Isolatıon of Potentıal Drug Candıdate Molecules from Rumex Acetosella L. and in Sılıco, in Vıtro Researches on Those Molecules

Abstract

Ozenver, N., Isolation of Potential Drug Candidate Molecules From Rumex acetosella L. and In Silico, In Vitro Researches on Those Molecules, Hacettepe University, Institute of Health Sciences, Pharmacognosy Program, Doctor of Philosophy Thesis, Ankara, 2018. In this thesis, biological activity studies on the extracts of R. acetosella as well as its compounds were conducted. Some extracts of the title plant and some isolated substances were investigated against diabetes and cancer, hence R. acetosella is traditionally used in diabetes and cancer. Initially, antioxidant studies were performed as preliminary researches so that oxidative stress may have a role in the etiology of these diseases, which indicated alcoholic extracts as good antioxidants. Then, isolation studies were conducted to view phytochemical profile of R. acetosella. Isolated compounds and the main anthraquinone aglycones were tested for their cytotoxicities by resazurin reduction and protease viability marker assays. Aloe-emodin was detected as the most cytotoxic compound and the mechanisms behind its cytotoxicity were further investigated. Inducement of cell cycle distribution, apoptosis and necrosis, reactive oxygen species, mitochondrial membrane potential breakdown, DNA damage were detected. Microarray hybridization revealed deregulated genes in aloe-emodin-treated cells, validating by qPCR analysis. Motif analysis pointed out NF-κB as a transcriptional regulator. Molecular docking and reporter cell assays revealed the aloe-emodin/NF-κB relation. Antidiabetic effects of the extracts and some of their chemical constituents were investigated by means of α-amylase and α-glucosidase inhibition assays, which emphasized the ethanol extracts as antidiabetic, confirming the traditional use of R. acetosella. All findings pointed out that R. acetosella and aloe-emodin may have potentials for the development of new drugs in the treatment of both diabetes and cancer. Key Words: Rumex acetosella, aloe-emodin, cancer, diabetes, phytochemistry. Acknowledgments: The studies in this thesis were supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) with 2214-A and 2211-C scholarship programmes as well as Hacettepe University Scientific Research Projects Coordination Unit (Project No: 1216, TED-2017-15246).