Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri

Abstract

Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.

Biomasa de gobernadora (Larrea tridentata) como forraje para borregos

“…In intestinal protozoa (Giardia lambia, Entamoeba histolytica and Naeglia fowleri) of considerable pathogenicity to humans, secondary metabolites of creosote matter were shown to be effective for the therapeutic treatment of amebiasis, giardiasis and primary amebic meningoencephalitis (Bashyal et al, 2017). This anti-protozoan mechanism of creosote bush lignans disrupts the modulation of cysteine protease activity in the trophozoites, thereby reducing their virulence (Bashyal et al, 2017). Information on the effect of creosote bush biomass components on nonpathogenic rumen protozoa is non-existent, but the anti-protozoan mechanism may be similar to that described for pathogenic protozoa in humans.…”

“…Extractos diclorometanólicos de biomasa de gobernadora mostraron actividad contra protozoos patógenos causantes de tripanosomiasis, leishmaniasis y plasmodiosis (Schmidt et al, 2012). En protozoos intestinales (Giardia lambia, Entamoeba histolytica y Naeglia fowleri) de patogenicidad considerable para humanos, los metabolitos secundarios de materia de gobernadora mostraron ser eficaces para el tratamiento terapéutico de amebiasis, giardiasis y de meningoencefalitis amebiana primaria (Bashyal et al, 2017). Este mecanismo anti protozoario de los Table 3.…”

“…lignanos de gobernadora irrumpe la modulación de la actividad de la proteasa cisteína en los trofozoítos, disminuyendo así su virulencia (Bashyal et al, 2017). La información sobre el efecto de componentes de la biomasa de gobernadora en protozoarios ruminales no patógenos es inexistente, pero el mecanismo anti protozoario puede ser similar al descrito para protozoarios patógenos en seres humanos.…”

“…También, en extractos de gobernadora se han identificado otros compuestos como fenoles, flavoniodes, saponinas, sapogeninas, taninos, esteroles y terpenos (Jitsuno & Mimaki, 2010;Gnabre, Bates, & Chih Huang, 2015). Estos compuestos bioactivos de gobernadora tienen efecto antioxidante (Skouta, Morán-Santibañez, Valenzuela, Vasquez, & Fenelon, 2018), antinflamatorio y anticonceptivo (De Melo et al, 2009), antifúngico (Aguirre-Joya, Pastrana-Castro, Nieto-Oropeza, Ventura-Sobrevilla, Rojas-Molina, & Aguilar, 2018), antimicrobiano (Hwu, Hsu, & Huang, 2008), antihelmíntico (Garcia et al, 2018) y anti protozoario (Schmidt, Rzeppa, Kaisr, & Brun, 2012;Bashyal, Li, Bains, Debnath, & LaBarbera, 2017).…”

Synthesis, Characterization, and In Vitro and In Vivo Evaluations of Cellulose Hydrogels Enriched with Larrea tridentata for Regenerative Applications

“…In addition, it is an important plant with a long history of medicinal use [13]. L. tridentata contains a series of lignans, flavonoids, condensed tannins, triterpene saponins, and naphtha quinones with antimicrobial, antioxidant, and antitumor activities [14]. Several studies have reported its ability to rejuvenate injured skin, wounds, and burned skin [12][13][14][15].…”