Anti‑inflammatory and anti‑migratory properties of wild‑grape‑derived &epsilon;‑viniferin in human endometrial cells:&nbsp;<br />A potential therapy for endometriosis

Lin,Yinzhi; Naiki,Yoshikazu; Kojima,Shiori; Hakamata,Masatoshi; Fukatsu,Hitomi; Hasegawa,Yoshiaki; Wakatsuki,Akihiko; Koide,Naoki; Umezawa,Kazuo

doi:10.3892/mmr.2025.13648

Anti‑inflammatory and anti‑migratory properties of wild‑grape‑derived ε‑viniferin in human endometrial cells:
A potential therapy for endometriosis

Authors:
- Yinzhi Lin
- Yoshikazu Naiki
- Shiori Kojima
- Masatoshi Hakamata
- Hitomi Fukatsu
- Yoshiaki Hasegawa
- Akihiko Wakatsuki
- Naoki Koide
- Kazuo Umezawa
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Affiliations: Department of Molecular Target Medicine, Aichi Medical University, Nagakute, Aichi 480‑1195, Japan, Department of Microbiology, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464‑8650, Japan, Fukuyu Medical Institute, Fukuyu Medical Corporation, Nisshin, Aichi 470‑0103, Japan, Department of Obstetrics and Gynecology, Aichi Medical University, Nagakute, Aichi 480‑1195, Japan, Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 480‑1195, Japan
Published online on: August 7, 2025 https://doi.org/10.3892/mmr.2025.13648
Article Number: 283
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometriosis is a chronic gynecological disorder characterized by the ectopic growth and proliferation of endometrial tissue outside the uterine cavity, leading to inflammation. Although low‑dose contraceptive pills are widely used for its treatment, these therapies are associated with side effects and are contraindicated in women trying to conceive. ε‑viniferin is a resveratrol dimer found in wild grapes (Ampelopsis brevipedunculata) with demonstrated antioxidant properties and an anti‑migratory effect in lung cancer cells. Because abnormal cell migration is a key process in endometriosis, we hypothesized that ε‑viniferin could also exhibit anti‑migratory effects in endometriotic cells, which remain to be elucidated. To test this hypothesis, the present study investigated the anti‑inflammatory and anti‑endometriotic effects of ε‑viniferin and wild‑grape extract. RAW264.7 and THP‑1 were used to evaluate the anti‑inflammatory effects of wild‑grape extract and ε‑viniferin by assessing cytotoxicity; nitric oxide (NO), reactive oxygen species and interleukin‑6 (IL‑6) production; and NF‑κB activity. Additionally, human endometrial stromal cells (HESCs) were used to investigate the anti‑endometriotic effects of ε‑viniferin, including its impact on cell migration, invasion and gene expression, using PCR array analysis. Both ε‑viniferin and wild‑grape extract significantly reduced lipopolysaccharide‑induced NO and IL‑6 production, indicating an anti‑inflammatory activity. Inhibition of NF‑κB activity at the cellular level further supported these findings. Moreover, both ε‑viniferin and wild‑grape extract effectively suppressed the migration and invasion of HESCs, indicating their potential to alleviate endometriosis symptoms. These findings suggest that ε‑viniferin is a promising therapeutic candidate for endometriosis, exhibiting both anti‑inflammatory and anti‑migratory effects. Our results present a novel approach for developing effective anti‑endometriotic therapies.

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