Anti-malarial activity of Holarrhena antidysenterica and Viola canescens, plants traditionally used against malaria in the Garhwal region of north-west Himalaya

<p>Abstract</p> <p>Background</p> <p>The increasing number of multidrug-resistant <it>Plasmodium </it>strains warrants exploration of new anti-malarials. Medicinal plant research has become more important, particularly after the development of Chinese anti-malarial drug artemisnin from <it>Artemisia annua</it>. The present study shows evaluation of anti-malarial effects of two plants commonly used against malaria in the Garhwal region of north-west Himalaya, in order to discover the herbal-based medicine.</p> <p>Methods</p> <p><it>In vitro </it>anti-plasmodial sensitivity of plant extracts was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined extracts were determined on L-6 cells of rat skeletal muscle myoblast. The 4-day test for anti-malarial activity against a chloroquine sensitive <it>Plasmodium berghei </it>NK65 strain in Swiss albino mice was used for monitoring <it>in vivo </it>activity of plant extracts.</p> <p>Results</p> <p>Chloroform extract of <it>H. antidysenterica </it>(HA-2) and petroleum ether extract of <it>V. canescens </it>(VC-1) plants significantly reduced parasitaemia in <it>P. berghei </it>infected mice. The extract HA-2 showed <it>in vitro </it>anti-plasmodial activity with its IC₅₀value 5.5 μg/ml using pLDH assay and ED₅₀value 18.29 mg/kg in <it>P. berghei </it>infected Swiss albino mice. Similarly petroleum ether extract of <it>V. canescens </it>(VC-1) showed <it>in vitro </it>anti-plasmodial activity with its IC₅₀value 2.76 μg/ml using pLDH assay and ED₅₀15.8 mg/kg in <it>P. berghei </it>infected mice. The extracts coded as HA-2 at 30 mg/kg and VC-1 at 20 mg/kg exhibited parasite inhibition in mice: 73.2% and 63.0% respectively. Of these two plant extracts, petroleum ether extract of <it>V. canescens </it>was found slightly cytotoxic.</p> <p>Conclusion</p> <p>The present investigation reflects the use of these traditional medicinal plants against malaria and these plants may work as potential source in the development of variety of herbal formulations for the treatment of malaria.</p

The GPI Anchor Signal Sequence Dictates the Folding and Functionality of the Als5 Adhesin from Candida albicans

Background: Proteins destined to be Glycosylphosphatidylinositol (GPI) anchored are translocated into the ER lumen completely before the C-terminal GPI anchor attachment signal sequence (SS) is removed by the GPI-transamidase and replaced by a pre-formed GPI anchor precursor. Does the SS have a role in dictating the conformation and function of the protein as well? Methodology/Principal Findings: We generated two variants of the Als5 protein without and with the SS in order to address the above question. Using a combination of biochemical and biophysical techniques, we show that in the case of Als5, an adhesin of C. albicans, the C-terminal deletion of 20 amino acids (SS) results in a significant alteration in conformation and function of the mature protein. Conclusions/Significance: We propose that the locking of the conformation of the precursor protein in an alternate conformation from that of the mature protein is one probable strategy employed by the cell to control the behaviour an