Abstract
We demonstrated the anti-inflammatory and anti-oxidative effects of Humulus lupulus (HL) extract on solar simulator-irradiated primary human keratinocytes (PHKs) by analyzing ERK and p38 MAPK phosphorylation and production of IL-6 and IL-8. The anti-inflammatory effect of topically applied HL was further tested in vivo on human skin. To this end, we developed an oil-in-water (O/W) and a water-in-oil (W/O) cream with a lipid content of 40%. The anti-inflammatory effect of 1% HL extract incorporated in these two vehicles was assessed in a randomized, prospective, placebo controlled, double-blind UVB erythema study with 40 healthy volunteers. Hydrocortisone acetate (HCA) in the corresponding vehicle served as positive control. Surprisingly, both HL and HCA were only effective in the O/W system but not in the W/O formulation. Release studies using vertical diffusion cells (Franz cells) revealed that HCA was released in much higher amounts from the O/W cream compared to the W/O formulation. In summary, we have shown that 1% HL extract exerts anti-inflammatory effects comparable to 1% HCA, but only when incorporated in our O/W cream. Our findings confirm the critical role of the vehicle in topical anti-inflammatory systems.
Highlights
Our previous in vitro and ex vivo experiments revealed that Humulus lupulus (HL, hop) extract is a promising anti-psoriatic agent with prominent anti-proliferative effects [1].Because epidermal barrier defects and scaling are pathogenetic key factors in psoriasis, the current guidelines and therapeutic concepts for psoriasis recommend a topical therapy with lipid-rich creams [2]
The so-induced local pro-inflammatory response eventually results in erythema formation [21,22]
The anti-inflammatory effects of HL extract and HC were comparable with respect to a reduction of the ERK phosphorylation, whereas for the p38 phosphorylation, HC showed a statistically significantly stronger effect than HL extract (p ≤ 0.05)
Summary
Our previous in vitro and ex vivo experiments revealed that Humulus lupulus (HL, hop) extract is a promising anti-psoriatic agent with prominent anti-proliferative effects [1]. Because epidermal barrier defects and scaling are pathogenetic key factors in psoriasis, the current guidelines and therapeutic concepts for psoriasis recommend a topical therapy with lipid-rich creams [2]. Other chronic inflammatory skin conditions with reduced lipid and ceramide content, such as atopic eczema, benefit from a lipid-rich cream [3–5]. While lipophilic vehicles are advantageous for dry skin conditions, hydrophilic vehicles are more suitable for acute, oozing skin conditions. The most common vehicles with a very high lipid content are water-in-oil (W/O) creams with a hydrophilic inner phase dispersed in a lipophilic outer phase [6]. Topical formulations with a similar high lipid content may be obtained with lipid-rich oil-in-water (O/W) creams [7]
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