Alisol B 23-Acetate Ameliorates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction by Inhibiting TLR4-NOX1/ROS...

Area of Science:

• Pharmacology
• Gastroenterology
• Cell Biology

Background:

• Alisol B 23-Acetate (AB23A), a triterpenoid from Alisma species, is known to regulate tight junction proteins.
• The precise mechanisms by which AB23A protects against intestinal barrier dysfunction are not fully understood.
• Intestinal barrier dysfunction is a critical issue in various gastrointestinal disorders.

Purpose of the Study:

• To evaluate the protective effects of AB23A on intestinal barrier dysfunction in lipopolysaccharide (LPS)-stimulated Caco-2 cells.
• To elucidate the underlying mechanisms of AB23A's protective action against LPS-induced barrier impairment.
• To investigate the role of the TLR4-NOX1/ROS signaling pathway in AB23A's effects.

Main Methods:

• Utilized LPS-stimulated Caco-2 cell monolayers as an in vitro model of intestinal barrier dysfunction.
• Assessed the effects of AB23A on pro-inflammatory cytokine production (IL-6, TNF-α, IL-1β).
• Investigated the impact of AB23A on tight junction protein expression (ZO-1, occludin), TLR4, NOX1, and reactive oxygen species (ROS) generation.
• Employed short hairpin RNA (shRNA) to silence TLR4 and NOX1 expression to determine their roles.

Main Results:

• AB23A significantly attenuated LPS-induced inflammation by reducing pro-inflammatory cytokines.
• AB23A prevented paracellular permeability and inhibited the disruption of tight junctions in LPS-treated Caco-2 cells.
• AB23A suppressed LPS-induced overexpression of TLR4 and NOX1, consequently reducing ROS generation.
• Silencing NOX1 diminished AB23A's positive effect on ZO-1 and occludin expression.
• Silencing TLR4 enhanced ZO-1 and occludin expression while reducing NOX1 expression and ROS generation.

Conclusions:

• AB23A ameliorates LPS-induced intestinal barrier dysfunction by inhibiting the TLR4-NOX1/ROS signaling pathway in Caco-2 cells.
• AB23A demonstrates potential therapeutic value in maintaining intestinal barrier integrity.
• Targeting the TLR4-NOX1/ROS pathway represents a viable strategy for managing intestinal barrier dysfunction.