# Resveratrol Alleviates Effects of LPS on Estrogen Synthesis, Oxidative Stress, Inflammation, and Pyroptosis of Goat Granulosa Cells by Activating the PPARG/NRF2/HO-1 Signaling Pathway

**Authors:** Jie Zhao, Xianyi Zhou, Zhen Cang, Xin Liu, Muhammad Tariq, Dagan Mao

PMC · DOI: 10.3390/antiox14111300 · 2025-10-29

## TL;DR

Resveratrol helps protect goat granulosa cells from LPS damage by activating a specific signaling pathway, reducing inflammation and oxidative stress.

## Contribution

The study reveals a novel mechanism by which resveratrol alleviates LPS-induced injury via the PPARG/NRF2/HO-1 pathway in goat granulosa cells.

## Key findings

- Resveratrol reduced LPS-induced oxidative stress and inflammation in goat granulosa cells.
- Resveratrol's protective effects were blocked by a PPARG antagonist, confirming pathway involvement.
- The PPARG/NRF2/HO-1 pathway was identified as a key mediator of resveratrol's actions.

## Abstract

This study aims to investigate the effect and mechanism of resveratrol (RES) on lipopolysaccharide (LPS)-induced injury in goat granulosa cells (GCs). First, the appropriate time and concentration were screened for LPS (4 μg/mL, 12 h), RES (1 μM, 6 h), and GW9662 (an antagonist of PPARG, 1 μM, 12 h) through CCK8 and RT-qPCR. Then, cells were treated with LPS, RES, or/and GW9662, to examine steroidogenesis, inflammation, oxidative stress, and pyroptosis by RIA, RT-qPCR, WB, flow cytometry, and IF, respectively. Results showed that RES inhibited LPS-induced increases in MDA content, ROS production, gene expressions of IL-1β, NLRP3, Caspase1, and GSDMD, as well as protein levels of IL-1β, and GSDMD, accompanied by decreases in SOD activity, T-AOC and E2 content, gene expressions of SOD, CYP19A1, and HSD3B, and protein levels of SOD and HSD3B. Furthermore, RES inhibited LPS-induced decreases in PPARG, NRF2, and HO-1 gene expressions and protein levels. However, GW9662 could block all the alleviating effects of RES on LPS. In conclusion, RES regulates the effects of LPS on hormone secretion, inflammation, oxidative stress, and pyroptosis by modulating the PPARG/NRF2/HO-1 pathway, providing a new theoretical basis for improving goat reproduction.

## Linked entities

- **Genes:** PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468], GABPA (GA binding protein transcription factor subunit alpha) [NCBI Gene 2551], HMOX1 (heme oxygenase 1) [NCBI Gene 3162], IL1B (interleukin 1 beta) [NCBI Gene 3553], NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548], Caspase1 (caspase-1) [NCBI Gene 692604], GSDMD (gasdermin D) [NCBI Gene 79792], SOD1 (superoxide dismutase 1) [NCBI Gene 6647], CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588], HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) [NCBI Gene 3283]
- **Proteins:** IL1B (interleukin 1 beta), GSDMD (gasdermin D), SOD1 (superoxide dismutase 1), HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1)
- **Chemicals:** resveratrol (PubChem CID 5056), GW9662 (PubChem CID 644213)

## Full-text entities

- **Genes:** CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, HSD3B1 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) [NCBI Gene 3283] {aka 3BETAHSD, HSD3B, HSDB3, HSDB3A, SDR11E1}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, GSDMD (gasdermin D) [NCBI Gene 79792] {aka DF5L, DFNA5L, FKSG10, GSDMDC1}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}
- **Diseases:** Inflammation (MESH:D007249)
- **Chemicals:** E2 (MESH:D004958), GW9662 (MESH:C457499), LPS (MESH:D008070), RES (MESH:D000077185), ROS (-), MDA (MESH:D015104)
- **Cell lines:** Goat Granulosa — Bos taurus (Bovine), Spontaneously immortalized cell line (CVCL_6572)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12649358/full.md

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Source: https://tomesphere.com/paper/PMC12649358