STANDARDISATION OF A STEM BARK EXTRACT OF NAUCLEA POBEGUINII AND ITS IN VIVO ANTIPLASMODIAL ACTIVITY

Abstract

Nauclea pobeguinii (Rubiaceae) is widely used in African traditional medicine against malaria-like symptoms. Alkaloids, such as the major compound strictosamide are assumed to be responsible for the activity. An HPLC method was developed and validated for the quantification of strictosamide in an 80% EtOH extract of the stem bark of N. pobeguinii. The method was validated according to the ICH guidelines. The response of ajmalicine.HCl, used as a secondary standard, was linear in a concentration range from 4.2 to 21.2 µg/mL. The accuracy of the method was validated by means of a recovery experiment (mean recovery of 92.2% (RSD of 9.4%)). The method was shown to be precise with respect to time (RSD of 2.2%, 3 days, n = 6) and concentration (RSD of 2.6%, 3 levels, n = 6). A crude ethanolic extract of the bark, containing 5.6% (w/w) strictosamide, was evaluated in vivo in the Plasmodium berghei mouse model in a suppressive treatment regimen. The test substance was formulated in PEG400 and orally dosed (PO) at 300 mg/kg twice daily for 5 days. One group received the treatment intraperitoneally (IP) using the same dosing regimen. Chloroquine (10 mg/kg) was used as positive control. Treatment with the crude extract, administered either orally or intraperitoneally, resulted in moderate depression of parasitaemia during administration period, followed by a quick and full relapse (mean survival time = about 13 days). At termination of the experiment at day 21, a single survivor in the PO group was apparently cured (no parasitaemia), the single survivor in the IP group showed high parasitaemia and was in a moribund state. It can be concluded that the crude extract of N. pobeguinii has slight antimalarial potential when administered orally in a suppressive dosing regimen of 2x 5 days at 300 mg/kg. Its action is likely to be static since full relapse occurs quickly after ending the daily dosing.