# Computational-experimental study reveals direct target and bioactives of Ajania fruticulosa against NAFLD via TLR2/NF-κB/PPAR-γ signaling

## TL;DR

A study finds that Ajania fruticulosa extract and its compounds help treat fatty liver disease by targeting specific biological pathways.

## Contribution

The study identifies specific bioactive compounds and their direct interaction with TLR2 in treating NAFLD.

## Key findings

- WEAF reduces obesity, lipid accumulation, liver injury, and inflammation in NAFLD mice.
- Glycitein and isorhapontigenin directly bind to TLR2 to modulate NF-κB/PPAR-γ signaling.
- Anti-NAFLD effects of the compounds are abolished by TLR2 agonist Pam3CSK4.

## Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with limited treatment options. This study investigated the therapeutic potential of water extract of Ajania fruticulosa (WEAF) against NAFLD in cellular and animal models. WEAF significantly attenuated obesity, lipid accumulation, liver injury, and inflammation in NAFLD mice. Next, UPLC-MS/MS-based network pharmacology and molecular biology revealed that WEAF alleviated NAFLD by TLR2-mediated MYD88/NF-κB and SREBP1/PPAR-γ pathways, with 3,4-dihydroxyphenylpropionic acid, glycitein, and isorhapontigenin identified as the primary bioactive compounds. Finally, molecular docking, molecular dynamics, drug affinity responsive target stability, and cellular thermal shift assay confirmed that glycitein and isorhapontigenin directly bind to TLR2 to modulate the NF-κB/PPAR-γ signaling, and their anti-NAFLD effects were abolished by TLR2 agonist Pam3CSK4. In conclusion, WEAF and its key active compounds, glycitein and isorhapontigenin, effectively ameliorate obesity-induced NAFLD via the NF-κB/PPAR-γ signaling pathway by targeting TLR2, supporting their potential as therapeutic target and agents for NAFLD.