In vitro ve in silico investigation on anti-inflammatory and anti-depression effects of Hypericum perforatum flavanoids with antioxidant activity

Medicinal plants today are still popular for treatment of many diseases due to their availability, efficacy and minimal side effects.St. John's Wort (Hypericum Perforatum L., HPL) has been used as a medicinal plant for the treatment of many disorders for centuries. It is known to show antioxidant activity by combating oxidative stress leading to biological macromolecule damage and metabolic dysfunctions. It isindicated for the treatment of anxiety and mild to moderately severe depression through the inhibition of the monoamine oxidase (MAO) enzyme and is also preferred for its wound-healing properties due to its anti-inflamatory effect. St. John's Wort extracts have been shown to inhibit Cyclooxygenases (COXs) and Lipooxygenases (LOXs). There are two forms of cyclooxygenases; cyclooxygenase-1 (COX-1), which is constitutively expressed, andcyclooxygenase-2 (COX-2), which is upregulated by diverse stimuli. COX-1 inhibitors have been associated with gastrointestinal (GI) side effects, while COX-2 inhibitors have relatively few GI side effects, but have a higher incidence of cardiovascular toxicity. LOXs are also another group of enzymes that affect inflammation similar to COXs but the selective LOX/COX inhibition studies have not yielded satisfactory results. Hence, the discovery of new anti-inflammatory drugs with minimum side effects is mandatory. Focusing on the simultaneous inhibition of both enzymes is promising for the discovery of new anti-inflammatory drugs with wider spectrum, reduced side effects and lower dosages. In this thesis study St. John's Wort patels and leaves were extracted by ethanol and further fractionated by methanol. Antioxidant activities of the total extract and the fractions have been determined and the compounds which wereisolated from alcoholicextract were identified. The plant extracts havedisplayed antioxidant activity similar to synthetic antioxidants. At the same time the binding affinities towards MAO, COX and LOX of the active compounds,which were selected from previous reports, were calculated by the docking method. Those compounds preferentially inhibited COX-2 when compared to COX-1. Quercetin displayed selective MAO-A activity while hypericin showed selective MAO-B activity. Hypericin and kaemferol are suggested for future studies as effective and promising dual inhibitors for COX-2/5-LOX enzymes.