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Contribution of aorta glycosaminoglycans and PCSK9 to hyperlipidemia in experimental rabbits: the role of 10-dehdrogingerdione as effective modulator

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Abstract

10-Dehydrogingerdione (10-DHGD) was previously reported to possess a hypolipidemic, anti-inflammatory and anti-oxidant properties in hyperlipidemic rabbit model. In this study, we investigated a possible new role for 10-DHGD in modulating atherogenic lipid profile by targeting proprotein convertase subtilisin kexin-9 (PCSK-9). Cholesterol (0.2% w/w)-fed rabbits received either atorvastatin (20 mg/kg) or 10-DHGD (10 mg/kg) for 12 weeks along with cholesterol feeding (HCD). Lipid profile, serum PCSK-9 and macrophage migration inhibitory factor (MIF), and aorta level of tumor necrosis factor-alpha (TNF-α) and glycosaminoglycans (GAGs) were measured. HCD-fed rabbits revealed an atherogenic lipid profile along with increased serum level of PCSK-9 (p < 0.001) and increased serum MIF and aortic TNF-α and GAGs (p < 0.001). 10-DHGD administration to HCD-fed rabbits prevented this atheogenicity by modulating the release of PCSK-9, inflammation extent (serum MIF and aortic TNF-α) and GAGs. These results provide new insights on the hypolipidemic potential of 10-DHGD. The effects of 10-DHGD was superior to that of atorvastatin in most studied parameters modulating atherogenicity. 10-DHGD is found to be able to suppress the release of PCSK-9, decrease aortic expression of GAGs in cholesterol-fed rabbits and halt the inflammation extent. These effects may provide new insights on the hypolipidemic potential of 10-DHGD.

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Acknowledgements

Authors would like to acknowledge the support given by Faculty of Pharmacy, Zagazig University for using Biotechnology Research and Pathological Markers laboratory and animal unit facilities. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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  1. Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

    Mohamed M. Elseweidy, Sahar E. Elswefy, Nahla N. Younis & Shaden Tarek

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  2. Sahar E. Elswefy
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MME is the principle investigator suggested the research point. STA and NNY carried out the experiments, performed statistical analysis and wrote the manuscript. MME and SEE revised the results and the manuscript. All authors revised and approved the manuscript for submission.

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Correspondence to Mohamed M. Elseweidy.

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Elseweidy, M.M., Elswefy, S.E., Younis, N.N. et al. Contribution of aorta glycosaminoglycans and PCSK9 to hyperlipidemia in experimental rabbits: the role of 10-dehdrogingerdione as effective modulator. Mol Biol Rep 46, 3921–3928 (2019). https://doi.org/10.1007/s11033-019-04836-1

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