Polar constituents from the aerial parts of Origanum vulgare L. Ssp. hirtum growing wild in Greece

From the polar extracts of Origanum vulgare L. ssp. hirtum 19 compounds have been isolated. The structures and relative stereochemistry have been elucidated by spectroscopic analysis and determined as apigenin, luteolin, chrysoeriol, diosmetin, quercetin, eriodictyol, cosmoside, vicenin-2, caffeic acid, p-menth-3-ene-1,2-diol 1-O-β-glucopyranoside, thymoquinol 2-O-β-glucopyranoside, thymoquinol 5-O-β-glucopyranoside, thymoquinol 2,5-O-β-diglucopyranoside, 12-hydroxyjasmonic acid, 12-hydroxyjasmonic acid 12-O-β-glucopyranoside, lithospermic acid B, rosmarinic acid, 10-epi-lithospermic acid, and epi-lithospermic acid B. The three latter products display unusual stereochemistry of the 3,4-hydroxyphenyllactic acid unit(s), which to the authors' best knowledge has never been reported before in similar compounds. Moreover, lithospermic acid B (and its stereoisomers), p-menth-3-ene-1,2-diol 1-O-β-glucopyranoside, 12-hydroxyjasmonic acid, and 12-hydroxyjasmonic acid 12-O-β-glucopyranoside were isolated for the first time from Origanum species. © 2006 American Chemical Society

Pain relieving effect of-NSAIDS-CAIs hybrid molecules: Systemic and intra-articular treatments against rheumatoid arthritis

PubMed ID: 31003542To study new target-oriented molecules that are active against rheumatoid arthritis-dependent pain, new dual inhibitors incorporating both a carbonic anhydrase (CA)-binding moiety and a cyclooxygenase inhibitor (NSAID) were tested in a rat model of rheumatoid arthritis induced by CFA intra-articular (i.a.) injection. A comparison between a repeated per os treatment and a single i.a. injection was performed. CFA (50 µL) was injected in the tibiotarsal joint, and the effect of per os repeated treatment (1 mg kg-1) or single i.a injection (1 mg ml-1, 50 µL) with NSAIDs-CAIs hybrid molecules, named 4 and 5, was evaluated. The molecules 4 and 5, which were administered daily for 14 days, significantly prevented CFA-induced hypersensitivity to mechanical noxious (Paw pressure test) and non-noxious stimuli (von Frey test), the postural unbalance related to spontaneous pain (Incapacitance test) and motor alterations (Beam balance test). Moreover, to study a possible localized activity, 4 and 5 were formulated in liposomes (lipo 4 and lipo 5, both 1 mg ml-1) and directly administered by a single i.a. injection seven days after CFA injection. Lipo 5 decreased the mechanical hypersensitivity to noxious and non-noxious stimuli and improved motor coordination. Oral and i.a. treatments did not rescue the joint, as shown by the histological analysis. This new class of potent molecules, which is able to inhibit at the same time CA and cyclooxygenase, shows high activity in a preclinical condition of rheumatoid arthritis, strongly suggesting a novel attractive pharmacodynamic profile. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Università degli Studi di FirenzeAuthor Contributions: Conceptualization, L.D.C.M., Carla Ghelardini, AR.B. and C.T.S; Methodology, L.M., E.L., O.A., and M.B.; Validation, F.C.; C.T.S., Carla Ghelardini, L.D.C.M; Formal Analysis, L.M., C.P., O.A. and Clizia Guccione; Investigation, L.M., E.L., L.C.; Resources, Clizia Guccione, AR.B. and C.T.S..; Data Curation, L.M. C.P.; Writing—Original Draft Preparation, L.M.; Writing—Review & Editing, L.M., M.C.B., AR.B., L.D.C.M.; Supervision, F.C., L.D.C.M. Carla Ghelardini, C.T.S.; Project Administration, L.D.C.M., Carla Ghelardini, C.T.S.; Funding Acquisition, Carla Ghelardini, C.T.S.” Funding: This research was found by the Italian Ministry of Instruction, University and Research and the University of Florence. -