Effect of Grilled Nux Vomica on Differential RNA Expression Profile of Gastrocnemius Muscle and Toll­Like Receptor 4 (TLR-4)/Nuclear Factor kappa B (NF-κB) Signaling in Experimental Autoimmune Myasthenia Gravis Rats.

BACKGROUND Myasthenia gravis (MG) is a progressive autoimmune disorder caused by the production of antibodies directed against acetylcholine receptors (AChRs), resulting in muscle weakness and fatigue. This study aimed to explore the effect and mechanism of grilled nux vomica (GNV) in experimental autoimmune myasthenia gravis (EAMG) rats. MATERIAL AND METHODS Rat 97-116 peptides were used to mediate disease in the EAMG model in SPF female Lewis rats. The treatment groups received grilled nux vomica (75 mg/kg, 150 mg/kg, and 225 mg/kg). The autoantibody and inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). RNA profiling was performed on high-dose and model group rats. Profiling results and TLR-4/NF-kappaB signaling were validated by q-PCR and Western blot analysis. RESULTS The results showed that GNV could attenuate the symptoms of EAMG rats. There was a decreased level of AChR-ab, IFN-γ, TNF-alpha, IL-2, IL-4, and IL-17 levels, and an increased level of TGF-ß1. In total, 235 differentially expressed genes (DEGs), consisting of 175 upregulated DEGs and 60 downregulated DEGs, were identified. Functional annotation demonstrated that DEGs were largely associated with leukocyte cell-cell adhesion, NF-kappa B signaling pathway, muscle contraction, and cardiac muscle contraction pathway. Rac2, Itgb2, Lcp2, Myl3, and Tnni1 were considered as hub genes with a higher degree value in the protein-protein interaction (PPI) network. The q-PCR and Western blot results of hub genes were consistent with RNA profiles. GNV treatment also significantly reduced the TLR-4 and NF-kappaB p65 protein expression in EAMG rats. CONCLUSIONS These results indicate that grilled nux vomica ameliorates EAMG by depressing the TLR-4/NF-kappaB signaling pathway, and hub genes may serve as potential targets for MG treatment.

Dihuang Yinzi, a Classical Chinese Herbal Prescription, for Amyotrophic Lateral Sclerosis: A 12-Year Follow-up Case Report.

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease with no effective treatment and death within 2 to 5 years after symptom onset. Here, we reported a case of ALS patient using modified Dihuang Yinzi (DHYZ), a classical traditional Chinese medicine (TCM) prescription, who has survived 12 years with significant improvement in bulbar paralysis.A 41-year-old Chinese Han nationality woman was admitted to the hospital with complaints of weakened bilateral grip, slurred speech, stumbling, and muscle twitching for 3 years. The electromyography showed neurogenic injury in bilateral upper limbs and tongue. She was diagnosed with ALS according to the revised El escorial criteria. The patient was orally administrated with Riluzole 100 mg daily for 10 months and then stopped. Subsequently, she resorted to TCM. Based on the TCM theory, the patient was diagnosed with Yinfei syndrome because of kidney deficiency. DHYZ was chosen because it has the function of replenishing kidney essence to treat Yinfei syndrome. Up to now, she has been using modified DHYZ continuously for 12 years. The patient survived with ALS and did not require permanent continuous ventilator. In addition, the symptoms of choking on liquids are improved, and the utility of 30 mL water swallow test was improved with grade 2. The symptoms of muscle fibrillations of limbs are also reduced. However, muscle strength worsened slowly. The repeated electromyography showed motor conduction amplitude reducing gradually and velocity not changing more when compared with the initial electromyography.Our findings suggested that DHYZ can be potentially used in ALS patients because of its multi-targeted neuroprotection and general safety, although ALS does not have a cure. In addition, we identified the area that is worthy of further study and DHYZ as a promising candidate for further clinical application and ALS trials. Rigorous randomized controlled trials are needed in the future.