Herbal complex ‘Buyang Huanwu Tang’ improves motor endplate function of denervated-dependent skeletal muscle atrophy in rat

Abstract

Denervated-dependent skeletal muscle atrophy is a disease induced by skeletal muscle associated peripheral neuro-disconnection. Its specific molecular mechanisms remain unknown. The treating for denervated-dependent skeletal muscle atrophy is applied with an herbal complex Buyang Huanwu Tang used in traditional Chinese medicine and subjected to the established denervated-dependent skeletal muscle atrophy in rat models, and the therapeutic effects and associated mechanisms were evaluated in the pathogenesis of denervated-dependent skeletal muscle atrophy. Denervated-dependent skeletal muscle atrophy in rats was established and randomly divided into eight groups, including Normal control, Model, Positive control, Model + Buyang Huanwu Tang, Model + astragalus extracts, Model + Buyang Huanwu Tang-astragalus, Buyang Huanwu Tang + LY294002, and astragalus extract + LY294002 group. Hematoxylin-eosin staining and quantitative RT-PCR (qRT-PCR) assay were used to examine the inflammatory response of muscle tissues. Quantitative RT-PCR and Western blotting assay were utilized to analyze mRNA and protein expression. Immunohistochemistry assay was used to detect molecule expression in anterior cervical muscle tissues. Motor endplate activity was examined using the wholemount acetylcholinesterase staining method. The wet mass ratio of anterior cervical muscle was measured. The results indicated that Buyang Huanwu Tang treatment significantly alleviated inflammatory response, enhanced acetylcholinesterase activity, and motor endplate functions, and promoted wet mass of anterior cervical muscle compared to denervated-dependent skeletal muscle atrophy rat models (P < 0.05). Buyang Huanwu Tang regulated molecules of PI3K/PKB/GSK3β/FOXO1 signaling pathway. Buyang Huanwu Tang significantly reduced muscle atrophy F-box protein, MuFR-1, Bax and caspase 9 expression, significantly enhanced Bcl-2 expression, and remarkably increased element-binding protein and vascular endothelial growth factor levels, compared to Model group (P < 0.05). Buyang Huanwu Tang suppressed caspase 9 and caspase 3 activity and associated apoptosis. Moreover, PI3K specific blocker, LY294002, significantly inhibited the effects of Buyang Huanwu Tang on the above molecule expression (P < 0.05). In conclusion, Buyang Huanwu Tang improved motor endplate functions of denervated-dependent skeletal muscle atrophy rat model through suppressing mitochondria-mediated apoptosis and activating PI3K/PKB/FOXO1 signaling pathway.

Pharmacological effects of denervated muscle atrophy due to metabolic imbalance in different periods

“…Furthermore, BYHWT treatment is also associated with decreased levels of skeletal muscle atrophy-specific molecules MAFbx and MuRF1. This finding aligns with the outcomes of inflammatory response and motor endplate alterations following BYHWT treatment (Zhou et al, 2020). NeuroHeal, a new neuroprotective drug for peripheral nerve injury, discovered using artificial intelligence is based on a combination of two approved drugs, acamprosate and ribavirin, which facilitate its preparation for clinical application.…”

“…The enhanced cross-sectional area was substantiated by diminished levels of TNF-α in the gastrocnemius and IL-6 in the soleus muscle (Choi et al, 2018). Buyang Huangwu Tang (BYHWT), a classic Chinese medicine formula, ameliorated the inflammatory response in denervation-dependent skeletal muscle atrophy rat models (Zhou et al, 2020). Wu et al (2019) found that negative regulation of pro-inflammatory cytokine mediated by salidroside attenuates denervation-induced skeletal muscle atrophy.…”