Enhanced antidiabetic efficacy and safety of compound K⁄β-cyclodextrin inclusion complex in zebrafish
| Autor: | Isabel Rodriguez, Tong Ho Kang, Ung-Jin Kim, Keonwoo Kim, Seo Yule Jeong, Rodrigo Castañeda, Eun-Young Kim, Min Gun Ji, Jineui hong, Youn Hee Nam, Yeong Ro Lee, Sang Ho Woo, Bin Na Hong, Hoa Thi Le, Tae Woo Kim |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Biochemistry Genetics and Molecular Biology (miscellaneous) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Therapeutic index lcsh:Botany Internal medicine adenosine triphosphate-sensitive potassium blocker medicine Zebrafish geography geography.geographical_feature_category TUNEL assay biology Pancreatic islets compound K pancreatic islet Islet biology.organism_classification lcsh:QK1-989 Bioavailability 030104 developmental biology Endocrinology medicine.anatomical_structure Complementary and alternative medicine chemistry β-cyclodextrin zebrafish larva Toxicity Adenosine triphosphate 030217 neurology & neurosurgery Research Article Biotechnology |
| Zdroj: | Journal of Ginseng Research Journal of Ginseng Research, Vol 41, Iss 1, Pp 103-112 (2017) |
| ISSN: | 1226-8453 |
| DOI: | 10.1016/j.jgr.2016.08.007 |
| Popis: | 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 (K ATP ) 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 (EC 50 = 2.158μM) enhanced the recovery of pancreatic islets, compared to CK alone (EC 50 = 7.221μM), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK (LC 50 = 20.68μM) was less toxic than CK alone (LC 50 = 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. |
| Databáze: | OpenAIRE |
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