Liposome-encapsulated glycyrrhizin alleviates hyperglycemia and glycation-induced iron-catalyzed oxidative reactions in streptozotocin-induced diabetic rats

Abstract

Glycyrrhizin, a bioactive constituent of Glycyrrhiza glabra has been reported to ameliorate diabetes. Here, the effects of liposome-encapsulated glycyrrhizin on STZ-induced diabetes and associated oxidative stress were investigated. Wistar rats were grouped as control (NC, received placebo), diabetic (DC, STZ-induced), diabetic treated with free glycyrrhizin (DTG, 3 i.v. doses, 1.6 mg/0.5 ml), empty liposomes (DTl, 3 i.v. doses), and liposome-encapsulated glycyrrhizin (DTbd, 3 i.v. doses, 1.6 mg/0.5 ml). Serum glucose, insulin, intraperitoneal glucose tolerance test and glycohemoglobin were estimated. Free iron and iron-mediated oxidative stress were examined. Histological examinations of the kidney and liver were performed. Liposomal-glycyrrhizin treatment caused significant improvement of hyperglycemia (DC vs. DTbd p < .05), glucose intolerance (DC vs. DTG p < .01 and DC vs. DTbd p < .05), insulin (DC vs. DTG p < .1, DTbd vs. DC p < .05 and DTbd vs. DTG p < .1) and glycohemoglobin (DC vs. DTG p < .1 and DC vs. DTbd p < .05) levels in the DTbd group. Alleviation of free iron release (DC vs. DTbd p < .05), lipid peroxidation (DC + H₂O₂ vs. DTbd + H₂O₂ p < .05), deoxyribose (DC + H₂O₂ vs. DTbd + H₂O₂, p < .05), and DNA degradation occurred in the DTbd group. The abnormalities of the kidney and liver were abolished in the DTbd group. The inhibitory effects were more pronounced compared to free glycyrrhizin. Liposome-encapsulated glycyrrhizin treatment caused inhibition of diabetic complications through its antioxidant effects and can be exploited for effective treatment of diabetes.

Keywords:

• Diabetes
• oxidative stress
• liposome
• glycyrrhizin
• insulin

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data are incorporated into the article and its online supplementary material.

Acknowledgements

The author is indebted to Dr. Nirmalendu Das and his laboratory members, Biomembrane Division, Indian Institute of Chemical Biology, Kolkata, India for the preparation of the liposome-encapsulated glycyrrhizin. The author is indebted to Prof. Ashoke Ranjan Thakur, Dept. of Biophysics, Molecular Biology, and Bioinformatics, University of Calcutta for competent cells and plasmid DNA. The author is indebted to Prof. Utpal Chaudhuri, Dept. of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta for the statistical analysis. The author acknowledges the help and guidance of Dr. Manoj Kar of the Dept. of Biochemistry, NRS Medical College and Hospital, Kolkata. The author acknowledges the overall guidance of Prof. Chanchal Dasgupta of the Dept. of Biophysics, Molecular Biology and Bioinformatics, University College of Science and Technology, Calcutta University for the sonictor and liposome preparation. The author is indebted to Dr. Dibyendu Samanta of the Dept. of Biophysics, Molecular Biology and Bioinformatics, University College of Science and Technology, Calcutta University for the sonicator. The author acknowledges Dr. Rahul Singh of the Emami Ltd, for the QC datasheet, TLC and HPLC of the G. glabra extract, glycyrrhizin and glabridin. The author acknowledges Prof. Amar K. Chandra, Dept. of Physiology, Rajabazar Campus, University of Calcutta for the histopathological studies.

Additional information

Funding

This work was supported by the Council of Scientific and Industrial Research, New Delhi [Grant no. 38(1129)/03/EMRII]. S.S. received a Senior Research Fellowship from the Indian Council of Medical Research, New Delhi.