Background. In folk medicine, extra virgin olive oil (EVOO) is used as a remedy for a variety of diseases. This study investigates the in vivo antinociceptive, anti-inflammatory, and anti-cancer effects of EVOO on mice and rats. Materials and Methods. In this experimental study, using the acetic acid-induced writhing and formalin tests in mice, the analgesic effect of EVOO was evaluated. Acetylsalicylic acid and morphine were used as standard drugs, respectively. The anti-inflammatory activity was investigated by means of the carrageenan-induced paw edema model in rats using acetylsalicylic acid and dexamethasone as standard drugs. Last, the xenograft model in athymic mice was used to evaluate the anticancer effect in vivo. Results. EVOO significantly decreased acetic acid-induced abdominal writhes and reduces acute and inflammatory pain in the two phases of the formalin test. It has also a better effect than Dexamethasone in the anti-inflammatory test. Finally, the intraperitoneal administration of EVOO affects the growth of HCT 116 tumours xenografted in athymic mice. Conclusion. EVOO has a significant analgesic, anti-inflammatory, and anticancer properties. However, further detailed studies are required to determine the active component responsible for these effects and mechanism pathway. 1. Introduction The Mediterranean diet rich in nuts, fruits, vegetables, legumes, whole-wheat bread, fish, and olive oil [1] has a well-established beneficial role in health promotion [2]. Virgin olive oil is an integral ingredient of this traditional diet and for centuries Mediterranean people have appreciated his nutritional, medical, and cosmetics benefits [3]. Indeed, virgin olive oil has been used as a folk remedy for combating diseases due to its pharmacological properties including cardioprotective, hypotensive, antihyperglycemic, antimicrobial, and anti-inflammatory effects [4–7]. Nowadays, epidemiological studies on virgin olive oil consumers reveal an important decrease in chronic disease, that is, cardiovascular diseases (CVD) [8], atherosclerosis [9], and some types of cancers especially colorectal and breast cancer [10]. In addition, Mediterranean people show a higher life expectancy compared with olive oil consume less populations worldwide [11]. Virgin olive oil is the oil obtained from the fruit of the olive tree solely by mechanical or physical means (the cold-pressed technique), which do not lead to alterations of the oil. Based on the acidity, the International Olive Oil Council has defined the classification of virgin olive oil as follows: extra
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