ORIGINAL_ARTICLE Apart from currently available therapeutics for the treatment of diabetes mellitus, much attention has been paid to discover phytochemicals from natural resources, mainly due to their low side-effects. Hypericum perforatum hairy root (HR) transformed with Agrobacterium rhizogenes A4 represent prospective experimental system enriched in xanthones, known as potent antidiabetic agents. Thus, the aim of this study was to evaluate HR extracts for their potential antihyperglycemic activity in streptozotocin (STZ)-induced diabetic rats, also compared to the effects of wild-growing Hyperici herba (HH). We conducted an acute-toxicity study, multiple dose study, and 24h blood glucose measurements after a single dose administration of HH and HR (200 mg/kg) in diabetic rats. Furthermore, we examined the effects of 14-days administration of HH and HR extracts on blood glucose levels, metabolic parameters, enzyme, and lipid status in healthy and diabetic rats. Both extracts produced a fall of about 70% in blood glucose level after 24h of administration. Two-week treatment with HH and HR induced a significant decrease (70-72%) in blood glucose levels. Moreover, we found an improvement of the dysregulated metabolic parameters (body weight, food, and water consumption and urine output). Serum enzyme (AST, ALT, and γ-GT) and lipid profile parameters (CHOL, TAG, and HDL) were also improved by both extracts. These findings might provide a new insight for managing diabetic hyperglycemia and dysregulated serum enzyme and lipid profile, using extracts from transgenic roots cultures from H. perforatum. https://macvetrev.mk/Files/Article/2021/10.2478/macvetrev-2021-0027/macvetrev-2021-0027.pdf 2022-03-15T09:00:00 5 15 10.2478/macvetrev- hairy roots hanthones STZ-diabetic rats Hypericum perforatum L. antihyperglycemic Elena Rafailovska false 1 Department of Experimental Physiology and Biochemistry, Institute of Biology, Faculty of Natural Sciences and Mathematics, University “St Cyril and Methodius”, 1000 Skopje, R. North Macedonia AUTHOR Oliver Tushevski false 2 Laboratory of Plant Cell and Tissue Culture, Institute of Biology, Faculty of Natural Sciences and Mathematics, University “St Cyril and Methodius”, 1000 Skopje, R. 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