Background and Purpose: Plant derived antimalarials are indispensable for malaria treatment and a reliable source of new drugs. The present study first time explores antimalarial efficacy of sinigrin present in ethanolic whole plant extract of Thlaspi arvense (EWETA) using in vitro, in silico and in vivo strategies. Experimental Approach: From EWETA, sinigrin was revalidated and quantified using HPLC. Schizont maturation inhibition assay was used to assess its in vitro antiplasmodial activity followed by the determination of cytotoxicity. Further, docking study was performed on key metabolic enzymes of P. falciparum using V-Life MDS tool. Peter’s 4-day test was employed to assess in vivo suppressive activity. Key Results: Sinigrin exhibited promising activity against both chloroquine (CQ)-resistant (RKL-9) IC50 5.14 μg/mL and CQ-sensitive (3D7) IC50 5. 47 μg/mL strains of P. falciparum and was safe in both in vitro (CC50> 640 μg/mL) and in vivo (LD50 > 2 g/kg) toxicity studies. In addition, virtual screening showed hydrogen bonding, hydrophobic and van der Waals interactions with amino acid residues of 3BPM (falcipain-3). Sinigrin illustrated good (ED50< 50 mg/kg) suppressive activity against P. berghei in monotherapy and enhanced the activity of artesunate (50 mg/kg) in combination with 100% survival and no parasite recrudescence. These observations are further corresponded and supported by Differential Leucocyte Count (DLC), biochemical and histopathological studies. Conclusions and implications: The outcomes of in vitro, in silico and in vivo studies suggest sinigrin as a HIT molecule which may potentially be used in many ways in drug and vaccine development approaches.

Background and Purpose: Day to day updates for increasing resistant cases even against artemisinin-based combination therapies has necessitated the need to develop new antiplasmodials. We evaluated the impact of crude ethanol extract of Bergenia ciliata (winter bignonia) rhizomes (EREBC), conventionally used as an antipyretic in the Himalayan region against the malaria parasite. Experimental Approach: HPTLC was performed to identify and quantify three marker compounds in EREBC. The in vitro antimalarial activity was evaluated by schizont maturation inhibition assay. MTT assay was employed to test the cytotoxicity of EREBC. Peter’s 4-day test and Peters method was employed to discern the suppressive and preventive activity of the extract respectively. Key Results: HPTLC analysis revealed the presence of bergenin, epicatechin and gallic acid in EREBC. It exhibited considerable inhibition (IC50<5µg/mL) of schizont maturation of both RKL-9 and MRC-2 strains of P. falciparum. EREBC was non-toxic to both HeLa cells and normal dermal fibroblasts (CC50>1000µg/mL). Selectivity index was >200 for both the strains. EREBC exhibited considerable in vivo suppressive activity with 96.48% inhibition at 500mg/kg in comparison to chloroquine (96.08%). The ED50 of the extract was <50mg/kg. No mortality was evident in mice administered with different doses of EREBC (50-500mg/kg) throughout the follow up period of 28 days. EREBC was also safe to liver and kidney function of mice as observed from biochemical analysis. Conclusions and implications: Overall, the study illustrates marked efficacy of EREBC as an antimalarial agent with bergenin, epicatechin and gallic acid as the major constituents of the extract.