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.
Naringin (Nr) has been identified to have antidepressant-like effects through repeated treatment. However, the underlying mechanism of the rapid antidepressant-like effects of Nr was still unclear. The present study used behavioral tests, classic depressive model and pharmacological methods to reveal the rapid antidepressant-like potential of Nr. We found that a single dose of Nr (20 mg/kg) produced antidepressant-like action after 2 h in the tail suspension test (TST) and forced swimming test (FST). Moreover, ketamine-like effects were also demonstrated by using the chronic mild stress model (CMS) and learned helplessness (LH), and the results showed that Nr reversed all behavioral defects, TST, FST, source preference test (SPT) in CMS, and LH testing, TST, FST in LH model, at 2 h after a single administration. In addition, Nr (20 mg/kg) could improve the abnormal expressions of NMDA receptor NR1 and PKA/CREB/BDNF pathway in hippocampus 2 h after a single administration in CMS mice. Further investigation revealed that activation of NMDA receptors by NMDA (750 mg/kg) could block the antidepressant effects of acute administration of Nr (20 mg/kg). However, the inhibition of NMDA receptors by MK-801 (0.05 mg/kg) promoted the subdose of Nr (10 mg/kg) to have antidepressant effect, which was similar to the effective dose Nr (20 mg/kg). Taken together, acute dose of Nr produces rapid antidepressant-like action, and the underlying mechanism could be through inhibiting NMDA receptors in the hippocampus.
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