# Panax notoginseng Saponins Ameliorate High‐Fat Diet‐Induced Liver Injury via Mechanisms Involving TLR4‐Mediated Signaling and Lipid Metabolism

## TL;DR

Panax notoginseng saponins reduce liver damage from high-fat diets by reducing inflammation and improving lipid balance through TLR4 signaling.

## Contribution

The study reveals that PNS protects the liver by suppressing TLR4-mediated NF-κB and MAPK pathways, improving lipid metabolism.

## Key findings

- PNS supplementation improved serum lipid profiles and reduced liver inflammation in mice on a high-fat diet.
- PNS suppressed TLR4/MyD88-mediated NF-κB and MAPK pathways in both mice and HepG2 cells.
- PNS's protective effects were not additive to a TLR4 inhibitor, suggesting shared mechanisms.

## Abstract

Panax notoginseng saponins (PNS), the primary bioactive constituents derived from the traditional herb Panax notoginseng, have been used in nutritional supplements. However, their molecular mechanisms against hyperlipidemia‐induced liver injury remain to be fully elucidated. In this study, supplementation with PNS (200 mg/kg diet) for 12 weeks significantly ameliorated high‐fat diet (HFD)‐induced liver injury in C57BL/6J mice, as evidenced by improved serum lipid profiles and attenuated hepatic oxidative stress and inflammation. Lipidomics analysis indicated that PNS administration restored hepatic lipid homeostasis, particularly by normalizing dysregulated triglycerides. Mechanistically, PNS markedly suppressed the activation of key inflammatory signaling pathways, including both the TLR4/MyD88‐mediated NF‐κB and MAPK (ERK, JNK, p38) cascades. Complementary in vitro experiments in LPS‐stimulated HepG2 cells confirmed that PNS attenuated cellular injury and downregulated these pathways. Notably, the protective effect of PNS was not additive to that of the specific TLR4 inhibitor TAK‐242, indicating a functional convergence on the TLR4 signaling axis. Collectively, these findings demonstrate that PNS protects against HFD‐induced liver injury by improving lipid metabolism and attenuating hepatic inflammation via mechanisms involving the suppression of TLR4‐mediated NF‐κB and MAPK signaling, providing a refined mechanistic basis for its application as a dietary supplement in metabolic liver health.

Panax notoginseng saponins (PNS) ameliorate high‐fat diet‐induced liver injury by modulating the LPS‐TLR4/MyD88 axis. This leads to the concurrent suppression of NF‐κB and MAPK signaling, which reduces oxidative stress and inflammation while improving lipid metabolism.