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. 2017 Jun 13;22(6):986.
doi: 10.3390/molecules22060986.

Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents

Da Hye Kim  1 , Hyun Ah Jung  2 , Hee Sook Sohn  3 , Jin Woong Kim  4 , Jae Sue Choi  5
Affiliations

Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents

Da Hye Kim et al. Molecules. .

Abstract

The therapeutic properties of Epimediumkoreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer's disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its deglycosylated icaritin and glycosylated flavonoids (icaeriside II, epimedin A, epimedin B, and epimedin C) were evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. The results show that icaritin and icariside II exhibit potent inhibitory activities, with 50% inhibition concentration (IC50) values of 11.59 ± 1.39 μM and 9.94 ± 0.15 μM against PTP1B and 74.42 ± 0.01 and 106.59 ± 0.44 μM against α-glucosidase, respectively. With the exceptions of icaritin and icariside II, glycosylated flavonoids did not exhibit any inhibitory effects in the two assays. Enzyme kinetics analyses revealed that icaritin and icariside II demonstrated noncompetitive-type inhibition against PTP1B, with inhibition constant (Ki) values of 11.41 and 11.66 μM, respectively. Moreover, molecular docking analysis confirmed that icaritin and icariside II both occupy the same site as allosteric ligand. Thus, the molecular docking simulation results were in close agreement with the experimental data with respect to inhibition activity. In conclusion, deglycosylated metabolites of icariin from E. koreanum might offer therapeutic potential for the treatment of type 2 diabetes mellitus.

Keywords: Epimedium koreanum Nakai; PTP1B; icariin metabolite; molecular docking simulation.; α-glucosidase.

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Conflict of interest statement

The authors declare that they have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
(a) Protein tyrosine phosphatase1B (PTP1B); and (b) α-glucosidase inhibitory activities of the MeOH extract from aerial parts of E. koreanum. Error bar indicates standard error of the mean (SEM).
Figure 2
Figure 2
Chemical structures of the compounds.
Figure 3
Figure 3
Dixon and Lineweaver–Burk plots of the inhibition of PTP1B by icaritin and icariside II. The results showed the effects of the presence of different concentrations of the substrate for: (a) icaritin; and (c) icariside II; and the effect of the presence of different concentration of: (b) icaritin; and (d) icariside II.
Figure 4
Figure 4
Molecular docking of PTP1B inhibition by compounds (compound 23, compound 2, icaritin and icariside II).
Figure 5
Figure 5
Molecular docking models for PTP1B inhibition of: (a) compound 2; (b) icaritin; and (c) icariside II.
See this image and copyright information in PMC

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