Methyl 3,4-dihydroxybenzoate alleviates oxidative damage in granulosa cells by activating Nrf2 antioxidant pathway

Shishi Li, Yuhang Fan, Chongyi Shu, Yier Zhou, Jing Shu
Journal of ovarian research · 2024 · vol. 17(1) , pp. 87 · doi:10.1186/s13048-024-01412-5 · PMID:38664755 · PMC11044314 · W4395464450
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Methyl 3,4-dihydroxybenzoate (MDHB) protects granulosa cells from oxidative damage and apoptosis by activating the Nrf2 antioxidant pathway, improving mitochondrial function and reducing reactive oxygen species.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

The paper investigated oxidative stress in granulosa cells from women with endometriosis-associated infertility and tested whether methyl 3,4-dihydroxybenzoate (MDHB) can protect human granulosa cells from oxidative damage. Using granulosa cells collected from 41 Han infertility patients (20 controls with tubal or male-factor infertility and 21 with laparoscopically visible endometriosis lesions) and a granulosa-like KGN cell line challenged with tert-butyl hydroperoxide (TBHP), the authors found that endometriosis granulosa cells had higher oxidative stress and apoptosis markers, and that MDHB reduced TBHP-induced ROS, mitochondrial superoxide, apoptosis/DNA fragmentation, and mitochondrial membrane potential disruption. Mechanistically, MDHB was reported to inhibit oxidative stress damage by promoting Nrf2-mediated antioxidant activity, including upregulation of antioxidant-related genes and proteins (e.g., SOD1, NQO1, GCLC, and Nrf2 signaling). A key caveat is that functional antioxidant/anti-apoptotic effects were largely demonstrated in vitro in the KGN model rather than directly in patients, and the excerpted methods/results do not fully detail in vivo outcomes. This paper is centrally about endometriosis — it links endometriosis to oxidative stress in granulosa cells and tests MDHB’s Nrf2-driven antioxidant protection in that context.

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Abstract

Oxidative damage induced granulosa cells (GCs) apoptosis was considered as a significant cause of compromised follicle quality, antioxidants therapy has emerged as a potential method for improving endometriosis pregnancy outcomes. Here, we found that GCs from endometriosis patients show increased oxidative stress level. Methyl 3,4-dihydroxybenzoate (MDHB), a small molecule compound that is extracted from natural plants, reversed tert-butyl hydroperoxide (TBHP) induced GCs oxidative damage. Therefore, the aim of this study was to assess the protective effect of MDHB for GCs and its potential mechanisms. TUNEL staining and immunoblotting of cleaved caspase-3/7/9 showed MDHB attenuated TBHP induced GCs apoptosis. Mechanistically, MDHB treatment decreased cellular and mitochondria ROS production, improved the mitochondrial function by rescuing the mitochondrial membrane potential (MMP) and ATP production. Meanwhile, MDHB protein upregulated the expression of vital antioxidant transcriptional factor Nrf2 and antioxidant enzymes SOD1, NQO1 and GCLC to inhibited oxidative stress state, further beneficial to oocytes and embryos quality. Therefore, MDHB may represent a potential drug candidate in protecting granulosa cells in endometriosis, which can improve pregnancy outcomes for endometriosis-associated infertility.

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Condition tags

endometriosisinfertility

MeSH descriptors

Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants Antioxidants

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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