Malaria is one of the world's leading killer infectious diseases with high incidence and morbidity. The problem of multidrug-resistant Plasmodium falciparum has been aggravating particularly in Southeast Asia. Therefore, development of new potential antimalarial drugs is urgently required. The present study aimed to investigate antimalarial activities of a total of 27 medicinal plants and 5 herbal formulations used in Thai traditional medicine against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) P. falciparum clones. Antimalarial activity of the ethanolic extracts of all plants/herbal formulations against K1 and 3D7 P. falciparum clones was assessed using SYBR Green I-based assay. All plants were initially screened at the concentration of 50 μg/ml to select the candidate plants that inhibited malaria growth by ≥50%. Each candidate plant was further assessed for the IC50 value (concentration that inhibits malaria growth by 50%) to select the potential plants. Selectivity index (SI) of each extract was determined from the IC50 ratio obtained from human renal epithelial cell and K1 or 3D7 P. falciparum clone. The ethanolic extracts from 19 medicinal plants/herbal formulation exhibited promising activity against both K1 and 3D7 clones of P. falciparum with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the eight medicinal plants (Plumbago indica Linn., Garcinia mangostana Linn., Dracaena loureiri Gagnep., Dioscorea membranacea Pierre., Artemisia annua Linn., Piper chaba Hunt., Myristica fragrans Houtt., Kaempferia galanga Linn.) and two herbal formulations (Benjakul Formulation 1 and Pra-Sa-Prao-Yhai Formulation) showed potent antimalarial activity with median range IC50 values of less than 10 μg/ml against K1 or 3D7 P. falciparum clone or both. All except G. mangostana Linn. and A. annua Linn. showed high selective antimalarial activity against both clones with SI>10. Further studies on antimalarial activities in an animal model including molecular mechanisms of action of the isolated active moieties are required.

Malaria remains a public health problem in tropical and subtropical regions. Resistance of Plasmodium falciparum to artemisinins in Southeast Asia is a great concern for disease control and research on discovery and development of new alternative antimalarial drugs is urgently required. In a previous study, the fruit of Piper chaba Hunt. was demonstrated to exhibit promising antimalarial activity against the asexual stage of 3D7 (chloroquine-sensitive) and K1 (chloroquine-resistant) P. falciparum clones. The aim of the present study was to further investigate the antimalarial activity of piperine, the major isolated constituent of Piper chaba Hunt. fruits against both P. falciparum clones. The antimalarial activity was determined using SYBR green-I-based assay and morphological change was observed under the light microscope with Giemsa staining. The median IC50 (concentration that inhibits parasite growth by 50%) values of piperine against 3D7 and K1 P. falciparum were 111.5 and 59 μM, respectively. A marked change in parasite morphology was observed within 48 hours of piperine exposure. Results of real-time PCR showed no effect of piperine on modulating the expression of the three genes associated with antimalarial drug resistance in P. falciparum, i.e., pfcrt, pfmdr1, and pfmrp1. Piperine could be a promising candidate for further development as an antimalarial drug based on its antimalarial potency and low risk of resistance development.

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Atractylodin and β-eudesmol, the major bioactive compounds in Atractylodes lancea, are promising candidates for anti-cholangiocarcinoma. The inhibitory effects of both compounds on human rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 and rCYP3A4 enzymes were investigated using luminogenic CYP450 kits. The modulatory effects were investigated in mouse livers following a daily oral dose of atractylodin or β-eudesmol at 100 mg/kg body weight for 1, 7, 14, and 21 days. The inhibitory effects of both compounds on all rCYP450s were weak (IC50: 167 to >686 µM). β-Eudesmol showed the most potent inhibitory effect on rCYP2C19 (IC50 = 172.7 µM) and rCYP3A4 (IC50 = 218.6 µM). Results of the ex vivo study showed that short exposure (1–7 days) of atractylodin and β-eudesmol resulted in the upregulation of mRNA. Prolonged exposure to the daily oral dose for at least 14 days significantly downregulated the expressions of mRNA and proteins, which correlated with the decrease in the activities of mCYP1A2 and mCYP3A11. Based on the results of the ex vivo study, clinical uses of atractylodin or β-eudesmol for the treatment of cholangiocarcinoma are of concern for the risk of toxicity due to hCYP3A4 inhibition following chronic dosing, as well as the metabolic interaction with the coadministered drugs that are metabolized by hCYP3A4.

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