Giardiasis, caused by the protozoan Giardia lamblia, is a prevalent global diarrheal disease associated with significant intestinal pathology, malabsorption, and systemic complications. Current treatments, such as metronidazole (MZ), are limited by side effects and potential resistance, underscoring the need for novel, safe, and effective therapeutic agents. Purslane (Portulaca oleracea L.) is a medicinal plant rich in bioactive compounds with documented antioxidant, antimicrobial, and immunomodulatory properties. This study evaluated the therapeutic potential of an aqueous purslane extract (PE), both alone and in combination with MZ, against giardiasis using a comprehensive in vitro and in vivo approach. Antigiardial efficacy was evaluated in vitro (MTT assay on trophozoites/cysts) and in vivo using Giardia-infected mice. Albino mice were divided into seven groups: uninfected control, infected control, PE-treated (50, 100, 200mg/kg diet), MZ-treated (200mg/kg), and a PE+MZ combination (200 mg/kg each). LC-MS identified major flavonoids (luteolin-7-O-glucoside, apigenin-7-O-glucoside), phenolic acids, and betalains in PE. PE exhibited substantial DPPH scavenging activity (IC₅₀ = 58µg/mL) and notable antimicrobial effects. In vitro, PE showed potent antigiardial activity (trophozoite IC₅₀ = 38.2µg/mL), surpassing MZ (IC₅₀ = 86.5µg/mL), and induced a synergistic effect in combination. PE also triggered a severe oxidative stress response in the parasite, upregulating antioxidant genes more intensely than MZ. In vivo, PE treatment caused a dose-dependent reduction in cyst shedding, with the highest dose (200mg/kg) achieving 98.7% clearance. It fully restored growth performance in infected mice (body weight, ADG, FER), normalized serum biochemical and inflammatory markers, and enhanced local immunity. PE significantly downregulated intestinal apoptotic caspases and, in combination with MZ, provided the most complete histopathological recovery of duodenal architecture, reversing villous atrophy, brush border disruption, and mucosal inflammation while supporting immune integrity. Purslane extract demonstrates potent, multi-faceted efficacy against Giardia lamblia. Its mechanism involves direct anti-parasitic activity, induction of lethal oxidative stress in the parasite. The synergistic interaction with metronidazole highlights PE’s potential as a powerful adjunct therapy, offering a strategy to enhance parasite clearance, accelerate mucosal healing, improve host defense, and optimize clinical outcomes in giardiasis.

To Cite This Article: Alzahrani AM, Almahallawi RS, AL-Essa LA, Albohiri HH, Khan SA, Aldamigh MA, Alharbi FA, Al-Rashidi HS, Almayouf MA, Alsulami MN and Taha R, 2026. Purslane extract as a novel phytotherapeutic agent against giardiasis in a rat model: mitigating drug resistance, enhancing intestinal immunity, and alleviating adverse effects of conventional treatments. Pak Vet J, 46(4): 839-852. http://dx.doi.org/10.29261/pakvetj/2026.092