Astragaloside IV: A Promising Drug to Prevent the Transition from Colitis to Colorectal Cancer

Area of Science:

• Immunology
• Gastroenterology
• Pharmacology

Background:

• Colorectal cancer (CRC) poses a global health challenge, particularly in treating transitions from inflammatory bowel disease (IBD) to malignancy.
• Effective treatments for IBD-associated CRC (IBD-CRC) are lacking.
• Astragaloside IV (AS-IV), from *Astragalus membranaceus*, exhibits immunomodulatory and gastrointestinal protective effects.

Purpose of the Study:

• To review the therapeutic potential and mechanisms of AS-IV in the context of IBD-CRC development.
• To evaluate AS-IV's effects across three pathological phases: inflammation, inflammation-to-cancer transition, and established IBD-CRC.
• To explore AS-IV's role in bidirectional M1/M2 macrophage modulation.

Main Methods:

• Literature review evaluating AS-IV's mechanisms of action.
• Analysis of AS-IV's impact on immune signaling pathways (NF-κB, PPARγ).
• Assessment of AS-IV's effects on gut microbiota and oxidative stress.

Main Results:

• AS-IV promotes M2 macrophage polarization during inflammation, reducing mucosal inflammation and repairing the intestinal barrier.
• AS-IV targets immune pathways, gut microbiota, and oxidative stress to prevent IBD-CRC transition.
• AS-IV promotes M1 macrophage polarization in IBD-CRC, suppressing tumor growth, inducing apoptosis, inhibiting metastasis, and enhancing chemosensitivity.

Conclusions:

• AS-IV demonstrates multi-target therapeutic effects across all stages of IBD-CRC.
• AS-IV can bidirectionally modulate the M1/M2 macrophage ratio, crucial for IBD-CRC prevention and treatment.
• AS-IV offers promising strategies for future drug development in IBD-CRC therapy.