Buyang Huanwu Tang improves denervation-dependent muscle atrophy by increasing ANGPTL4, and increases NF-κB and MURF1 levels

Abstract

Denervated-dependent skeletal muscle atrophy (DSMA) is a disorder caused by the peripheral neuro-disconnection of skeletal muscle. The current study aimed to investigate the molecular mechanism and potential therapeutic strategies for the DSMA. A DSMA rat model was established. A lentiviral vector expressing small interfering RNA (siRNA) targeting angiopoietin-like protein 4 (ANGPTL4) was generated and injected into the rats that were also treated with Buyang Huanwu Tang (BYHWT). Reverse transcription-quantitative polymerase chain reaction was performed to examine ANGPTL4 mRNA expression in anterior cervical muscle samples. Western blot assay was used to evaluate ANGPTL4, nuclear factor-κB (NF-κB) and muscle RING-finger protein-1 (MURF1) expression. The ultrastructure of muscle tissues was viewed using transmission electron microscopy. The cell apoptosis in muscle tissues was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling. The results indicated that BYHWT treatment increased ANGPTL4 mRNA and protein levels in muscle tissues. The suppression of ANGPTL4 using siRNA significantly increased inflammatory cells compared with the control siRNA group. BYHWT protected the ultrastructure muscle tissues and inhibited cell apoptosis in the DSMA model. The protective effect of BYHWT protected may be mediated by increased expression of NF-κB p65 and MURF1. In conclusion, BYHWT may improve denervation-dependent muscle atrophy by increasing ANGPTL4 expression, involving NF-κB and MURF1 signaling.

Meningitic Escherichia coli Induction of ANGPTL4 in Brain Microvascular Endothelial Cells Contributes to Blood–Brain Barrier Disruption via ARHGAP5/RhoA/MYL5 Signaling Cascade

“…A study showed that nANGPTL4 is an orphan ligand that mainly controls lipid metabolism and cANGPTL4 binds-e.g., β-integrins, VE-cadherin, and claudin-5-to induce vascular leakage and tumor progression [19]. An increasing number of studies have indicated the possible involvement of ANGPTL4 in the development of cardiovascular diseases [20][21][22], inflammatory diseases [23][24][25][26], cancers [27][28][29], etc. However, there are still no reports on the role of ANGPTL4 in bacterial meningitis.…”

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

“…BYHWT exhibited substantial neuroprotective roles, nerve-function improving functions, and anti-ischemic stroke effects (Wei et al, 2013). Our previous study (Zhao et al, 2017;Zhou et al, 2018) reported that BYHWT participates in improvements of denervation-dependent muscle atrophy in DSMA models. Moreover, in another study, we also indicated that BYHWT could improve the motor endplate function of DSMA rats through activating cellular response to the interferon-gamma, integral component of the plasma membrane, and voltage-gated potassium channel activity genes and Figure 6.…”

“…Buyang Huangwu Tang was mainly composed of Rhizoma Chuanxiong (12 g), Peach seeds (12 g), Astragalus (480 g), Pheretima (12 g), Tangkuei tail (24 g), Red flower (12 g), Paeoniae (20 g), all of which were purchased from Tongrentang Co. Ltd. (Beijing, PRC). These ingredients were treated, mixed, and purified according to our previously published study (Zhou et al, 2018). Chemical reagents involving in BYHWT production, including MgCl2, K3PO4, and K2HPO4, were obtained from Chengdu Kelong Co. Ltd.…”

“…Briefly, SD rats were anesthetized by injecting intraperitoneally with 7% chloral hydrate (at a final concentration of 0.5 ml/100 g body weight). In short detailed processes for establishing the DSMA model were conducted according to our previously published report (Zhou et al, 2018). The model establishment processes and sample isolating processes mainly included the following items: anesthesia, rat peroneal nerve injury, seaming, intragastric administration, intramuscular injection, cut-off skin fascia, tibialis anterior muscle isolation, shear-off tibialis anterior muscle and washing of tibialis anterior muscle.…”

“…BYHWT could promote blood-circulation, clear collaterals, remove blood stasis, treat vascular dementia, and cerebral ischemia-reperfusion (Liu et al, 2003). Furthermore, BYHWT could also effectively suppress activation of caspase, inhibit apoptosis, and modulate mitochondrial functions (Tang et al, 2006;Zhou et al, 2018). However, there are even no studies reporting the side-effects of BY-HWT till now.…”