# 14-Deoxy-11,12-didehydroandrographolide Alleviates IL-1β-Induced Insulin Resistance by Modulating NOX2-Driven ROS Generation and Restoring Insulin Signaling in 3T3-L1 Adipocytes

## TL;DR

A compound from Andrographis paniculata reduces insulin resistance in fat cells by blocking oxidative stress and restoring insulin signaling.

## Contribution

The study reveals a novel mechanism by which deAND alleviates IL-1β-induced insulin resistance in adipocytes.

## Key findings

- DeAND inhibits NOX2-driven ROS production in IL-1β-stimulated adipocytes.
- DeAND restores IRS-1/AKT phosphorylation and glucose uptake impaired by IL-1β.
- DeAND suppresses ERK/JNK activation and oxidative stress to improve insulin signaling.

## Abstract

Obesity is closely associated with the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM), primarily due to dysfunctional adipose tissue expansion and the secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). 14-Deoxy-11,12-didehydroandrographolide (deAND), a major diterpenoid component of Andrographis paniculata, has demonstrated notable antioxidant and anti-inflammatory activities. This study aimed to investigate the protective effects and mechanisms of deAND against IL-1β-induced IR in 3T3-L1 adipocytes. Network pharmacology analysis indicated that deAND targets several IR-related signaling pathways, particularly the MAPK and IRS-1/AKT pathways. The experimental results show that IL-1β stimulated p67phox membrane translocation and reactive oxygen species (ROS) production, contributing to impaired insulin signaling by activating ERK and JNK and reducing IRS-1/AKT phosphorylation, which ultimately decreased insulin-stimulated glucose uptake. Pretreatment with deAND effectively inhibited NOX2-derived ROS generation, suppressed ERK/JNK activation, restored IRS-1/AKT phosphorylation, and reversed the reduction in glucose uptake caused by IL-1β. These findings suggest that deAND can alleviate IR by inhibiting NOX2-mediated oxidative stress, restoring insulin signaling and improving glucose uptake, highlighting its potential as a therapeutic agent for obesity-related IR.