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

Abstract

Background20(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.

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

“…In another study, beta-cyclodextrin-conjugated CK (β-CD) was used to modulate diabetes against an alloxan-induced zebrafish model. The recovery of affected pancreatic islets in CD-CK conjugate was significantly higher (EC 50 = 2.16 μM) than in CK (EC 50 = 7.22 μM) [ 72 ]. Furthermore, the protective effect of CK on diabetic nephropathy in HFD/ streptozotocin-induced mice has been demonstrated through significant reduction of oxidative stress and down-regulating expressions of NADPH oxidase (Nox)-1 and-4 proteins.…”

Panax ginseng (Korea Red Ginseng) repairs diabetic sensorineural damage through promotion of the nerve growth factor pathway in diabetic zebrafish

“…First, we established diabetic sensorineural damage in the zebrafish using alloxan, which is a well known experimental diabetogenic agent that causes pancreatic β-cell necrosis leading to a decreased β-cell mass and consequently an inhibition of insulin secretion. Moreover, we previously reported alloxan-induced diabetic zebrafish [27], [28]. To establish diabetic sensorineural damage in zebrafish, we confirmed neuromast presence in zebrafish using YO-PRO, which is a fluorescent dye for staining hair cells [23].…”

Flavonoid 8-O-Glucuronides from the Aerial Parts of Malva verticillata and Their Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish

“…PI size was 40.2% lower ( p < 0.0001) in the AX treatment group than in the normal group ( Figure 3 ). According to this model, after the exposure to AX, an enhanced recovery from that damage could be observed after treating the zebrafish with some Coms or extracts, the GLM is used as a positive control, since it is a well-known antidiabetic drug, and like the AX, has also been proven in the zebrafish model [ 30 , 31 ]. GLM was used as a positive control, as it promotes insulin secretion by closing the K ATP channel [ 32 ].…”