Diethyl Ether Extract of Senna siamea Exhibits Anti-plasmodial Polypharmacology Activity via Modulation of pbEMPI and hepatolipodystrophy Genes

Senna siamea (Lam.) H.S. Irwin & Barneby, Fabaceae, has been used by the locals for the management of malaria over the years. The aim of the research is to experimentally validate the usage of different extracts in the treatment of malaria using both in vitro and in vivo models and unveil the probable mechanism of action. Peter’s 4-day anti-malarial protocol was used, and a mechanistic elucidation was carried out using an appropriate genomic assay. The aqueous extract was observed to possess a weak anti-plasmodial activity due to 10.20 ± 2.52% and 1.44 ± 0.52% suppression and curation, respectively. Upon subjection to confirmatory bioassay, diethyl ether extract showed IC₅₀ of 0.0650 ± 0.01, which is significantly different from 0.8838 ± 0.01 observed in the chloroquine-treated group. About 100 mg/kg of diethyl ether extract also significantly suppresses the expression of the pbEMPI gene of Plasmodium berghei (post-treatment), relative to the untreated group and chloroquine methanol-treated group. Also, 100 mg/kg of diethyl ether extract showed reversed hepatic lipodystrophy by downregulating FAS, HMG-CoA reductase, and acetyl-CoA carboxylase genes relative to overexpressions observed in untreated, chloroquine, and methanol-treated groups. Inhibition of overexpression of 1L-1b, TNF-G, and 1L-10 hepatic portal tract inflammation genes was noted in 100 mg/kg of diethyl ether extract when compared with untreated, chloroquine, and methanol-treated groups. GC–MS of bioactive diethyl ether extract showed that squalene was the main constituent. In conclusion, the observed activity might be linked to the non-polar constituents with polypharmacology anti-plasmodial activity, in which squalene is the most abundant.