# Growth Inhibition and Additive Effect to Antimalarial Drugs of Brucea javanica Extracts on Asexual Blood-Stage Plasmodium falciparum

## TL;DR

This study shows that Brucea javanica plant extracts can inhibit malaria parasite growth and work well with existing antimalarial drugs.

## Contribution

The study demonstrates the additive effect of Brucea javanica extracts with artesunate and chloroquine against malaria parasites.

## Key findings

- Bracea javanica root and fruit extracts inhibited Plasmodium falciparum growth without causing red blood cell hemolysis.
- The plant extracts showed additive effects when combined with artesunate and chloroquine, reducing parasite development.
- Extract-treated parasites exhibited nuclear clumping and pyknotic cell death, indicating effective inhibition.

## Abstract

Malaria is a parasitic infectious disease that is endemic in many tropical countries. Even though several effective antimalarial agents have been implemented, treatment failure still occurs, and malaria continues to cause neurological complications and death, particularly in severe or drug-resistant cases. Hence, novel therapeutic agents with distinct mechanisms of action, as well as alternative chemical compounds that can overcome resistance, are still needed to improve malaria therapy. This study aimed to investigate the antimalarial activities of Brucea javanica, a tropical plant extracts against Plasmodium falciparum, the major species associated with severe malaria. In this study, malaria parasites were treated with plant extracts using single and co-incubation methods, along with artesunate and chloroquine, and their inhibitory effect on parasite development was determined by microscopy. The results show that all tested doses of the extracts that effectively inhibited malaria parasites did not cause hemolysis of red blood cells (RBCs). The root extract (RE) and fruit extract (FE) inhibited parasite growth at IC50 values of 0.41 ± 1.14 µg/mL and 0.26 ± 1.15 µg/mL, respectively. These plant extracts significantly interrupted malaria development at the ring stage, as presented by a reduction in the conversion rate to trophozoites and schizonts. The defective parasites treated with plant extracts were characterized by nuclear clumping, leading to pyknotic cell death. Moreover, RE and FW extracts elicited an additive effect with artesunate and chloroquine, significantly reducing IC90 levels for the inhibition of parasite development. In conclusion, B. javanica extracts inhibited the asexual blood-stage development of malaria parasites. They distinctively show the additive effects of ATS and CRQ, elucidating their potential for further studies on novel formulas of antimalarial drug regimens.