Antimalarial Efficacy of a Quantified Extract of Nauclea pobeguinii Stem Bark in Human Adult Volunteers with Diagnosed Uncomplicated falciparum Malaria. Part 2: A Clinical Phase IIB Trial

Abstract

According to the promising results of the Phase I and Phase IIA clinical trials with the herbal medicinal product PR 259 CT1 consisting of an 80 % ethanolic extract of the stem bark of Nauclea pobeguinii containing 5.6 % strictosamide, a Phase IIB study was conducted as a single blind prospective trial in 65 patients with proven Plasmodium falciparum malaria to evaluate the effectiveness and safety of this herbal drug. The study was carried out simultaneously using an artesunate-amodiaquine combination (Coarsucam®) as a positive control. This combination is the standard first-line treatment for uncomplicated malaria recommended by the National Programme of Malaria Control in the Democratic Republic of Congo (DR Congo). With regard to PR 259 CT1, patients were treated with a drug regimen of two 500-mg capsules three times daily for three days in the inpatient clinic, followed by out-patient treatment of one 500-mg capsule three times daily during the next four days; the positive control group received two tablets containing 100 mg artesunate and 270 mg amodiaquine (fixed-dose) once daily during three consecutive days. Antimalarial responses were evaluated according to the WHO 2003 guideline for a 14-day test. The results from the physical and laboratory examinations did not show any significant changes in values of vital signs, ECG, biochemical, and haematological parameters. The study showed a significant decreased parasitaemia in patients treated with PR 29 CT1 and artesunate-amodiaquine with adequate clinical parasitological responses (APCR) at day 14 of 87.9 and 96.9 %, respectively. The former product was better tolerated than the latter since more side effects were observed for the artesunate-amodiaquine combination. These results indicated that PR 259 CT1 can be considered as a promising candidate for the development of a herbal medicine for the treatment of uncomplicated falciparum malaria.

Ethnobotanical study of plants used against malaria in Sélingué subdistrict, Mali

“…It is also non-toxic: no acute toxicity was observed in mice after a single 2 g/kg oral dose, nor after 4 weekly doses (Mesia et al, 2010). Furthermore it is safe and effective against uncomplicated malaria in humans (Mesia et al, 2011;Mesia et al, 2012a;Mesia et al, 2012b). One of the active compounds is thought to be strictosamide.…”

The value of central-African traditional medicine for lead finding: Some case studies

“…Moreover, all symptoms progressively disappeared, and no symptoms were observed on day 14. Although the number of patients included in this study was rather limited, the statistical analysis nevertheless suggested the efficacy and tolerability of PR 259 CT1, which indicated that this herbal medicinal product might be considered as a putative candidate for a large scale clinical trial (Mesia et al, 2012a).…”

“…Without trying to be complete, Table 1 gives a list of some successful examples of this approach in our team, where lead compounds have been isolated from Central-African medicinal plants, and in some cases used as starting point for the synthesis of analogues or derivatives in order to study structure-activity relationships, and to optimize the activity . The last example even led to successful clinical studies of a standardised extract developed from the investigated medicinal plant (Mesia et al, 2012a(Mesia et al, , 2012b.…”

“…N 1 ,N 1 -Diethyl-N 4 -(5-methyl-5H-indolo[2,3-b]quinolin-8-yl)pentane-1,4-diamine.A.J. Vlietinck et al / Journal of Ethnopharmacology ∎ (∎∎∎∎) ∎∎∎-∎∎∎ evaluate the effectiveness and safety of this herbal drug(Mesia et al, 2012b). The study was carried out simultaneously using an artesunate-amodiaquine combination (ASþAQ) (Coaresucam s ) as a positive control.…”

Phytochemical analysis with free radical scavenging, nitric oxide inhibition and antiproliferative activity of Sarcocephalus pobeguinii extracts

“…The ethanolic extract of Sarcocephalus pobeguinii has been reported to exhibit good antimalarial activity in vitro against Plasmodium falciparum [8] and in vivo against Plasmodium berghei and Plasmodium yoellii mice models [9]. Clinical trials of an herbal medicine prepared with the ethanolic extract of the stem bark of S. pobeguinii indicated the safety and efficacy of this herbal medicine in the treatment of uncomplicated malaria [10–12]. Extracts and some isolated compounds from the bark of S. pobeguinii were identified with antiproliferative potential against drug-resistant cancer cell lines [13].…”