Traditional Chinese herbal medicines suppress endometriosis development through modulating macrophage-mediated immune responses in the peritoneal cavity

Background: Due to unique dietary culture, Asian patients with endometriosis usually seek assistance through traditional Chinese herbal medicine (TCHM), making combined treatments of Western and Chinese medicine quite common in Asia. However, limited molecular evidence has been provided to demonstrate the therapeutic benefits of TCHM in treating endometriosis. Aims: To investigate the functional impacts of TCHM treatment in their traditional formulae on peritoneal immunity, lesion growth, and adhesion formation, we performed studies by using a disease mouse model that exhibits the features of blood stasis and stagnation. Methods: Four well-known TCHM formulae, frequently used for treating symptoms similar to endometriosis, were applied to a mouse model with human endometriosis features. Lesion growth, modulation of peritoneal immune responses, pain-associated behaviors, and endometriosis adhesion were analyzed after TCHM treatment. Results: Among the formulae, Danggui Buxue Tang (DBT) and Shaofu Zhuyu Tang (SZT) can promote blood circulation into the peritoneal cavity, resulting in increased large (LpMs) and small (SpMs) peritoneal macrophages with M1 phenotype polarization. Macrophage activation restrained lesion formation, chronic inflammation, and nerve fiber growth in the treated mice. Behavioral studies further confirmed pain-relief effects that enhanced spontaneous locomotor activity and reduced evoked mechanical hyperalgesia. Interestingly, DBT and SZT treatments can also downregulate the expression of key adhesion molecules, such as ICAM-1 and AKAP12, in the lesions, leading to reduced endometriosis adhesion in treated mice. Conclusion: These findings reveal the functional effects of TCHM formulae, especially DBT and SZT, on macrophage-mediated immune responses in the peritoneal cavity, which may benefit patients with endometriosis.