Metabolome and transcriptome analyses reveal quality change in the orange-rooted Salvia miltiorrhiza (Danshen) from cultivated field

Zhilai Zhan; Wentao Fang; Xiaohui Ma; Tong Chen; Guanghong Cui; Ying Ma; Liping Kang; Tiegui Nan; Huixin Lin; Jinfu Tang; Yan Zhang; Changjiangsheng Lai; Zhenli Ren; Yanan Wang; Yujun Zhao; Ye Shen; Ling Wang; Wen Zeng; Juan Guo; Luqi Huang

doi:10.1186/s13020-019-0265-6

Metabolome and transcriptome analyses reveal quality change in the orange-rooted Salvia miltiorrhiza (Danshen) from cultivated field

Chin Med. 2019 Oct 2:14:42. doi: 10.1186/s13020-019-0265-6. eCollection 2019.

Authors

Zhilai Zhan^#¹, Wentao Fang^#^{1

2}, Xiaohui Ma^{1

3}, Tong Chen¹, Guanghong Cui¹, Ying Ma¹, Liping Kang¹, Tiegui Nan¹, Huixin Lin¹, Jinfu Tang¹, Yan Zhang¹, Changjiangsheng Lai¹, Zhenli Ren⁴, Yanan Wang¹, Yujun Zhao¹, Ye Shen¹, Ling Wang¹, Wen Zeng¹, Juan Guo¹, Luqi Huang¹

Affiliations

¹ 1State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700 China.
² 2School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012 China.
³ 3College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Kunming, 650500 China.
⁴ Shandong Danhong Pharmaceutical Co., Ltd., Heze, 27400 Shandong China.

^# Contributed equally.

Abstract

Background: The dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known, traditional Chinese medicine. Tanshinones are active compounds that accumulate in the periderm, resulting in red-colored roots. However, lines with orange roots have been observed in cultivated fields. Here, we performed metabolome and transcriptome analyses to investigate the changes of orange-rooted Danshen.

Methods: Metabolome analysis was performed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof-MS) to investigate the metabolites variation between orange Danshen and normal Danshen. RNA sequencing and KEGG enrichment analysis were performed to analyzing the differentially expressed genes between orange-rooted and normal Danshen.

Results: In total, 40 lipophilic components were detected in metabolome analysis, and seven compounds were significantly decreased in the orange Danshen, including the most abundant active compounds, tanshinone IIA and tanshinone I in normal Danshen. Systematic analysis of transcriptome profiles revealed that the down-regulated genes related to catalytic dehydrogenation was not detected. However, two genes related to stress resistance, and four genes related to endoplasmic reticulum (ER)-associated degradation of proteins were up-regulated in orange Danshen.

Conclusions: Decreases in the content of dehydrogenated furan ring tanshinones such as tanshinone IIA resulted in phenotypic changes and quality degradation of Danshen. Transcriptome analysis indicated that incorrect folding and ER-associated degradation of corresponding enzymes, which could catalyze C₁₅-C₁₆ dehydrogenase, might be contributed to the decrease in dehydrogenated furan ring tanshinones, rather than lower expression of the relative genes. This limited dehydrogenation of cryptotanshinone and dihydrotanshinone I into tanshinones IIA and I products, respectively, led to a reduced quality of Danshen in cultivated fields.

Keywords: ER-associated degradation; Metabolome profiling; Salvia miltiorrhiza Bunge (Danshen); Tanshinones; mRNA expression profiling.