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KMID : 0352720170410010103
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Journal of Ginseng Research
2017 Volume.41 No. 1 p.103 ~ p.112
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Enhanced antidiabetic efficacy and safety of compound K?β-cyclodextrin inclusion complex in zebrafish
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Nam Youn-Hee
Le Hoa Thi
Rodriguez Isabel
Kim Eun-Young
Kim Keon-Woo
Jeong Seo-Yule
Woo Sang-Ho
Lee Yeong-Ro
Castaneda Rodrigo
Hong Jin-Eui
Ji Min-Gun
Kim Ung-Jin
Hong Bin-Na
Kim Tae-Woo
Kang Tong-Ho
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Abstract
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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.
Conclusion: 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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KEYWORD
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β-cyclodextrin, adenosine triphosphate-sensitive potassium blocker, compound K, pancreatic islet, zebrafish larva
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