The discovery of new antimalarial drugs from medicinal plants is urgently neededdue to the development of multidrug-resistant Plasmodium falciparum. Therefore, Piper sarmentosum(kaduk), a commonly used as a herbal medicine to treat malarial symptoms was screened for antimalarial as well as toxicological activities of their methanol and water leaves extracts. The inhibitory concentration (IC50) of P. sarmentosum methanol and water extracts against a chloroquine-sensitive strain (3D7) of P. falciparumwas determined by using a malarial SYBR Green I-based fluorescence (MSF) assay. The lethal concentration (LC50) of the plant extracts was evaluated by using a brine shrimp lethality test (BSLT). The presence of heavy metal contents in the crude extract was alsodetected by using an atomic absorption spectrometry (AAS). Both methanol and water extracts showed an inactive antimalarial activity with an IC50value of 138.8 ± 0.122 μg/mL and 229.7 ± 0.125 μg/mL, respectively. The water extract was considered non-toxic (LC50= 2741.7 3.16 ppm), while the methanol extract was toxic (LC50= 894.94 0.018 ppm). The heavy metals such as plumbum (Pb), zinc (Zn), cadmium (Cd) and chromium (Cr) were identified in the crude extract but they were below the safety limits recommended except for arsenic (As). Further investigations are required to determine the toxicological profiles of P. sarmentosum extracts on mammalian models.
Pyrogallol has a capability of generating free radicals like other antimalarial drugs such as artemisinin, which is thought to inhibit the proton pump located in the membrane of the Plasmodium falciparum digestive vacuole, thus alkalinising this acidic organelle. This study aimed to determine pH changes of the malaria parasite’s digestive vacuole following treatment with pyrogallol. The antimalarial activity of this compound was evaluated by a malarial SYBR Green 1 fluorescence-based assay to determine the 50% inhibitory concentration (IC50). Based on the IC50 value, different concentrations of pyrogallol were selected to ensure changes of the digestive vacuole pH were not due to parasite death. This was measured by flow cytometry after 4-hour pyrogallol treatment on the fluorescein isothiocyanate-dextran-accumulated digestive vacuole of the mid-trophozoite stage parasites. Pyrogallol showed a moderate antimalarial activity with the IC50 of 2.84 ± 9.40 µM. The treatment of 1.42, 2.84 and 5.67 µM pyrogallol increased 2.9, 3.0 and 3.1 units of the digestive vacuole pH, respectively as compared with the untreated parasite (pH 5.6 ± 0.78). The proton pump, V-type H+-ATPase might be inhibited by pyrogallol, hence causing the digestive vacuole pH alteration, which is similar with the result shown by a standard V-type H+-ATPase inhibitor, concanamycin A. This study provides a fundamental understanding on the antimalarial activity and mechanism of action of pyrogallol that has a potential to be the antimalarial drug candidate.