The Possible Use of Stevioside as a Therapeutic Alternative in Amoebiasis
Introduction
Amoebiasis has emerged as the third most common cause of death by parasites worldwide after malaria and schistosomiasis infections. According to the report of World Health Organization, over 40 million people are disturbed by this disease worldwide, 10% of whom may develop severe condition, with 50,000 to 100,000 reported deaths annually. Metronidazole is frequently prescribed for amoebiasis, but it has numerous side effects such as vomiting, diarrhea, nausea, headache, and a sharp metallic taste in the mouth.To this end, increasing attention is being directed towards the search for phytochemical compounds with anti-amoebic effects. One such compound, stevioside (STV), is a diterpene glycoside derived from the natural plant stevia rebaudiana. In addition to a range of health benefits, including anti-inflammatory, anti-hypertensive, anti-tumor, and anti-viral activities, it has also shown anti-amoebic properties and is expected to be a promising alternative for the treatment of amebiasis.
About amoebiasis
Amoebiasis, also known as amoebic dysentery, is a parasitic disease prevalent in tropical and subtropical areas, which is caused by infection of Entamoeba histolytica, an anaerobic parasitic amoebozoan existing as trophozoites (active parasites) or cysts (dormant parasites). Generally, there are two types of amoebiasis: intestinal amoebiasis and extraintestinal amoebiasis. The extraintestinal type encompasses conditions such as hepatic amoebiasis, amoebic lung abscess, amoebic brain abscess, and cutaneous amoebiasis, with amoebic liver abscess being the most prevalent.
Morphological, ultrastructural and histological changes in STV-treated trophozoites
Morphologically, the decrease in the basic structures related to the movement and adherence to the substrate is observed in Entamoeba histolytica trophozoites exposed to STV.
Ultrastructurally, there is a loss of regularity on the cell membrane, an increase in cytoplasmic granularity, and an increase in apparent autophagic vacuoles in Entamoeba histolytica trophozoites following STV treatment.
Histologically, STV-treated trophozoites provokes a bigger inflammatory response, areas of necrosis like the control, and the formation of multiple granulomas of smaller size than the control, delimited mainly by inflammatory and non-epithelioid palisade cells.
Effect of stevioside on Entamoeba histolytica trophozoites
STV at 10 mM to 25 mM suppresses the viability of Entamoeba histolytica trophozoites in a dose- and time-dependent way. Besides, STV decreases the adhesion capacity to fibronectin by E. histolytica trophozoites, interferes with actin fiber polymerization (decreased actin cytoskeleton structure formation) and affects the capacity of the destruction of monolayers of trophozoites (eg. a smaller amount of trophozoites and decreased lytic areas).
Moreover, STV represses the virulence of Entamoeba histolytica trophozoites, as manifested by the decreased expression of cysteine protease cp1 and weak proteolytic capacity of Cp1 and Cp5. Cysteine proteases are important virulence factors secreted by the amoeba within its microenvironment, and are considered essential in the ability of this parasite to destroy human tissues and to degrade different components of the extracellular matrix, such as fibronectin, laminin, and collagen.
Conclusion
Based on morphological, ultrastructural, and histological observations, STV treatment leads to reduced viability, mobility, adhesion, and virulence of Entamoeba histolytica trophozoites, suggesting its potential as a therapeutic option for amoebiasis.
Reference
Ortega-Carballo KJ, Gil-Becerril KM, Acosta-Virgen KB, Casas-Grajales S, Muriel P, Tsutsumi V. Effect of Stevioside (Stevia rebaudiana) on Entamoeba histolytica Trophozoites. Pathogens. 2024;13(5):373. Published 2024 Apr 30. doi:10.3390/pathogens13050373BONTAC Stevioside RD
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