Alpha-Momorcharin Inhibits Proinflammatory Cytokine Expression by M1 Macrophages but Not Anti-Inflammatory Cytokine Expression by M2 Macrophages

Background: Alpha-momorcharin (alpha-MMC) is a natural medicine derived from bitter melon and has been found to exert immuno-modulatory effects. Our previous study indicated that alpha-MMC can regulate cytokine release from monocytes, but it remains unknown about its regulatory effect on different types of cytokines, such as inflammatory cytokines or anti-inflammatory cytokines.Methods: LPS-induced M1-type macrophages model and IL-4-induced M2-type macrophages model were established, and the expression of proinflammatory cytokines and anti-inflammatory cytokines were assessed by ELISA after alpha-MMC was administered. Then, a LPS-induced acute pneumonia mouse model was established, the proinflammatory cytokines levels and inflammatory lesions in lung tissues were examined by ELISA or H&E staining. Furthermore, omics screening analysis and Western blotting verification were performed on TLR4 and JAK1-STAT6 signalling pathway-related proteins to elucidate the regulatory mechanism of alpha-MMC in those M1 macrophages and M2 macrophages.Results: At a noncytotoxic dose of 0.3 mu g/mL, alpha-MMC significantly inhibited the LPS-induced expression of inflammatory cytokines, such as TNF-alpha, IL-1 beta, IL-6, IL-8, MIP-1 alpha and MCP-1, by M1 macrophages in a time-dependent manner, but alpha-MMC did not inhibit the IL-4-induced synthesis of anti-inflammatory cytokines, such as IL-10, IL-1RA, EGF, VEGF, TGF-beta and CCL22, by M2 macrophages. Moreover, alpha-MMC also inhibited inflammatory cytokine expression in an LPS-induced acute pneumonia mouse model and alleviated inflammation in lung tissues. Furthermore, omics screening and Western blotting analysis confirmed that alpha-MMC inhibited TAK1/p-TAK1 and subsequently blocked the downstream MAPK and NF-Kappa B pathways, thus inhibiting the LPS-induced inflammatory cytokine expression.Conclusion: Our results reveal that alpha-MMC inhibits proinflammatory cytokine expression by M1 macrophages but not anti-inflammatory cytokine expression by M2 macrophages. The efficacy of alpha-MMC in selectively inhibiting proinflammatory cytokine expression renders it particularly suitable for the treatment of severe inflammation and autoimmune diseases characterized by cytokine storms.

Automated summary

Alpha-MMC can regulate the immune system by inhibiting the expression of inflammatory cytokines without affecting anti-inflammatory cytokines. The findings suggest that Alpha-MMC may be a potential treatment for severe inflammation and autoimmune diseases characterized by cytokine storms.