title: Enhanced antidiabetic efficacy and safety of compound K⁄β-cyclodextrin inclusion complex in zebrafish.
abstract: BACKGROUND
  20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic β-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability.
  
  
  METHODS
  In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with β-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK.
  
  
  RESULTS
  The CD-CK conjugate (EC50= 2.158μM) enhanced the recovery of pancreatic islets, compared to CK alone (EC50= 7.221μM), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK (LC50= 20.68μM) was less toxic than CK alone (LC50= 14.24μM). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively.
  
  
  CONCLUSIONS
  The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Nam
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi, Seoul, Korea.
authors.forename: Hoa Thi
authors.initials: HT
authors.lastname: Le
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodriguez
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Keonwoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Seo Yule
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Woo
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Yeong Ro
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Castañeda
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Jineui
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Min Gun
authors.initials: MG
authors.lastname: Ji
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Ung-Jin
authors.initials: UJ
authors.lastname: Kim
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea; Department of Audiology, Nambu University, Gwangju, Seoul, Korea.
authors.forename: Bin Na
authors.initials: BN
authors.lastname: Hong
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi, Seoul, Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea; Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Seoul, Korea.
authors.forename: Tong Ho
authors.initials: TH
authors.lastname: Kang
keywords: adenosine triphosphate-sensitive potassium blocker; compound K; pancreatic islet; zebrafish larva; β-cyclodextrin