Artemisia Annua Ethanolic Extract Mitigated Small Intestinal Lesions in Hamsters Infected With Giardia Lamblia Possibly Through Modulation of Mucosal Immunity

Abstract

Giardiasis is a worldwide health problem caused by Giardia lamblia. Unfortunately, G. lamblia developed drug resistance against commonly used therapeutic agents. Artemisia annua (A. annua) derivatives showed therapeutic efficacy against a number of parasitic infestations. Here, we aimed to elucidate the effect of A. annua on giardiasis-induced small intestinal changes in hamsters. Thirty-two hamsters were divided into 4 groups. GI: Uninfected, GII: infected with G. lamblia cysts and untreated, GIII: infected and treated with metronidazole, served as a positive control, and GIV: infected and treated with the A. annua ethanolic extract. The efficacy of the extract was assessed by trophozoite counts, serum cytokine levels and histopathology. Infection of gerbils with G. lamblia cysts significantly decreased serum nitrite, while increased serum IL-6, INF-γ and TNF-α. Additionally, G. lamblia increased intraepithelial lymphocytes (IEL) while reduced villus heights, goblet cell (GC) number and muscularis externa (ME) thickness. Immunohistochemical analysis showed that G. lamblia increased inducible nitric oxide synthase (iNOS) and caspase-3 expression. In contrast, treating infected animals with A. annua significantly reduced the mean trophozoite counts, serum nitrite, IL-6, INF-γ, TNF-α levels and IEL numbers while increased villus heights, GC numbers and ME thickness. Moreover, A. annua reversed giardiasis-induced changes in iNOS and caspase-3 expression. In conclusion; we showed clearly that A. annua extract reduced the severity and morphological changes of giardiasis possibly through modulation of nitric oxide production and mucosal immunity. These effects were comparable to effects of metronidazole. Therefore, we assume that A. annua extracts could be used as adjuvant therapy during treatment of giardiasis.