Pakistan Journal of Biological Sciences1028-88801812-5735Asian Network for Scientific Information10.3923/pjbs.2020.313.320MohamedSherif S. ElkhamisyAbeer El Sayed 32020233Background and Objective: Garden cress (Lepidium sativum L.) is a fast growing annual plant, the garden cress seed is the herbal edible seeds used in traditional medicine. A number of experimental have been conducted on rats that proven the efficacy of garden cress seeds (GCS) and its protective role in many diseases. Also, the GCS was used in the fortification of different food items. In this study focusing on the potent activity of polyphenol in the natural GCS extract or nanoemulsion of GCS extracts to reduce the oxidative stress in rat induction by paracetamol (PCM) and determined of the potentiality of the two GCS extracts which to be limited. Materials and Methods: The current study evaluated the polyphenol content of the GCS estimated by HPLC in vitro and in vivo determined polyphenols effects in a healthy Wister male rats (32 rats weighing 130±15) which divided into 4 groups to examine antioxidant activity of 2 extracts (Natural and nano) forms. In addition, the best average size of nanoparticles was 198.1±0.553 nm and 90% of the distribution determined by dynamic light scattering (DLS) instrument showed in A1sample nanoemulsion. Results: The findings showed that the natural GCS extract more potential than the nanoemulsion in the antioxidant activity, it may be related to destroyed some of active polyphenols exist naturally in the GCS extract during formulation GCS nanoemulsion by sonication process. 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