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 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF). Fur...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2016-11-01
|
Series: | Molecules |
Subjects: | |
Online Access: | http://www.mdpi.com/1420-3049/21/11/1500 |
id |
doaj-5840f5571327418c8b2a7a0f5f1d2fbd |
---|---|
record_format |
Article |
spelling |
doaj-5840f5571327418c8b2a7a0f5f1d2fbd2020-11-24T22:28:10ZengMDPI AGMolecules1420-30492016-11-012111150010.3390/molecules21111500molecules21111500Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking StudyArmaghan Shafaei0Md Shamsuddin Sultan Khan1Abdalrahim F. A. Aisha2Amin Malik Shah Abdul Majid3Mohammad Razak Hamdan4Mohd Nizam Mordi5Zhari Ismail6Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, MalaysiaEMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, MalaysiaDepartment of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, MalaysiaEMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, MalaysiaCentre for Drug Research, Universiti Sains Malaysia, Minden, Penang 11800, MalaysiaCentre for Drug Research, Universiti Sains Malaysia, Minden, Penang 11800, MalaysiaDepartment of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, MalaysiaThis 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 3′-hydroxy-5,6,7,4′-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 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC50 15.35 ± 4.49 µg/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.http://www.mdpi.com/1420-3049/21/11/1500angiotensin-converting enzymehypertensionflavonoidsHPLC-UVmolecular ducking study |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Armaghan Shafaei Md Shamsuddin Sultan Khan Abdalrahim F. A. Aisha Amin Malik Shah Abdul Majid Mohammad Razak Hamdan Mohd Nizam Mordi Zhari Ismail |
spellingShingle |
Armaghan Shafaei Md Shamsuddin Sultan Khan Abdalrahim F. A. Aisha Amin Malik Shah Abdul Majid Mohammad Razak Hamdan Mohd Nizam Mordi Zhari Ismail Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study Molecules angiotensin-converting enzyme hypertension flavonoids HPLC-UV molecular ducking study |
author_facet |
Armaghan Shafaei Md Shamsuddin Sultan Khan Abdalrahim F. A. Aisha Amin Malik Shah Abdul Majid Mohammad Razak Hamdan Mohd Nizam Mordi Zhari Ismail |
author_sort |
Armaghan Shafaei |
title |
Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study |
title_short |
Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study |
title_full |
Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study |
title_fullStr |
Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study |
title_full_unstemmed |
Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study |
title_sort |
flavonoids-rich orthosiphon stamineus extract as new candidate for angiotensin i-converting enzyme inhibition: a molecular docking study |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2016-11-01 |
description |
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 3′-hydroxy-5,6,7,4′-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 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC50 15.35 ± 4.49 µg/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. |
topic |
angiotensin-converting enzyme hypertension flavonoids HPLC-UV molecular ducking study |
url |
http://www.mdpi.com/1420-3049/21/11/1500 |
work_keys_str_mv |
AT armaghanshafaei flavonoidsrichorthosiphonstamineusextractasnewcandidateforangiotensiniconvertingenzymeinhibitionamoleculardockingstudy AT mdshamsuddinsultankhan flavonoidsrichorthosiphonstamineusextractasnewcandidateforangiotensiniconvertingenzymeinhibitionamoleculardockingstudy AT abdalrahimfaaisha flavonoidsrichorthosiphonstamineusextractasnewcandidateforangiotensiniconvertingenzymeinhibitionamoleculardockingstudy AT aminmalikshahabdulmajid flavonoidsrichorthosiphonstamineusextractasnewcandidateforangiotensiniconvertingenzymeinhibitionamoleculardockingstudy AT mohammadrazakhamdan flavonoidsrichorthosiphonstamineusextractasnewcandidateforangiotensiniconvertingenzymeinhibitionamoleculardockingstudy AT mohdnizammordi flavonoidsrichorthosiphonstamineusextractasnewcandidateforangiotensiniconvertingenzymeinhibitionamoleculardockingstudy AT zhariismail flavonoidsrichorthosiphonstamineusextractasnewcandidateforangiotensiniconvertingenzymeinhibitionamoleculardockingstudy |
_version_ |
1725747503231401984 |