Antifilarial activity of caffeic acid phenethyl ester on <i>Brugia pahangi in vitro</i> and <i>in vivo</i>

<p>Lymphatic filariasis (LF) is a vector borne disease caused by parasitic worms such as <i>Wuchereria bancrofti</i>, <i>Brugia malayi</i> and <i>B. timori</i>, which are transmitted by mosquitoes. Current therapeutics to treat LF are mainly microfilarcidal, and lack activity against adult worms. This set back, poses a challenge for the control and elimination of filariasis. Thus, in this study the activities of caffeic acid phenethyl ester (CAPE) against the filarial worm <i>B. pahangi</i> and its bacterial endosymbiont, <i>Wolbachia</i> were evaluated. Different concentrations (2, 5, 10, 15, 20 μg/ml) of CAPE were used to assess its effects on motility, viability and microfilarial (mf) production of <i>B. pahangi in vitro</i>. Anti-<i>Wolbachial</i> activity of CAPE was measured in worms by quantification of <i>Wolbachial wsp</i> gene copy number using real-time polymerase chain reaction. Our findings show that CAPE was found to significantly reduce adult worm motility, viability, and mf release both <i>in vitro</i> and <i>in vivo</i>. 20 μg/ml of CAPE halts the release of mf <i>in vitro</i> by day 6 of post treatment. Also, the number of adult worms recovered <i>in vivo</i> were reduced significantly during and after treatment with 50 mg/kg of CAPE relative to control drugs, diethylcarbamazine and doxycycline. Real time PCR based on the <i>Wolbachia fts</i>Z gene revealed a significant reduction in <i>Wolbachia</i> copy number upon treatment. Anti-<i>Wolbachia</i> and antifilarial properties of CAPE require further investigation as an alternative strategy to treat LF.</p>