Stroke Fitoterapi Edit

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MANAGEMENT OF CORONARY ARTERY

DISEASE AND HEART FAILURE

FOR CURING

EVEN STROKE PREVENTION



CAD

Atherosclerosis

Risk Factors

( , BP, DM,

Insulin Resistance, Platelets,

Fibrinogen, etc)

The cardiovascular continuum of events

DYSLIPIDEMIA

Adapted fromDzau et al. Am Heart J. 1991;121:1244-1263

Myocardial

Ischemia

plaque



CAD

Atherosclerosis

Risk Factors

( , BP, DM,


Fibrinogen, etc)


DYSLIPIDEMIA


Myocardial

Ischemia

Coronary

Thrombosis



Penyumbatan pembuluh darah

Pembuluh

darah normal

Al

ir

a

ndarah

kolesterol PlakPembuluh

darah

Pembuluh

darah

dengan kadar

kolesterol tinggi

Plak akibat

kolesterol Yang

menempel

pada dinding

pembuluh



Otak yang terkena stroke

Arteri

Penyumbatan

karena plak



CAD

Atherosclerosis

Risk Factors

( , BP, DM,


Fibrinogen, etc)


DYSLIPIDEMIA


Myocardial

Ischemia

Coronary

Thrombosis

ACS



ACS

Coronary

Thrombosis

Myocardial

Ischemia

CAD

Atherosclerosis

Risk Factors

( Dyslipidemia, BP, DM,


Fibrinogen, etc) Adapted fromDzau et al. Am Heart J. 1991;121:1244-1263


Arrhythmia andLoss of Muscle

Remodeling

Ventricular

Dilatation

Congestive

Heart Failure

End-stage

Heart Disease

Primaryprevention

Secondaryprevention



Blood pressure

classification

Systolic BP

(mm Hg)

Diastolic BP

(mm Hg)

Normal <120 <80

Prehypertension 120-139 80-89

Stage 1

hypertension 140-159 90-99

Stage 2

hypertension>160 >100

JNC VII: Classification of blood pressure

or

or

or

or

The JNC VII. JAMA 2003;289:2560-72



INDICATIONS FOR INDIVIDUAL DRUG CLASSES

Diuretic-

blocker

ACE

inhibitor ARB CCB

Aldo-

antagonist

Heart failure • • • • •

Post-MI • • •

High coronary

disease risk • • • •

Diabetes • • • • •

Chronic kidney

disease • • Stroke

prevention • •

The JNC VII Report. JAMA 2003;289:2560-2572



MOST PATIENTS NEED

TWO OR MORE

ANTIHYPERTENSIVE

AGENTS TO CONTROL

THEIR BLOOD PRESSURE



Diuretics

ACE inhibitors

ACs

CCBs

-blockers

-blockers

Possible combinations of antihypertensive agents

2003 ESH/ESC guidelines for the management of arterial hypertension



Lipid Value (mg/dl) Classification

LDL-C

<100

100-129

130-159

160-189

190

Optimal

Near or above optimal

Borderline high

High

Very high

TC<200200-239

240

DesirableBorderline high

High

HDL-C<40

60

Low (increased risk)

High (cardioprotective)

TG

<150

150-199

200-499

500

Normal

Borderline high

High

Very high

NCEP-ATP III guidelines. JAMA 2001;285:2486-2497

NCEP Classification of Blood Lipid Values In Adults



NCEP-ATP III: TARGET OF TREATMENT

NCEP-ATP III. JAMA 2001;285:2486-2497

ELEVATED LDL CHOLESTEROL

METABOLIC SYNDROME



Pleiotropic effects of a drug are actions

other than those for which the agents

was specifically developed. It may be

undesireble (such as side effects or

toxicity), neutral, or, as is especially the

case with statin, beneficial.

Davignon J. Circulation 2004;109[suppl III]:III-39 – III-43



PLANTS RESOURCE

FOR PREVENTION

EVENFOR CURING STROKE



Allii Sativi Bulbus

(Garlic)

Clasification

Kingdom : Plantae

Division : SpermatophytaSubdivision : Angiospermae

Class : Monocotyledonae

Ordo : Liliales

Famili : LiliaceaeGenus : Alium

Spesies : Al l ium sat ivum Linn



Description

1. 30-60 cm tall,

2. strong smelling when crushed.3. The underground portion consists of a compound bulb with numerous

fibrous rootlets;

4. the bulb gives rise above ground to a number of narrow, keeled, grass-

like leaves.

5. The leaf blade is linear, flat, solid, 1.0-2.5cm wide, 30-60 cm long, and has

an acute apex.6. Leaf sheaths form a pseudostem. Inflorescences are umbellate; scape

smooth, round, solid, and coiled at first, subtended by membraneous,

long-beaked spathe, splitting on one side and remaining attached to

umbel.

7. flowers are variable in number and sometimes absent, seldom open and

may wither in bud.8. Flowers are on slender pedicels; consisting of perianth of 6 segments,

about 4-6mm long, pinkish; stamens 6, anthers excerted; ovary superior,

3-locular.

9. Fruit is a small loculicidal capsule.



STRUCTURE AND SUBSTANCE

Allicin

Alliin



PHARMACOLOGY

1. In-vivo (dog, rabbit, mice) causing decreasing blood

presure

2. Reducing vascular resistension with smooth muscle

relaxation

3. Changes of potential

membrane Hyperpolarization Kalium chanel open

frequently Ca Chanel closed Vasodilatation

4. Active substance of this effect is unknow5. Increasing NO synthesis decreasing blood presure



PHARMACOLOGY

ANTIPLATELET AGGREGATION

Reuteur HD, Allium sativum and Allium ursinum : Part 2 Pharmacology and

Medicinal Aplication, Phytomedicine 2 (1) : 73-91

IN THE ACTIVATING EFFECT OF GARLIC ON FIBRINOLYSIS

AND ITS INHIBITORY EFFECT ON PLATELET AGGREGATION

HAVE BEEN DEMONSTRATED IN TOTAL 16 EXPERIMENTALSTUDIES, IN VITRO AND VIVO.

THE STUDIED SHOWED THAT THE GARLIC ACT

TO STIMULATE ANDOGENOUS FIBRINOLYSIS AND

INHIBIT PLATELET AGGREGATION



PHARMACOLOGY


KIESELWETTER H.LUNG.F., JUNG. E.M., et al., EUROPEAN JOURNAL OF CLINICAL

PHARMACOLOGY, 1993, 45 : 336-338

LEGNANI C., FRASCARO M, GUAZZALOCA G, et al, ARZZNEIMITTEL FORSCHING,

1993, 43(2) : 119-122

A PLATELET INHIBITING EFFECT HAD BEEN STUDIED

IN A DOUBLE BLIND, PLACEBO CONTROLLED

STUDY ON 60 VOLUNTEERS WITH GARLIC POWDER

OVER 4 WEEKS.

THE RESULT LED TO A SIGNIFICANT REDUCTION IN

PLATELET AGGREGRATION



PHARMACOLOGY

ANTI THROMBOXANE

ALI M., THOMSON., PROSTAGLANDINS, LEUKOTRIENES AND ESSENTIAL

FATTY ACIDS, 1995, 53 : 211-212

CONSUMPTION OF GARLIC DAILY

FOR PERIOD OF 16 WEEKS

REDUCED THROMBOXANE BY ABOUT 80 %

PHARMACOLOGY



PHARMACOLOGY


Srivasta K.C. Antiplatelet Constituens of Garlic and their Mechanism of Action.

Abstrac Int Garlic Symposium Pharmacy, Pharmacology and Clinical Application

of Allium sativum, 1991.

MECHANISM OF ACTION

REDUCED THE FORMATION OF THROMBOXANE FROM

EXOGENOUS ARACHIDONATE

INHIBIT THE DEGRADATION OF PHOSPHOLIPID INDUCED BY

Ca2+ IONOPHORE

REDUCE THE GENERATION OF THROMBOXANE AND

12-LIPOXYGENASE PRODUCT FROM ARACHIDONATE PLATELETS

INHIBIT THE INCORPORATION OF ARACHIDONATE INTO PLATELET

PHOSPHOLIPIDS



PHARMACOLOGY


• Apitz-Castro R, et al. Effect of Garlic and of three pure

components isolated from it on human platelet aggregation,

arachidonate metabolism, realcascreation and platelet

ultrastructure. Thrombosis Research 32: 155-169, 1983.

Apitz-Castro R, et al. Ajoen, the antiplatelet priciple of Garlic,

synergetically potentiates the anti-aggregation of prostacyclin, foskolin,

indometacin and dipyridamole on human platelets. Thrombosis Research42: 303-311, 1986.

SEVERAL IN VITRO STUDIES REPORT

THAT GARLIC, OR ITS EXTRACTS,

REDUCE PLATELET AGGREGATION

INDUCED BY ADP COLLAGEN OR ADRENALIN



GARLIC

PHARMACOKINETICS

After oral administration, the total in all

Organs reached in 4 hours, and in 8 hours itwas reduced to half of the peak value.

(CHANG H.M, PHARMACOLOGY AND APPLICATIONS OF CHINESE

MATERIA MEDIKA, WORLD SCIENTIFIC, PHILADELPHIA, 1986 : 88.



GARLIC

TOXICITY

LD 50 OF THE GARLIC OIL IN MICE

BY I.V INJECTION WAS 134,9 mg/kg BW.

LD 50 OF NATURAL DIALLYLTHIOSULPHONATE

BY I.V WAS 70 mg/kg BW AND BY ORAL WAS 600 mg/kg BW.

NO PATHOLOGICAL CHANGE WAS OBSERVED IN LIVER,

SPLEEN, ADRENAL GLANDS, AND LUNG.

(CHANG H.M., PHARMACOLOGY AND APPLICATION OF CHINESEMATERIA MEDIKA, WORLD SCIENTIFIC, PHILLADELPHIA, 1986 : 88)



Qualitative and quantitative assay

for sulfer constituents (alliin, allicin etc.) :

by High-Performance Liquid Chromatographyor gas chromatography-mass spectroscopymethods.

Analysis



Apii graveolentisHerbs (Celery)

Clasification

Kingdom : PlantaeDivision : Magnoliophyta

Class : Magnoliosidae

Subclass : Rosidae

Ordo : Apiales

Family : Apiaceae

Genus : ApiumSpecies :Apium graveolens L



1. Aromatic smell, spicy, and thicken taste.

2. Green texture until brownish.

3. Leaves has complex fin, thin, brittle

4. Sub leaves amount 3 –

7 pieces, 2 –

7,5 cm long, 2-5 cm wide.

5. Main stalk has 12,5 cm long, rounded, stretch out,

6. Sub stalk 1-2,7 cm long.

7. Short stalk with stretch out skeleton.

8. Sturdy root with cylinder shape. If it cut a half has 10 mm diameter.

9. It have much Sub root with style like yarn and has 15 cm long,2 mm wide, brownish texture until gray.

DESCRIPTIONS




O

OH

O

O

OH

GluApiose-

ApiinO

O

OHOCH 2

OHHO

OH

OH

OH

O

Apigenin



PHARMACOLOGY

1. Preface analysis showed that hypotension effect

caused by chemoreseptor stimulation at karotid and

aorta.

2. On the perfusion experiment believe that apigenin

has vasodilator perifer effect

3. Another experiment showed that hypotension effect

is related to nerve integrity sympatic system.

4. 200 g fresh celery can causes diuretic effect



Analysis

Qualitative and quantitative assay

for Celery constituents (Apiin,Apigenin etc.) content by means ofhigh-performance liquidchromatography.



Syzygium polyanthum folium

(Indonesian Bay-Leaf)

Division Spermatophyta

Subdivision Angiospermae

Class Magnoliatae

Subclass Rosidae

Order Myrtales

Family Myrtaceae

Species Syzygium polyanthum (Wight) Waplers

Clasification



DESCRIPTIONS

1. Tree with spreading branches and simple leaves

2. Indonesian bay leaf can reach a height of 90 feet

although 60 feet is more common.

3. The flowers are pink and somewhat fragrant whilethe fruits are round; red at first, later brown.

4. The seeds are small and brown.

5. The dried brown leaves of Indonesian Bay-leaf are

aromatic and somewhat sour



PHARMACOLOGY

Antihypertension effect was showed

by decreasing of arterial blood tension

in male rat that became Hypertensionby difference of decreasing model with

verapamil.



Analysis

1. High-performance liquidchromatography Indonesian Bay-leafhas 28 essential oils, e.g Eugenol

2. Gas chromatography methods Containof sesquiterpenes-lactone.

Rauwolf iae serpentina Radix



Rauwolf iae serpentina Radix



DESCRIPTIONS

Rauwolfiae Radix consist of dry root

of Rauwolf ia serpent ina ( L).

• odourless,• feel bitterly,

• brown colour

•

length 5-15 cm




contains at least 1% alkaloids:

- reserpine, rescinnamine and deserpidine (group of reserpine)

- ajmaline, raupine, yohimbine and serpentine (ajmaline group)- ajmalicine (raubasine)


Reserpin

OH3C N

H

N

H H

H

CO

OCH 3

OCH 3

OC

O



PHARMACOLOGY

Reserpine possesses ant isympathicus (reduces

cateco lamines reserve, epinefr in and norepinefr in

and central sedative propert ies

ajmal ine group cause a quick ly act ing, but sho rtcont inu ing blood pressure lower ing by blockade

of a- adrenoreceptors .

Ajm alic ine (= raubasine) wo rks central and

peripheral vessel-extend ing and contr ibutes tothe bloo d p ressure-lowering to tal effect.



Analysis

Qualitative and quantitative assay for

Celery constituents (Reserpin, serpentineetc.) content by means of high-performance liquid chromatography.



Temulawak

Klasifikasi botani temu lawak adalah sebagaiberikut:

Divisi :Spermatophyta

Sub divisi :AngiospermaeKelas :MonocotyledonaeOrdo :ZingiberalesKeluarga :Zingiberaceae

Genus :CurcumaSpesies :Curcuma xanthorrhiza Roxb.



Kandungan Kimia Rimpang Temulawak

• Fraksi pati

• Fraksi kurkuminoid

• Fraksi minyak atsiri



Kurkuminoid Temulawak

Fraksi kurkuminoid rimpang temulawak terdiri atas duakomponen yaitu kurkumin dan desmetoksikurkumin,berwarna kuning atau kuning jingga, berbentuk serbuk

dengan rasa sedikit pahit, larut dalam aseton, alkohol,asam asetat glasial, dan alkali hidroksida.

Rumus kimia :kurkumin = C21H20O6 (BM = 368)

desmetoksikurkumin = C20H18O5 (BM = 338)



Struktur kurkuminoid

Kurkumin : 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6- diene-3,5-dione

Desmetoksikurkumin :

O O

OH

OMe

OH

OMe

O O

OHOH

OMe



PHARMACOLOGY

SRVASTA., DIKSHAR M., SRIMED R. C., 1985, THROMB.RES, 40:413-417

CURCUMIN INHIBITED

THROMBOXANE B2 PRODUCTION



PHARMACOLOGY

REFF :

SRIVASTA, R., M. DIKSHIT, R.C.SRIMAL, B.N.,DHAWAN, 1985, AntiThrombotic effect of Curcumin,

THROMBOSIS RES, 40 (3) : 413-417

SRIVASTA, R., V.PURI, R.C.SRIMAL, B.N. DHAWAN, 1986, Effect of Curcumin on Platelet

Aggregation and Vascular Prostacyclin Synthesis, ARZNEIMFORSCH, 36 (4) : 715-17

CURCUMIN HAD DEMONSTRATED

ANTI THROMBOTIC ACTION WHILE PRESERVING

PROSTACYCLIN, AN INFLAMATORY MEDIATOR.



PHARMACOLOGY

REFF :

AMMON, H.P.T and WAHL, M., 1991., Pharmacology of Curcuma longa, PLANTAMEDICA, 57 : 5-6

SRIVASTA, K.C., 1989, Extract from two frequently consumed spices, Cumin (Cucinumcyminum) and tumeric (Curcuma longa), inhibit platelet aggregation and alter alcosaniodbiosynthesis in human blood platelets, PROSTAGLANDIN LEUKOT ESSENT FATTY

ACIDS, 37 (1) : 57-64.

CURCUMIN HAD SHOWN NUMEROUS

ANTI INFLAMATORY EFFECTS IN VITRO AND IN VIVO,

SUCH AS ARACHIDONIC ACID PATHWAY ENZYME

MODIFICATION, DIMINISHED NEUTROPHYL RESPONSES

STABILIZATION OF INFLAMATORY CELL MEMBRANS, AND INHIBITION OF PLATELET AGGREGATION



PHARMACOLOGY

REFF :

SHAH, B.H, et al., 1999., Inhibitory effect of Curcumin. A food spice from

Tumeric on platelet activating factor and arachidonic acid mediated platelet

aggregation through inhibition of Thromboxane formation and Ca++ signaling,

BIOCHEM PHARMACOL., 58 (7) : 1167-1172.

CURCUMIN

INHIBITED PLATELET AGGREGATION

MEDIATED BY THE PLATELET AGONIST EPINEPHRIN,

ADP, PLATELET ACTIVATING FACTOR (PAF),

COLLAGEN, AND ARACHIDONIC ACID



PHARMACOLOGY

REFF :

SRIVASTA, K.C., BORDIA A., VERMA, S.K., 1995., Curcumin, a major

component of food spice turmeric (Curcuma longa) inhibits aggregation and

alters alcosanoid metabolism in human blood platelets, PROSTAGLANDIN

LEUKOT ESSENT FATTY ACIDS, 52 (4) : 223-227

CURCUMIN INHIBITED PLATELET AGGREGATION INDUCED

BY ARACHIDONATE, ADRENALIN, AND COLAGEN.

IT INHIBITED THROMBOXANE B2 (TXB2) PRODUCTION

FROM EXOGENOUS ARACHIDONATE WITH CONCOMITANTINCREASE IN THE FORMATION OF 12-LIPOXYGENASE

PRODUCTS

EFFECT OF TURMERIC EXTRACT ON THE



EFFECT OF TURMERIC EXTRACT ON THE

CONVERSION OF ARACHIDONIC ACID TO TXB2 AND

12-HETE IN HUMAN PLATELETS

REFF :

SRIVASTA. K.C., 1989, PROSTAGLANDINS LEUKOT ESSENT FATTY ACID, 37 (1) :

57-64.

CONTROL TXB2 12-HETE

2961 ± 338 10796 ± 2301

DOSE 1 (10 μg/mL)

N = 8

2122 ± 646

(**)

11956 ± 2620

(*)

DOSE 2 (20 μg/mL)

N = 8

1620 ± 510

(**)

13630 ± 3021

(**)

DOSE 3 (40 μg/mL)

N = 7

1168 ± 548

(**)

15262 ± 3801

(**)

DOSE 4 (80 μg/mL)

N = 3

898 ± 414 17923 ± 2575

(*) p < 0.05 (**) p < 0.01

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