Echinacea purpurea-derived alkylamides exhibit potent anti-inflammatory effects and alleviate clinical symptoms of atopic eczema

K

Features of Idebenone and Related Short-Chain Quinones that Rescue ATP Levels under Conditions of Impaired Mitochondrial Complex I

Short-chain quinones have been investigated as therapeutic molecules due to their ability to modulate cellular redox reactions, mitochondrial electron transfer and oxidative stress, which are pathologically altered in many mitochondrial and neuromuscular disorders. Recently, we and others described that certain short-chain quinones are able to bypass a deficiency in complex I by shuttling electrons directly from the cytoplasm to complex III of the mitochondrial respiratory chain to produce ATP. Although this energy rescue activity is highly interesting for the therapy of disorders associated with complex I dysfunction, no structure-activity-relationship has been reported for short-chain quinones so far. Using a panel of 70 quinones, we observed that the capacity for this cellular energy rescue as well as their effect on lipid peroxidation was influenced more by the physicochemical properties (in particular logD) of the whole molecule than the quinone moiety itself. Thus, the observed correlations allow us to explain the differential biological activities and therapeutic potential of short-chain quinones for the therapy of disorders associated with mitochondrial complex I dysfunction and/or oxidative stress

The lipophilic Echinacea purpurea root extract exhibit anti-inflammatory and anti-pruritic properties in vitro and in vivo

L

Non‐neuronal kappa‐opioid receptor activation enhances epidermal keratinocyte proliferation, and modulates mast cell functions in human skin ex vivo

Kappa‐opioid receptor (KOR) activation reportedly elicits anti‐inflammatory responses and can downregulate neuropeptide release from sensory nerve fibers. While this renders KOR agonists (KORAs) potentially interesting therapeutics in skin diseases associated with neurogenic inflammation, it remains poorly understood how KOR agonists impact on human skin and dermal mast cells (MCs) ex vivo, in the absence of functional innervation. The KORA 5a was administrated to the culture medium (200 nmol/L and 1 µmol/L) in human skin organ culture, thus mimicking a “systemic” mode of application. We show that KORA significantly increased epidermal thickness and upregulated the number and proliferation of epidermal keratinocytes. Unexpectedly, it also stimulated epidermal keratinocyte apoptosis in situ, compared with vehicle. Moreover, KORA significantly decreased the number of c‐Kit‐positive MCs, but did not significantly alter the number or degranulation of mature (tryptase‐ or toluidine blue‐positive) MCs. These pilot observations render the tested KORA (5a) an interesting candidate for the management of inflammatory dermatoses in which MC‐dependent neurogenic skin inflammation plays an important role (e.g. atopic dermatitis, psoriasis)