# Metabolome and transcriptome analyses provide insights into the podophyllotoxin content difference in different Sinopodophyllum hexandrum provenances

**Authors:** Wei Liu, Sensen Chen, Xiaoqiu Yuan, Zheng Zhang, Kai Duan, Longwei Li

PMC · DOI: 10.3389/fpls.2025.1722118 · Frontiers in Plant Science · 2026-01-05

## TL;DR

This study explores why the cancer-fighting compound podophyllotoxin varies in different regions of a medicinal plant, using genetic and chemical analysis.

## Contribution

The study identifies key genes, transcription factors, and transporters linked to podophyllotoxin content differences in Sinopodophyllum hexandrum.

## Key findings

- 2-ODD, SDH, and C3H are essential genes for podophyllotoxin content differences.
- WRKY and AP2/ERF-ERF are key transcription factors influencing podophyllotoxin levels.
- ABCE1 and ABCC2 are primary transporters associated with podophyllotoxin variation.

## Abstract

Sinopodophyllum hexandrum is a perennial herb medicinal plant and mainly distributes in high-altitude areas. Its rhizome is a primary material source for anticancer active ingredient podophyllotoxin (PTOX) production. The PTOX content was significantly different in rhizomes of different provenances, but this formation reason remains unclear. In this study, S. hexandrum provenances of ShaanXi (SX), GanSu (GS) and Tibet (XZ) were collected from the resource nursery of S. hexandrum. Through the combined analysis of non-targeted metabolomics and transcriptomics, candidate genes, transcription factors, and transporters significantly related to the PTOX content difference were screened to reveal the formation reason of the difference in PTOX content from different provenances. The results showed that deoxypodophyllotoxin synthase (2-ODD), secoisolariciresinol dehydrogenase (SDH) and coumarate 3-hydroxylase (C3H) were essential genes that lead to the PTOX content differences in S. hexandrum from different provenances, WRKY and AP2/ERF-ERF were considered to be key transcription factors, and ABCE1 and ABCC2 were the primary transporters. The results can provide a new perspective and excellent genes for revealing the cause of the different PTOX contents in S. hexandrum from different provenances.

## Linked entities

- **Genes:** SARDH (sarcosine dehydrogenase) [NCBI Gene 1757], LOC123224750 (cytochrome P450 98A2) [NCBI Gene 123224750], WRKY (probable WRKY transcription factor 33) [NCBI Gene 103865671], ABCE1 (ATP binding cassette subfamily E member 1) [NCBI Gene 6059], ABCC2 (ATP binding cassette subfamily C member 2) [NCBI Gene 1244]
- **Chemicals:** podophyllotoxin (PubChem CID 10607), deoxypodophyllotoxin (PubChem CID 345501), secoisolariciresinol (PubChem CID 65373)
- **Species:** Sinopodophyllum hexandrum (taxon 93608)

## Full-text entities

- **Chemicals:** PTOX (MESH:D011034)
- **Species:** Sinopodophyllum hexandrum (Himalayan mayapple, species) [taxon 93608]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12813045/full.md

## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12813045/full.md

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Source: https://tomesphere.com/paper/PMC12813045