The roots of cryptolepis, also known as nibima, kadze, gangamau, Ghanaian quinine and yellow-dye root (Cryptolepis sanguinolenta) have been used in Ghanaian traditional medicine for treatment of malaria for many generations. A Ghanaian drug company developed an herbal tea formulation trademarked as Phyto-Laria based on this plant, and the clinical evaluation of its potential as a herbal drug treatment for malaria was conducted, with the results published in this issue of the journal by Bugyei, et al (page 3). The active antiplasmodial components found in the root are known to be the indoquinoline alkaloids, which independently have been to have shown to have both in vitro and in vivo activity against Plasmodium falciparum, including chloroquine-resistant strains.1–5 A previously published open label anti-malarial clinical study on the water extract of this plant containing the Cryptolepis alkaloids taken orally indicated efficacy comparable to chloroquine.6 Therefore, the authors expected that the tea bag formulation, which contains significant amounts of the Cryptolepis alkaloids, would also be clinically efficacious.
An herbal tea bag preparation, free of preservatives (including chloroform found on other herbal preparations), based on 2.5 grams of dried ground roots of C. sanguinolenta, was studied in forty four patients with clinical features of uncomplicated malaria. Potential patients who had taken chloroquine or sulfadoxine/pyremethamine within the previous two and four weeks, respectively, where excluded from this study. In three open label out-patient settings in Ghana, the patients were dosed three times daily for five days under the WHO extended seven day test, and followed for 28 days post-treatment. More than half of the patients were cleared of P. falciparum parasitaemia within 72 h, with mean clearance of 82.3 h. The mean fever clearance time was 25.2 h compared to 48 h typical for chloroquine treatment, which is consistent with the previously reported antipyretic activity of C. sanguinoleta. Besides fever, the other symptoms of chills, vomiting and nausea were cleared totally in 72 h. The majority of biochemical parameters were not significantly modified following treatment, although ALP (alkaline phosphatase) and uric acid levels where elevated during the treatment period, with uric acid levels returning to normal by day 28. In comparison, halofantrine has also been reported to produce elevated levels of ALP during treatment.7 Overall, Phyto-Laria appears to be quite safe when taken orally, which is consistent with numerous animal toxicity testing data (mice, rats and rabbits) reported previously).8
It should be noted that there were two cases of late recrudescence on days 21 and 28, which may be attributed to reinfection, due to the out-patient trial design. However, as no genetic testing was included as part of the study design, this remains a hypothesis. Any further testing of Cryptolepis should include this a part of the trial design if an out-patient clinical setting is used.
Overall, the antimalarial cure rate in this patient population was 93.5%, and suggests that Phyto-Laria could be used as a safe effective treatment of acute uncomplicated malaria, and may also be useful in treatment of patients infected with chloroquine-resistant strains of P. falciparum as well.
Michael S. Tempesta, PhD
Phytica, Inc. P.O. Box 2439 El Granada, CA 94018-2439 USA
E-mail: natprod@aol.com
References
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