Flavonoids from Sideritis Species: Human Monoamine Oxidase (hMAO) Inhibitory Activities, Molecular Docking Studies and Crystal Structure of Xanthomicrol.

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-ß-D-allopyranosyl-(1→2)]-ß-D-glucopyranoside (2), isoscutellarein 7-O-[6'''-O-acetyl-ß-D-allopyranosyl-(1→2)]-6''-O-acetyl-ß-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.

In vivo anti-inflammatory and antinociceptive activity evaluation of phenolic compounds from Sideritis stricta.

An acetone extract obtained from aerial parts of S. stricta Boiss. & Heldr. apud Bentham, its fractions and phenolic compounds were investigated for their in vivo anti-inflammatory and antinociceptive activities. For the anti-inflammatory activity and for the antinociceptive activity assessment, carrageenan-induced hind paw edema and p-benzoquinone-induced abdominal constriction tests were used, respectively. The acetone extract of the plant and its phenolic fraction exhibited potent inhibitory activity against both bioassay models in mice. From the active phenolic fraction a well-known phenylethanoid glycoside, verbascoside (acteoside) (1), and two flavonoid glycosides, isoscutellarein 7-O-[6"'-O-acetyl-beta-D-allopyranosyl-(1-->2)]-beta-D-glucopyranoside (2) and isoscutellarein 7-O-[6"'-O-acetyl-beta-D-allopyranosyl-(1-->2)]-6"-O-acetyl-beta-D-glucopyranoside (3), were isolated. During phytochemical studies we also isolated a methoxyflavone, xanthomicrol (4), from the non-polar fraction. The structures of the isolated compounds were established by spectroscopic evidence (UV, IR, 1D- and 2D-NMR, MS). Although antinociceptive and anti-inflammatory activities of the phenolic components were found not significant in the statistical analysis, compounds 1 to 3 showed a notable activity without inducing any apparent acute toxicity as well as gastric damage. Furthermore, a mixture of flavonoid glycosides (2 + 3) exhibited a significant inhibitory effect in both models at a higher dose.

Phenolic compounds of Sideritis ozturkii and their in vivo anti-inflammatory and antinociceptive activities.

Acetone extract from aerial parts of Sideritis ozturkii Aytaç & Aksoy and its fractions were investigated for its in vivo anti-inflammatory and antinociceptive activities. For the anti-inflammatory activity assessment, carrageenan-induced hind paw edema and for the antinociceptive activity, p-benzoquinone-induced abdominal constriction tests were used. Acetone extract of the plant and its phenolic fraction were found to possess significant inhibitory activity on these in vivo models in mice. Ozturkoside A (chrysoeriol 7-O-[2'''-O-caffeoyl-6'''-O-acetyl-beta-d-glucopyranosyl-(1-->2)-beta-d-glucopyranoside]); ozturkoside B (chrysoeriol 7-O-[2'''-O-caffeoyl-beta-d-glucopyranosyl-(1-->2)-beta-d-glucopyranoside]); and ozturkoside C (chrysoeriol 7-O-[2'''-O-p-coumaroyl-6'''-O-acetyl-beta-d-glucopyranosyl-(1-->2)-beta-d-glucopyranoside]) were isolated from the active phenolic fraction. The structures of isolated compounds were elucidated by spectroscopic techniques (UV, IR, 1D- and 2D-NMR, MS). Ozturkoside C showed notable antinociceptive and anti-inflammatory activities without inducing any apparent acute toxicity or gastric damage. Although the activity of ozturkosides A and B were found insignificant in statistical analysis, some inhibitory effect was observed. Accordingly, it is suggested that these components in phenolic fraction might possibly share the antinociceptive and anti-inflammatory activities together.

ent-7alpha,18-Hydroxykaur-16-ene ethanol solvate.

The ent-kaurene diterpene in the title compound, 7-epicandicandiol ethanol solvate, C20H32O2.C2H6O, was isolated from the aerial parts of Sideritis ozturkii Aytaç & Aksoy. The molecule has the usual conformation and stereochemistry found in related ent-kaurene derivatives. The methyl-substituted ring junction has a trans arrangement and the other junction is cis. The six-membered rings have chair or slightly distorted chair conformations and the five-membered ring has an envelope conformation. Intermolecular hydrogen bonds link the 7-epicandicandiol and ethanol molecules into two-dimensional networks, part of which comprise co-operative O-H...O-H...O-H... chains.

Three acylated flavone glycosides from Sideritis ozturkii Aytac & Aksoy.

From the aerial parts of Sideritis ozturkii, three new flavonoids, chrysoeriol 7-O-[2'''-O-caffeoyl-O-acetyl-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside], chrysoeriol 7-O[2'''-O-caffeoyl-beta-D-glucopyranosyl-(1 -->2)-beta-D-glucopyranoside] and chrysoeriol 7-O[2'''-O-p-coumaroyl-6'''-beta-O-acetyl-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside] named as ozturkosides A, B and C, respectively, were isolated, along with three known phenylethanoid glycosides, verbascoside, leucoseptoside A, martynoside and five known diterpenoids, 7-epicandicandiol, linearol, sidol, sideroxol, epoxyisolinearol. The structures were elucidated mainly by spectroscopic methods.

Neo-clerodane diterpenoids from Scutellaria orientalis subsp. sintenisii.

The previously known neo-clerodane scutalpin J has been isolated from Scutellaria orientalis subsp. sintenisii together with a new diterpenoid, scutenisin, whose structure was established as (13R*)-6alpha,7beta-diisobutyryloxy-4alpha,18;8beta, 13-diepoxy-19-hydroxy-neo-clerodan-15,16-olide by spectroscopic means.