Recently, TCM has been widely recognized worldwide. She-xiang as a traditional Chinese herb, has been found to facilitate the recovery of facial paralysis. However, the mechanism of the effect of She-xiang on facial paralysis has not been illuminated. In the present study, the active ingredients of herb She-xiang were predicted based on the records of TCMID. The protein targets of active ingredients were predicted by the BATMAN and differentially expressed genes analysis. Finally, pharmacology network was constructed with 33 protein targets, 15 chemical components and 4 signaling pathways.
Our results showed that testosterone was an active ingredient of She-xiang, which has been validated in the pharmacology network. Testosterone is a primary male hormone and plays an essential role in human health and well-being . Evidence has shown that testosterone as an anabolic steroid is applied for male hypogonadism treatment and certain types of breast cancer [33–34]. In addition, testosterone has been documented to be implicated in muscle growth and development of humans . It is reported that androgens show function in stimulating muscle generation, and facilitating reinnervation and angiogenesis . Testosterone, a kind of androgens, has been found to stimulate the activation of androgen receptor of nerve, which promotes reinnervation in the process of muscle grafts [37–38]. Previous evidence has suggested that testosterone plays a differential regulatory role in the regeneration of facial motoneurons . A study in male hamsters showed that testosterone mediated the accelerative recovery of facial paralysis , which was consistent with therapeutic effect of She-xiang on facial paralysis.
Besides, JUN was predicted to be a protein target for testosterone. Jun protein family plays a regulatory role in collagenase expression after stimulated by various extracellular signals . Jun protein has been found to be selectively expressed in peripheral nerves of rats after axotomy and plays a role in nerve generation . Besides, the expression of Jun protein is increased after the activation of mitogen-activated protein kinase (MAPK) pathway induced by UV radiation in skin . Previous report has suggested that MAPK is activated in mice with facial pain induced by occlusal interference . MAPK signaling pathway has been suggested to be involved in the evolution of facial palsy in the mice model . A previous study suggested that MAPK signaling was one of the downstream pathways underlying the role of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in improving facial nerve regeneration and functional recovery . In the present study, the interaction was identified between JUN protein and MAPK signaling pathway. Taken together, we suggested that JUN protein and MAPK signaling pathway were implicated in the recovery of facial nerve disorder.
Furthermore, our data showed that cAMP signaling was another pathway involved with Jun protein. cAMP is the second messenger involved in the central nervous system (CNS) axonal regeneration. The level of cAMP is elevated under the process of advanced growth of CNS neurite induced by neurotrophies such as BDNF and glia-derived neurotrophic factor (GDNF) . In addition, the up-regulated cAMP induced by trk receptor signaling plays a key role in improving axonal outgrowth of peripheral nerve. Testosterone has been suggested as one of the agents that show consideration promise for the treatment of peripheral nerve injury . In our study, the JUN protein was predicted to be the target for testosterone and pathway analysis showed that cAMP signaling pathway was a significant pathway involved with JUN. Thus, we suggested that testosterone may improve the recovery of facial paralysis by targeting JUN involved in cAMP signaling pathway.
Testosterone and ASD co-exist in human plasma . In our study, the interactive docking of 1FOS-ASD was predicted. ASD is found to show proliferative effect on androgen-sensitive LNCaP cells , while there was rare evidence for the therapeutic role of ASD on facial paralysis. Our data show that ASD targeting 1FOS may play a key role in treating facial paralysis. However, further analyses are urgently needed.
In conclusion, this work hypothesized testosterone as the effective component of She-xiang which may advance the recovery of facial paralysis by targeting FUN, MAPK and cAMP signaling pathway; docking of ASD and 1FOS might play a critical role in facial paralysis treated by She-xiang. The future work can take this as a breakthrough to continue studying the mechanism and improving clinical outcomes of She-xiang in treating facial paralysis.