REVIEW ARTICLE Bioactive Compounds and Pharmacological Potential of Pomegranate (Punica granatum) Seeds - A Review Mariam Fourati 1 & Slim Smaoui 1 & Hajer Ben Hlima 2 & Khaoula Elhadef 1 & Olfa Ben Braïek 3 & Karim Ennouri 4 & Ahlem Chakchouk Mtibaa 1 & Lotfi Mellouli 1 Accepted: 1 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract The use of complementary medicine has recently increased in an attempt to find effective alternative therapies that reduce the adverse effects of drugs. Pomegranate (Punica granatum L.) by-products, such as seeds, is a rich source of phytochemicals with a high antioxidant activity, thus possessing health benefits. For the identification and quantification of the pomegranate seeds chemical compounds, particular attention has been drawn to the latest developments in the HPLC coupling with electrospray ionization (ESI) MS/MS detection. In fact, a wide range of phytochemicals including phenolic acid, anthocyanins, flavonoids, hydrolysable tannins and other polyphenols were characterized. Furthermore, an exhaustive review of the scientific literature on pomegranate seeds on biomedicine and pharmacotherapy was carried out. Indeed, both in vitro and in vivo studies have demonstrated how pomegranate seeds possess antioxidant, anti- cardiovascular diseases, anti-osteoporosis, antidiabetic, anti- inflammatory and anticancer activities. The present review describes a recent tendency in research focusing on the chemical and biomedical features of the pomegranate seeds to value them as natural additives or active compounds for first-order diseases. Keywords Pomegranate seed . Bioactive compounds . Analytical chemistry . Biological activity . Health benefits Abbreviations 2-ME 2-methoxyestradiol ALAT Alanine aminotransferase ALP Alkaline phosphatase ASAT Aspartate aminotransferase BMD Bone mineral density CAE Catechin equivalents CAT Catalase CGE Cyanidin-3-glucoside equivalents CVD Cardiovascular diseases DMBA 7,12-dimethyl benz(a)anthracene DOX Doxorubicin DW Dry weight DXM: Dexamethasone FBS Fasting blood glucose FM Fresh matter FW Fresh weight GAE Gallic acid equivalent GC-MS Gas chromatography-mass spectrometry GPx Glutathione peroxidase GSH Glutathione HADMSC Human adipose-derived mesenchymal stem cells HDL High-density lipoprotein HFD High-fat-high fructose diet LDL Low-density lipoprotein MDA Malondialdehyde OVX Ovariectomized PA Punic acid Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11130-020-00863-7) contains supplementary material, which is available to authorized users. * Slim Smaoui slim.smaoui@cbs.rnrt.tn 1 Laboratory of Microbial, Enzymatic Biotechnology and Biomolecules (LBMEB), Center of Biotechnology of Sfax, University of Sfax-Tunisia, Road of Sidi Mansour Km 6, P. O. Box 1177, 3018 Sfax, Tunisia 2 Laboratoire de Génie Enzymatique et de Microbiologie, Equipe de Biotechnologie des Algues, Ecole Nationale d’Ingénieurs de Sfax, Université de Sfax, 3038 Sfax, Tunisia 3 Laboratory of Transmissible Diseases and Biologically Active Substances (LR99ES27), Faculty of Pharmacy, University of Monastir, Monastir, Tunisia 4 Laboratory of Amelioration and Protection of Olive Genetic Resources, Olive Tree Institute, Sfax University, Sfax, Tunisia Plant Foods for Human Nutrition https://doi.org/10.1007/s11130-020-00863-7