JURNAL ILMU KEFARMASIAN INDONESIA
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Pemodelan Farmakokinetika Tablet Floating Aspirin pada Kelinci dengan PKSolver
Aspirin selain sebagai analgetik juga efektif digunakan sebagai antiplatelet untuk profilaksis stroke. Aspirin diabsorpsi secara cepat di saluran pencernaan bagian atas terutama di bagian pertama usus halus. Formulasi dalam bentuk tablet floating diharapkan mampu memperbaiki profil farmakokinetika aspirin. Tujuan penelitian ini adalah untuk menentukan model farmakokinetika tablet floating aspirin pada kelinci dengan PKSolver. Penentuan model dengan PKSolver berdasarkan parameter: 1) visual goodness of fit (GOF) dan 2) parameter statistik yang meliputi Akaike’s information criteron (AIC) dan Schwarz criterion (SC). Berdasarkan kedua parameter tersebut menunjukkan bahwa model multiple site absorption (MAS) merupakan model terbaik untuk menjelaskan farmakokinetika tablet floating aspirin. Pelepasan dan absorpsi aspirin dari tablet floating terjadi melalui 2 tahap sehingga menghasilkan profil farmakokinetika dengan puncak ganda akibat absorpsi yang terjadi secara paralel di dalam lambung.Aspirin is an effective analgesic which is also used as an antiplatelet therapy for stroke prophylaxis. Aspirin is rapidly absorbed in the upper gastrointestinal tract, especially in the first of the small intestine. Formulation of floating drug delivery system are designed to improve the bioavailability of aspirin. The aim of this study was to determine pharmacokinetic model of floating tablets of aspirin in rabbits with PKSolver. PKSolver was used to evaluate the models based on the parameters: 1) visual goodness of fit (GOF), and 2) statistical criteria including the Akaike Information Criterion (AIC) and the Schwarz criterion (SC). Both the GOF and statistical criteria evaluations indicated multiple absorption site model as the best model describing pharmacokinetic of aspirin floating tablet. The release and absorption of aspirin floating tablet occurs through two phases resulting pharmacokinetic profile with a double peak due to absorption occur in parallel in the stomach
Studi Genotipe Sitokrom P450 2A6 Alel CYP2A6*4 dan CYP2A6*9 pada Subyek Uji Perokok Suku Jawa Indonesia
CYP2A6 belongs to the CYP2 family of P450 cytochromes were highly polimorphy. CYP2A6*1 (wild type) was an active allele, CYP2A6*9 was agen decreased allele and the CYP2A6*4 was an inactive allele. By using the polymerase chain reaction technique (PCR), the CYP2A6 polymorphism was studied among Javanese Indonesian smokers. In the process of genotyping the CYP2A6*9 allele, some subjects who had been genotyped as CYP2A6*1/*4 in our previous studies were regenotyped as CYP2A6*9 in this study. The primer forward 2A6*9S and the primer reverse 2A6*9AS-wild type were used in these study. The Promega Go Taq Green Master Mix reagent were used to amplifl y the allele CYP2A6*1 in the positions at -395 to -28 of the CYP2A6 gene. The sample studied consisted of 20 smokers with Cigarrete per-Day (CPD) <10 and 13 smoker with CPD 11-20 from Javanese Indonesian population. In theses research, the subjects had been genotyped as CYP2A6*1/*4 in our previous studies. The allele frequencies of CYP2A6*1, CYP2A6*4, and CYP2A6*9 were 48.5%, 48.5%, and 3%, respectively. When these allele were considered simultaneously, among the subject, 63.9% were genotyped for CYP2A6*1/*4 and 6.1% were genotyped for CYP2A6*1/*4/*9. Based on the data collected, it could be concluded that the polymorphism of CYP2A6 among Javanese population sample study was not aff ected on smoking behavior.CYP2A6 merupakan salah satu enzim golongan sitokrom P450 yang memiliki bentuk polimorfi . Bentuk aktif enzim ini adalah CYP2A6*1, sedangkan bentuk alel CYP2A6*9 merupakan enzim yang memiliki penurunan aktivitas dan bentuk tidak aktif enzim ini adalah CYP2A6*4. Adanya bentuk polimorfi enzim ini dapat dideteksi menggunakan metode polymerase chain reaction technique (PCR). Pada penelitian ini, identifi kasi CYP2A6*9 dilakukan terhadap subjek uji yang pernah terlibat pada penelitian terdahulu dan telah teridentifi kasi memiliki genotipe CYP2A6*1/*4. Primer yang digunakan pada penelitian ini adalah primer forward 2A6*9S dan primer reverse 2A6*9AS-wild type. Proses amplifi kasi DNA pada posisi -395 sampai -28 dari gen CYP2A6 dilakukan menggunakan enzim Promega Go Taq Green Master Mix. Subjek uji berasal dari suku Jawa Indonesia yang terdiri dari 20 orang perokok dengan Cigarrete per-Day (CPD) <10 dan 13 smoker dengan CPD 11-20. Hasil penelitian menunjukkan frekuensi alel CYP2A6*1, CYP2A6*4, and CYP2A6*9 berturut-turut sebesar 48,5%; 48,5%; dan 3%. Bentuk genotipe CYP2A6*1/*4 diantara subjek uji sebesar 63,9%, sedangkan genotipe CYP2A6*1/*4/*9 sebesar 6,1%. Berdasarkan hasil penelitian ini, maka dapat disimpulkan bahwa adanya bentuk polimorfi CYP2A6 diantara subjek uji bersuku Jawa Indonesia yang diteliti tidak mempengaruhi perilaku merokok subjek uji
Virtual Screening and Bonding Mode Elucidation of Curcumin Analogue in Cyclooxygenase-2 Enzyme Using EE_COX2_V.1.0 Protocol
Kurkumin adalah senyawa fenol bewarna kuning yang terkandung dalam Curcuma longa. Kurkumin diketahui memiliki aktivitas biologi antara lain sebagai inhibitor beberapa enzim metabolisme. Modifikasi struktur kurkumin telah banyak dilakukan. Pada penelitian ini dilakukan penapisan virtual dan elusidasi moda ikatan analog kurkumin menggunakan EE_COX2_V.1.0 sebagai protokol skrining virtual berbasis struktur yang telah tervalidasi. Pengaturan simulasi docking dilakukan menggunakan berbagai aplikasi yang terintegrasi seperti SPORES, PLANTS, BKchem, OpenBabel dan Pymol yang dapat mengidentifikasi senyawa inhibitor siklooksigenase-2 (COX-2). Dari hasil penapisan virtual didapatkan senyawa demetoksikurkumin dengan 3 residu asam amino dan 1,7-bis(3-metoksifenil)-1,6-heptadien-3,5-dion dengan 6 residu asam amino aktif in silico sebagai inhibitor COX-2.Curcumin is the yellow colored phenolic compounds contained in Curcuma longa. Curcumin is known to have biological activity as an inhibitor of some metabolic enzymes. The structure modification of curcumin has been done in many ways. In this research, virtual screening and bonding mode elucidation of curcumin analogue were done using EE_COX2_V.1.0 as validated structure based virtual screening (SBVS) protocol. Docking simulations were done using a variety of integrated applications such as, SPORES, PLANTS, BKchem, OpenBabel and Pymol which are able to identify cyclooxygenase-2 (COX-2) inhibitor substances. From the virtual screening using EE_COX2_V.1.0 protocol, demetoxicurcumin with 3 active amino acid residues and 1,7-bis(3-metoxiphenyl)-1,6-heptadiene-3,5-dion with 6 amino acid residues were obtained as active COX-2 inhibitors
LD50 and LC50 Values of Ethanol Extracts From Herbs of Ketumpangan Air (Peperomia pellucida (L.) Kunth)
Ketumpangan air (Peperomia pellucida (L.) Kunth), an Indonesian wild plant, is commonly found in every Indonesian region with moist shady place. People usually consume ketumpangan air as a fresh vegetables. Empirically, ketumpangan air is consumed to treat fever, stomach disease, kidney disorders, drug abscesses, boils acne, headaches, pain in arthritic and rheumatic gout, or other external treatment. In this research, we tested the acute toxicity of ethanol extract from ketumpangan air using experimental animals mice DDY strain. We also tested the Brine Shrimp Lethality Test (BSLT) using Artemia salina Leach larva shrimp. The main aim of this reseach was to determine the LD50 and LC50 values of ethanol extract from Ketumpangan air. The results showed that the ethanol extract was categorized as ‘mild toxic’. The calculation of LD50 with Reed and Munich method showed that the LD50 value for male and female group was 15.13 g/ kg and 11.87 g/kg respectively. The BSLT result showed that the LC50 values of Ketumpangan air was 81.28 ppm.Ketumpangan air (Peperomia pellucida (L.) Kunth), an Indonesian wild plant, is commonly found in every Indonesian region with moist shady place. People usually consume ketumpangan air as a fresh vegetables. Empirically, ketumpangan air is consumed to treat fever, stomach disease, kidney disorders, drug abscesses, boils acne, headaches, pain in arthritic and rheumatic gout, or other external treatment. In this research, we tested the acute toxicity of ethanol extract from ketumpangan air using experimental animals mice DDY strain. We also tested the Brine Shrimp Lethality Test (BSLT) using Artemia salina Leach larva shrimp. The main aim of this reseach was to determine the LD50 and LC50 values of ethanol extract from Ketumpangan air. The results showed that the ethanol extract was categorized as ‘mild toxic’. The calculation of LD50 with Reed and Munich method showed that the LD50 value for male and female group was 15.13 g/ kg and 11.87 g/kg respectively. The BSLT result showed that the LC50 values of Ketumpangan air was 81.28 ppm
Aktivitas Ekstrak Buah Adas (Foeniculum Vulgare Mill.) terhadap Uterin Tikus Wistar Betina yang Belum Dewasa
Fennel fruit (Foeniculum vulgare Mill.) is one of traditional plant medicine known having effects as anti-infl ammatory, analgesic and antioxidant. It also has been reputed to increase milk secretion, promote menstruation, facilitate birth, alleviates the symptoms of the male climacteric andincrease libido. Fennel fruit contains mainly with essential oils, such as anethole. It also contains lignan and flavonoids that are predicted having an estrogen-like eff ect or as phytoestrogen. Phytoestrogen is weak agonists for estrogen and can elicit statistic signifi cantly increases in uterine wet weight, at definite dose, in the uterothrophic bioassay. It is known that estrogen has eff ect on woman’s sexual organ, such as proliferation of uterine, mammary and ovary. The aim of this research was to investigate the estrogenic eff ect of fennel fruit’s ethanolic extract in immature, 19 days old, Wistar female rats. These models represent the climacteric/menopause phase, where estrogen level is very low because in this age, estrogen not yet produced by ovary. The testing animals were divided into fi ve groups, namely normal group, estradiol control group and three level doses of fennel extract (30 mg/200 g BW; 60 mg/200 g BW and 120 mg/200 g BW). The result indicated that start on 60 mg/200 g BW, fennel extract signifi cantly (α=0.05) increased wet weight of uterine. Fennel extract also lengthen the uterine and increased proliferation of uterine, such as uterine diameters, endometrium diameters and uterine thickness on dose 60mg/200gBW and 120mg/200gBW. Analysis of vaginal smear showed vaginal lubrication eff ect, surprisingly start on 60mg/200BW could induce estrous cycle.Buah adas (Foeniculum vulgare Mill.) merupakan salah satu tanaman obat tradisional yang dikenal memiliki efek sebagai anti-infl amasi, analgesik dan antioksidan. Dikenal juga untuk meningkatkan sekresi susu, mempromosikan menstruasi, memfasilitasi kelahiran, meringankan gejala klimakterik laki-laki dan meningkatkan libido. Buah adas banyak mengandung minyak esensial, seperti anethole, serta mengandung lignan dan fl avonoid yang diprediksi memiliki efek seperti estrogen atau sebagai fi toestrogen. Fitoestrogen adalah agonis lemah untuk estrogen dan dapat menimbulkan peningkatan yang signifi kan dalam berat basah uterus, pada dosis tertentu, dalam bioassay uterothrophic. Telah diketahui bahwa estrogen memiliki efek pada organ seksual wanita, seperti proliferasi uterus, kelenjar susu dan ovarium. Tujuan dari penelitian ini adalah untuk menyelidiki efek estrogenik ekstrak etanol buah adas pada tikus Wistar yang belum dewasa berusia 19 hari. Model-model ini mewakili faseklimakterik / menopause, di mana tingkat estrogen sangat rendah karena pada usia ini, estrogen belum diproduksi oleh ovarium. Hewan uji dibagi menjadi lima kelompok, yaitu kelompok normal, kelompok kontrol estradiol dan tiga tingkat dosis ekstrak adas (30 mg/200 g BB; 60 mg/ 200 g BB dan 120 mg/200g BB). Hasilnya menunjukkan bahwa mulai dari 60 mg/200 g BB, ekstrak adas secara signifi kan (α =0,05) meningkatkan berat basah uterus. Ekstrak adas juga memperpanjang uterus dan meningkatkan proliferasi uterin, seperti diameter uterus, diameter endometrium dan ketebalan uterus pada dosis 60mg/ 200gBW dan 120mg / 200gBB. Analisis pulasan cairan vagina menunjukkan efek lubrikasi vagina, secara mengejutkan dimulai pada 60 mg/ 200 g BB dapat menginduksi siklus estrus
Aktivitas Antibakteri Ekstrak Etil Asetat Media Kultur Fungi Endofi t Nigrospora oryzae dari Rhizophora mucronata
The purpose of this study was to provide information on the antibacterial activity of ethyl acetate culture broth extract of endophytic fungi associated with Rhizophora mucronata. An isolated fungi was identifi ed as Nigrospora oryzae using microscopic and molecular analysis. Theantibacterial activity was carried out using micro dilution method to get MIC value. The ethyl acetate extract showed antibacterial activity with MIC value of 250 μg/mL against and Escherichia coli and 500 μg/mL against Staphylococcus aureus.Tujuan penelitian ini adalah untuk memberikan informasi mengenai sifat antibakteri ekstraketil asetat media kultur fungi endofi t daun bakau (R. mucronata).Fungi endofit yang telah diisolasi dari daun R. mucronata diidentifikasi secara makroskopik, mikroskopik, dan molekuler. Ekstrak etil asetat dari media kultur fungi endofi t diuji aktivitas antibakterinya pada Staphylococcus aureus dan Escherichia coli menggunakan metode mikrodilusiuntuk mendapatkan nilai Konsentrasi Hambat Minimum (KHM). Hasil penelitian diperoleh isolat fungi endofi t yaitu Nigrospora oryzae. Ekstrak etil asetat (EtOAc) media kultur fungi endofi t yang diujikan pada E. coli menunjukkan nilai KHM 250 μg/mL terhadap bakteri E. coli dan 500 μg/mL terhadap bakteri S. aureus
Analisis Korelasi antara Efek Proliferasi Limfosit dengan Kandungan Fenolik dan Flavonoid Subfraksi Etil Asetat Myrmecodia tuberosa (Non Jack) Bl. secara In Vitro pada Mencit BALB/C
Ethyl acetate fraction of Myrmecodia tuberosa (non Jack) Bl. expressed potential immunomodulatory effect in preliminary study. This study was aimed to determine the stimulation index of each subfraction towards lymphocyte of BALB/C mice by in vitro technique and to explore the activityof lymphocyte proliferation correlated to total phenolic contents. lymphocyte proliferation assay was performed by MTT. Determination of total flavanoid content was done by a colorimetric method while the total phenolic was tested by the Folin-Ciocalteu method. The result showed stimulation index profile was positively correlated with the total flavanoid content( R2 = 0,606) while weak correlation was observed on the total phenolic content (R2 = 0,167). Fraksi etil asetat tumbuhan sarang semut (Myrmecodia tuberosa (non Jack) Bl.) memiliki efek sebagai imunomodulator berdasarkan penelitian sebelumnya. Penelitian ini bertujuan untuk menentukan indeks stimulasi dari masing-masing subfraksi terhadap aktivitas proliferasi sel limfosit mencit BALB/C secara in vitro dan untuk mengetahui aktivitas proliferasi sel limfosit tersebut berkorelasi dengan lemah (R2 = 0,167)
Penetapan Parameter Mutu Ekstrak yang Memiliki Aktivitas sebagai Antioksidan dari Daun Cincau Hijau (Cyclea barbata L.Miers.)
Cincau Hijau leaves (Cyclea barbata L.Miers ) has been used empirically as a medicinal plant because it contains many potential compounds such as flavonoids. Cincau Hijau leaves has been known as antioxidant activity. Determination of pharmacognosy parameters and phytochemical screening of dry leaves and extracts have been carried out as well as determination of total fl avonoids content. Fresh leaves were extracts with water and Dry leaves were macerated with 96% ethanol and were then concentrated by rotavapor to obtain viscous extracts. Free radical scavenging activity of the extracts was evaluated using DPPH method. Afterwards, determination of specifi c and non-specifi c parameters were performed. Results of phytochemical screening of powder and 50% and 96% ethanol extract showed that tall the tested samples contained alkaloid, fl avonoids, saponins, tannins, steroids/ triterpenoids, coumarin. The examination of specifi c parameter showed that the extract has a thick consistency, tawny color, bitter taste, characteristic odor. In addition, water-soluble compound and 96% ethanol extract are 46.64 and 62.13% respectively whereas ethanol-soluble compounds are 39.22 and 74.72%, respectively. While the results of nonspecifi c parameters of 50% and 96 % ethanol extract displayed total ash content of 9.69 and 9.49%, respectively, acid insoluble ash content of 0.30 and 0.16%, respectively, content of water soluble ash of 9.17 and 4.30%, respectively, loss on drying of 9.35 and 8.9%, respectively, water content of 8.45 and 7.25%, respectively. Based on heavy metal contamination, Pb concentration in 50 and 96% ethanol extract are 0.0227 and 0.0333 mg/kg, respectively whereas Cd concentration are 0.1206 and 0.0022 mg/kg, respectively and total number of CFU of 4,22 x 103 and 2,30 x 103 colonies/g, respectively while molds and yeasts number of colony of 0,48 x 102 and 8,88 x 102 colonies/g, respectively. Moreover, the total flavonoid was 0,19 %. Result of DPPH inhibition test showed that IC50 96 % ethanol extract are 83,280 ppm and water extracts are 102,01 ppmCyclea barbata dikenal masyarakat sebagai obat tradisional dan dapat diolah menjadi minuman penyegar. Manfaat lainnya yaitu sebagai antioksidan yang dapat meredam radikal bebas. Penelitian ini bertujuan untuk menguji aktivitas antioksidan dengan metode peredaman radikal bebas DPPH dan menetapkan mutu ekstrak, serta kadar flavonoid total daun cincau hijau. Hasil penapisan fitokimia simplisia, ekstrak, dan air perasan menunjukkan adanya senyawa alkaloid, flavonoid, saponin, tanin, steroid, triterpenoid, dan kumarin. Hasil penetapan mutu ekstrak etanol 96% menunjukkan ekstrak dengan konsistensi kental, berwarna hijau kehitaman dan berbau khas spesifik. Kadar sari larut air 74,72%, kadar sari larut etanol 62,13%, susut pengeringan 10,86%, kadar air 9,26%, kadar abu total 9,49%, kadar abu tidak larut asam 0,16%, sisa pelarut etanol 0,46%, cemaran logam Pb 0,03 mg/kg dan Cd 0,02 mg/kg, cemaran mikroba dengan angka lempeng total 2,30x103 koloni/g dan angkakapang khamir 8,88x102 koloni/g. Hasil penetapan kadar flavonoid total menunjukkan kadar flavonoid sebesar 8,30%. Dari hasil penelitian dapat disimpulkan bahwa ekstrak etanol 96% daun cincau hijau memiliki mutu ekstrak yang baik dan aktivitas antioksidan dengan metoda peredaman radikal bebas menggunakan DPPH adalah pada ekstrak kental menunjukkan nilai IC50 sebesar 83,28 bpj, dan air perasan dengan IC50 102,01 bpj
Efek Anti-Agregasi Platelet Ekstrak Etanol Daun Salam (Syzygium polyanthum (Wight) Walp.) pada Mencit
Salam leaves (Syzygium polyanthum (Wight) Walp.) contains fl avonoids, volatile oil and phenolic acid that can inhibiting platelet aggregation induced by ADP (adenosine diphospate), arachidonic acid, epinephrine, thrombin, collagen and aff ecting the activity enzyme ectonucleotidase so it can be used as anti-platelet drug. The purpose of this study was to investigated 70% ethanol extract of salam leaves have anti-platelet aggregation eff ect and increase of dose can also increase anti-platelet aggregation. This study was performed in 5 groups, each group consisted of 5 mice there were: groups of positive control, normal control, 70% ethanol extract leaves doses (150, 300, 450) mg/ kg, each group is given orally once daily during 8 days and measurements of parameters at day-0 and day-9th. The results of this study was 70% ethanol extract of leaves of salam leaves doses (150,300, 450) mg/kgBW showed the eff ects prolong bleeding time, coagulation time, enhance the decreased plasma absorbance after the addition of ADP. From the measurement parameter bleeding time, coagulation time and measurement decreased plasma absorbance after the addition of ADP that 70% ethanol extract of salam leaves doses 150, 300 and 450 mg/kgBW have anti-platelet aggregation eff ect and increase of dose was able to increase the eff ect anti-platelet aggregation.Daun salam (Syzygium polyanthum (Wight) Walp.) memiliki kandungan fl avonoid, minyak atsiri dan asam fenolat yang berkhasiat menghambat agregasi platelet yang diinduksi ADP(Adenosin difosfat), asam arakidonat, epinefrin, trombin, kolagen dan mempengaruhi aktivitas enzim ektonukleotidase sehingga dapat digunakan sebagai obat anti-platelet. Tujuan dari penelitian ini untuk mengetahui bahwa ekstrak etanol 70% daun salam memiliki efek anti-agregasi platelet serta peningkatan dosisnya memiliki kemampuan meningkatkan efek anti-agregasi platelet. Penelitian ini dilakukan pada 5 kelompok mencit yang terdiri dari masing-masing 5 mencit, yaitu: kelompok kontrol positif, kontrolnormal, ekstrak etanol 70% daun salam dosis (150, 300, 450) mg/kg BB, masing–masing kelompok diberikan secara per oral satu kali sehari selama 8 hari dan dilakukan pengukuran parameter pada hari ke-0 dan hari ke-9. Hasil uji efek anti-agregasi platelet menunjukkan bahwa ekstrak etanol 70% daun salam dosis (150, 300, 450) mg/kg BB menunjukkan efek memperpanjang waktu pendarahan, waktu koagulasi serta memperbesar penurunan serapan plasma setelah penambahan ADP. Dari hasil pengukuran parameter waktu pendarahan, waktu koagulasi dan penurunan serapan plasma setelah penambahan ADP bahwa ekstrak etanol dosis 150, 300 dan 450 mg/kg BB daun salam memiliki efek anti-agregasi platelet dan peningkatan dari dosis dapat meningkatkan efek anti-agregasi platelet
Aktivitas Antimalaria Ekstrak n-Hexana Daun Artemisia Cina Galur Iradiasi terhadap Plasmodium berghei ANKA
Teknik mutasi dengan iradiasi telah terbukti meningkatkan kandungan artemisinin dalam daun . Pada penelitian ini dilakukan uji aktivitas antimalaria ekstrak daun galur radiasi 10, 20, dan 40 Gy serta optimasi dosis terapi bertujuan untuk mendapatkan ekstrak daun yang mempunyai aktivitas antimalaria yang terbaik dan dosis terapi yang optimum. Penelitian Tahap Optimasi dosis radiasi dilakukan secara in vivo dengan menggunakan mencit yang diinfeksi dengan 1 x 107 P. berghei yang di bagi menjadi 4 kelompok yaitu kontrol positif, dosis 10 Gy, dosis 20 Gy, dosis 40 Gy. Pemberian artemisinin dilakukan selama 3 hari setelah derajat parasitemia telah mencapai 5%. Pengamatan parasitemia dilakukan setiap hari hingga hari ke-7 paska terapi. Hasil penelitian diketahui artemisinin 10 Gy memberikan hasil yang terbaik karena pertumbuhan parasitnya paling rendah dan mencit bertahan hidup lebih lama. Tahap optimasi dosis terapi dilakukan dengan metode yang sama dengan variasi dosis terapi 100, 200, dan 300 mg/kg BB. Hasil penelitian menunjukkan ekstrak daun galur mutan bisa menghambat pertumbuhan P.berghei secara signifikan (p <0,05) terhadap kontrol dengan Efektif dosis (ED50) dari 238,7 mg /kg BB. Kesimpulan ekstrak daun galur mutan 10 Gy yang terbaik dengan efektif dosis terapi (ED50) 238,7 mg/kg BB.Mutation techniques with irradiation has been shown to increase the artemisinin content of the leaves. In this study antimalarial activity test of leaf extracts radiation strains 10, 20, and 40 Gy and dose optimization of therapy aims to get leaf extract which has antimalarial activity of the best and optimum therapeutic dose. Research phase radiation dose optimization is done in vivo using mice infected with 1 x 107 P. berghei were divided into 4 groups: positive control, radiated 10 Gy, 20 Gy, 40 Gy. Giving artemisinin conducted for 3 days after the degree of parasitaemia has reached 5%. Observations parasitaemia was performed daily until day 7 post-treatment. The survey results revealed artemisinin 10 Gy provide the best results for the lowest parasite growth and the mice live longer. Phase therapeutic dose optimization performed by the same method with a variety of therapeutic doses of 100, 200, and 300 mg / kg. The results showed the mutant strains leaf extract can inhibit the growth P.berghei significantly (p <0.05) against a control with ED 238,7 mg/kg body weight. Conclusion leaf extract mutant 10 Gy with efectif of therapeutic dose (ED50) 238,7 mg / kg BW