mild effect in delaying disease progression and extending life (Miller et al, 2012; Watanabe et al, 2018).

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