Methyl eugenol increases neural microcirculation to promote nerve repair by regulating endothelial cell and Schwann cell communication via Ptn/Sdc4.

Overview

Authors: Zifeng Zhuang¹, Shaozi Lin¹, Yixuan Li², Xiaokang Xie¹, Hongling Chen¹, Yuting Hao¹, Lan Lin¹, Guoping Zhao¹, Di Zhang¹

ORCID iDs: Di Zhang

College of Traditional Chinese Medicine, Jinan University, Guangzhou, China
Guangzhou Medical University Affiliated Traditional Chinese Medicine Hospital, Guangzhou, China

Institutions: Jinan University (China); Guangzhou University of Chinese Medicine (China); Guangzhou University (China); Guangdong Provincial Hospital of Chinese Medicine (China); Guangzhou Medical University (China)

Journal: Natural products and bioprospecting, volume 16, issue 1, article 91

Dates: received 1 December 2025; accepted 23 February 2026; published online 2 October 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1007/s13659-026-00617-z · PMID 42823554 · PMCID PMC13631155 · OpenAlex W7215081049

Open access: diamond, a free copy (OpenAlex)

Status: data only (how the code is found and verified)

Categories: rat (organism), cellular / molecular (subfield)

Methods: Statistics, Smoothing, state filtering, decompositions

Keywords: Methyl eugenol, Schwann cells, Endothelial cells, Ptn, Sdc4

Topic: Nerve injury and regeneration (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex

Funding: China Postdoctoral Science Foundation (2024M751136, GZC20230979, 2023TQ0135); National Natural Science Foundation of China (82405081, 82274294)

Citations: not cited yet (Europe PMC); 38 references in the paper

Abstract

Neuromicrocirculatory disorders often accompany nerve injury. Improving neural microcirculation can promote the repair of injured nerves. Methyl eugenol is a major bioactive component of Asarum heterotropoides and has been reported to exert analgesic effects in chronic pain. This study aimed to demonstrate that methyl eugenol can enhance neural microcirculation and thereby promote nerve repair. A combination of single-cell sequencing and mRNA sequencing revealed that pleiotrophin (Ptn)/syndecan-4 (Sdc4) is vital for coupling between endothelial cells and Schwann cells. A total of 32 rats were randomly assigned to four groups, namely, the Sham, chronic constriction injury (CCI) 7d, CCI 14d, and CCI 21d groups, to assess whether endothelial Schwann cell communication is diminished following CCI. After an endothelial cell–Schwann cell coculture system was established, methyl eugenol, Ptn siRNA, and Sdc4 siRNA were administered. In a separate experiment, 32 SD rats were randomly divided into four experimental groups: the Sham, CCI, ibuprofen, and methyl eugenol groups. CellChat analysis revealed that nerve injury reduced the degree of communication between endothelial cells and Schwann cells, especially communication via Ptn/Sdc4. CCI disrupted neural microcirculation, lowered Ptn levels, and increased Sdc4 expression. In cell experiments, methyl eugenol promoted rat aortic endothelial cells tube formation and increased the release of Ptn, which acted on Sdc4 in rat Schwann cells (RSC96) to promote migration, but did not directly promote RSC96 cell migration in the absence of endothelial cell–derived factors. Treatment with methyl eugenol increased neural microcirculation to promote nerve repair in rats subjected to CCI. In addition, methyl eugenol further increased Ptn levels. CCI led to neural microcirculatory dysfunction and nerve injury. Methyl eugenol promote nerve repair by enhancing neural microcirculation through regulation of endothelial cell and Schwann cell communication via Ptn/Sdc4.

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Data

Datasets cited

geo:GSE146958, at NCBI GEO; found in the text, “Bioinformatics analysis of single-cell…”

Availability of data and materials

The datasets supporting this study are accessible from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 6 October 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 2 funders, 38 references.

Cite

This paper

Zhuang, Z., Lin, S., Li, Y., Xie, X., Chen, H., Hao, Y., Lin, L., Zhao, G., & Zhang, D. (2026). Methyl eugenol increases neural microcirculation to promote nerve repair by regulating endothelial cell and Schwann cell communication via Ptn/Sdc4. Natural products and bioprospecting, 16(1), 91. https://doi.org/10.1007/s13659-026-00617-z

BibTeX

@article{zhuang2026methyl, author = {Zhuang, Zifeng and Lin, Shaozi and Li, Yixuan and Xie, Xiaokang and Chen, Hongling and Hao, Yuting and Lin, Lan and Zhao, Guoping and Zhang, Di}, title = {{Methyl eugenol increases neural microcirculation to promote nerve repair by regulating endothelial cell and Schwann cell communication via Ptn/Sdc4}}, journal = {Natural products and bioprospecting}, year = {2026}, month = oct, volume = {16}, number = {1}, pages = {91}, publisher = {Springer}, issn = {2192-2195}, doi = {10.1007/s13659-026-00617-z}, url = {https://doi.org/10.1007/s13659-026-00617-z}, pmid = {42823554}, pmcid = {PMC13631155} }

RIS

TY - JOUR AU - Zhuang, Zifeng AU - Lin, Shaozi AU - Li, Yixuan AU - Xie, Xiaokang AU - Chen, Hongling AU - Hao, Yuting AU - Lin, Lan AU - Zhao, Guoping AU - Zhang, Di TI - Methyl eugenol increases neural microcirculation to promote nerve repair by regulating endothelial cell and Schwann cell communication via Ptn/Sdc4 T2 - Natural products and bioprospecting J2 - Nat Prod Bioprospect PY - 2026 DA - 2026/10/02 VL - 16 IS - 1 SP - 91 SN - 2192-2195 PB - Springer DO - 10.1007/s13659-026-00617-z UR - https://doi.org/10.1007/s13659-026-00617-z LA - en ER -

CSL-JSON

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