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Sickle cell disease remains a major public health problem in Burkina Faso and Africa. For the management of this pathology in young children, the Institute for Research in Health Sciences has developed an herbal drug called FACA® syrup. The objective of this study was to verify the safety and pharmacological efficacy of this formulation for its use in the management of sickle cell disease. Acute and subacute oral toxicity tests were performed on Wistar rats in accordance with Organization for Economic Cooperation and Development test guidelines and anti-sickling activity of FACA® syrup was evaluated according to the Emmel test. In the acute test, FACA® syrup didn’t cause mortality or any behavioral change at dose of 2000 mg/kg/b.w suggesting that the test product estimated LD50 is 5000 mg/kg b.w. The results of subacute toxicity study indicate that the daily administration of FACA® syrup during 28 days did not result in significant change on physical, haematological and biochemical parameters up to dose of 1000 mg/kg b.w. The evaluation of effect of FACA® syrup in vitro on sickling revealed that, FACA® syrup possesses a real antisickling activity. Regarding these results FACA® syrup would be considered as safe in both acute and subacute exposure and could be used in the management of sickle cell diseases. Keywords: FACA® syrup, oral toxicity, sickle cell anemia, Antisickling activity

The side effects prediction is a regulatory requirement prior the effective use of a new product as drug or pesticide constituent is allowed. The handling hazards of Cymbopogon schoenanthus essential oils (CSEO) were determined by investigating their acute and subacute toxicities as well as irritancy potential for eye and skin in compliance with the Organization for Economic Cooperation and Development guidelines. In mice, the essential oils did not induce mortality at the limit single dose of 2000 mg/kg b.w., meaning that the test product estimated LD50 is 5000 mg/kg b.w. In the 28 days sub-acute oral toxicity study in rats, there was no mortality observed for all tested doses in both sex. Furthermore, besides body weight gain that slightly dropped, there was no significant difference observed in food and water consumption, relative organs weight, and blood biochemical proi¬le in test animals, compared to the control. No eye irritant reaction was shown in the rabbits exposed to CSEO. To assess dermal irritation, rabbits were dermally exposed to CSEO for 4 h. The results showed that no adverse reactions such as erythema and edema were observed throughout the test. Based on these i¬ndings, CSEO do not cause either oral toxicity up to 28 days in repeated administration, nor dermal and eye irritation, and seems to be safe for animal in the study conditions. These results constitute a new scientific support for the safe use of C. scheonanthus essential oils as alternatives to synthetic pesticides. However, for further clinical relevance of the results and complete toxicological profile elucidation, toxicity studies must be extended to long term toxicity test as subchronic and chronic toxicities, reprotoxicity, carcinogenicity, teratogenicity, and mutagenicity investigations. Key words: Cymbopogon schoenanthus, Wistar rat, essential oils, sub-acute toxicity, blood chemistry, naturel insecticide.

Waltheria indica L. (Malvaceae) is a plant used in Burkina Faso for the treatment of various ailments including asthma. The aim of the study was to evaluate the pharmacological relaxant effect of the leafy stem extracts of Waltheria indica and thereby verify claim of use in treating asthma. Aqueous decoction and hydroalcoholic extracts obtained from the powdered leafy stems were screened for the presence of some phytoconstituents. The in vitro relaxant effect of the two extracts was evaluated on acetylcholine- (ACh 10−5 M) and potassium chloride- (KCl 6 × 10−2 M) induced contractions on rat-isolated tracheal preparations. To examine whether the potassium (K+) channels are involved in the relaxant effect, glibenclamide, an ATP-sensitive potassium channel inhibitor, was used. Moreover, to assess the safety of the extracts, acute oral toxicity was carried out on mice. The phytochemical screening revealed the presence of alkaloids, flavonoids, saponins, steroids, triterpenoids, tannins, and coumarins in the hydroalcoholic extract. Tannins, steroids, triterpenoids, and coumarins were not detected in the aqueous decoction. With respective EC50 values of 1.517 ± 0.002 mg/mL and 1.433 ± 0.001 mg/mL on ACh-and KCl-provoked contractions, the hydroalcoholic extract was found more potent in relaxing the isolated rat tracheal preparations compared to the aqueous decoction. In the presence of glibenclamide, the relaxant effect of the hydroalcoholic extract (EC50 = 0.191 ± 0.002 mg/mL) increased and was higher than that of the aqueous decoction. At dose of 5000 mg/kg of body weight, the extracts did not produce deaths or any significant changes in the general behavior of mice. The results suggest that different mechanisms including modulation of calcium and potassium channels, particularly the ATP-sensitive K+ channels, could be involved in the relaxation effect. These findings could justify the traditional use of W. indica in the management of asthma.

Chronic inflammation is a deleterious process occurring in several pulmonary diseases; it is a driving force promoting tumorigenesis. By regulating local cyclic nucleotide concentration, cyclic nucleotide phosphodiesterases (PDE) govern important biological processes, including inflammation and proliferation. The aim of this study was to investigate the anti-inflammatory and anti-proliferative effects of NCS 613, a specific PDE4 inhibitor, on TNFα-treated human lung adenocarcinoma cell line (A549) and on human lung adenocarcinoma explants. PDE4 isoforms and inflammatory pathways mediated by p38 MAPK, ERK1/2, and IκBα were analyzed by Western blot and immunostainings. Proliferation were performed using [3H]-thymidine incorporation under different experimental conditions. TNFα-stimulation increased p38 MAPK phosphorylation and NF-κB translocation into the nucleus, which was abolished by NCS 613 treatment. Concomitantly, NCS 613 restores IκBα detection level in human adenocarcinoma. An IC50 value of 8.5 μM was determined for NCS 613 on anti-proliferative properties while ERK1/2 signaling was down-regulated in A549 cells and lung adenocarcinoma explants. These findings shed light on PDE4 signaling as a key regulator of chronic inflammation and cancer epithelial cell proliferation. It suggests that PDE4 inhibition by NCS 613 represent potential and interesting strategy for therapeutic intervention in tackling chronic inflammation and cell proliferation.

Background:Anogeissus leiocarpusis a Sahel tree traditionally used by the residents of Burkina Faso for its antihypertensive properties. In this study, experiments were conducted to evaluate whether an aqueous extract of theAnogeissus leiocarpus(AEAL) trunk bark induces a vasorelaxant effect on porcine coronary artery rings and to investigate the underlying mechanism.Methods:AEAL-induced relaxations were assessed using porcine coronary artery rings suspended in organ chambers. The phosphorylation levels of Src, Akt and endothelial nitric oxide synthase (eNOS) were assessed in a primary endothelial cell culture by Western blot. The reactive oxygen species (ROS) formation was assessed using dihydroethidine.Results:In porcine coronary artery rings, AEAL at 0.1–300 μg/mL induced endothelium-dependent relaxations, which were inhibited in the presence of inhibitors of nitric oxide (NO) and the endothelium-derived hyperpolarization pathways. Moreover, the AEAL-induced NO-mediated relaxations were significantly reduced by the inhibitors of Src and PI3-kinase as well as by the membrane-permeant ROS scavengers. In cultured porcine coronary artery endothelial cells, treatment with AEAL is associated with an intracellular generation of ROS. Moreover, the AEAL induced the phosphorylations of Akt (Ser473), eNOS (Ser1177) and a transient phosphorylation of Src (Ser17) in a time-dependent manner.Conclusions:These findings indicate that AEAL is a potent inducer of endothelium-dependent NO-mediated relaxations in porcine coronary arteries through the redox-sensitive Src/PI3-kinase/Akt pathway-dependent activation of eNOS.

Neuropeptide Y binds to G-protein coupled receptors whose action results in inhibition of adenylyl cyclase activity. Using HEK293 cells stably expressing the native neuropeptide Y Y1 receptors, we found that the NPY agonist elicits a transient phosphorylation of the extracellular signal-regulated kinases (ERK1/2). We first show that ERK1/2 activation following Y1 receptor stimulation is dependent on heterotrimeric Gi/o since it is completely inhibited by pre-treatment with pertussis toxin. In addition, ERK1/2 activation is internalization-independent since mutant Y1 receptors unable to recruit beta-arrestins, can still activate ERK signaling to the same extent as wild-type receptors. We next show that this activation of the MAPK pathway is inhibited by the MEK inhibitor U0126, is not dependent on calcium signaling at the Y1 receptor (no effect upon inhibition of phospholipase C, protein kinase C or protein kinase D) but instead dependent on Gbeta/gamma and associated signaling pathways that activate PI3-kinase. Although inhibition of the epidermal-growth factor receptor tyrosine kinase did not influence NPY-induced ERK1/2 activation, we show that the inhibition of insulin growth factor receptor IGFR by AG1024 completely blocks activation of ERK1/2 by the Y1 receptor. This Gbeta/gamma-PI3K-AG1024-sensitive pathway does not involve activation of IGFR through the release of a soluble ligand by metalloproteinases since it is not affected by the metalloproteinase inhibitor marimastat. Finally, we found that a similar pathway, sensitive to wortmannin-AG1024 but insensitive to marimastat, is implicated in activation of ERK signaling in HEK293 cells by endogenously expressed GPCRs coupled to Gq-protein (muscarinic M3 receptors) or coupled to Gs-protein (endothelin ETB receptors). Our analysis is the first to show that beta-arrestin recruitment to the NPY Y1 receptor is not necessary for MAPK activation by this receptor but that transactivation of the IGFR receptor is required.

Sickle cell disease is a major public health problem. It is the first genetic disease in the world. FACA syrup offers an alternative treatment. It is a dry powder preparation of two components, the roots barks of Zanthoxylum zanthoxyloides Lam. (Rutaceae) Zepernick, Timler and Calotropis procera. Ait. R.B.r. (Asclepiadaceae). The product was developed at Institute for Research in Health Sciences (IRSS) from a traditional recipe used in Burkina Faso for treatment of sickle cell crises. This study aimed to establish physical-chemical, pharmaco technical and microbiological control parameters essential for the standardization of the phytomedicine. This valuation concerned specifications of moisture content, pH, the fingerprint by thin layer chromatography, pesticide residues, heavy metal content, microbial quality, and total ash. These charcteristics were determined by the methods prescribed by the World Health Organization (1998) and the European Pharmacopoeia 6th edition. The results have shown that dry syrups and reconstituted syrups were sweet, slightly spicy with a bitter after taste, a white room color and a faint odor. The density at the preparation was 0.985 and the pH was 5.93. After 2 months of storage in the laboratory, the organoleptic parameters of the reconstituted syrups have not changed. They were mold free, the density remained around 1 and the pH between 5 and 4. These parameters have shown that the quality of plants powders and these medicine comply with the recommendations of the European pharmacopoeia. Faca syrup may contribute to the better management of sickle cell disease in children.