Isolation, characterization and UPLC-DAD based quantification of antiplasmodial isoquinoline alkaloids from Cissampelos pareira L.

C. pareira L. is a centuries-old traditional medicinal plant utilized to treat various diseases like asthma, diarrhea, fever, heart disorders, snakebite, vomiting, malaria, pneumonia, dog bite, inflammation and abdominal pain. Globally, based on traditional knowledge, different parts of this plant are being used individually or in combination in various forms to manage malaria. However, the scientific investigation for validating the most effective part of this plant against malaria parasite has not been done. Therefore, current study aimed to evaluate in vitro antiplasmodial activity of extracts/fractions (whole plant) and decoctions from different parts (roots, stem, leaves and whole plant) of C. pareira against different strains of Plasmodium falciparum followed by antiplasmodial activity guided isolation and quantification of isoquinoline alkaloids in extracts/fractions and decoctions. All extracts/fractions/decoctions and molecules isolated from active fractions were investigated for antiplasmodial activity. Results showed that the chloroform fraction of whole plant was the most promising with IC50 (µg/mL) of 0.79 (Pf3D7) and 2.26 (PfINDO) followed by root decoction having IC50 (µg/mL) 10.22 (Pf3D7) and 7.7 (PfINDO). Among three isolated molecules, two bisbenzylisoquinoline alkaloids namely curine (2) [IC50 (µM) 1.46 (Pf3D7) and 0.51 (PfINDO)], and O,O-dimethylcurine (1) [IC50 (µM) 0.92 (Pf3D7) and 2.6 (PfINDO)], were found to be the most potent against P. falciparum strains. The antiplasmodial activity of chloroform fraction was further validated by the developed UPLC-DAD method, which showed the highest quantities of curine (2) (~107 mg/g) and O,O-dimethylcurine (1) (~15 mg/g) in this fraction. This study showed that the root decoction was more effective than decoctions of each of the other parts of the plant and whole plant hydroalcoholic extract. Further, for the first time, this study validates the traditional use of C. pareira whole plant to manage malaria, providing further opportunity to explore the tremendous structural and chemical diversity of isoquinoline alkaloids for antimalarial drug development