BACKGROUND MALARIA -HEALTH PROBLEM IN THE WORLD -HIGH PREVALENCE AND MORTALITY -CONTROL?

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2 BACKGROUND MALARIA -HEALTH PROBLEM IN THE WORLD -HIGH PREVALENCE AND MORTALITY -CONTROL? NEW DRUGS NATURAL SUBSTANCES

3 BACKGROUND information WHO MALARIA HEALTH PROBLEM IN THE WORD 2,4 MILLION PEOPLE LIFE IN AREA ENDEMIS AFRICA 45 ; AMERICA 21; MEDITERANIA 14 ; ASIA 8 EUROPA 4 ; ASIA PASIFIC 9 PARASITES PROTOZOA GENUS PLASMODIUM INDONESIA DRUG RESISTANCE TO ANTIMALARIA

4 NATURE SOURCE SOURCES DRUGS FOR MALARIA FLAVONOID PROPOLIS CONTENT SEKUNDER METABOLIT ACTIVITY PLASMODIUM ACTION MECHANISM

5 PROPOLIS STICKY SUBTANCE FROM THE BARK AND BUDS OF TRES PROTECT TREE FROM ENVIRONMENTAL HAZARD COLLECTED BY BEES TO PROTECT THEIR HIVES MIX WITH SALIVARY SECRETION BEE PROPOLIS

6 1. Propolis (bee glue) is a dark-colored resinous substance collected by bees from poplar buds and other plants and used to seal their hives. 2. These compounds can be grouped as follows: free aromatic acids; flavonoids; benzyl, methyl butenyl, phenylethyl,cinnamyl and other esters of these acids; chalcones and dihydrochalcones; terpenoids and others such as sugars, ketones, alcohol

7 CHEMICAL COMPOSITION - FLAVONOIDS - ALIPHATIC ACID - AROMATIC ACID - ESTERS - TERPENOIDS - AMINO ACIDS - ALDEHYDES - STEROID - ALCOHOLS - SUGAR

8 BIOLOGICAL ACTIVITIES 1. ANTIMICROBIAL 2. ANTIINFLAMATORY 3. ANTIOXIDANT 4. ANTIFUNGI 5. ANTIPROTOZOA : INHIBITION GROWTH - GIARDIA LAMBLIA IN VITRO - TRIPANOSOMA CRUZI IN VIVO & IN VITRO - PLASMODIUM? 6. IMMUNOMUDULATOR : MØ ACTIVATION

9 Cycle of parasite in the mosquito & Human body

10 Mechanism of action of hemozoin and new permease Line (NPP) MALARIA DRUG DISCOVERY Target Potensial Fraksi flavonoid Source of drug Transport membrane parasit Host protein breakdown parasit NPP Flavonoid fraction Sitosol Plasmodium Asam amino Sintesis protein Vakuola makanan & aktivitas biokimia Hb Globin heme Beta hematin (hemozoin) Flavonoid fraction of compounds suspected to have constraints on the degradation of hemoglobin and heme detosifikasi parasites as well as the parasite membrane inhibitor The death of the malaria parasite

11 MATERIALS AND METHODS Thirty male balb/c mice weighing approximately g aged between 6 and 8 weeks old were used for propolis treatment in vivo. The mice infected with 0.1 ml of the P. Berghei suspension at a concentration of 107 parasites per mouse on day The control group was given the solven in equal volume for the same duration. During the experimental period, the animals were housed under standard laboratory conditions with adlibitum water and balanced food.

12 Animals.. 1. Thirty male balb/c mice weighing approximately g aged between 6 and 8 weeks old were used for propolis treatment in vivo. The mice infected with 0.1 ml of the P. Berghei suspension at a concentration of 10 7 parasites per mouse on day The control group was given the solven in equal volume for the same duration. During the experimental period, the animals were housed under standard laboratory conditions with adlibitum water and balanced food.

13 Parasitemia analysis.. The methods of Giemsa blood smear was used to count the number of the parasits The blood in the periphery was taken from the tails of mice and prepared to a sample of thin and thick smeared blood method with Giemsa coloring. The number of parasitemia was calculated by determining the percentage of red blood cells infected by P. berghei in 1000 red blood cells.

14 Technique Painted with Giemsa 1.The metode of blood Giemsa blod smear was used to count the number of parasites 2.The Blood in the periphery was taken from the tails of mice and prepared to the sample 3.The Number of Parasitemia was calculated by determining the persentage of RBC by Infected P. Berhgei

15 OBSERVATION RESULTS After Induction plasmodium berghei 40 % Parasitemia D0 D1 D2 D3 D4 D5 D6 KONTROL - DOSIS 100 DOSIS 50 DOSIS 25 DOSIS 10 Figure 1 : Percentage parasitemia of inducted- Swiss mouse

16 Thin blood smears before and after treatment of Ethanol Extracts of Propolis 1 2

17 Result From the research results shown on Figure 1, we can see that the group of mice PHS-administered in the dosage of 50 mg kg-1 BW has higher concentration than those in the dosage of 10 and 25 mg kg-1 BW. Figure 2: there was visible difference in the development of Plasmodium berghei in early the first day of treatment and who have been given the treatment of ethanol extract of propolis on the sixth day

18 DISCUSSION - Ethanol extract of propolis Hydroalcoholic Solutions (PHS) showed immunostimulatory activity over antiplasmodial activity, evidenced by an increase in capacity in doses of 10, 25, 50 and 100, mg kg-1 BW. - PHS most potent antiplasmodial activity that attack mice was at 50 ml / kg body weight

19 CONCLUSION - Propolis ethanol extract Hydroalcoholic Solutions (PHS) showed immunostimulatory activity over antiplasmodial activity, evidenced by an increase in IgG immune systems in doses of 10, 25, 50 and 100, mg kg-1 BW. - Antiplasmodial activity of PHS is due to an increase in immune mice so they live longer. The most potent dose in the study were at 50 mg / kg.w

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