According to the World Health Organization (WHO), malaria incidence was less than 40% and mortality rate was less than 25% in Indonesia in 2021 (WHO, 2021). Annual parasite incidence (API), defined as the number of malaria cases per thousand people in each province in a year, was used to assess the success of the malaria eradication program of Indonesia. In 2021, 304 thousand malaria cases were recorded in Indonesia, with the highest number of cases observed in Papua, East Nusa Tenggara Province, and West Papua, with API >1% (Kemenkes, 2021).

The discovery of new antimalarial agents is pivotal in covering antimalarial drug resistance incidence. Since 1950, Plasmodium falciparum and Plasmodium vivax chloroquine resistance have contributed to the higher morbidity and mortality of malarial cases, notably children in endemic areas (Wellems and Plowe, 2001). Fortunately, artemisinin was discovered by a phytochemist from China in 1972, and the derivatives were successfully used to treat malaria patients in China (Liao, 2009). Those phenomena attracted the world's attention, and WHO announced artemisinin combination therapy as the first-line treatment for uncomplicated malaria in 2001 (WHO, 2019). Nevertheless, several cases related to artemisinin resistance were reported in western Cambodia, where the success rate of artemisinin-based combination therapies is decreasing (Dondorp et al., 2009). Those cases force researchers, WHO, and regional governments to increase their awareness of antimalarial medication. In addition, antimalarial resistance is not the only problem of malarial eradication; the limitation of public health service facilities in developing countries also contributes to the higher prevalence of malaria infections (Mutabingwa, 2005).

Therefore, using medicinal plants, such as Carica papaya leaves, Strychnos lucida stems, and Andrographis paniculate herbs, to prevent and treat malaria in remote areas plays an important role (Taek et al., 2018). S. lucida R. Br. is endemic to Southeast Asia, Indonesia, Malaysia, Thailand, and Northern Australia. In Indonesia, S. lucida is also known as Bidara laut and Kayu songga and found in Dompu-Bima (Sumbawa Island), West Bali Island, Timor Island, and the Tunak Ecotourism Park in Lombok (Setyayudi et al., 2019). Ethnopharmacological studies revealed S. lucida as an antimalarial and anthelmintic agent against snake poisoning, diarrhea, stomach ache, toothache, and fever (Ogi et al., 2014; Taek et al., 2018). Moreover, relative frequency of citation of S. lucida (0.34) is higher than that of other plants used as antimalarial agents. Tetun, the indigenous people of Timor Island, consume the boiled water of S. lucida seeds or stems to prevent and treat malaria (Taek et al., 2018).

Development of products containing S. lucida extracts is recommended owing to the benefits of S. lucida as an antimalarial agent. The Indonesian Drug and Food Agency classifies herbal medicinal products into three categories: traditional medicines or Jamu, standardized herbal medicines, and phytopharmaceutical products (BPOM, 2004). Determination of the marker compound concentration is crucial to adhere to the limits for standardized herbal medicines and phytopharmaceutical products set by the Indonesian Drug and Food Agency. The Indonesian Herbal Pharmacopeia lists brucine as a marker compound for S. lucida (Kementerian Kesehatan Republik Indonesia, 2017).

S. lucida contains indole alkaloids strychnine and brucine, which are toxic compounds (Chen et al., 2014; Liu et al., 2015; Lu et al., 2020; Philippe et al., 2004), necessitating its safety assessment before use. Some species of the Strychnos genus, such as S. nux-vomica, exhibit toxicity due to strychnine concentrations (Chen et al., 2011, 2014). A subchronic toxicity study of the S. lucida and artemisinin combination (800 + 333 mg/kg body weight [BW]) revealed an improvement in the histopathological, biochemical, and hematological profiles two weeks post-treatment (Sadiah et al., 2023). However, specific effects of the acute administration of S. lucida crude extract remain unknown. Therefore, evaluation of the acute toxicity of S. lucida crude extract using histopathology and biochemistry is necessary to determine its safety.

S. lucida ethanol extract exhibits antiplasmodial activity and reduces the growth of Plasmodium berghei by 33.06–43.74%. Ethanol and water extracts of S. lucida also exhibit high selectivity index of 211.47 and 78.46, respectively, as antimalarial agents (Khasanah et al., 2023). However, the antimalarial activity of S. lucida tablet (SLT) remains unknown. Therefore, in this study, we aimed to develop a tablet containing 100 mg of standardized S. lucida extract and assess its antiplasmodial activity against P. berghei in vivo.