[ABSTRAK
Latar belakang: Salah satu tantangan terbesar dalam upaya pengobatan malaria adalahterjadinya penurunan efikasi pada penggunaan obat antimalaria, seperti kasus resistensi.Kejadian resistensi terhadap beberapa jenis obat mendorong penemuan obat antimalariabaru terus dilakukan. Beberapa studi yang telah dilakukan menyebutkan bahwaandrografolid (ANDRO) memiliki efek sebagai antimalaria. Dehidroksiandrografolid(DeOH-AND) adalah senyawa yang memiliki kemiripan struktur dengan ANDRO.Penelitian ini bertujuan untuk mengetahui efek DeOH sebagai antiplasmodium danmekanisme kerjanya.Metode: Penelitian ini merupakan penelitian eksperimental dengan teknik in vitro. Padapenelitian ini digunakan galur parasit Plasmodium falciparum 3D7 (chloroquinesensitive). Percobaan dilakukan untuk menjawab tiga tujuan penelitian; pertamabertujuan untuk mengetahui potensi DeOH-AND sebagai antiplasmodium denganmelakukan uji IC50, uji hambatan bergantung stadium parasit dan melihat morfologi selparasit menggunakan mikroskop cahaya dan TEM (Transmission Electron Microscope).Kedua bertujuan untuk mengetahui efek sitotoksik DeOH-AND terhadap sel mamaliayang diujikan pada sel hati galur sel HepG2 dan sel darah merah. Ketiga, bertujuan untukmempelajari pengaruh DeOH-AND terhadap status oksidatif parasit dilihat dari kadarROS intraseluler parasit, rasio GSH/GSSG dan aktivitas enzim SOD.Hasil: DeOH-AND memiliki aktivitas antiplasmodium dengan nilai IC50 sebesar 4 μMsedangkan kontrol klorokuin yang digunakan memiliki nilai IC50 sebesar 0.06 μM(60x10-9 M). Kedua senyawa ini dapat menghambat pertumbuhan sel parasit pada stadiumring, tropozoit dan skizon. Hasil pengamatan menggunakan mikroskop cahaya dan TEMmempelihatkan kerusakan pada sel parasit bila dibandingkan dengan kontrol. SenyawaDeOH-AND tidak toksik terhadap sel hati (HepG2) dengan nilai CC50 yakni 394.67 μMserta tidak toksik pada sel darah merah. Hasil percobaan bagian ketiga menunjukkanbahwa DeOH-AND tidak mempengaruhi kadar ROS, rasio GSH/GSSG serta aktivitasenzim SOD.Kesimpulan: Senyawa DeOH-AND memiliki potensi sebagai antiplasmodium dan tidakmemiliki efek toksik terhadap sel mamalia baik hati (HepG2) dan sel darah merah.DeOH-AND tidak mempengaruhi status oksidatif parasit secara signifikan.

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ABSTRACT
Background: One of the biggest challenges in malaria treatment is the occurrence ofdecreasing efficacy on antimalarial drugs like resistancy cases. Insidence of some drugresistance encourages the new antimalarial drugs continue to discover. Severeal studiesmentioned that andrographolide (ANDRO) has an antimalarial effect.Dehidroksiandrographolide (DeOH) is a compound which has structural similarities withANDRO. This study aims to determine the effect of DeOH as antiplasmodium and itsmechanism.Methods: This is an experimental study using in vitro techniques. In this study were usedPlasmodium falciparum 3D7 strains (chloroquine sensitive). The experiments has three aims;the first part was aimed to known about the potential of DeOH-AND as an antiplasmodiumusing IC50 assay technique, stage dependent antiplasmodium activity, and analyse the P.falciparum morphology using light microscope and TEM (Transmission ElectronMiscroscope) technique. The second parts was aimed to investigate the cytotoxic effect ofDeOH-AND on mamalian cell (hepar cell-HepG2 and red blood cell). And the third aims isto investigate the effect of DeOH-AND on parasite oxidative stress status with analyse theintracellular ROS (Reactive Oxygen Species) concentration, GSH/GSSG ratio and SOD(Superoxide Dismutase) enzyme activity.Results: DeOH-AND has antiplasmodium activity with IC50 value of 4 μM whereaschloroquine has IC50 values of 0.06 μM (60x10-9M). These compounds was found to inhibitthe ring, tropozoit and skizon stage of the parasite. Treated P. falciparum 3D7 parasites showthe crisis of their morphology cell which compared with untreated parasites (control). DeOHANDis not toxic to liver cells (HepG2) with CC50 values 394.67 and also not toxic to redblood cells which were seen from the results of hemolysis potential test. DeOHantiplasmodium effect were seen on all stage of the parasite (either ring, trophozoit andschizont) and caused parasite cell damage effect activity at all stages of the parasite (eitherring, trophozoit and schizonts) and shown to cause damage. The third experiment showed thatDeOH-AND did not affect the intracellular ROS (Reactive Oxygen Species) concentration,GSH/GSSG ratio and also SOD enzyme activity.Conclusions: DeOH compounds has antiplasmodium activity. These compound has no toxiceffect on both of the liver cells (HepG2) and red blood cells. DeOH-AND did not affect parasitoxidative status with significantly, Background: One of the biggest challenges in malaria treatment is the occurrence ofdecreasing efficacy on antimalarial drugs like resistancy cases. Insidence of some drugresistance encourages the new antimalarial drugs continue to discover. Severeal studiesmentioned that andrographolide (ANDRO) has an antimalarial effect.Dehidroksiandrographolide (DeOH) is a compound which has structural similarities withANDRO. This study aims to determine the effect of DeOH as antiplasmodium and itsmechanism.Methods: This is an experimental study using in vitro techniques. In this study were usedPlasmodium falciparum 3D7 strains (chloroquine sensitive). The experiments has three aims;the first part was aimed to known about the potential of DeOH-AND as an antiplasmodiumusing IC50 assay technique, stage dependent antiplasmodium activity, and analyse the P.falciparum morphology using light microscope and TEM (Transmission ElectronMiscroscope) technique. The second parts was aimed to investigate the cytotoxic effect ofDeOH-AND on mamalian cell (hepar cell-HepG2 and red blood cell). And the third aims isto investigate the effect of DeOH-AND on parasite oxidative stress status with analyse theintracellular ROS (Reactive Oxygen Species) concentration, GSH/GSSG ratio and SOD(Superoxide Dismutase) enzyme activity.Results: DeOH-AND has antiplasmodium activity with IC50 value of 4 μM whereaschloroquine has IC50 values of 0.06 μM (60x10-9M). These compounds was found to inhibitthe ring, tropozoit and skizon stage of the parasite. Treated P. falciparum 3D7 parasites showthe crisis of their morphology cell which compared with untreated parasites (control). DeOHANDis not toxic to liver cells (HepG2) with CC50 values 394.67 and also not toxic to redblood cells which were seen from the results of hemolysis potential test. DeOHantiplasmodium effect were seen on all stage of the parasite (either ring, trophozoit andschizont) and caused parasite cell damage effect activity at all stages of the parasite (eitherring, trophozoit and schizonts) and shown to cause damage. The third experiment showed thatDeOH-AND did not affect the intracellular ROS (Reactive Oxygen Species) concentration,GSH/GSSG ratio and also SOD enzyme activity.Conclusions: DeOH compounds has antiplasmodium activity. These compound has no toxiceffect on both of the liver cells (HepG2) and red blood cells. DeOH-AND did not affect parasitoxidative status with significantly]