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

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• 作者：Youn Hee Nam¹ ; ^☆ ; Hoa Thi Le² ; ^☆ ; Isabel Rodriguez¹ ; Eun Young Kim¹ ; Keonwoo Kim¹ ; Seo Yule Jeong¹ ; Sang Ho Woo¹ ; Yeong Ro Lee¹ ; Rodrigo Castañ ; eda¹ ; Jineui Hong¹ ; Min Gun Ji³ ; Ung-Jin Kim¹ ; Bin Na Hong³ ; ⁴ ; Tae Woo Kim² ; ^{tw1275@khu.ac.kr} ; Tong Ho Kang¹ ; ³ ; ^{panjae@khu.ac.kr}
• 关键词：β-cyclodextrin ; adenosine triphosphate-sensitive potassium blocker ; compound K ; pancreatic islet ; zebrafish larva
• 刊名：Journal of Ginseng Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：41
• 期：1
• 页码：103-112
• 全文大小：3019 K
• 卷排序：41

文摘

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.MethodsIn 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.ResultsThe 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.ConclusionThe 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.