Abstract
Hochu-ekki-to (Bojungikgi-Tang (BJIGT) in Korea; Bu-Zhong-Yi-Qi Tang in Chinese), a traditional herbal prescription, has been widely used in Asia. Hochu-ekki-to (HET) is used to enhance the immune system in respiratory disorders, improve the nutritional status associated with chronic diseases, enhance the mucosal immune system, and improve learning and memory. Amyotrophic lateral sclerosis (ALS) is pathologically characterized by motor neuron cell death and muscle paralysis, and is an adult-onset motor neuron disease. Several pathological mechanisms of ALS have been reported by clinical and in vitro/in vivo studies using ALS models. However, the underlying mechanisms remain elusive, and the critical pathological target needs to be identified before effective drugs can be developed for patients with ALS. Since ALS is a disease involving both motor neuron death and skeletal muscle paralysis, suitable therapy with optimal treatment effects would involve a motor neuron target combined with a skeletal muscle target. Herbal medicine is effective for complex diseases because it consists of multiple components for multiple targets. Therefore, we investigated the effect of the herbal medicine HET on motor function and survival in hSOD1G93A transgenic mice. HET was orally administered once a day for 6 weeks from the age of 2 months (the pre-symptomatic stage) of hSOD1G93A transgenic mice. We used the rota-rod test and foot printing test to examine motor activity, and Western blotting and H&E staining for evaluation of the effects of HET in the gastrocnemius muscle and lumbar (L4–5) spinal cord of mice. We found that HET treatment dramatically inhibited inflammation and oxidative stress both in the spinal cord and gastrocnemius of hSOD1G93A transgenic mice. Furthermore, HET treatment improved motor function and extended the survival of hSOD1G93A transgenic mice. Our findings suggest that HET treatment may modulate the immune reaction in muscles and neurons to delay disease progression in a model of ALS.
Highlights
Amyotrophic lateral sclerosis (ALS), known as Lou Gehrig’s disease, is characterized by a loss of motor neurons, muscle weakness, and spasticity [1]
We found that hSOD1G93A transgenic mice had increased neuroinflammation, indicated by an increase in CD11b, GFAP, Iba-1, and TLR4 [33,34]
To investigate the effect of HET on neuroinflammation of the spinal cord in hSOD1G93A mice, we investigated the expression of neuroinflammation-related proteins (Iba-1, GFAP, and TLR4) using immunoblotting
Summary
Amyotrophic lateral sclerosis (ALS), known as Lou Gehrig’s disease, is characterized by a loss of motor neurons, muscle weakness, and spasticity [1]. ALS can be divided into familiar ALS (fALS), which is caused by autosomal dominant mutations in genes such as superoxide dismutase (SOD), and sporadic ALS (sALS). Some gene mutations have been found to be involved in both fALS and sALS, including mutations of TAR DNA-binding protein (TDP) 43, fused in sarcoma (FUS), valosin-containing protein (VCP), and TATA-binding protein-associated factor 15 (TAF15) [2]. Nutrients 2019, 11, 2644 a dysregulated immune response plays a critical role in disease progression, as revealed by both ALS animal model and clinical studies [4,5,6].
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