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"Malaria merupakan salah satu penyakit infeksi yang paling berbahaya. Data WHO pada tahun 2023 melaporkan sebanyak 249 juta kasus malaria di dunia. Hal ini menunjukkan bahwa penyakit malaria memerlukan tindakan penanggulangan. Namun, maraknya kasus resistensi obat antimalaria menjadi salah satu penghambat dalam upaya tersebut, salah satunya resistensi obat antimalaria atovaquone. Untuk itu, dibutuhkan suatu upaya penanggulangan penyakit malaria, salah satunya adalah dengan pengembangan obat antimalaria baru. Diketahui bahwa tumbuhan mangrove Sonneratia alba memiliki potensi antimalaria terhadap Plasmodium berghei secara ex vivo. Penelitian ini bertujuan untuk mengetahui aktivitas antimalaria ekstrak metanol S.alba terhadap beberapa jenis P.berghei resisten terhadap atovaquone secara ex vivo dan in vivo, serta prediksi interaksi ikatan kimia senyawa utamanya secara in silico. Uji antimalaria secara ex vivo dengan konsentrasi ekstrak 100, 30, 10, 1 μg/mL menghasilkan nilai IC50 dari rentang 16,26 μg/mL – 39,08 μg/mL. Secara in vivo ekstrak metanol S.alba dengan dosis 100, 30, 10, 1 mg/kg BW tidak menunjukkan aktivitas antimalaria. Secara in silico, dua senyawa utama yang terkandung memiliki ikatan kimia kuat dengan model protein mitokondria sitokrom b P.berghei yaitu oleanolic acid dan fipronil. Uji keamanan ekstrak terhadap mencit sehat juga dalam kategori aman. Oleh karena itu, penelitian ekstrak metanol S.alba sebagai kandidat antimalaria perlu dikembangkan.

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Malaria is one of the most dangerous infectious diseases. WHO reports in 2023, 249 million malaria cases happened in the world. So that, malaria requires control measures. However, increasing number of antimalarial drug resistance cases is a burden, one of them is antimalarial drug atovaquone resistance. For this reason, development of new antimalarial drug candidate are needed. Previous study reports, Sonneratia alba mangrove plant has antimalarial potency against Plasmodium berghei in ex vivo. This study aims to determine the antimalarial activity of S.alba methanol extract against several types of P.berghei resistant to atovaquone ex vivo and in vivo, also predicted chemical bond interactions of the main compounds in silico. Ex vivo antimalarial tests with extract concentrations of 100, 30, 10, 1 μg/mL showed IC50 values in the range16.26 μg/mL – 39.08 μg/mL. In vivo, methanol extract of S. alba in 100, 30, 10, 1 mg/kg BW dose did not show antimalarial activity. In silico, the two main compounds have strong chemical bonds with mitochondrial cytochrome b protein of P.berghei model, namely oleanolic acid and fipronil. Safety test of the extract tested on healthy mice was also in the safe category. Therefore, development of methanol extract of S. alba as antimalarial candidate needs further research."

"Kemunculan resistensi parasit terhadap obat antimalaria, seperti artemisinin, sulfadoksin, dan piperakuin, menjadi tantangan besar dalam eliminasi malaria di negara-negara endemik, termasuk Indonesia. Hal ini meningkatkan urgensi pengembangan obat antimalaria baru yang dapat membunuh parasit sensitif dan resisten. Penggunaan model parasit Plasmodium berghei resisten diperlukan untuk merepresentasikan keberagaman populasi alami parasit ke skala laboratorium. Seleksi P.berghei resisten dilakukan melalui Repeated Incomplete Treatment (RIcT) dengan memaparkan dosis terapeutik obat pada parasit tanpa menyelesaikan pengobatan. Metode ini menyerupai kondisi kegagalan pengobatan berulang yang memicu terbentuknya resistensi pada parasit. Siklus pengobatan mencit dan pemulihan parasit dilakukan berulang sampai fenotipik resisten parasit teramati. Setelah empat regimen RIcT berbeda dilakukan, fenotipik resisten P.berghei terhadap artemisinin belum ditemukan. Pertumbuhan parasit tidak dapat ditekan selama pemberian obat pada siklus 2 berlangsung. Namun analisis molekuler target gen k13 tidak menunjukkan terbentuknya mutasi. Fenotipik resisten parasit terhadap sulfadoksin belum diperoleh setelah 3-4 siklus RIcT. RIcT sub-klon parasit menemui kondisi yang sama. Analisis molekuler target gen dhps tidak menujukkan keberadaan mutasi. Menariknya, gametositemia terjadi pada siklus terakhir RIcT. Kondisi ini meningkatkan risiko transmisi parasit ke nyamuk. RIcT piperakuin tidak dapat dilanjutkan setelah 2 siklus berlalu dikarenakan parasit habis selama pengobatan. Fenotipik resisten parasit tiga obat antimalaria pada eksperimen RIcT belum ditemukan

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The emergence of antimalarial drug resistance, such as artemisinin, sulfadoxine, and piperaquine, is an enormous hindrance to malaria elimination in endemic countries, including Indonesia. This increases the urgency in novel antimalarial drug development to obtain antimalarial drugs that are effective in clearing sensitive and resistant parasites. The use of a resistant Plasmodium berghei parasite model can represent the variety of parasites spreading in natural populations to a laboratory scale. The selection of P.berghei-resistant model was done through Repeated Incomplete Treatment (RIcT) by exposing a therapeutic dosage of the antimalarial drug to the parasites without finishing the treatment. This method mimics repeated treatment failure that induces resistance in parasites. The cycles of drug treatment and parasite recovery were repeated until phenotypic resistance was observed. After four different RIcT regimens, the parasite’s phenotypic resistance to artemisinin has not yet been observed. The parasite growth keeps rising during treatment in cycle 2. However, no mutation was found in k13 gene. Parasite phenotypic resistance to sulfadoxine has not been identified after 3-4 RIcT cycles. RIcT in sub-clone parasite faced the same situation. Molecular analisys at the target gene dhps did not show any mutation. Interestengly, gametocytemia was observed at the last cycle of RIcT. This condition increases the risk of parasite transmission into the mosquitoes. RIcT piperaquine could not be continued after 2 cycles duet o parasite clearance during drug treatment. Phenotypic resistant of the parasite to 3 of the antimalarial drugs used in this RIcT experiment is not yet observed."