Antiplasmodial, Antimalarial and Hemozoin Inhibitory Potential of Nauclea pobeguinii Rootbark Methanol Extract

Purpose: Nauclea pobeguinii is one of the medicinal plants commonly used to manage malaria in Nigeria. This study sought to assess its antimalarial mechanism of action by evaluating its phytochemical content, antiplasmodial activity, cytotoxicity, and heme detoxification potential. Furthermore, we conducted an in silico ADME of the β-carboline alkaloids reported to be responsible for it’s their antimalarial activity. Phytochemical screening revealed the presence of several phytometabolites, including alkaloids. The extract was non-toxic to HUH cells and inactive against the malaria parasite in culture. Given its in vitro inactivity, we assessed its antimalarial activity and probed for inhibition of heme biocrystallization in vivo. Methods: Blood was taken from the hearts of 3 mice each in the control and study groups, and the blood was lysed to release the parasites, whose parasitophorous vacuole and digestive vacuole (DV) membranes were disrupted, releasing DV contents from which free heme was quantified. Results: There was a dose-dependent decrease in parasitemia and hemozoin concentration, suggesting that higher doses of the extract led to greater inhibition of heme biocrystallization. However, on day 10, parasitemia levels in N. pobeguinii-treated mice reached levels comparable to those of untreated controls, negatively impacting mouse survival. Our in-silico study revealed that the N. pobeguinii-derived β-carboline alkaloids are not only substrates of Permeability glycoprotein but also of several Cytochrome P450 enzymes.. Conclusion: The result of our study thus suggests that while N. pobeguinii may kill the malaria parasite by inhibiting heme biocrystallization; its antimalarial activity may be impacted by poor oral pharmacokinetics.