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The excretions-secretions (E-S) of Acanthocheilonema viteae consist mainly of one product, molecular weight 62kDa. This molecule is synthesized during the vertebrate phase of the parasite life-cycle and is first detectable in the E-S of L4 parasites. It is cross-reactive with E-S of human filarial parasites as a consequence of possessing a phosphorylcholine (PC) moiety. The 62 kDa molecule has been employed as a model for the study of the origin and fate of filarial E-S. Immunohistological analysis has shown the molecule to be located predominantly in the parasite gut. Transplantation of adult female [35S] methionine pulsed worms into uninfected jirds resulted in the radio-labelled secreted 62 kDa antigen being detected in the bloodstream within 4 h by SDS-PAGE/immunoprecipitation analysis. The systemic half-life of the molecule as estimated by clearance of injected, purified 125I-labelled material was measured in naive and infected jird hosts. It was reduced from 2-7 h in naive animals to less than 30 min in 4-10 week infected rodents, a finding which correlated with clearance of antigen by antibody in the infected group. In animals infected for longer time periods the serum half-life returned to the values observed in naive jirds. The idea that this change in half-life may reflect differences in the nature of 62 kDa antigen containing circulating immune complexes as infection progresses is discussed. The 125I-labelled antigen is predominantly removed from the circulation via the liver and ultimately excreted in the urine in a non-antigenic form. This work provides the first description of the origin, kinetics of circulation and fate of a defined filarial E-S product and may aid in determining the function and assessing the diagnostic utility of PC-bearing E-S components.

Piperine, an active alkaloidal constituent of the extract obtained from Piper longum and Piper nigrum, was evaluated for its antihepatotoxic potential in order to validate its use in traditional therapeutic formulations. This plant principle exerted a significant protection against tert-butyl hydroperoxide and carbon tetrachloride hepatotoxicity by reducing both in vitro and in vivo lipid peroxidation, enzymatic leakage of GPT and AP, and by preventing the depletion of GSH and total thiols in the intoxicated mice. Silymarin, a known hepatoprotective drug was tested simultaneously for comparison. Piperine showed a lower hepatoprotective potency than silymarin.

In the present study, chlorogenic acid (CGA) isolated from Anfhocephalus cadamba was screened for hepatoprotective activity by in uifro and in uiuo assay methods using carbon tetrachloride (CCI,) as a model of liver iqjury. Intraperitoneal administration of CGA to mice at a dose of 100 mgkg body weight for 8 days caused significant reversal in lipid peroxidation, enzymatic leakage, cytochrome P450 (Cyt P450) inactivation and produced enhancement of cellular antioxidant defence in CC4-intoxicated mice, revealii that the antioxidative action of CGA is responsible for its liver protective activity. CGA exhibited a better therapeutic protective action than silymarin (SM), in CCl.,-administered mice.

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Table 1 depicts the growth of Leishrnania donovani in the absence or in the presence of piperine or pentamidine. The piperine experiments at 80, 100, and 120 pg per tube, in triplicate, inhibited the parasites to an extent of about 70, 86, and 100%, respectively. Pentamidine, a known antileishmanial drug, was tested simultaneously for comparision. The runs with 80, 100, and l2Opg per tubes of pentamidine caused 90, 100, and 100% inhibition of promastigotes, respectively. Piperine exhibited a concentration-dependent inhibition of Leishmania clonovani promastigotes in vitro, in culture within the concentration range used in this study. Thus, piperme possesses an interesting antileishmanicidal activity.Piperine was obtained from the N. P. C. Division of the laboratory, promastigote parasites (UR6 strain) stationary phase (1 x i05 parasite/ml) were taken in culture tubes containing BHI-Agar as the solid phase and HBSS as the liquid phase. To these tubes, different concentrations (10 pg to 120 pg in 0.1 ml, DMSO/PBS) of piperine and pentamidine were added respectively. The inhibitory effect of piperine was compared with pentamidine which is known to be active against leishmaniasis, and with untreated control cultures. The whole operation was carried out aseptically in an ultraviolet chamber and the tubes were incubated for 5 days at 22 °C.The toxicity of DM80 was checked by adding different amounts of solvent (0.1 to 1.5%) to suspensions of promastigotes in the conditions described above. After 5 days, the value of the non-toxic dilutions was found to be 0.6 % and growth inhibition (upto 15%) was observed between 0.6 and 1 %, therefore higher concentrations of DM80 were never used. The antileishmanial activity of each of the compounds was determined by counting the number of parasites per field microscopically and percent mortality was calculated.Chemotherapeutic agents against Leishmania (pentavalent antimony compounds, pentamidine, and amphotericin B) are toxic and expensive. Very few antiprotozoal natural products such as gyrocarpine, daphnandrine, obaberine (1), diospyrin (2), and pinifolic acid derivatives are known (3). Further in vivo studies on the biological activity of piperine would thus be worthwhile to validate any employment suggested by these results. Table 1 The leishmanicidal activity of piperine. Parasite/compounds 120 100 80 Concentration 60 (gig)40 20 10 control -------Promastigote + 100 0.0 86 1.0 70 2.0 60 5.0 35 5.0 20 2.0 5 0.0 piperine Promastigote+ 100 0.0 100 0.0 90 2.0 78 2.0 60 5.0 40 2.0 30 1.0 pentamidine -___________________________________________________________ The values are (mean S.D.( of triplicate determinations from three experiments. Downloaded by: University of Illinois. Copyrighted material.

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