Buyang Huanwu Tang alleviates inflammation and improves motor endplate functions in DSMA rat models by activating several biological molecules and associated signaling pathways

Am J Transl Res. 2019 May 15;11(5):3056-3068. eCollection 2019.

Abstract

Denervated-dependent skeletal muscle atrophy (DSMA) is considered to be the neuro-disconnection of skeletal muscle. This study aimed to investigate the protective effects of Buyang Huanwu Tang (BYHWT) on the DSMA and clarify associated molecular and genetic mechanisms. DSMA rat models were established according to the previously published study and divided into Model group and BYHWT group. Meanwhile, normal rats were assigned as Normal control (NC) group. Hematoxylin and eosin (HE) staining was used to examine inflammatory responses. Motor endplate activity was evaluated with wholemount acetylcholinesterase (AChE) staining. Mass-spectrometry analysis was conducted to compare differentially expressed proteins. RNAs were prepared and applied to gene functional analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze biological functions. The results indicated that BYHWT remarkably alleviated inflammatory responses and significantly improved motor endplate function, compared to that in DSMA Model rats (P<0.05). In BYHWT group, there were 393 differentially up-regulated and 576 differentially down-regulated molecules compared to that in Model group. Comparing to Model group, the cellular response to interferon-gamma, integral component of plasma membrane and voltage-gated potassium channel activity genes in BYHWT group were the most biological process (BP), cellular component (CC) and molecular function (MF) differential genes, respectively. Fructose/mannose metabolism and glycerolipid metabolism KEGG signaling pathways illustrated the most significant enrichment of differentially expressed genes. In conclusion, BYHWT alleviated the inflammations and improved the motor endplate function of DSMA rats by activating cellular response to interferon-gamma, integral component of plasma membrane and voltage-gated potassium channel activity genes and associated signaling pathways.

Keywords: Buyang Huanwu Tang; Denervated-dependent skeletal muscle atrophy; differentially expressed genes; inflammatory response.