Macrophage polarization: a potential therapeutic target for ulcerative colitis in TCM

Epidemiological studies suggest that the incidence and prevalence of ulcerative colitis (UC) is relatively high in Western countries, but the overall trend is stable
.
Over the past 20 years, the incidence and prevalence of UC in Eastern countries has increased rapidly, and UC has gradually become a global disease
.
Many studies have shown that the longer ulcerative colitis develops, the higher
the prevalence of colon cancer.
The probability of developing colon cancer is 1.
6% at 10 years, 8.
3% in 20 years, and 18.
4%
in 30 years.
Because of its complex etiology, difficult to cure, easy to recur, poor prognosis, and increased risk of colon cancer, it has been listed as one of
the modern refractory diseases by the World Health Organization.

At present, the therapeutic drugs for UC mainly include anti-inflammatory drugs (5-aminosalicylic acid and glucocorticoids), immunosuppressants and biologics
.
However, many patients are prone to relapse after stopping the drug and are difficult to cure
.
In addition, long-term use of conventional therapeutic drugs such as anti-inflammatory drugs, hormones and immunosuppressants has significant side effects
.
Therefore, there is an urgent need to find new therapeutic targets to reduce the use of anti-inflammatory drugs, hormones and immunosuppressants, and to reduce adverse drug reactions
.
Clinical studies have shown that traditional Chinese medicine (TCM) has good clinical efficacy in the treatment of UC, which can effectively improve clinical symptoms and quality of life, alleviate intestinal inflammatory reaction and disease progression, and reduce disease recurrence
.

Outline the different biological and physiological features of macrophage polarization:

Intestinal macrophages are major players
in intestinal immune homeostasis and intestinal inflammation.
Under different environmental stimuli, intestinal macrophages can be polarized to the classic activated pro-inflammatory phenotype (M1) and the alternative activated anti-inflammatory phenotype (M2).

Its different polarization states are "guides"
for the development and resolution of inflammation.
Under normal circumstances, intestinal macrophages protect the intestines from inflammatory damage
.
However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages can lead to imbalance in the regulation of intestinal inflammation, transforming physiological inflammatory responses into pathological intestinal damage
.
In UC patients, diseases of intestinal inflammation are closely related to
the imbalance of intestinal M1 / M2 macrophage polarization.
Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for
UC.
There is evidence that Traditional Chinese Medicine (TCM) has a positive therapeutic effect
on UC by restoring the balance of M1/M2 macrophage polarization.

The role of intestinal macrophage polarization in the pathogenesis of UC and the potential mechanism of TCM UC based on intestinal macrophage polarization:

In summary, there is increasing evidence that targeted therapy for macrophage polarization can re-establish intestinal immune microenvironment homeostasis and restore tissue homeostasis after inflammation, making macrophage polarization a new focus for
exploring UC treatments.
In recent years, although TCM research has paid more and more attention to the role of macrophage polarization in ulcerative colitis, there have been few studies exploring the regulatory mechanism of macrophage polarization in TCM, and most of them are limited to the cellular level, and there are few
animal and clinical trials.
In addition, most current research has focused on protecting tissue damage from a simple anti-inflammatory perspective or from a direct repair and regeneration perspective, without paying enough attention to the complete pathway chain to achieve tissue regeneration
.

Therefore, in the future, we should further strengthen the clinical and basic research on the intervention of macrophage polarization by traditional Chinese medicine to enrich the scientific connotation
of traditional Chinese medicine in the treatment of UC.
In the future, we should pay attention to the drug treatment strategy based on the whole chain of inflammation repair, so as to play the key role of immune cells represented by M2 macrophages related to tissue regeneration and repair in inflammatory diseases, and highlight the scientific and effective
theory of "strengthening vitality and eliminating pathogenic factors" of traditional Chinese medicine.

Original source:

Yang Z, Lin S, Feng W, Liu Y, Song Z, Pan G, Zhang Y, Dai X, Ding X, Chen L, Wang Y.
A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization.
Front Pharmacol.
2022 Sep 6; 13:999179.
doi: 10.
3389/fphar.
2022.
999179.
PMID: 36147340; PMCID: PMC9486102.