Efficacy of Small Molecule Phytochemicals of Petroleum Ether Pod Extract of Prosopis cineraria (L.) Druce on HMG-CoA Reductase and Biomarker Indices of Lipoproteins: In-vitro, In-vivo and In-silico Study

The assigned goals of the study were examined to HMG-CoA reductase inhibition and antioxidants potential of the small molecule phytochemicals of petroleum ether pod extract of Prosopis cineraria (L.) Druce by in-vitro, in-vivo, and in-silico assessments. The phytochemical fingerprinting of the extract was done by LC-MS analysis, and compounds were identified using mass hunter software. In-vitro HMG-CoA reductase assay performed by sigma Aldrich kit. According, in-vivo investigations were conducted by using a hypercholesterolemic rabbit animal model. Further, in-silico analyses of molecular docking and ADMET were conducted by standard protocol. The leading identified compounds, i.e., prosogerin-A, luteolin, and gallic acid, were docked with the target enzyme of HMG-CoA reductase, which demonstrated significant binding energies up to -7.2 to 8.1(Kcal/mol). Subsequently, the ADMET predictions revealed druggability and ideal pharmacokinetics profile. Accordingly, the in-vitro HMG-CoA reductase inhibition assay was showed 53.1% inhibition capability of the test extract. The in-vivo investigation shown that the test extract caused significant reductions in the atherogenic index (log (Total cholesterol/triglyceride), Castelli risk index-I (CRI-I), and Castelli risk -II(CRI-II) along with lipid profile and antioxidants levels. It can be concluded that small-molecule phytochemicals such as Prosogerin A, Luteolin, Gallic acid are present in petroleum ether pod extract of Prosopis cineraria (L.) Druce possesses the capability to subside hypercholesterolemia and ameliorations in biomarker lipoproteins indices through HMG-CoA reductase inhibition and antioxidant potential.

Download Full-text

Ameliorations in the Biomarker Indices of Dyslipidemia and Atherosclerotic Plaque by the Inhibition of HMG – CoA Reductase and Antioxidant Potential of Phytoconstituents of an Aqueous Seed Extract of Acacia Senegal (L.) Willd in Rabbits

10.21203/rs.3.rs-314959/v1 ◽

2021 ◽

Author(s):

Jaykaran Charan ◽

Priyanka Riyad ◽

Heera Ram ◽

Ashok Purohit ◽

Sneha Ambwani ◽

...

Keyword(s):

Atherosclerotic Plaque ◽

In Silico ◽

Risk Index ◽

Seed Extract ◽

Atherogenic Index ◽

Acacia Senegal ◽

Hmg Coa Reductase ◽

Coa Reductase

Abstract Background: The HMG-CoA inhibitor are used to control adverse cardiovascular event caused by Hypercholesterolemia and dyslipidaemia. The current study was aimed to evaluate the ability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regress the formation of atherosclerotic plaque. Methods: The chemical fingerprinting of the test extract was assessed by LC-MS. Consequently, the assessments of in-vitro, in-vivo, and in-silico were performed by following the standard methods.Results: The in-vitro assessment of the test extract revealed 74.1 % inhibition potential of HMG-CoA reductase. In-vivo evaluations of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (𝑃 ≤ 0.001) ameliorations in the biomarker indices of the dyslipidaemia, such as the atherogenic index, Castelli risk index (I&II), atherogenic coefficient along with lipid profile. Concomitantly, significant reductions were observed in the atherosclerotic plaque area and antioxidants. The in-silico study of molecular docking shown interactions capabilities of key phytoconstituents of the test extract with target protein of HMG-CoA reductase which further validated by the molecular dynamics through potentail energy, NPT, NVT, RSMD and others. Subsequently, the ADMET analysis shown ideal druggability. Conclusion: The results indicate that phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd. could inhibit HMG-CoA reductase and improve the levels of antioxidants activity that may reduce symptoms associated with hypercholesterolemia.

Download Full-text

Novel Phytoconstituents of an Aqueous Pod Extract of Prosopis Cineraria (L.) Druce Attenuate Atherosclerotic Plaque and Hypercholesterolemia in Rabbits

10.21203/rs.3.rs-56652/v1 ◽

2020 ◽

Author(s):

Heera Ram ◽

Noopur Jaipal ◽

Pramod Kumar ◽

Jaykaran Charan ◽

Priya Kashyap ◽

...

Keyword(s):

Atherosclerotic Plaque ◽

In Silico ◽

Reductase Activity ◽

Hmg Coa Reductase ◽

Prosopis Cineraria ◽

Oral Supplementation ◽

Coa Reductase ◽

Leading Compounds

Abstract Background and objectives: The pod of Prosopis cineraria traditionally used in several ailments and key component of traditional food recipe of the Panchkuta of western Rajasthan, India. The current study was targeted to assess ability of phytoconstituents of aqueous pod extract of Prosopis cineraria to inhibit HMG-CoA reductase activity and regress atherosclerotic plaque were investigated in in-vitro, in-vivo, and in-silico studies. Material and Methods: LCMS, GCMS, and FTIR analysis were used to characterize the phytoconstituents of the test extract. Accordingly, the in-vitro, in-vivo and in-silico assessments were performed by following the standard methods. Results: The phytochemical results shown the presence of cloprostenol, cinecromen, and dirithromycin as leading compounds. Accordingly, in-vivo assay of test extract shown HMG-CoA inhibition activity by 78.1 % (IC50 was 0.03 μg/ml). Hypercholesterolemia was induced in rabbits through oral supplementation of a high fat diet (21 % fat) with cholesterol powder supplementation. Administration of the test extract caused significant (𝑃 ≤ 0.001) improvement in the lipid profile and antioxidant levels in the test rabbits, relative to the hypercholesterolemic control rabbits. Subsequently, the reductions in the atherosclerotic plaque and improvement in lumen volume were pointedly observed in the treated groups. In-silico analyses of molecular docking and ADMET revealed significant interactions and druggability profile. Conclusion: It can be stated that the phytoconstituents of aqueous pod extract of Prosopis cineraria have the capacity to inhibit HMG-CoA reductase and regress the atherosclerotic plaque which may be beneficial to the treatment of hypercholesterolemia.

Download Full-text

An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro

Circulation ◽

10.1161/01.cir.103.2.276 ◽

2001 ◽

Vol 103 (2) ◽

pp. 276-283 ◽

Cited By ~ 366

Author(s):

Masanori Aikawa ◽

Elena Rabkin ◽

Seigo Sugiyama ◽

Sami J. Voglic ◽

Yoshihiro Fukumoto ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Tissue Factor ◽

Reductase Inhibitor ◽

Hmg Coa Reductase ◽

Hmg Coa Reductase Inhibitor ◽

Coa Reductase

Download Full-text

Pharmacological studies on NK-104, a novel potent HMG-CoA reductase inhibitor (1): Inhibitory effects on the enzyme (in vitro) and sterol synthesis (in vivo) in rats and hypolipidemic effects in dogs

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)46359-2 ◽

1995 ◽

Vol 67 ◽

pp. 99

Author(s):

Shunji Nakagwa ◽

Taro Aoki ◽

Hideo Suzuki ◽

Taro Tamaki ◽

Yasushi Wada ◽

...

Keyword(s):

Reductase Inhibitor ◽

Sterol Synthesis ◽

Inhibitory Effects ◽

Hmg Coa Reductase ◽

Pharmacological Studies ◽

Hmg Coa Reductase Inhibitor ◽

Coa Reductase

Download Full-text

Dual Inhibition of DPP-4 and Cholinesterase Enzymes by the Phytoconstituents of the Ethanolic Extract of Prosopis cineraria Pods: Therapeutic Implications for the Treatment of Diabetes-associated Neurological Impairments

Current Alzheimer Research ◽

10.2174/1567205016666191203161509 ◽

2020 ◽

Vol 16 (13) ◽

pp. 1230-1244

Author(s):

Heera Ram ◽

Noopur Jaipal ◽

Pramod Kumar ◽

Purbajyoti Deka ◽

Shivani Kumar ◽

...

Keyword(s):

Insulin Resistance ◽

In Silico ◽

Ethanolic Extract ◽

Positive Interactions ◽

Model Assessment ◽

Pancreatic Cell ◽

Prosopis Cineraria ◽

In Silico Studies

Background: Insulin resistance causes decreased uptake of glucose which promotes the susceptibility of type 2 associated neurological impairments. Methods: The study was aimed to evaluate the inhibition potential of the ethanolic extract of Prosopis cineraria (EPC) pods against DPP-4 and cholinesterase enzymes by in-vitro, in-vivo and in-silico assessments. The present study consists of in vivo studies on a diabetes-induced rat model by HOMA (Homeostasis model assessment) and related parameters, in vitro studies through the DPP-4 enzyme assay and cholinesterase assays using Ellman’s reaction. The in-silico studies were conducted by the molecular docking of Cinerin C with targeted enzymes. The phytochemical characterization of the extract was demonstrated through LCMS studies. The antioxidant studies on the extract were performed by FRAP and TEAC assays. Results: The extract showed 64.8% maximum inhibition of DPP-4, 34.91% inhibition of AChE and 74.35% inhibition of BuChE. The antioxidant capacity of the extract was observed to be 847.81±16.25μM Fe2+ equivalent in the FRAP assay and 0.40 ± 0.08 mmol/l of Trolox equivalent in the TEAC assay. The in vivo study showed competent glycaemic control against significant HOMA IR (1.5), HOMA % β (26.5) and HOMA % S (68.8) as well as pancreatic cell mass proliferation. The insilico analysis also revealed positive interactions of Cinerin C with targeted enzymes (DPP4 and cholinesterase). Conclusion: It can be concluded that the phytoconstituents of Prosopis cineraria pod extract can be significantly considered in neuropharmacology to resolve insulin resistance-induced neurological complications as it showed inhibition against DPP-4, AChE and BuChE target enzymes.

Download Full-text

The Cholesterol-Lowering Effect of Alisol Acetates Based on HMG-CoA Reductase and Its Molecular Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/4753852 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Fei Xu ◽

Hui Yu ◽

Cai Lu ◽

Jun Chen ◽

Wei Gu

Keyword(s):

Molecular Simulation ◽

Reductase Activity ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Hmg Coa Reductase ◽

Coa Reductase ◽

The Impact

This study measured the impact of alisol B 23-acetate and alisol A 24-acetate, the main active ingredients of the traditional Chinese medicine Alismatis rhizoma, on total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) levels of hyperlipidemic mice. The binding of alisol B 23-acetate and alisol A 24-acetate to the key enzyme involved in the metabolism of TC, 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, was studied using the reagent kit method and the western blotting technique combined with a molecular simulation technique. According to the results, alisol acetates significantly lower the TC, TG, and LDL-C concentrations of hyperlipidemic mice, while raising HDL-C concentrations. Alisol acetates lower HMG-CoA reductase activity in a dose-dependent fashion, both in vivo and in vitro. Neither of these alisol acetates significantly lower the protein expression of HMG-CoA. This suggests that alisol acetates lower the TC level via inhibiting the activity of HMG-CoA reductase by its prototype drug, which may exhibit an inhibition effect via directly and competitively binding to HMG-CoA. The side chain of the alisol acetate was the steering group via molecular simulation.

Download Full-text