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Phytochemistry. 2019 Aug;164:223-227. doi: 10.1016/j.phytochem.2019.04.002. Epub 2019 Jun 7.

Repurposing of ginseng extract as topoisomerase I inhibitor based on the comparative analysis of gene expression patterns.

Author information

1
College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
2
College of Korean Medicine, Wonkwang University, Iksan, Cheonbuk, 54538, Republic of Korea.
3
Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk, 54538, Republic of Korea; College of Korean Medicine, Wonkwang University, Iksan, Cheonbuk, 54538, Republic of Korea. Electronic address: host@wku.ac.kr.
4
College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: jinwoo.ch@khu.ac.kr.
5
College of Korean Medicine, Wonkwang University, Iksan, Cheonbuk, 54538, Republic of Korea. Electronic address: sklee@wku.ac.kr.

Abstract

Repositioning of plant extracts and chemical drugs can accelerate drug development. However, its success rate may depend on what the clue is for the repositioning. Recently, repositioning based on correction of unwarranted gene expression pattern has suggested the possibility of new drug development. Here, we designed a similar method for the repositioning of nutraceutical ginseng (Panax ginseng C.A.Mey.), which is one of the most validated natural therapeutic products for various diseases. We analyzed ginseng-induced gene expression profiles using the connectivity map algorithm, which is a database that connects diseases, chemical drugs, and gene expression. Ginseng was predicted to show the same effects as those of topoisomerase I inhibitors. In a subsequent in vitro assay, ginseng extract unwound coiled or supercoiled DNA, an effect comparable to that of the topoisomerase I inhibitor, camptothecin. Furthermore, ginseng extract induced synthetic lethality with suppression of the Werner syndrome gene. The collected data implicate ginseng as a candidate antitumor agent owing to its topoisomerase I inhibitory activity and further validate the usefulness of differentially expressed gene similarity-based repurposing of other natural products.

KEYWORDS:

Connectivity map; Panax ginseng C.A.Mey Araliaceae; Repurposing; Topoisomerase I inhibitor

PMID:
31181353
DOI:
10.1016/j.phytochem.2019.04.002
[Indexed for MEDLINE]

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