1 | INTRODUCTION
Infection or tissue damage can
trigger the body’s innate immune activation and protective inflammation
responses. For an organism that has been invaded by viruses, bacteria,
etc., an appropriate inflammatory response is a favorable regulation to
prevent the most threat of disease. The lack or excessive inflammation
is not only a part of many diseases, but also an important mechanism of
these diseases, such as sepsis, acute lung injury (ALI), rheumatoid
arthritis (RA), atherosclerosis, diabetes, hemorrhagic shock,
pancreatitis, Alzheimer’s disease (AD), multiple sclerosis,
cardiovascular and cerebrovascular diseases, and even cancer (Tracey,
2002). According to the Coronavirus disease 2019 (COVID-19) outbroke,
the patients with the highest morbidity and mortality after severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly
developed into hyperinflammatory syndromes such as acute respiratory
distress syndrome and septic shock. That is, the immune system was
triggered by the cytokine storm to attack the body violently, and it
also caused serious damage to the body because of excessive
inflammation. Excessive inflammation is a serious injury to the body.
Clinically, inflammatory diseases are treated by drug treatment,
acupuncture, meditation, hypnosis, relaxation therapy, and physical
exercise improvement, along with increased vagal activities and reduced
inflammatory cytokine levels. In addition to these treatments by humoral
regulation as we know, there are other ways to do it? The nerve and
immune system do not exist completely independently, and they regulate
the balance of the body through neurotransmitters and cytokines. The
nervous system integrates inflammatory response information, signals are
sent out to regulate inflammation mainly through the vagus nerve, the
release of activated macrophages and cytokines is inhibited, and
inflammation is rapidly regulated. This pathway is known as the
”cholinergic anti-inflammatory pathway (CAP)” (Borovikova et al., 2000).
In this pathway, the central nervous system receives the body’s immune
stimulation information and projects it to the vagal nucleus, activating
the efferent fibers of the vagus nerve. Acetylcholine (ACh) is released
from peripheral nerve endings. After ACh binds to receptors such as
nicotinic acetylcholine receptor α7 (α7nAChR), it connects Janus kinase
2/ Signal transducer and activator of transcription 3 (JAK2/STAT3) and
nuclear factor kappa-B (NF-κB), inhibits NF-κB activation, prevents T
cell differentiation, and inhibits neutrophils and monocytes Cell
lethality, thereby inhibiting the inflammatory response. It’s a
physiological mechanism that inhibits cytokine production and minimizes
tissue damage during inflammation. Compared with the humoral pathway,
this pathway is characterized by more sensitive induction and faster
response. Overall, scholars have two key research points on this
pathway. On the one hand, the focus is on studying the mechanism of CAP
(including related pathways, target sites, and the relationship between
diseases). On the other hand, the focus is on the mechanism of drugs
through CAP to treat inflammatory diseases. In future research, we will
explore how the brain regulates the body’s inflammation, which pathways
are regulated by drugs, and which ways dominate.
With the widespread application of Chinese herbal medicine (CHM) in
anti-inflammatory immunity has attracted more attention. CHM is a
complex of natural pharmaceutical ingredients, which contains a variety
of anti-inflammatory ingredients such as alkaloids, glycosides,
polysaccharides, etc. The combination of various CHM in the traditional
Chinese medicine prescriptions can achieve the effect of increasing
efficacy and reducing toxicity. With the gradual increase in researches,
the anti-inflammatory mechanism of CHM is not only related to NF-κB,
JAK2/STAT3, MAPK pathway in traditional sense, but also related to CAP,
especially in sepsis, Alzheimer’s disease, arthritis, cardiovascular
disease, and other diseases. This review summarizes and analyzes CAP key
parts, focusing on the relationship between CAP and inflammatory
diseases, as well as mechanism research progress of CHM prescriptions,
single herb, extracts and components on these inflammatory disease
through CAP (analytical framework shown in Figure 1). It is expected to
provide a reference for the drug treatment of inflammatory diseases,
expand the treatment of CAP-related diseases, and provide new targets,
ideas, and theoretical basis for the study of immunomodulation.