Astragalus Polysaccharide RAP Induces Macrophage Phenotype Polarization to M1 via the Notch Signaling Pathway

Area of Science:

• Immunology
• Pharmacology
• Cell Biology

Background:

• Macrophages exhibit diverse phenotypes (e.g., M1, M2) influencing tumor progression.
• M1 macrophages possess anti-tumor properties, while M2 macrophages often support tumor growth.
• Previous research indicated a polysaccharide from Radix Astragali (RAP) induces cancer cell cytotoxicity.

Purpose of the Study:

• To elucidate the mechanism by which RAP influences macrophage polarization.
• To investigate RAP's effect on M1 macrophage markers and anti-tumor activity.
• To determine the role of the Notch signaling pathway in RAP-mediated macrophage polarization.

Main Methods:

• Gene expression analysis of M1 markers (iNOS, IL-6, TNF-a, CXCL10) in RAW264.7 cells treated with RAP.
• In vivo studies involving transplantation of RAP-induced bone marrow-derived macrophages (BMDMs) with 4T1 tumor cells in BALB/c mice.
• Investigation of Notch signaling pathway activation in RAW264.7 cells using RAP and a γ-secretase inhibitor.

Main Results:

• RAP significantly upregulated M1 macrophage markers (iNOS, IL-6, TNF-a, CXCL10) compared to controls.
• Co-transplantation of RAP-induced BMDMs with 4T1 tumor cells led to reduced tumor volume and weight.
• RAP treatment activated the Notch signaling pathway in RAW264.7 cells, a process confirmed by γ-secretase inhibitor treatment.

Conclusions:

• Astragalus polysaccharide RAP effectively induces macrophage polarization towards the M1 phenotype.
• The Notch signaling pathway is a key mediator of RAP-induced M1 polarization.
• RAP demonstrates potential as an immunomodulatory agent for cancer therapy by enhancing anti-tumor macrophage responses.