Lowering Cholesterol Natural

Products Drug Development

Leonardus B.S. Kardono
University of Indonesia, July 14, 2013
INTRODUCTION
Cardiovascular diseases are the leading
cause of death in Indonesia where one of
the common pathological substrate
underlying this process is atherosclerosis.
The OxLDL plays a key role in the
initiation and progression of
atherosclerosis (Ross, 1993). One of the
potentially atherogenic properties of
OxLDL is its cytotoxicity to the cells of the
artery wall
INTRODUCTION
Statins remain the first-line therapy for
preventing atherosclerotic cardiovascular
diseases, but undesirable side effects have
received much attention (Rosenson, 2004),
however, some of them showed the
disadvantages, such as being hepatotoxic and
increased the blood sugar level. So the search
for new and safe antiatherosclerotic drugs has
prompted researchers to investigate the efficacy
of natural products (Wang et al., 2006).
SEARCH FOR LOWERING
CHOLESTEROL
Search from Marine and Terrestrial Natural Products
(Medicinal Plants (Jamu), Jelly Fishes or Fermented
Microbes)
In the past mostly was conducted using animal model,
classical pharmacology.
Anticholesterol activity was evaluated in the laboratory or
by anticholesterol kits.
Some were studied in silico (Computer aided drug
design)
Currently the search is studied through molecular
biology, such as, using enzyme of Hydroxy methyl
glutaryl Co A inhibitory evaluation.
Various Herbs Reported Active
for Lowering Chelsterol
Curcuma xanthorrhiza Roxb.
The first useful anti cholesterol herb to be
discussed is Curcuma spp.
Our liver makes cholesterol as needed. If
we consume foods high in saturated fats,
the liver produces LDL cholesterol, which
is harmful to us. Curcuma rhizomes
extract works by limiting the production of
LDL cholesterol via a compound known as
curcumin, xanthorrhizol.






Capsicum
Capsicum is a well known spicy herb
commonly used in much more than just
chili. Its stimulating properties have the
ability to increase blood flow as well as
sluggish circulation along with it.
Researchers have determined that this
herb has been shown to lower both high
cholesterol and high blood pressure.
Garlic

Garlic is another herb that has been used for
centuries in the treatment of many illnesses due
to its high content of sulfur compounds. It
contains roughly four times that of other
vegetables - cauliflower, onion and broccoli, also
high in sulfur. It keeps cholesterol levels in
balance by lowering LDL cholesterol levels, and
at the same time raising HDL cholesterol.
Garlic is a great herb. Indeed, besides being a
useful anti cholesterol herb, it has countless
other health benefits.


Chinese Red Yeast Rice Extract

Researchers have proven that monacolin,
an ingredient in red yeast rice, has the
ability to inhibit cholesterol production by
halting enzymes in the liver responsible for
producing it.
Ginger
One more of the anti cholesterol herbs is
ginger, which helps to raise HDL
cholesterol as well as reduce both
triglyceride and overall cholesterol levels.


GARCINIA MANGOSTANA
-Mangostin sustains the cardiac mechanic
activities and decrease infarc area , prevent
the decrease of cardiac ATP and phospho
creatinine level in muscle cardiac
reperfusion. The xanthone protective effect
is related to oxidative stress. n -Mangostin
prevents the protein oxidation induced by
reperfusion ulcer, lipid peroxidation
(malondialdehyde and 4-hydroxynonenal
content) and the decrease of glutation.
Heterobasidiomycetes (jelly
fungi) and Other Mushrooms
Auricularia auricula
Auricularia polytricha (Hirneola
polytricha)
Tremella fuciformi
Termitomyces eurrhizus

Some of the active compounds are beta-
glucan
O PEK BOK NIE (PREVENTING THE ARTERI
BLOCKING DUE TO CHOLESTEROL )
Auricularia polytricha/Auricularia
auricula (Jamur hitam putih/Jamur
Kuping) : 45 Gram
Ang Cho (Red Fruits): 10 fruits
Sliced Ginger: 8 sliced (2mm thickness)
Meat (non fat): 60 Gram (optional ?)
Water : 8 Glass
After washed thoroughly, boiled all
materials up 2 glasses, taken twice a
day (early in the morning and night).

SAINTIFICATION OF JAMU FOR HEALTH CARE
RESEARCH SERVICES
Hiperglicemia
Hiper-tension
Hiperuricemia
Hipercholestrolemia

Implementation 2012
Osteo Arthritis
Anti-obesity
Anti-dispepsia
Anti-haemorrhoid

Breast Cancer
Hepatoprotector
Imunomodulator
Asma
Cervical Cancer
Dermatitis alergy
Common cold
Aphrodisiac
Anemia
Prostate Cancer




Implementation (2013-
2014)
Implementation (2011)
RESEARCH BASED ON DEGENERATIVE
DISEASES
Obesity
Formula based on Guazuma
ulmifolia and Kaempferia
rotunda
Diabetes Hyper-lipidemia
Hyper
uricaemia
Atherosclerosis
and
cardiovascular
Arthritis
Improvement for
Senility
Formula based on
Andrographis
paniculata
Formula based on Curmua
xanthorrhiza
Formula based on
Stelecocarpus
burahol
Formula based on
Artocarpus altilis
Formula based on Nicolaia
speciosa and Zingiberis
rhizomes
Formula based on Centella
asiatica
Immune
Response
Pandanus
conozoides
Current Jamu Generic Preparation
Androgaphis paniculata, Tinospora crispa,
Sonchus arvensis, (for Diabetes)
Caesalpinia sappan, Stelechocarpus burahol, (for
Hyperurecemia)
Muraya paniculata, Guazuma ulmifolia, Curcuma
domestica, Curcuma xanthorhiza, (for
Hypercholesteroemia)
Apium graviolens, Orthosiphon aristatus, Centela
asiatica (for Hypertension).
The clinical observations showed that these
generic jamus are working well, although some
improvement are needed.
SEARCH ON ANTICHOLESTEROL FROM
INDONESIAN FERMENTED RED YEAST


Red yeast was purchased in Serpong
market
Solid State Fermentation resulted to the
isolation of Lovastatin/Monacolin and other
derivatives.
Further work on Anticholesterol Lovastatin
derived into Dehydrolovastatin.
INTERACTION
Lovastatin and HMG-CoA Reductase
Interaction of Subnstrate (ball)
with HMG-CoA reductase Active site
(wire string)
Interaction of Dehydrolovastatin i
(grey wire string)
with HMG-CoA reductase Active site
(dark wire string)

QSAR ANALYSIS USING HyperChem 7.0
Treatment
30 Wistar rats were divieded into 5 groups.

Group I = Normal Control
Group II = Induced High Cholestrol Rats
Group III = Simvastatin (7,2 mg/200 g bw rat)
Group IV = Dehydrolovastatin 7,2 mg/200 g bw rat)
Group V = Dehydrolovastatin 14,4 mg/200 g bw rat)

ANTICHOLESTEROL EVALUATION
Cholesterol Total
(mg/dl)
Triglyceride
(mg/dl)
HDL
(mg/dl)
LDL
(mg/dl)
106.29
172.53
102.28
103.85
94.79
0.00
20.00
40.00
60.00
80.00
100.00
120.00
140.00
160.00
180.00
Kadar
trigliserida
(mg/dl)
1 2 3 4 5
Kelompok
1
1. Normal Control, 2. Cholesterol Induced, 3.Simvastatin 7,2 mg/200 g
bb/day, 4.Dehidrolovastatin 7.2 mg/200 g bb/day, 5. Dehidrolovastatin
14.4 mg/200 g bb/day,
ANTICHOLESTEROL EVALUATION
Anticholesterol Evaluation Activity Results
Antikolesterol Dehydrolovastin and Simvastatin
Evaluation
Parameter
Normal
Control
Hyperlipide
mia
Simvastatin
(7,2 mg/200 g
bb)
Dehidrolovastatin
(7,2 mg/200 g bb)
Dehydrolovastatin
(14,4 mg/200 g bb)
Total
Cholesterol
(mg/dl)
(%)
111,7
9
156,66 112,03
(28,49%)
106,64
(31,93 %)
105,54
(32,55 %)
Triglyserides
(mg/dl)
(%)
106,2
9
172,53 102,28
(40,72%)
103,85
(40,0%)
94,79
(45,06%)
LDL-
Cholesterol
(mg/dl)
(%)
32,34
72,99 30,23
(58,58%)
25,00
(65,75%)
28,77
(60,58%)
HDL-
Cholesterol
(mg/dl)
(%)
58,20
49,16 61,34
(24,77%)
60,87
(23,82%)
57,81
(17,60%)


CONCLUSION
Indonesia is rich on Natural Products for the development of
new anticholesterol active compounds.
Various studies were conducted using classical
pharmacology and biology molecular
Dehydrolovastatin showed anticholesterol activity and
increased the HDL value in rodent experiment.
THANK YOU