Plumericin Modulates the AhR-NFκB-Nrf2 Signaling Network to Counteract Indoxyl Sulfate-Induced Intestinal Epithelial...

Area of Science:

• Nephrology
• Gastroenterology
• Pharmacology

Background:

• Chronic kidney disease (CKD) affects over 800 million people globally and is characterized by systemic inflammation.
• The intestine is a key source of inflammation in CKD, exacerbated by uremic toxins like indoxyl sulfate (IS).
• Indoxyl sulfate (IS) increases intestinal permeability, microbial translocation, and inflammatory responses, contributing to CKD progression.

Purpose of the Study:

• To investigate the therapeutic potential of plumericin against IS-induced intestinal impairment.
• To elucidate the molecular mechanisms by which plumericin counteracts IS effects in intestinal epithelial cells.

Main Methods:

• Utilized IEC-6 intestinal epithelial cells as an in vitro model.
• Exposed cells to indoxyl sulfate (IS) and treated with plumericin.
• Assessed effects on apoptosis, inflammation, oxidative stress, epithelial repair, and key molecular pathways (Nrf-2, NF-kB, AhR).

Main Results:

• Plumericin significantly reduced apoptosis and inhibited inflammation and oxidative stress in IS-treated cells.
• Plumericin promoted epithelial wound repair, Nrf-2 activation, and inhibited NF-kB and AhR activation induced by IS.
• These protective effects were also observed under conditions mimicking CKD's systemic inflammation.

Conclusions:

• Plumericin demonstrates significant protective effects against IS-induced intestinal damage.
• Plumericin acts through integrated mechanisms involving anti-inflammatory, antioxidant, and wound repair pathways.
• Plumericin shows promise as a therapeutic agent for intestinal dysfunction in chronic kidney disease.