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Bioactivity guided fractionation and hypolipidemic property of a novel HMG-CoA reductase inhibitor from Ficus virens Ait.
Lipids Health Dis. 2015 Mar 04; 14:15.LH

Abstract

BACKGROUND

The current perspective for the search of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor has been shifted towards a natural agent also having antioxidant property. Thus, this study was intended to isolate and identify the bioactive compounds from methanolic extract of Ficus virens bark (FVBM) and to evaluate their antioxidant, HMG-CoA reductase inhibitory and hypolipidemic activity.

METHODS

Bioactivity guided fractionation and isolation of bioactive compound from FVBM extract has been done to isolate and characterize the potent HMG-CoA reductase (HMGR) inhibitor with antioxidant activity by using repeated extensive column chromatography followed by spectroscopic methods, including Infrared (IR), 1H & 13C nuclear magnetic resonance (NMR) and Mass spectrum analysis. The in vitro HMGR inhibition and enzyme kinetic assay was determined using HMG-CoA as substrate. In addition, antioxidant activity of the new isolated compound, was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and FRAP value. In-silico molecular informatics of HMGR enzyme type inhibition and pharmacokinetics data of the new compound was further evaluated through molecular docking and ADME-T studies. Further, in-vivo hypolipidemic property of FVBM extract and newly isolated compound was also analyzed in triton-WR 1339 induced rats.

RESULTS

Thereby, we report the discovery of n-Octadecanyl-O-α-D-glucopyranosyl(6'→1″)-O-α-D-glucopyranoside (F18) as a novel HMG-CoA reductase inhibitor with strong antioxidant property. This inhibitor exhibited not only higher free radical scavenging activity but also marked HMG-CoA reductase inhibitory activity with an IC50 value of 84±2.8 ng/ml. This inhibitory activity concurred with kinetic study that showed inhibition constant (K i) of 84 ng/ml via an uncompetitive mode of inhibition. The inhibition was also corroborated by molecular docking analysis and in silico pharmacokinetics data. The in vivo study revealed that administration of FVBM extract (at higher dose, 100 mg/rat) and the inhibitor (1 mg/rat) to Triton WR-1339-induced hyperlipidemic rats significantly ameliorated the altered levels of plasma lipids and lipoproteins including hepatic HMG-CoA reductase activity; this effect was comparable to the effect of standard drug atorvastatin.

CONCLUSIONS

The in vitro, in silico and in vivo results clearly demonstrated the antioxidant potential and therapeutic efficacy of the inhibitor as an alternate drug against hyperlipidemia.

Authors+Show Affiliations

Department of Biosciences, Clinical Biochemistry & Natural Product Research Lab, Integral University, Lucknow, 226026, India. danishik786@gmail.com.Department of Biosciences, Clinical Biochemistry & Natural Product Research Lab, Integral University, Lucknow, 226026, India. contactskhan@gmail.com.Department of Biosciences, Clinical Biochemistry & Natural Product Research Lab, Integral University, Lucknow, 226026, India. sajid_987@rediffmail.com.Department of Biosciences, Clinical Biochemistry & Natural Product Research Lab, Integral University, Lucknow, 226026, India. ahmadsaheem@gmail.com.Department of Pharmacy, Integral University, Lucknow, 226026, India. sarfarajpharma@gmail.com.Department of Pharmacognosy & Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India. maliphyto@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25884722

Citation

Iqbal, Danish, et al. "Bioactivity Guided Fractionation and Hypolipidemic Property of a Novel HMG-CoA Reductase Inhibitor From Ficus Virens Ait." Lipids in Health and Disease, vol. 14, 2015, p. 15.
Iqbal D, Khan MS, Khan MS, et al. Bioactivity guided fractionation and hypolipidemic property of a novel HMG-CoA reductase inhibitor from Ficus virens Ait. Lipids Health Dis. 2015;14:15.
Iqbal, D., Khan, M. S., Khan, M. S., Ahmad, S., Hussain, M. S., & Ali, M. (2015). Bioactivity guided fractionation and hypolipidemic property of a novel HMG-CoA reductase inhibitor from Ficus virens Ait. Lipids in Health and Disease, 14, 15. https://doi.org/10.1186/s12944-015-0013-6
Iqbal D, et al. Bioactivity Guided Fractionation and Hypolipidemic Property of a Novel HMG-CoA Reductase Inhibitor From Ficus Virens Ait. Lipids Health Dis. 2015 Mar 4;14:15. PubMed PMID: 25884722.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bioactivity guided fractionation and hypolipidemic property of a novel HMG-CoA reductase inhibitor from Ficus virens Ait. AU - Iqbal,Danish, AU - Khan,M Salman, AU - Khan,Mohd Sajid, AU - Ahmad,Saheem, AU - Hussain,Md Sarfaraj, AU - Ali,Mohd, Y1 - 2015/03/04/ PY - 2014/12/19/received PY - 2015/02/13/accepted PY - 2015/4/18/entrez PY - 2015/4/18/pubmed PY - 2016/1/27/medline SP - 15 EP - 15 JF - Lipids in health and disease JO - Lipids Health Dis VL - 14 N2 - BACKGROUND: The current perspective for the search of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor has been shifted towards a natural agent also having antioxidant property. Thus, this study was intended to isolate and identify the bioactive compounds from methanolic extract of Ficus virens bark (FVBM) and to evaluate their antioxidant, HMG-CoA reductase inhibitory and hypolipidemic activity. METHODS: Bioactivity guided fractionation and isolation of bioactive compound from FVBM extract has been done to isolate and characterize the potent HMG-CoA reductase (HMGR) inhibitor with antioxidant activity by using repeated extensive column chromatography followed by spectroscopic methods, including Infrared (IR), 1H & 13C nuclear magnetic resonance (NMR) and Mass spectrum analysis. The in vitro HMGR inhibition and enzyme kinetic assay was determined using HMG-CoA as substrate. In addition, antioxidant activity of the new isolated compound, was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and FRAP value. In-silico molecular informatics of HMGR enzyme type inhibition and pharmacokinetics data of the new compound was further evaluated through molecular docking and ADME-T studies. Further, in-vivo hypolipidemic property of FVBM extract and newly isolated compound was also analyzed in triton-WR 1339 induced rats. RESULTS: Thereby, we report the discovery of n-Octadecanyl-O-α-D-glucopyranosyl(6'→1″)-O-α-D-glucopyranoside (F18) as a novel HMG-CoA reductase inhibitor with strong antioxidant property. This inhibitor exhibited not only higher free radical scavenging activity but also marked HMG-CoA reductase inhibitory activity with an IC50 value of 84±2.8 ng/ml. This inhibitory activity concurred with kinetic study that showed inhibition constant (K i) of 84 ng/ml via an uncompetitive mode of inhibition. The inhibition was also corroborated by molecular docking analysis and in silico pharmacokinetics data. The in vivo study revealed that administration of FVBM extract (at higher dose, 100 mg/rat) and the inhibitor (1 mg/rat) to Triton WR-1339-induced hyperlipidemic rats significantly ameliorated the altered levels of plasma lipids and lipoproteins including hepatic HMG-CoA reductase activity; this effect was comparable to the effect of standard drug atorvastatin. CONCLUSIONS: The in vitro, in silico and in vivo results clearly demonstrated the antioxidant potential and therapeutic efficacy of the inhibitor as an alternate drug against hyperlipidemia. SN - 1476-511X UR - https://www.unboundmedicine.com/medline/citation/25884722/Bioactivity_guided_fractionation_and_hypolipidemic_property_of_a_novel_HMG_CoA_reductase_inhibitor_from_Ficus_virens_Ait_ L2 - https://lipidworld.biomedcentral.com/articles/10.1186/s12944-015-0013-6 DB - PRIME DP - Unbound Medicine ER -