Targeting selected diabetes-associated risks of atherogenesis with Bauhinia bowkeri stem bark extracts

Abstract

Atherosclerosis is the main underlying cause of diabetes-associated cardiovascular disease mortalities. Persistent hyperglycemia upregulates other glucose metabolising pathways such as polyol and protein glycation pathways. These pathways contribute to the AGEs formation and ROS production. AGEs and ROS can modify key proteins, including low-density lipoprotein (LDL). LDL’s oxidative modification is the major step in atherosclerosis pathogenesis. This study searched the potential of Bauhinia bowkeri extracts (hexane, dichloromethane and methanol) to inhibit the polyol pathway and LDL modification in vitro. The in vitro aldose reductase (ALR) and sorbitol dehydrogenase (SDH) inhibition assays were used to investigate the extracts’ potential to inhibit the polyol pathway activity. Their inhibitory activity on protein glycation was investigated on LDL (and BSA) using fructose and methylglyoxal as glycating agents. The extracts’ antioxidant activity was determined using the in vitro antioxidant assays like ferric reducing power, ABTS and DPPH radical scavenging assays. Their antioxidant activity was also investigated in the copper sulphate-induced LDL peroxidation. The selected major compounds’ bioactivities were investigated using the same assays. In silico molecular docking against ALR and SDH was performed, and their ADMET properties were also studied. FTIR and GC-MS results indicated the presence of various compounds. The crude extracts showed high inhibitory activity on ALR with IC50 values ranging from 75-90.8 µg/ml, and low on SDH (IC50  185 µg/ml). The extracts also showed 59.6 - 77.8 % inhibitory activity on LDL glycation. In addition to high reducing potential, the extracts chelated Fe2+ ions and scavenged DPPH and ABTS radicals. The extracts further showed antioxidant activity on LDL oxidation with a percentage range of 13 - 74 %. While all six selected compounds showed good ADMET properties, five showed good docking scores on ALR and SDH. Monoethylhexyl phthalate showed inhibitory activity on LDL glycation and oxidation, with the highest percentage inhibitions of 43.2 % and 54.13 %, respectively. The inhibition of the polyol pathway activity, and LDL glycation and oxidation, indicates the potential of B. bowkeri extracts and their compounds to be used as therapeutic agents in the amelioration of diabetes associated macrovascular complications, like atherosclerosis.