Naringenin Alleviates the Autophagy-Associated AMPK-Akt/mTOR Pathway to Regulate Inflammation and Barrier Function,...

Area of Science:

• Gastroenterology
• Pharmacology
• Molecular Biology

Background:

• Intestinal fibrosis leading to strictures is a major complication for ulcerative colitis (UC) patients.
• Current treatments for UC-associated fibrosis are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the protective effects of naringenin (NAR) against dextran sodium sulfate (DSS)-induced intestinal fibrosis in a UC mouse model.
• To elucidate the molecular mechanisms underlying NAR's anti-fibrotic action in the colon.

Main Methods:

• Mice with DSS-induced colitis were orally administered naringenin (40 mg/kg).
• Clinical symptoms, histological damage, colonic F4/80 and MPO levels were assessed.
• Serum proinflammatory cytokines, NLRP3 inflammasome activation, Nrf2/Keap1 pathway, AMPK-Akt/mTOR pathway, autophagy, α-SMA, and Collagen-I were analyzed.

Main Results:

• Naringenin treatment significantly reduced clinical and histological signs of intestinal fibrosis in UC mice.
• NAR decreased colonic inflammatory markers (F4/80, MPO) and serum proinflammatory cytokines.
• NAR inhibited NLRP3 inflammasome activation, reduced oxidative stress via the Nrf2/Keap1 pathway, and enhanced autophagy through the AMPK-Akt/mTOR pathway, decreasing α-SMA and Collagen-I.

Conclusions:

• Naringenin demonstrates significant protective effects against the development and progression of intestinal fibrosis in UC.
• NAR's therapeutic potential lies in its ability to modulate inflammatory responses, oxidative stress, and autophagy via specific molecular pathways.
• Naringenin represents a promising therapeutic agent for managing intestinal fibrosis in ulcerative colitis.