Non-enzymatic glycation mediated advanced glycation end products (AGEs) generation results in the pathogenesis of diabetic complications and atherosclerotic cardiovascular disease (ASCVD) which is greatly influenced by 3-hydroxy-3-methyl-glutaryl Co-A reductase (HMG-R) activity. HMG-R inhibitors, statins, are well known for reducing mortality and morbidity of ASCVD in patients with diabetes due to their pleiotropic effects independent of cholesterol lowering. Due to distinct chemical structures, various statins may play important role in the inhibition of AGEs mediated pathologies. Herein, we evaluated the anti-glycating potential of atorvastatin (AT), rosuvastatin (RT), pitavastatin (PT), fluvastatin (FT), simvastatin (ST) alone as well in combination with ezetimibe (EZ) and tocotrienol (TT) against d-ribose mediated BSA and LDL glycation by various physicochemical approaches. Our data suggested that AT, TT, RT, EZ, EZ-AT, and EZ-RT were able to substantially inhibit the AGEs formation via modulation of hyperchromicity, fluorogenic AGEs, % contribution of α-helix and β-sheets to protein secondary structure, amide-I band stretching, carbonyl and HMF content in Gly-BSA as well as Gly-LDL. On the basis of above findings, we concluded that HMG-R inhibitors and TT, alone or in combination with EZ, may be established as terrific therapeutic agents for the patients suffering from AGEs induced diabetic cum ASCVD complications.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.05.115 | DOI Listing |
RSC Med Chem
January 2023
Chemistry Department, Lomonosov Moscow State University GSP-1, Leninskie Gory 1/3 Moscow 119991 Russian Federation
Statins are effective 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R) inhibitors, which are successfully used for cardiovascular disease treatment. Statins' side effects are generally attributed to poor bioavailability and hepatoselectivity, which are closely related to their high lipophilicity. Targeted delivery of statins to the liver is considered as a way to reduce unwanted side effects.
View Article and Find Full Text PDFEXCLI J
January 2022
IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, U.P. 226026, India.
Atherosclerotic cardiovascular disease (ASCVD) stands amongst the leading causes of mortality worldwide and has attracted the attention of world's leading pharmaceutical companies in order to tackle such mortalities. The low-density lipoprotein-cholesterol (LDL-C) is considered the most prominent biomarker for the assessment of ASCVD risk. Distinct inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-R), the chief hepatic cholesterogenic enzyme, are being used since last seven decades to manage hypercholesterolemia.
View Article and Find Full Text PDFLife Sci
August 2020
IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow 226026, U.P., India. Electronic address:
Polydatin (PD) is a monocrystalline metabolite from the underground parts of Polygonum cuspidatum Sieb. et Zucc., a member of the Polygonaceae family, which has been traditionally used in Asian countries as both foodstuffs and medicine.
View Article and Find Full Text PDFLife Sci
October 2019
IIRC-5, Clinical Biochemistry & Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P., India. Electronic address:
Aims: Advanced glycation end products (AGEs) trigger intracellular reactive oxygen species (ROS) generation, activation of receptor for AGEs (RAGE) expression/functionality and RAGE-associated signalling pathways which influence the diabetic-cum-atherosclerotic complications, whereas, the atherosclerosis progression is greatly influenced by hepatic β-Hydroxy-β-methyl-glutaryl-Co-A reductase (HMG-R) activity. The present report was premeditated to uncover the regulatory role of HMG-R inhibitors and ezetimibe (EZ) in attenuating the LDL-AGEs-induced pathogenicity via targeting cellular-ROS and RAGE-associated signalling in HEK-293 cells.
Main Methods: The MTT assay was used to assess either the cytotoxic or cytoprotective impact of each HMG-R inhibitors, EZ, and LDL-AGEs, whereas, quantification of ROS was performed by DCFDA method.
Curr Diabetes Rev
August 2019
Clinical Biochemistry & Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P, India.
Introduction: Diabetes Mellitus (DM) acts as an absolute mediator of cardiovascular risk, prompting the prolonged occurrence, size and intricacy of atherosclerotic plaques via enhanced Advanced Glycation Endproducts (AGEs) formation. Moreover, hyperglycemia is associated with enhanced glyco-oxidized and oxidized Low-Density Lipoprotein (LDL) possessing greater atherogenicity and decreased the ability to regulate HMG-CoA reductase (HMG-R). Although aminoguanidine (AG) prevents the AGE-induced protein cross-linking due to its anti-glycation potential, it exerts several unusual pharmaco-toxicological effects thus restraining its desirable therapeutic effects.
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