The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases and psychiatric disorders such as depression and anxiety, thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study, four Sideritis flavonoids, xanthomicrol (1), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-β-D-glucopyranoside (2), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-6''-O-acetyl-β-D-glucopyranoside (3) and salvigenin (4) were docked computationally into the active site of the human monoamine oxidase isoforms (hMAO-A and hMAO-B) and were also investigated for their hMAO inhibitory potencies using recombinant hMAO isoenzymes. The flavonoids inhibited hMAO-A selectively and reversibly in a competitive mode. Salvigenin (4) was found to be the most potent hMAO-A inhibitor, while xanthomicrol (1) appeared as the most selective hMAO-A inhibitor. The computationally obtained results were in good agreement with the corresponding experimental values. In addition, the x-ray structure of xanthomicrol (1) has been shown. The current work warrants further preclinical studies to assess the potential of xanthomicrol (1) and salvigenin (4) as new selective and reversible hMAO-A inhibitors for the treatment of depression and anxiety.

Verbascoside, also known as acteoside/kusaginin, has attracted a great attention due to its pharmacological features. In this study, we aimed to determine the cytotoxic effects of pure verbascoside isolated from Phlomis nissolii L. plant in both MCF-7 and MDA-MB-231 cell lines in vitro. MCF-7 and MDA-MB 231 cells were treated with verbascoside (100, 48, 25, 10, 1, 0.5, and 0.1 μM) for 24, 48, and 72 hours. Cytotoxic effect of verbascoside in MCF-7 and MDA-MB-231 cells was assessed using TEBU-BIO cell counting kit 8. IC₅₀ values for 24, 48, and 72 h verbascoside exposure of MCF-7 cells were determined as 0.127, 0.2174, and 0.2828 μM, respectively. R² values were calculated as 0.9630, 0.8789 and 0.8752, respectively. Two-Way ANOVA multiple comparison test results showed that 100 μM verbascoside has the highest cytotoxic effect on MCF-7 breast cancer (BC) cells after 72 h of exposure. IC₅₀ values for 24, 48 and 72 h verbascoside exposure of MDA-MB 231 cells were determined as 0.1597, 0.2584 and 0.2563 μM, respectively and R² values were calculated as 0.8438, 0.5107 and 0.9203, respectively. Two-Way ANOVA multiple comparisons test results showed that 100 μM verbascoside has the highest cytotoxic effect on MDA-MB 231 BC cells after 24, 48 and 72 h of exposure.

As the sixth-largest Angiosperm family, Lamiaceae contains more than 245 genera and 7886 species that are distributed worldwide. It is also the third-largest family based on the number of taxa in Turkey where it is represented by 46 genera and 782 taxa with a high endemism ratio (44%). Besides, Lamiaceae are rich in plants with economic and medicinal value containing volatile and nonvolatile compounds. Many aromatic plants of Lamiaceae such as Salvia, Sideritis, Stachys, Phlomis, and Teucrium species are used in traditional herbal medicine throughout Turkey as well as in other Mediterranean countries. Salvia (Sage tea “Adaçayı”), Sideritis (Mountain tea “Dağçayı”), Stachys (Hairy Tea “Tüylü Çay”), and Phlomis (Turkish sage “Çalba or Şalba”) are the largest genera that are used as herbal teas. This review focuses on the volatile and nonvolatile compounds of Lamiaceae from the genera Phlomis and Eremostachys of the subfamily Lamioideae with emphasis on iridoids, phenylethanoid glycosides, and essential oils. ^# Dedicated to Prof. Dr. Otto Sticher on the occasion of his 85th birthday. Received: 12 March 2021 Accepted after revision: 09 June 2021 Publication Date: 20 August 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Non-polar and polar compounds were isolated from the leaves and chemical composition of the essential oil from aerial parts of Sideritis cypria endemic in Northern Cyprus was also determined. The structures of all the isolated compounds were elucidated by means of spectroscopic (UV, NMR: 1D and 2D-NMR: 1H, 13C, COSY, HSQC, HMBC) methods and comparison with literature data. The essential oil composition of the plant material was analysed by GC-FID and GC-MS, simultaneously. To the best of our knowledge, secondary metabolites of this endemic species were determined for the first time. As a result, two mixtures of four ent-kaurane diterpenes; sidol (1) and isosidol (2), linearol (3) and isolinearol (4); four phenylethanoid glycosides; verbascoside (5), lavandulifolioside (6), leonoside A (7), leucoseptoside A (8); four flavone glycosides, apigenin-7-O-glucopyranoside (9), isoscutellarein-7-O-[6'''-O-acetyl-allopyranosyl-(1->2)-glucopyranoside] (10) and a mixture of apigenin-7-O-(4''-O-p-coumaroyl)-glucopyranoside (11) and apigenin-7-O-(3''-O-p-coumaroyl)-glucopyranoside (12) were elucidated. 7-O-acetyl-8-epi-loganic acid (13), an iridoid glycoside, was reported herein for the first time for genus Sideritis. In addition, major compounds of the essential oil were determined as a-pinene (14.73±0.15%), b-pinene (16.60±0.20%), b-phellandrene (17.83±0.23%) and epi-cubebol (7.70±0.20%), respectively.

Cholinesterase (ChE) inhibition is an important treatment strategy for Alzheimer’s disease (AD) as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are involved in the pathology of AD. In the current work, ChE inhibitory potential of twenty-four natural products from different chemical classes (i.e., diosgenin, hecogenin, rockogenin, smilagenin, tigogenin, astrasieversianins II and X, astragalosides I, IV, and VI, cyclocanthosides E and G, macrophyllosaponins A-D, kokusaginin, lamiide, forsythoside B, verbascoside, alyssonoside, ipolamide, methyl rosmarinate, and luteolin-7-O-glucuronide) was examined using ELISA microtiter assay. Among them, only smilagenin and kokusaginine displayed inhibitory action against AChE (IC₅₀ = 43.29 ± 1.38 and 70.24 ± 2.87 µg/mL, respectively). BChE was inhibited by only methyl rosmarinate and kokusaginine (IC₅₀ = 41.46 ± 2.83 and 61.40 ± 3.67 µg/mL, respectively). IC₅₀ values for galantamine as the reference drug were 1.33 ± 0.11 µg/mL for AChE and 52.31 ± 3.04 µg/mL for BChE. Molecular docking experiments showed that the orientation of smilagenin and kokusaginine was mainly driven by the interactions with the peripheral anionic site (PAS) comprising residues of hAChE, while kokusaginine and methyl rosmarinate were able to access deeper into the active gorge in hBChE. Our data indicate that similagenin, kokusaginine, and methyl rosmarinate could be hit compounds for designing novel anti-Alzheimer agents.