Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study
This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 30-hydroxy-5,6,7,40-tetramethoxyflavone (TMF)....
Saved in:
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI
2016
|
Subjects: | |
Online Access: | http://eprints.usm.my/39195/1/Flavonoids-Rich_Orthosiphon_stamineus_Extract_as_New_Candidate_for_Angiotensin_I-.pdf http://eprints.usm.my/39195/ https://www.ncbi.nlm.nih.gov/pubmed/27834876 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition
activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely
rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 30-hydroxy-5,6,7,40-tetramethoxyflavone
(TMF). Furthermore, to identify possible mechanisms of action based on structure–activity
relationships and molecular docking. The in vitro ACE inhibition activity relied on determining
hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by
the action of ACE enzyme. A High Performance Liquid Chromatography method combined with
UV detection was developed and validated for measurement the concentration of produced HA.
The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide
reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX: BioSolveIT’s
LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC50 value
(45.77 � 1.17 �g/mL) against ACE compared to the other extracts. Among the tested reference
compounds, EUP with IC50 15.35 � 4.49 �g/mL had highest inhibition against ACE and binding
ability with Zn (II) (56.03% � 1.26%) compared to RA, TMF and SIN. Molecular docking studies
also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is
stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated
that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that
ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc
ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of
flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors
of ACE. |
---|