# Exploring the Anti-Inflammatory Potential of Isoembigenin: A Flavonoid Glycoside from Piper aduncum L. – A Case Exploration through In Vitro, In Vivo, and In Silico Models

## TL;DR

This study explores how a compound from Piper aduncum L., called isoembigenin, reduces inflammation in macrophages and improves survival in a sepsis model.

## Contribution

The study demonstrates the anti-inflammatory effects of isoembigenin on macrophages and its protective role in a sepsis model.

## Key findings

- IEGN significantly suppressed TNF-α expression in LPS-stimulated RAW 264.7 macrophages.
- IEGN pre-treatment reduced proinflammatory cytokines and improved survival in a murine sepsis model.
- Molecular docking suggested potential interactions between IEGN and iNOS and COX-2.

## Abstract

Piper aduncum L. has long been used in traditional medicine for its notable antimicrobial, anti-diarrheal, and anti-inflammatory properties. Flavonoids are recognized as the principal bioactive constituents of this plant, among which isoembigenin (IEGN) has been shown to inhibit dendritic cell–mediated inflammatory responses. However, its effects on other immune cell types involved in inflammation remain unclear. In this study, we examined whether IEGN pre-treatment could attenuate macrophage activation triggered by lipopolysaccharide (LPS). Our results demonstrated that IEGN significantly suppressed TNF-α expression in RAW 264.7 macrophages upon LPS stimulation. Moreover, in a murine sepsis model, IEGN pre-treatment markedly reduced the production of proinflammatory cytokines, including TNF-α and IL-1β, shortly after LPS challenge. Importantly, IEGN administration substantially improved the survival rate of BALB/c mice subjected to endotoxin-induced shock. Finally, the molecular docking simulation was a hypothetical assessment of the interaction between IEGN and iNOS and COX-2. Taken together, these findings highlight the therapeutic potential of IEGN as a candidate for preventing inflammation driven by macrophage activation.