in silico anti aterosclerosis activity of … · andrographolide are compounds of sambiloto...
TRANSCRIPT
IN SILICO ANTI ATEROSCLEROSIS ACTIVITY OF
ANDROGRAPHOLIDE FROM SAMBILOTO ( ANDROGRAPHIS
PANICULATA (BURM. F NESS) N.M.P Susanti
1*, N.K. Warditiani
1, N.P.L.Laksmiani
1, I.M.A.G. Wirasuta
1
1. Pharmacy Departement, Faculty of Mathematic and Natural Science, Udayana University, Indonesia
Email :[email protected]
Abstract Atherosclerosis, hardening of the blood vessels, can be treated through a process of RTC
(reverse cholesterol transport) involving proteins PPARα, PPARγ, and LXRα.
Andrographolide are compounds of Sambiloto (Andrographis paniculata (Burm.f Ness)
which have many pharmacological activity such as anti-cancer, anti-diabetic, anti-
inflammatory, anti-infective, antipyretic, and antiaterosclerotic activity. Molecular docking
is an in silico method used to determine the molecular activity of a compound. This study
aims to determine andrografolid activity as antiaterosclerotic with plaque-decay mechanism
trough RCT.
Molecular docking performed includes the preparation of 3D structures of proteins using
chimera 1.10.1 software, optimization of the 3D structure of andrographolide using
hyperchem 8 software (semi-empirical AM1), molecular docking method validation (RMSD
1-3 Å) and molecular docking to the protein PPARα (3ET1), PPARγ (3D6D), and LXRα
(2ACL) using Autodock 4.2. software. The lower the binding energy, the stronger and more
stable the bond between the protein and andrografolid.
The results showed that andrografolid is able to bind to proteins PPARα, PPARγ, and LXRα
with bond energy -8,74; -9,47; -10.34 kcal/mol respectively. It also has the same active site as
the native ligand shown by the hydrogen bonds formed between O atom of andrografolid
with H atom of SER280, ARG288 and THR300 amino acid of proteins. This can conclude
that andrografolid has activity as antiaterosklerosis with plaque decay mechanism trough
RCT.
Key word : Andrographolid, Atherosclerosis, RCT, In silico,
IN SILICO ANTIATEROSCLEROSIS ACTIVITY
OF ANDROGRAPHOLIDEFROM SAMBILOTO (
ANDROGRAPHIS PANICULATA(BURM. F NESS)
by Ni Made Pitri Susanti
Submission date: 13-Jan-2018 11:08AM (UTC+0700)Submission ID: 902347374File name: Abstrak_NMPS-revised.docx (18.03K)Word count: 263Character count: 1666
FINAL GRADE
/0
IN SILICO ANTI ATEROSCLEROSIS ACTIVITY OFANDROGRAPHOLIDE FROM SAMBILOTO ( ANDROGRAPHISPANICULATA (BURM. F NESS)GRADEMARK REPORT
GENERAL COMMENTS
Instructor
PAGE 1
Result and discussion Preparation of protein PPARα (3ET1), PPARγ (3D6D), and LXRα (2ACL), downloaded from http://www.rcsb.org/pdb/home/home.do, aims to separate the native ligand and protein to provide space (pocket / cavity) during the docking process. The preparation is done using a chimera software 1.10.1. in order to obtain protein without native ligand (Figure 1) (A) (B)
Figure 1. Protein structure (A) and the native ligand (B)
IN SILICO ANTI ATEROSCLEROSIS ACTIVITY OF
ANDROGRAPHOLIDE FROM SAMBILOTO ( ANDROGRAPHIS
PANICULATA (BURM. F NESS) Ni Made P Susanti1, Ni Kadek Warditiani1, Ni Putu L. Laksmiani1, I M A G Wirasuta1
1Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Udayana, Bukit Jimbaran, Badung, 80363, Indonesia E-mail: [email protected]
Optimization of Andrografolid was performed using semiempiris AM1 in Hyperchem 8 program with -5509.50 kcal / mol of energy obtained (Figure 2) . This energy shows the amount of energy required to break one mole of bonding species in a gaseous state. The lower the total energy of the molecule andrografolid, the more stable three-dimensional structure of andrographolide (Azam, 2012).
Figure 2. 3-dimensional structure of optimized Andrographolide Validation aims to determine the validity of docking methods used RMSD (Root Mean Square Deviation) as parameter. RMSD values 1-3 Å stated that the experimental crystal structures resembling the native ligand crystallography in the PDB (Protein Data Bank) so that the molecular docking method is valid and accurate. The RMSD result of native ligand validation on protein PPARα, PPARγ, and LXRα are 1.47; 2.9; and 2.06 Å respectively. Docking andrographolide on the protein PPARα, PPARγ, and LXRα using Autodock 4.2 software, and coordinates was set according to the coordinates of the native ligand. The results of andrografolid docking with protein PPARα, PPARγ, and LXRα shown in Figure 3.
(A) (B) (C)
(A) (B) (C) Figure 3. Interaction between andrografolid with protein PPARα (A), PPARγ (B), and LXRα (C)
Post docking result shows that binding energy of Andrografolid with PPARα (-8.74 Kcal/mol) and LXRα (-10.34 Kcal/mol) are greater than their native ligand (-9.82 Kcal/mol and -10.66Kcal/mol respectively). Binding energy between Andrografolid with PPARγ (-9.47 Kcal/mol) is smaller than the native ligand (-9.01 Kcal/mol). Andrografolid also has the same active site as the native ligand shown by the hydrogen bonds formed between O atom of andrografolid with H atom of SER280, ARG288 and THR300 amino acid of PPARα, PPARγ, and LXRα proteins respectively. These results prove that andrografolid from bitter plant (Andrographis paniculata (Burm.f) .Ness) can form bonds with proteins PPARα, PPARγ and LXRα that play a role in the RCT process.
Conclusion Andrografolid from bitter plant (Andrographis paniculata (Burm.f) .Ness) has activity as antiaterosklerosis with fatty plaque decay mechanism through RCT (reverse cholesterol transport).
Acknowledgements
This research was supported by Ministry of Research, Technology and Higher Education of the Republic of Indonesia
abstract Atherosclerosis, hardening of the blood vessels, can be treated through a process of RTC (reverse cholesterol transport) involving proteins PPARα, PPARγ, and LXRα. Andrographolide are compounds of Sambiloto (Andrographis paniculata (Burm.f Ness) which have many pharmacological activity such as anti-cancer, anti-diabetic, anti-inflammatory, anti-infective, antipyretic, and antiaterosclerotic activity. Molecular docking is an in silico method used to determine the molecular activity of a compound. This study aims to determine andrografolid activity as antiaterosclerotic with plaque-decay mechanism trough RCT. Molecular docking performed includes the preparation of 3D structures of proteins using chimera 1.10.1 software, optimization of the 3D structure of andrographolide using hyperchem 8 software (semi-empirical AM1), molecular docking method validation (RMSD 1-3 Å) and molecular docking to the protein PPARα (3ET1), PPARγ (3D6D), and LXRα (2ACL) using Autodock 4.2. software. The lower the binding energy, the stronger and more stable the bond between the protein and andrografolid. The results showed that andrografolid is able to bind to proteins PPARα, PPARγ, and LXRα with bond energy -8,74; -9,47; -10.34 kcal/mol respectively. It also has the same active site as the native ligand shown by the hydrogen bonds formed between O atom of andrografolid with H atom of SER280, ARG288 and THR300 amino acid of proteins. This can conclude that andrografolid has activity as antiaterosklerosis with plaque decay mechanism trough RCT. Keywords : Andrographolid, Atherosclerosis, RCT, In silico
Methods Native ligand of the protein PPARα, PPARγ and LXRα obtained from http://www.rcsb.org/pdb/home /home.do. removed by Chimera 1.10.1 software to provide space (pocket / cavity), to determine the shape of the pocket, coordinate pocket, binding site center and radius cavity. Andrographolide structure is optimized by using Hyperchem 8 with semi-empirical AM1 method.. Validation of molecular docking method carried out by redocking native ligands to proteins using Autodock 4.2 software. Docking method is valid if the value of RMSD (Root Mean Square Distances) 1-3 Å. The result of docking Andrographolide to PPARα, PPARγ and LXRα using Autodock 4.2. will show the conformation of compounds with the lowest binding energy to the target protein.
Introduction Atherosclerosis is the underlying pathology of CHD (Coronary Heart Disease), where the presence of atherosclerotic plaque will cause constriction of blood vessels and inhibit blood flow to the heart (Cavallari and Robert, 2008). Atherosclerosis is hardening of the arteries caused by the accumulation of fatty deposits and other substances so that the lumen of blood vessels becomes narrow and its elasticity decreases resulting in disruption of blood flow (Ross, 1999). Atherosclerosis treatment can be done through the decay of atherosclerotic plaque through a process of RCT (reverse cholesterol transport) mediated by HDL (High-density lipoprotein). Andrografolid from the bitter plant (Andrographis paniculata Nees) is is one diterpene lactone class that have various pharmacological activities such as antioxidants, analgesics, lowering blood sugar, triglycerides and LDL, and antiaterosklerosis (Lin et al., 2009; Nugroho et al., 2012; Azlan et al., 2013). Based on this background, this research will be carried out molecular docking andrografolid of Andrographis paniculata with target proteins PPARα, PPARγ, and LXRα triggered ABCA1 and ABCG1 expression that play a role in RTC process.
References Azlan, A., Younis, L., Mahmud, N.H. and Dardiri, N.A. 2013. European International Journal of Science and Technology. Vol. 2(2). P. 1-6. Cavallari, L.H and Robert J.D. 2008. Ischemic Heart Disease. In: Pharmacotherapy Principles and Practice. USA: The McGraw-Hill Companies. Lin, F.L., Wu, S.J. and Lee, S.C. 2009. Phytother Res. Vol. 23(7). P. 958-64. Nugroho, A.E., Andrie, M., Warditiani, K., Siswanto, E., Pramono, S. dan Lukitaningsih, E. 2012. Indian Journal Pharmacol. Vol. 44(3). P. 377-381. Ross, R. 1999. Aterosclerosis and Inflamatory Disease. The New England Journal of Medicine. Vol. 340. No. 2. P. 115-126.
IN SILICO ANTIATEROSCLEROSIS ACTIVITY
OF ANDROGRAPHOLIDEFROM SAMBILOTO (
ANDROGRAPHISPANICULATA (BURM. F NESS)
by Ni Made Pitri Susanti
Submission date: 13-Jan-2018 11:07AM (UTC+0700)Submission ID: 902347191File name: Poster_Pitri.pdf (824.32K)Word count: 1122Character count: 6265
FINAL GRADE
/0
IN SILICO ANTI ATEROSCLEROSIS ACTIVITY OFANDROGRAPHOLIDE FROM SAMBILOTO (ANDROGRAPHIS PANICULATA (BURM. F NESS)GRADEMARK REPORT
GENERAL COMMENTS
Instructor
PAGE 1
2nd Bandung
al Conference
(ICMC20I7)Institut Teknologi Bandung
Indonesia
5-6 October 2017
H
Ml
u
Mi
o
Q- -<U O ID;@@@@@ -5 B-s
@a
PI! c* c 'a.
11^
s
5 3
s3f
@ roro 0)to.u
o
.@Ci CD
SI
II< 5"
1 2
@ O ot*= 1-
!
a
uiinl
@St.*
m
S3: @ i @
1 @ :
o
311
IIi2 Q
PS
la
*n
D O @as s <
I
IITO 3
en
SI'S
-g !@@
lai
2 ~"5 @ @@
Hi'!%@@'@-
Ip/:-:
p; aC -ti B'
.1
d...Q.:. :
@h at
?$
>^ii.E
^ o
si'\ CD
5* -'sz,'
1.1
.3:5 S
If tl
c<@@!
s2it
rM0cLOl
2
Q.
0
ics
rcot
z
=?
8t>1^
X
wtn
1in
0
1
roc15
IDOQ.CL
-a
T3
sC
f~Q.
m
IDCmbu
irisi
Di
a;tamir
Q.
10
(Analysi
<
nts
0)
Pig
I
0)
1Can
Serial
.Gc<
c
uli>ro
0d.CL
to-0noi
0>Fla
1:ro
'5
uro
ptial
c@sQ_<Uf_
@asin
s:2C31
roc2
0
n.a.
0
Oibit
c
cu.enfo.c<u-
loo
.>-Utn<
13
-3" TTvv
-o'=
o ?"51 X)
% m s
.= -T
B =
111>- o
ro 9- '5
o J ,̂ >- \
g 2 i-aS .t x uz z O <
to
E O
ro "g
!M .2
gig-1
IB S
illlal
lo>5'@& 5 Q.
^ cu a;Li .E &(7i
_roas: o
ns o ll
fe.il
| SISs ^ -53 s"? 9 s
3$'
ra iS -6CD (U C
v is IS ^
5^ Si
1
>
i/i
&
oi _
s: Si25
c Jg01 !U uI<3 ifC rn "OOj > @<
@S w Q
S S bU TO Ch 7 -u-) -̂s S S
PiIf?
(0 -C>-"O
5 I
i 9
<y Si
CO
rp1
8? 'V^m^fi- 8lS"f>(si*;5,1.r.
o o
I a
u
s
^ I c@5 a. o
PI.3 > .y
o oQ Q H
J2 ~ '5
131
"5 @*
vJi O
z J9a; c 1c
IIIi 8 g
i<m
JZ
D
rej=
._nant
2
Ln
r-
g
Z>
at1-
3a.
3@?
CL
cSCon
nds
Q.
O
>."OStu
?ctioi
era
Int
IT}CKui
(vrslQ.a.
r^-
@Si
Q_
1
SGranatu
.2
ro
Een<v
cUJ
rculosis
@si
iI
c<u
V}SO;
berc
titu
<
(_>
ID
U
@
UJc.
eteplase
01
Solu
f@ctioi
3-0
'c-Ria
Cai
COrMa.a.
<o
1Vector
no
V)V)Expn
ing
Usi
po
JDETO
</1
Ep
u_
tu33oQ.2
@
@oc<
in8zLJ_
E
^S,
.2c;5iCt.
uX00
u@aroial,
Otimic
c<
udy,
to
?
Q
|
01c
3>-ro
N3z
CTI
Q.Q.
roire
5-Dial
2"
0)ro>.0ctyofB
:ivi
<
iya
Q
O
ico
1
5Idwracteri
u
Cro
1/)
0)
c5?
IBtts
@0
Ginosl
-cul
<u3
<toro
>riva
Su
T3rsjro-0>.sz
JZ
gOJ.roeriv
andIts
0
s
Study
ction
roInter
ro'toE
3z
D.a.
fN
01Recep
(BCL
sa:
|>.
B-Ce
toc
51
idsoun
a.
Sa)
@
3S"Sn
c
Blind
BrocSdra
c
co>
"8Q
fN(NlQ.Q.
rM
11
COicti
red
a.
u
1
raturo
enLipoxy
in<i>EEnzy
S@@
<*SP
-a
a.
as%
m ^ \S * @
Eu 8
ssS "
<a
c/5
ro
QJ
0305
ucCD
D)
CO
CD
C0COCD
0^@>
CO
r?cc LL
Wi
CM
o
o