Towards understanding antimicrobial activity, cytotoxicity and the mode of action of dichapetalins A and M using in silico and in vitro studies

Dichapetalum madagascariense Poir (Dichapetalaceae) is traditionally used to treat bacterial infections, jaundice, urethritis and viral hepatitis in Africa. Its root contains a broad spectrum of biologically active dichapetalins. To evaluate the plant's effect on human MCF-7 cells and its' antibacterial and antiparasitic potentials, we isolated and identified the known dichapetalins A and M from the roots. Both dichapetalins were tested on six bacterial strains (Shigella fiexneri, Bacillus cereus, Salmonella paratyphi B, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus) and two parasite strains; Trypanosoma brucei brucei, and Leishmania donovani using the Alamar Blue assay system. Dichapetalins A and M were more potent against B. cereus with IC50 values of 11.15 and 3.15 mu g/ml, respectively, compared to the positive control ampicillin (IC50 = 19.50 mu g/ml). Dichapetalins A (IC50 = 74.22 mu g/ml) and M (IC50 = 72.34 mu g/ml were less active against T. b. brucei, compared to the standard Suramin (IC50 = 4.96 mu g/ml. Dichapetalin M showed moderate activity against L. donovani (Amphotericin B: IC50 = 0.21 mu g/ml with an IC50 of 16.80 mu g/ml. In human MCF-7 cells expressing the NR1I2 receptor, the activity of dichapetalin M was higher (IC50 = 4.71 mu M and 3.95 mu M) for 48 and 72 h of treatment, respectively compared to Curcumin with IC50 of 17.49 mu M and 12.53 mu M for 48 and 72 h of treatment, respectively. Results from in vitro expression studies with qPCR confirmed an antagonistic effect of dichapetalin M on PXR (NR1I2) signaling; supporting the PXR signaling pathway as a possible mode of action of dichapetalin M as predicted by in silico results. These findings confirm previous studies that D. madagascariense can be a source of potential lead compounds for development of novel antibiotic, antiparasitic and anticancer medicines, and provide further insights into the mechanism of action of the dichapetalins.

Automated summary

Dichapetalum madagascariense is traditionally used in Africa to treat bacterial infections, jaundice, urethritis, and viral hepatitis. The plant's root contains biologically active dichapetalins, and experimental results suggest that dichapetalins have antibacterial and antiparasitic properties.