Analyses of the possible anti-tumor effect of yokukansan

Cheolsun Han, Miho Kawata, Yusuke Hamada, Takashige Kondo, Junna Wada, Katsunori Asano, Hitoshi Makabe, Katsuhide Igarashi, Naoko Kuzumaki, Michiko Narita, Hiroyuki Kobayashi, Minoru Narita

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The Kampo medicine yokukansan (YKS) has a wide variety of properties such as anxiolytic, anti-inflammatory and analgesic effects, and is also thought to regulate tumor suppression. In this study, we investigated the anti-tumor effect of YKS. We used Lewis lung carcinoma (LLC)-bearing mice that were fed food pellets containing YKS and then performed a fecal microbiota analysis, a microarray analysis for microRNAs (miRNAs) and an in vitro anti-tumor assay. The fecal microbiota analysis revealed that treatment with YKS partly reversed changes in the microbiota composition due to LLC implantation. Furthermore, a miRNA array analysis using blood serum showed that treatment with YKS restored the levels of miR-133a-3p/133b-3p, miR-1a-3p and miR-342-3p following LLC implantation to normal levels. A TargetScan analysis revealed that the epidermal growth factor receptor 1 signaling pathway is one of the major target pathways for these miRNAs. Furthermore, treatment with YKS restored the levels of miR-200b-3p and miR-200c-3p, a recognized mediator of cancer progression and controller of emotion, in the hypothalamus of mice bearing LLC. An in vitro assay revealed that a mixture of pachymic acid, saikosaponins a and d and isoliquiritigenin, which are all contained in YKS, exerted direct and additive anti-tumor effects. The present findings constitute novel evidence that YKS may exert an anti-tumor effect by reversing changes in the fecal microbiota and miRNAs circulating in the blood serum and hypothalamus, and the compounds found in YKS could have direct and additive anti-tumor effects.

Original languageEnglish
Pages (from-to)468-479
Number of pages12
JournalJournal of Natural Medicines
Volume73
Issue number3
DOIs
Publication statusPublished - 14-06-2019

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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