# Carnosic Acid Protects against Bisphenol A-Induced NLRP3 Inflammasome Activation by Attenuating Oxidative Stress in Human Microglial Cells

## TL;DR

Carnosic acid from rosemary reduces BPA-induced inflammation and oxidative stress in human microglial cells.

## Contribution

This study shows carnosic acid protects against BPA-induced NLRP3 inflammasome activation via antioxidant mechanisms.

## Key findings

- CA reduced BPA-induced NLRP3 fluorescence and cleaved caspase-1 in microglial cells.
- CA attenuated BPA-induced oxidative stress and restored antioxidant enzyme expression.
- CA's protective effects were blocked by BSO, indicating a glutathione-dependent mechanism.

## Abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical commonly found in consumer products and is known to induce neuroinflammation and oxidative stress via microglial activation. Carnosic acid (CA), a phenolic diterpene from rosemary (Rosmarinus officinalis L.), has potent antioxidant and neuroprotective properties. This study investigated the protective effects of CA against BPA-induced neuroinflammation and oxidative stress in human HMC3 microglial cells. Firstly, BPA induced the expression of NLRP3 inflammasome–related proteins and increased NLRP3 fluorescence intensity. CA reduced the fluorescence intensity of NLRP3 and cleaved caspase-1 induced by BPA. CA also attenuated BPA-induced protein levels in the inflammasome, proinflammatory cytokines, and phosphorylated tau, as well as the transcription factors FoxO1 and p65. CA improved the effects in BPA-induced ROS level and reduced the expression of catalase, glutathione reductase, superoxide dismutase 2 (SOD2), glutathione peroxidase 1, heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf2), and UDP-glucuronosyltransferase 1A1 (UGT1A1). In addition, CA restored BPA-suppressed expression of UGT1A1 and SOD2 in the striatum of mice. L-Buthionine-sulfoximine (BSO) treatment abolished CA’s ability to counteract BPA-induced oxidative stress and inflammatory responses. These findings indicated that CA was associated with attenuation of BPA-induced NLRP3 inflammasome-related protein expression and downstream neuroinflammatory signaling by reducing oxidative stress in HMC3 cells.