In this study, 11 hydroxybenzoic acids, 6 hydroxycinnamic acids, 6 flavonoids, and 2 synthetic phenolic antioxidants were evaluated according to their scavenging capacity and structure relationships. The IC50 was calculated for all compounds and the effects of the concentration of antioxidant and the length of the reaction on antioxidant capacity were taken into consideration. Based on the data of tested phenolics some structure-activity relationships were suggested and discussed in detail. Poor correspondence of the results between ABTS+• and DPPH• assays was attained, indicating that the antioxidant properties of each compound differ with regards to the applied method. Nevertheless, it can be argued that the number of electron-donating substituents (-OH and -OCH3) and their configuration has a significant impact on the antioxidant capacity. Undoubtedly, concerns about the reliability of these assays demand further in-depth investigations to give detailed insight into the structure and antioxidant activity relationships.

: The strategies to combat Alzheimer’s Disease (AD) have been changing with respect to the failures of many drug candidates assessed in clinical studies, the complex pathophysiology of AD, and the limitations of the current drugs employed. So far, none of the targets, either validated or nonvalidated, have been shown to be purely causative in the generation and development of AD. Considering the progressive and the neurodegenerative characteristics of the disease, the main strategy has been based on the design of molecules capable of showing activity on more than one receptor, and it is defined as multi-target ligand design strategy. The hybrid molecule concept is an outcome of this approach. Donepezil, as one of the currently employed drugs for AD therapy, has also been utilized in hybrid drug design studies. This review has aimed to present the promising donepezil-like hybrid molecules introduced in the recent period. Particularly, multi-target ligands with additional activities concomitant to cholinesterase inhibition are preferred.

Origanum spp. are used both for culinary purposes and for their biological activities. In this study, commercial Origanum majorana, Origanum minutiflorum, Origanum vulgare, and Origanum onites essential oils and their prominent constituent carvacrol were evaluated for their in vitro and in silico angiotensin-converting enzyme 2 and lipoxygenase enzyme inhibitory potentials. The essential oils were analysed by gas chromatography-flame ionisation detection and gas chromatography-mass spectrometry, where carvacrol was identified as the major component (62 – 81%), confirming the quality. In vitro enzyme inhibition assays were conducted both with the essential oils (20 µg/mL) and with carvacrol (5 µg/mL). The comparative values of angiotensin-converting enzyme 2 percent inhibition for O. majorana, O. minutiflorum, O. vulgare, and O. onites essential oils were determined as 85.5, 79.1, 74.3, and 42.8%, respectively. As a result of the enzyme assays, carvacrol showed 90.7% in vitro angiotensin-converting enzyme 2 inhibitory activity. The in vitro lipoxygenase inhibition of the essential oils (in the same order) was 89.4, 78.9, 81.1, and 73.5%, respectively, where carvacrol showed 74.8% inhibition. In addition, protein–ligand docking and interaction profiling was used to gain structural and mechanistic insights into the angiotensin-converting enzyme 2 and lipoxygenase inhibitory potentials of major Origanum essential oil constituents. The in silico findings agreed with the significant enzyme inhibition activity observed in vitro. Further in vivo studies are suggested to confirm the safety and efficacy of the oils. ^# Dedicated to Professor Dr. Gerhard Franz on the occasion of his 85th birthday. Received: 01 December 2021 Accepted after revision: 08 April 2022 Accepted Manuscript online: 19 April 2022 Article published online: 28 September 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Objectives: This study was designed to investigate the anti-inflammatory effects of Pelargonium endlicherianum Fenzl. and Pelargonium quercetorum Agnew. root extracts compared with the effects of commercial Pelargonium sidoides root extract by production of pro-inflammatory substances and inflammatory signal transduction on LPS-stimulated macrophages. Materials and Methods: To measure the effects of root extracts on pro-inflammatory mediators, we used the following methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (cell viability or cytotoxcicity), enzyme-linked immunosorbent assay (cytokine production, prostoglandin E2 production), reverse transcriptase-polymerase chain reaction (COX-2, iNOS mRNA), Western blotting analysis [MAPK activation and NE-kappa B (p65) traslocation] and the Griess reaction (NO production). Results: Stimulation of the RAW 264.7 cells with LPS (0.5 mu g/mL, 6 hrs treatment) caused an elevated production of pro-inflammatory cytokines (TNF-alpha and IL-6), increased mRNA expression of COX-2 and inducible NO synthase with release of PGE2 and NO, activated MAPK (phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, P38) signalling pathway, and nuclear translocation of NF-kappa B (p65), which were markedly inhibited by the pre-treatment with 11% ethanol and 70% methanol root extracts of P. endlicherianum without causing any cytotoxic effects. P. quercetorum root extract only decreased TNF-alpha production and P. sidoides root extract alleviated P38/MAPK activation and COX-2 mRNA expression with PGE2 production. Conclusion: Our data indicate that especially 11% ethanol root extract of P. endlicherianum targets the inflammatory response of macrophages via inhibition of COX-2, IL-6, and TNF-alpha through inactivation of the NE-kappa B signalling pathway, supporting the pharmacologic basis of P. endlicherianum as a traditional herbal medicine for the treatment of inflammation and its associated disorders.