Phytoconstituents of an ethanolic pod extract of Prosopis cineraria triggers the inhibition of HMG-CoA reductase and the regression of atherosclerotic plaque in hypercholesterolemic rabbits

Abstract

Background: The HMG-CoA reductase is key enzyme of cholesterol biosynthesis which potentially contributes in management of hypercholesterolemia. The present study was designed to assess the inhibitory effect of phytoconstituents of an ethanolic extract of Prosopis cineraria pods on HMG - CoA reductase and regression potential of atherosclerotic plaque.

Methods: Healthy, adult male, albino rabbits in which hypercholesterolemia was induced by supplying the high fat diet and a supplement of cholesterol powder with coconut oil (500 mg/5 ml/Day/kg body weight) for 15 days, were used as a disease model. Phytochemical analysis of an ethanolic extract Prosopis cineraria pods was conducted using LCMS, GCMS and FTIR analysis. Further, in-vitro, in-vivo and in-silico assessments were performed.

Results: The in-vitro assessment of HMG -CoA reductase activity indicated a 67.1 and 97.3% inhibition by the extract and a standard drug (Pravastatin), respectively. Additionally, an in-silico evaluation was made using appropriate docking software and results also indicated as significant interactions of the identified compounds with the target enzyme. Treatment of rabbits with the ethanolic extract of P. cineraria pod resulted in significant (P ≤ 0.001) reductions in total cholesterol, LDL cholesterol, VLDL cholesterol, and triglyceride. Accordingly, reductions were occurred in atherosclerotic plaque, intima and media of aortal wall along with lumen volume of the aorta significantly increased (P ≤ 0.001).

Conclusion: It can be illustrating that the ethanolic extract of Prosopis cineraria pod contains potent bioactive phytocompounds might be inhibit HMG - CoA reductase and have regression potential of atherosclerotic plaque.

Keywords: Antioxidants; Atherosclerosis; HMG-CoA reductase; Hypercholesterolemia; Lipid profile; Prosopis cineraria.

Fig. 1

a HMG – CoA reductase Inhibition potential of Pravastatin. b HMG – CoA reductase Inhibition potential of ethanolic pod extract of Prosopis cineraria

Fig. 2

Phytochemical analysis of UPLC chromatogram of ethanolic pod extract of Prosopis cineraria of LCMS analysis

Fig. 3

Phytochemical analysis GC/MS of ethanolic pod extract of Prosopis cineraria

Fig. 4

Phytochemical analysis by FTIR of ethanolic pod extract of Prosopis cineraria

Fig. 5

Serum antioxidants levels of ethanolic pod extract of Prosopis cineraria in treated groups. (Data are means ± S.E.M. (n = b8); a, P ≤ 0.05 and c,. P ≤ 0.001 as compared to the respective control values and g, P ≤ 0.001 as compared to the respective values of the Chol diet fed group)

Fig. 6

a Vehicle control (Gr. 1): Microphotograph of thoracic aorta exhibiting normal histology with aorta wall consists of intima, media and adventitia. (200x H&E). b Hypercholesterolemic control (Gr. 2): Microphotograph of thoracic aorta exhibiting atherosclerotic lesions with formation of plaque indicating by arrow, thickened intima contained foam cells and extracellular lipid (200x H&E). c Ethanolic Propopis cineraria pod extract treatment (Gr. 3): Microphotograph of thoracic aorta depicting regression in plaque indicating by arrow and normalcy in intima and media (200x H&E). d Atorvastatin treatment (Gr. 4): Microphotograph of thoracic aorta describing regression in plaque indicating by arrow and normal histoarchitecture of intima and media (200x H&E)

Fig. 7

a Interaction of Atorvastatin with target enzyme HMG – CoA reductase. b Interaction of Pravastatin with target enzyme HMG – CoA reductase. c Interaction of Prosogerin - A with target enzyme HMG – CoA reductase. d Interaction of Prosopilosine with target enzyme HMG – CoA reductase. e Interaction of β-sitosterol with target enzyme HMG – CoA reductase