5 | CONCLUSION AND PERSPECTIVES

The interaction of nervous system and immune system is essential for regulating innate immune response and controlling inflammation. CAP has broad development prospects in the treatment of inflammatory diseases. With the in-depth study of CAP pathway, its relationship with various inflammatory diseases has not been fully elucidated, so the pharmacological effect of drugs through CAP has accounted for a large share of disease treatment, which is still unknown. Inflammatory diseases also include depression, shock, allergic asthma, colitis, cancer, and other diseases with high incidence rates. Many CHM that treats inflammatory diseases has not yet been studied whether they are related to CAP. It may become a potential treatment for such diseases. Therefore, it is necessary to thoroughly study the relationship among CAP, pathways, and diseases. Studying the mechanism of CHM in CAP is also more conducive to understanding its mechanism from a new entry point and promoting the clinical application of CHM. In the drug studies compiled in this review, most of them focused on the activation of α7nAChR and the regulation of ACh level in CAP. The mechanism researches of most drugs are still needing to be explored for further applications. Characteristics of the multicomponent-multitarget-multipathway of CHM, more therapeutic drugs can be developed from CHM prescriptions or active ingredients. It has better clinical application value as an alternative therapy for CAP activation through secondary advance research.
Some researchers have suggested that COVID-19 may be a cholinergic system disease in the late stage of development. It has clinical manifestations of cytokine storm, insomnia, and thromboembolic complications, indicating that it is related to cholinergic dysfunction (Farsalinos et al., 2020). ACE-2 is the main receptor used by SARS-CoV-2 to enter the host cell and nicotine upregulates ACE-2 through α7nAChR (Leung, Yang, & Sin, 2020; Russo et al., 2020). So that it has become a possible treatment that changes the expression of ACE-2 through α7nAChR antagonist to prevent SARS-CoV-2 from entering the cells. The present review found that Chinese medicines such as Liang-Ge-San, Huanglian Jiedu Decoction, Shenfu Injection, Scutellariae Radix, Coptidis Rhizoma, and total flavonoids of litchi have the effect of treating ALI and sepsis. In the COVID-19 epidemic, Huanglian Jiedu Decoction, Shenfu Injection, and other drugs have also been recommended for clinical using, which have achieved remarkable results. In the SARS epidemic, it has also been revealed that in the treatment of such major coronavirus infections, glucocorticoid drugs, ribavirin, alpha-interferon, lopinavir/ritonavir after long-term application, it will produce a certain degree of sequelae such as liver damage, pulmonary fibrosis, and femoral head necrosis. In the treatment of CHM, more emphasis is placed on increasing efficacy and reducing toxicity, improving the security of medication, enhancing self-immunity, and improving the ability to clear viruses. Therefore, CHM based on CAP exerting anti-inflammatory effect is also one of the treatment methods in COVID-19, which can reduce dosage or use of hormone drugs to a greater extent, reduce liver damage and sequelae, and the combination of Chinese and Western medicine is more conducive to overcoming such problems at an early date. The mechanism and clinical application need to be further explored.
Although there are no clinical drugs that have clinical side effects with α7nAChR as the target, due to the limitations of cholinergic drugs, they have side effects on the organs under the parasympathetic nervous system. For instance, when acting on M2 mAChR may cause bradycardia, when acting on M3 mAChR may cause blood pressure drop, abdominal cramps caused by smooth muscle contraction and bronchial asthma, etc., and cholinergic drugs entering the brain may also affect nerves. Consequently, purely safe drugs do not exist, the usage and dosage of drug are crucial. In clinical applications, CHM emphasizes dialectical medicine to avoid contraindications (such as bronchial asthma, arrhythmia, intestinal resection, urinary tract obstruction, etc.). It is reasonably matched with medicines to enhance the therapeutic effect and reduce toxicity, and exert the advantage of the anti-inflammatory effect of CHM with accurate curative effect and small side effects. In summary, CAP is an important mechanism for inflammatory disease treatment with CHM. There are still a lot of research that needs to be explored in-depth, which can be utilized as a new perspective for clinical application.