Polarity directed solvent extracts from Bukiniczia Cabulica (Boiss.) Lincz. ameliorate scopolamine induced amnesia: HPLC-DAD polyphenolics analysis, cholinesterase, COX2, BACE1 inhibitory, anti-amyloid, antioxidant, molecular docking and behavioral correlates

Medicinal plants and polyphenolics of the family Plumbaginaceae have ethnomedicinal relevance in the management of neurological disorders. The current study was aimed to assess protective potentials of Bukiniczia cabulica (Boiss.) Lincz. against scopolamine induced amnesia. Quantitative polyphenolics assessment of the crude extract (Bc.Cme) was performed using HPLC-DAD analysis. In vitro cholinesterase (AChE/BChE), cyclooxygenase-2 (COX2) inhibitory and antioxidant (DPPH/ABTS) studies were performed following standard protocols. Spatial memory and neurocognitive benefits of the samples were tested in amnesic animals using Shallow Water Maze (SWM), Elevated Plus Maze (EPM), Y-Maze paradigms. The BACE1 inhibitory and anti-amyloid (A beta) studies were performed using western blotting technique in amnesic animals. Binding affinity of the identified compounds against the target enzymes were evaluated via MOE software. A total of thirteen bioactive polyphenols including syringic acid (129.9 +/- 0.9 mg/g), 4-Caffeoylquinic Acid (67.6 +/- 0.3 mg/g), qurecetin-3-O-rutinoside (33.6 +/- 0.5 mg/g), quercetin-3-feruloyl sophoroside (16.9 +/- 0.3 mg/g), quercetin pentosyl hexoside (14.0 +/- 0.3 mg/g), isorhamnetin-3-caffeoyl-7-glucoside (15.6 +/- 0.5 mg/g), quercetin-3-(p-coumaroyl diglucoside)-7-glucoside (11.8 +/- 0.3 mg/g), procyanidin trimer (10 +/- 0.2 mg/g), were quantified. The Bc.Cme was found highly active against both AChE/BChE with IC50 values of 23.1 and 42.62 ug/ml respectively. In a DPPH and ABTS radical scavenging assay Bc.Cme considerable radicals scavenging activity. Further, Bc.Cme effectively inhibited COX-2 enzyme with IC50 value of 74.3 ug/ml. The Bc.Cme offered protection against scopolamine induced amnesia in various behavioral models. The BACE1 enzyme was inhibited significantly as compared to amnesia group animals and a considerable decline in A beta load was observed in Bc.Cme treated animals. Affinity was observed for the identified compounds against target enzymes.