Ruellia simplex C. Wright (Acanthaceae): Antinociceptive, anti-inflammatory, and antidiabetic activities of a novel fatty acid isolated from its leaf extract

Ruellia simplex is a medicinal plant whose leaf is used to treat pains, inflammation, and diabetes in Nigeria. The current study was undertaken to determine the antinociceptive (analgesics), anti-inflammatory, and antidiabetic activities of a novel fatty acid isolated from the leaf extract of R. simplex. Isolation of a novel fatty acid from the most active fraction was carried out on silica gel column chromatography while, antinociceptive, anti-inflammatory, and antidiabetic activities of the isolated compound were evaluated by acetic acid, carrageenan, and alloxan-induced animal models respectively. The chemical structure of the new compound was elucidated by FT-IR, NMR, GC-MS, and LC-MS. The isolated fatty acid showed inhibition of pains by decreasing abdominal writhing in mice in dose dependent fashion as well as reduced paw volume in the carrageenan-induced paw edema in rats at IC50 = 12.5 ± 1.08 μg/ml and 10.21 ± 1.02 μg/ml, respectively, whereas the antidiabetic activity showed a dose dependent reduction in blood sugar levels with IC50 = 6.02 ± 0.01 μg/ml. The compound showed the following features: R-COOH functional group at 3327 wavelength cm-1 by FTIR; EI-MS [M]+* at m/z 467, peak area 62.231% and RT 14.086 min by GC-MS; singly charged fragments at m/z 116.1 and m/z 465.1, RT 1.31 min by LC-MS and eight proton signals consisting of singlets and multiplets (1H), thirty carbon atoms (13C) NMR data. From the study, the novel fatty acid from R. simplex extract was potentially active for the treatment of pains, inflammation, and diabetes

In Vivo Efficacy of Artemether-Lumefantrine and Chloroquine against Plasmodium vivax: A Randomized Open Label Trial in Central Ethiopia

Background In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used. Methods and Findings In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8–82.5) for AL and 90.8% (95% CI 83.6–94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1–95.1) for AL and to 97.2% (91.6–99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml. Conclusions In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections. Trial Registration ClinicalTrials.gov NCT0105258

In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia

<p>Abstract</p> <p>Background</p> <p><it>In vivo </it>efficacy assessments of the first-line treatments for <it>Plasmodium falciparum </it>malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated <it>P. falciparum </it>malaria since 2004.</p> <p>Methods</p> <p>Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for <it>P. falciparum </it>in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented <it>P. falciparum </it>mono-infection were enrolled and followed according to the standard 2009 World Health Organization <it>in vivo </it>drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively.</p> <p>Results</p> <p>Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight <it>P. falciparum </it>patients (6.7%) presented with <it>Plasmodium vivax </it>infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events.</p> <p>Conclusions</p> <p>AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with <it>P. vivax </it>possibly from relapse or new infection was observed.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052584">NCT01052584</a></p

Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

BACKGROUND: Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. METHODS: Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed. RESULTS: Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. CONCLUSIONS: Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems

Quinine Sulphate Microparticles as Treatment for Leishmaniasis

Background. Leishmaniasis is a neglected tropical disease caused by the Leishmania parasite and transmitted by the female phlebotomine sandfly. The disease can affect the skin (least fatal) or internal organs (most fatal). Current treatment options for leishmaniasis have a number of adverse effects, and there appears to be resistance by the protozoan parasite (Leishmania spp.). Reports suggest that quinine sulphate, not indicated for leishmaniasis, is effective in killing the Leishmania parasite. Indeed, the efficacy of any drug is dependent on the concentration at the target site, which is also almost dependent on drug formulation. The current study assessed the pharmacokinetic profile of the microparticulate formulation of quinine sulphate and its in vitro and in vivo efficacy against Leishmania donovani. Methods. Quinine sulphate was encapsulated in bovine serum albumin by the spray-drying method. Quinine sulphate microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency, and in vitro release properties. Afterwards, the pharmacokinetic characteristics of quinine sulphate microparticles were estimated and in vivo efficacy studies were also conducted. Results. The size range of the quinine sulphate microparticles was between 2.0 and 5.0 µm. Microparticles had an average zeta potential of −35.2 mV and an encapsulation efficiency of 94.5%. Also, Cmax, t1/2, and AUC were all significantly desirable for quinine sulphate microparticles compared to the drug powder. Quinine sulphate microparticles significantly reduced parasite load in rat organs than amphotericin B. Conclusion. Overall, quinine sulphate microparticles had better pharmacokinetic profile and showed higher efficacy against Leishmania donovani parasites in vivo. Thus, quinine sulphate microparticles have the potential, especially, in treating visceral leishmaniasis

Determination of Oseltamivir Quality by Colorimetric and Liquid Chromatographic Methods

We developed a colorimetric and chromatographic assay for oseltamivir to assess the authenticity of Tamiflu (F. Hoffmann-La Roche Ltd., Basel, Switzerland) because of a growing concern about counterfeit oseltamivir. The colorimetric assay is quantitative and relies on an extractable colored ion-pair complex of oseltamivir with Congo red or bromochlorophenol blue. The reverse-phase chromatographic assay uses an alkaline mobile phase with UV detection. Both methods were evaluated for variability and selectivity and subsequently applied to batches of oseltamivir products acquired through the Internet. The Congo red test showed greater assay sensitivity, linearity, and accuracy. Colorimetric and chromatographic analysis showed all batches of oseltamivir product were within ±15% of the stated amount of active ingredient