PUBLICATION

Enhanced antidiabetic efficacy and safety of compound K⁄β-cyclodextrin inclusion complex in zebrafish

Authors
Nam, Y.H., Le, H.T., Rodriguez, I., Kim, E.Y., Kim, K., Jeong, S.Y., Woo, S.H., Lee, Y.R., Castañeda, R., Hong, J., Ji, M.G., Kim, U.J., Hong, B.N., Kim, T.W., Kang, T.H.
ID
ZDB-PUB-170127-3
Date
2017
Source
Journal of ginseng research   41: 103-112 (Journal)
Registered Authors
Keywords
adenosine triphosphate-sensitive potassium blocker, compound K, pancreatic islet, zebrafish larva, β-cyclodextrin
MeSH Terms
none
PubMed
28123328 Full text @ J Ginseng Res
Abstract
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.
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.
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.
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.
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