ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1682504
This article is part of the Research TopicExtracts From Plants and Other Natural Sources: Application, Characterization, Optimization, and Their Use - Volume IIView all 3 articles
Parishin E from ginger-processed Gastrodia elata Bl. alleviates Rheumatoid Arthritis by regulating Histone 3 lactylation at H3K18la and H3K27la sites
Provisionally accepted
Kang Xu1*
Xinyue Liu1
Yijing Pan1Chenxi Deng1Meiliang Zhu1Dongmei Guo1
Jiaqin Wu1
Fan Feng1
Lianhong Pan2
Chunli Wang1- 1Hubei University of Chinese Medicine, Wuhan, China
- 2Chongqing Three Gorges Medical College, Chongqing, China
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Background: This study investigated the natural small molecule drug Parishinparacine E (PE) derived from the orchid plant Gastrodia elata Bl. (GEB). We evaluated the therapeutic effects of ginger-processedtreated Gastrodia elata Bl. (G-GEB) on rheumatoid arthritis (RA) and focused on paracine E to elucidate its potential regulatory mechanisms. Methods: An Sprague-Dawley rat model of rheumatoid arthritis was constructed to evaluate the pharmacological effects of G-GEB. Plant non-targeted metabolomics, serum non-targeted metabolomics, and RAW264.7 inflammation models elucidate Parishin E as the core anti-inflammatory component of G-GEB. Subsequently, transcriptomic and metabolomic analyses were performed to elucidate the molecular signaling mechanism of Parishin E in the treatment of RA. Results: G-GEB significantly improves RA, with 363 active compounds identified by untargeted metabolomics. PE, its main active component, affects cell glycolysis by downregulating HK2 and LDHA to inhibit macrophage polarization. PE also shows anti-inflammatory properties by suppressing H3 lactylation at H3K18la and H3K27la. Conclusion: PE in G-GEB exerts an RA ameliostatic effect by inhibiting macrophage polarization by regulating cellular glycolysis and by inhibiting the emulsification modification of histone H3 sites, specifically H3K18la and H3K27la. Therefore, PE is a promising drug candidate for the development of RA treatments.
Keywords: Rheumatoid arthritis, ginger-processedtreated Gastrodia elata Bl., Gastrodia elata Bl., non-targeted metabolomics, Glycolysis, H3 histone lactylation
Received: 09 Aug 2025; Accepted: 07 Oct 2025.
Copyright: © 2025 Xu, Liu, Pan, Deng, Zhu, Guo, Wu, Feng, Pan and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kang Xu, kangxu05@hbucm.edu.cn
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