ABSTRACT
Malaria remains a major global public health concern, and nearly half of the global populations are still at risk of malaria infection. However, continuous emergence and spread of drug-resistant malaria parasite strains lead to ineffectiveness of conventional antimalarials. Therefore, development of novel antimalarial agents is of urgent need for malaria elimination. As an important component of the host natural immune defense system, antibacterial peptides provide the first line of defense against pathogenic invasion, and the mechanism of preferentially attacking the cell membrane makes them difficult to develop drug resistance. Antimicrobial peptides are therefore considered as a promising candidate for novel antimalarial agents. This review summarizes the advances in researches on antimicrobial peptides with antimalarial actions and discusses the potential of antimalarial peptides as novel antimalarials.
ABSTRACT
Artemisinin is the antimalarial active ingredient, which is discovered by Chinese scientists in 1970s. The chemical structure of artemisinin is modified or altered to obtain a series of analogues to satisfy the medication requirements. According to the physicochemical properties of medicines and actual clinical necessities, the preparations of artemisinins are developed and the common preparations include tablet, suppository, injection, etc.. With the developing of technology, researchers have conducted a large number of studies on the artemisinins nanoparticles injection, transdermal drug delivery systems, mucosal drug delivery systems and etc. This article systematically collected and discussed the recent studies on the antimalarial preparations of artemisinins in line with different administration routes.
ABSTRACT
OBJECTIVE@#To evaluate in vivo antimalarial activity of methanol leaf extract of Icacina senegalensis.@*METHODS@#The extract was investigated for activity against early and established malaria infections using Swiss albino mice infected with Plasmodium berghei at dose levels of 25, 50 and 100 mg/kg. Chloroquine (10 mg/kg) was used as positive control.@*RESULTS@#A dose dependent chemo-suppression of the parasites was observed at different dose levels of the extract tested with a considerable mean survival time.@*CONCLUSIONS@#The results support further investigation on components of traditional medicines as potential new antimalarial agents.
ABSTRACT
Objective: To evaluate in vivo antimalarial activity of methanol leaf extract of Icacina senegalensis. Methods: The extract was investigated for activity against early and established malaria infections using Swiss albino mice infected with Plasmodium berghei at dose levels of 25, 50 and 100 mg/kg. Chloroquine (10 mg/kg) was used as positive control. Results: A dose dependent chemo-suppression of the parasites was observed at different dose levels of the extract tested with a considerable mean survival time. Conclusions: The results support further investigation on components of traditional medicines as potential new antimalarial agents.
ABSTRACT
This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.
Subject(s)
Animals , Female , Humans , Rats , Amniotic Fluid , Artemisinins , Body Weight , Eating , Fetal Death , Fetus , Incidence , Kidney , Plasma , Rats, Sprague-Dawley , Ribs , Spectrum Analysis , Thoracic Vertebrae , Thymus GlandABSTRACT
Hydroxypiperaquine (HPQ) and its phosphate (HPQP) are a new long-acting antimalarial agent synthesized in our Lab.The 95% fiducial limits of i.g.LD50 of HPQP and chloroquine phosphate (CQP) in mice were 387~491 and 253~330 mg/kg, respectively.The i.v.convulsive doses of HPQP and CQP in dogs were 40 and 8 mg/kg, respectively.The i.g.convulsive doses of HPQP and CQP in dogs were 200 and 40 mg/kg, while their MLD were 600 and 40 mg/kg, respectively.The acute cardiovascular toxicity of HPQP in rabbits was lower than that of CQP significantly.The intoxicated manifestations of HPQP in dogs were characterized by the signs of stimulation of cholinergic and central nervous system such as emesis, excitation, salivation, urination, defecation, tremor and convulsion.The acute toxic manifestations of CQP were similar to those of HPQP but developed more rapidly and markedly.The transient elevated activities of sGPT demonstrated that hepatic function was impaired to some extent and that th; liver may be the toxic target organ.The results obtained show that HPQP has a lower toxicity and a broader margin of safety as compared with CQP.Thess results may be useful for the control of its side effects during clinical use.