188
S. D. Shnyder and C. W. Wright
2010 to 2018, the rate of improvement has slowed since 2014, and there were an estimated 228 million cases worldwide in 2018. Meanwhile, the most important malaria
parasite, Plasmodium falciparum, responsible for 99.7% cases globally, has developed resistance to artemisinin derivatives in some areas, especially along the Thai–
Cambodia border [34, 35], so that there is an urgent need for new antimalarial drugs.
In addition, attention is again being given to the eradication of malaria, which will
require antimalarial drugs with activity against the liver and gametocyte stages of the
parasite as well as the blood stages targeted by most currently available antimalarial
agents.
The aqueous root extract of C. sanguinolenta is used widely in West Africa for the
treatment of malaria. In Ghana, the herbal product, Phyto-laria, is marketed for the
treatment of malaria in the form of tea bags and a number of other Cryptolepis-based
aqueous formulations are also available. The efficacy of Phyto-laria was assessed
in a prospective, open clinical study in patients over the age of 11, with clinical
symptoms of malaria and a diagnosis of malaria by examination of blood films
[36]. Parasitemia in all of the patients evaluated cleared within seven days, with two
patients showing recrudescence within 28 days, although this could have been due
to re-infection. Hematological and biochemical abnormalities present before being
treated generally improved during treatment but blood alkaline phosphatase levels
were elevated persistently during the study compared with pre-treatment values, and
serum uric acid levels showed a significant rise during treatment. The study suggests
that Phyto-laria may be effective for the treatment of malaria in patients aged between
11 and 50 years. However, an important limitation of the study was the exclusion of
young children, who are the most susceptible to serious complications and death due
to malaria. Hence, it cannot be assumed that Phyto-laria would be effective in this
group, as those under five years of age especially are likely to have little immunity
to malaria. Pregnant women, who are also at increased risk of severe malaria, were
also excluded from this study [36].
In a pharmacovigilance study in which 14 Cryptolepis-based aqueous formulations were examined, it was found that the content of cryptolepine (1) was variable and
could not be detected in two brands [37]. Only three brands passed the microbial limit
test and perhaps most worrying, 11 of the 14 products contained artesunate. None
of the brands complied with packaging and labeling requirements. Another concern
with respect to herbal products containing C. sanguinolenta is that the roots are
sourced entirely from the wild leading to declining populations [38]. Some attempt
is being made to domesticate C. sanguinolenta and to determine the optimum growing
conditions and time of harvest for maximum yields of cryptolepine. Thus, it has been
found that at 289 days after planting, the content of 1 in the dried roots reached a
maximum of 1.84% w/w [38].
Cryptolepine (1) has moderately potent antiplasmodial activity against both
chloroquine-sensitive (HB3) and resistant (K1) strains of Plasmodium falciparum
cultured in red blood cells (IC 50 = 0.27 and 0.44 μM against 3D7 and K1 strains,
respectively). However, it was not able to cure mice infected with P. berghei berghei
when given orally (80.5% suppression of parasitemia compared to untreated infected
controls at 50 mg/kg/day) whereas 100% suppression is required for a cure [39].
S. D. Shnyder and C. W. Wright
2010 to 2018, the rate of improvement has slowed since 2014, and there were an estimated 228 million cases worldwide in 2018. Meanwhile, the most important malaria
parasite, Plasmodium falciparum, responsible for 99.7% cases globally, has developed resistance to artemisinin derivatives in some areas, especially along the Thai–
Cambodia border [34, 35], so that there is an urgent need for new antimalarial drugs.
In addition, attention is again being given to the eradication of malaria, which will
require antimalarial drugs with activity against the liver and gametocyte stages of the
parasite as well as the blood stages targeted by most currently available antimalarial
agents.
The aqueous root extract of C. sanguinolenta is used widely in West Africa for the
treatment of malaria. In Ghana, the herbal product, Phyto-laria, is marketed for the
treatment of malaria in the form of tea bags and a number of other Cryptolepis-based
aqueous formulations are also available. The efficacy of Phyto-laria was assessed
in a prospective, open clinical study in patients over the age of 11, with clinical
symptoms of malaria and a diagnosis of malaria by examination of blood films
[36]. Parasitemia in all of the patients evaluated cleared within seven days, with two
patients showing recrudescence within 28 days, although this could have been due
to re-infection. Hematological and biochemical abnormalities present before being
treated generally improved during treatment but blood alkaline phosphatase levels
were elevated persistently during the study compared with pre-treatment values, and
serum uric acid levels showed a significant rise during treatment. The study suggests
that Phyto-laria may be effective for the treatment of malaria in patients aged between
11 and 50 years. However, an important limitation of the study was the exclusion of
young children, who are the most susceptible to serious complications and death due
to malaria. Hence, it cannot be assumed that Phyto-laria would be effective in this
group, as those under five years of age especially are likely to have little immunity
to malaria. Pregnant women, who are also at increased risk of severe malaria, were
also excluded from this study [36].
In a pharmacovigilance study in which 14 Cryptolepis-based aqueous formulations were examined, it was found that the content of cryptolepine (1) was variable and
could not be detected in two brands [37]. Only three brands passed the microbial limit
test and perhaps most worrying, 11 of the 14 products contained artesunate. None
of the brands complied with packaging and labeling requirements. Another concern
with respect to herbal products containing C. sanguinolenta is that the roots are
sourced entirely from the wild leading to declining populations [38]. Some attempt
is being made to domesticate C. sanguinolenta and to determine the optimum growing
conditions and time of harvest for maximum yields of cryptolepine. Thus, it has been
found that at 289 days after planting, the content of 1 in the dried roots reached a
maximum of 1.84% w/w [38].
Cryptolepine (1) has moderately potent antiplasmodial activity against both
chloroquine-sensitive (HB3) and resistant (K1) strains of Plasmodium falciparum
cultured in red blood cells (IC 50 = 0.27 and 0.44 μM against 3D7 and K1 strains,
respectively). However, it was not able to cure mice infected with P. berghei berghei
when given orally (80.5% suppression of parasitemia compared to untreated infected
controls at 50 mg/kg/day) whereas 100% suppression is required for a cure [39].