Molecular docking and in vitro studies of soap nut trypsin inhibitor (SNTI) against phospholipase A2 isoforms in therapeutic intervention of inflammatory diseases

Gandreddi V D Sirisha; K Vijaya Rachel; Kunal Zaveri; Nagendra Sastry Yarla; P Kiranmayi; Magdah Ganash; Huda Mohammad Alkreathy; Nisreen Rajeh; Ghulam Md Ashraf

doi:10.1016/j.ijbiomac.2018.03.139

Molecular docking and in vitro studies of soap nut trypsin inhibitor (SNTI) against phospholipase A₂ isoforms in therapeutic intervention of inflammatory diseases

Int J Biol Macromol. 2018 Jul 15:114:556-564. doi: 10.1016/j.ijbiomac.2018.03.139. Epub 2018 Mar 23.

Authors

Gandreddi V D Sirisha¹, K Vijaya Rachel², Kunal Zaveri¹, Nagendra Sastry Yarla³, P Kiranmayi⁴, Magdah Ganash⁵, Huda Mohammad Alkreathy⁶, Nisreen Rajeh⁷, Ghulam Md Ashraf⁸

Affiliations

¹ Department of Biochemistry/Bioinformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Andhra Pradesh, India.
² Department of Biochemistry/Bioinformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Andhra Pradesh, India. Electronic address: [email protected].
³ Department of Biochemistry/Bioinformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Andhra Pradesh, India; Departmentof Animal Biology, University of Hyderabad, Hyderabad, 500 046, Telangana, India.
⁴ Department of Biotechnology, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Andhra Pradesh, India.
⁵ Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
⁶ Department of Pharmacology, Faculty of Medicine, King Abdulaziz Universuty, Jeddah, Saudi Arabia.
⁷ Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁸ King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: [email protected].

PMID: 29578020
DOI: 10.1016/j.ijbiomac.2018.03.139

Abstract

Therapeutic value of allelochemicals in inflammatory disorders and the potential drug targets need to be elucidated to alleviate tissue and vascular injury. Natural anti-inflammatory agents are known to cause minimal adverse effects. Presence of different secondary metabolites (allelochemicals), protease inhibitors like soap nut trypsin inhibitor (SNTI) from Sapindus trifoliatus and allied compounds from natural sources cannot be blithely ignored as natural therapeutics. In the present study, SNTI, a prospective protease inhibitor isolated from the seeds of Sapindus trifoliatus were subjected to docking against three isoforms of Phospholipase A₂ (PLA₂) molecules of the inflammatory pathways which are localized in the membrane, cytosol and pancreas. Eleven ligand molecules were selected from Sapindus trifoliatus and docked against membrane, cytosolic and pancreatic PLA₂. Cytosolic PLA₂ showed a strong inhibition by Kampferol, a secondary metabolite from seed endosperm of Sapindus trifoliatus. SNTI showed best interaction with membrane PLA₂ in both in silico as well as in in vitro studies. SNTI showed IC₅₀ value of 29.02 μM in in vitro assay. Docking interaction profiles and in vitro studies validate selected molecules from Sapindus trifoliatus as immunomodulators and can mollify inflammatory responses.

Keywords: Allelochemicals; Docking; Homology modeling; PLA(2); Protein interaction; SNTI; sPLA(2).

MeSH terms

Animals
Humans
Immunologic Factors* / chemistry
Immunologic Factors* / isolation & purification
Immunologic Factors* / therapeutic use
Inflammation / drug therapy
Inflammation / metabolism
Isoenzymes / chemistry
Isoenzymes / metabolism
Mice
Molecular Docking Simulation*
Phospholipases A2 / chemistry*
Phospholipases A2 / metabolism
Plant Proteins* / chemistry
Plant Proteins* / isolation & purification
Plant Proteins* / therapeutic use
Sapindus / chemistry*
Trypsin Inhibitors* / chemistry
Trypsin Inhibitors* / isolation & purification
Trypsin Inhibitors* / therapeutic use

Substances

Immunologic Factors
Isoenzymes
Plant Proteins
Trypsin Inhibitors
Phospholipases A2