Research paperIn vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo
Graphical abstract
A cream containing a Hypericum perforatum extract protects against radical formation.
Introduction
The skin is our barrier against the oxidative environment such as nitrogen oxide, cigarette smoke, and ozone [1]. The most prominent oxidative noxe is the sunlight, which induces reactive oxygen species (ROS) mainly in the UVB and UVA spectral range. However, recent investigations have shown that in the visible and infrared spectral range, ROS are also produced [2], [3]. ROS are responsible for premature skin aging and skin cancer and should be in balance with the antioxidative defense system. Therefore, the skin is equipped with an enzymatic and non-enzymatic antioxidative system. In order to strengthen the antioxidative defense system, several cosmetic formulations containing antioxidants are available for topical application. Among various plant extracts, lipophilic extract from St. John’s Wort (Hypericum perforatum, HP) is used for the treatment of atopic skin. A major constituent of such lipophilic extracts is hyperforin, which is known to provide anti-inflammatory, anti-tumor, and anti-bacterial properties [4], [5], [6]. Topical treatment of mild atopic dermatitis with a cream containing 1.5% HP extract was significantly superior to the vehicle [7]. Investigations on antioxidative properties of aqueous extracts of several Hypericum species have shown that Hypericum perforatum has the highest radical scavenging activity [8]. Hyperforin was only partly present in the aqueous extracts because of its lipophilicity. Sagratini et al. [9] have shown that more lipophilic methanol–acetone extracts contain pharmacologically important compounds that exhibited a mild to moderate antioxidant activity. Hypericum perforatum s.l. (subsp. veronense in particular) was found to be the richest in hypericin, hyperforin, and particularly in phenolic compounds [9]. Although these studies have shown antioxidative properties of HP extracts, no information about the radical scavenging activity of hyperforin in vitro on skin cells, ex vivo on excised skin, or in vivo is available.
Therefore, we investigated the antioxidative effect of hyperforin on skin cells irradiated with solar simulated radiation (SSR). The radical scavenging activity of a cream containing a hyperforin-rich HP extract was measured by determining the radical protection factor (RPF) of the formulation. Furthermore, we assessed whether HP cream application on skin biopsies can decrease subsequent infrared-induced radical formation. Finally, we tested whether skin treatment with HP cream may reduce UVB-induced skin erythema on human skin in vivo.
Section snippets
Topical formulations
For ex vivo and in vivo investigations, a verum cream containing 1.5% of a HP CO2-extract with 44.3% hyperforin (Flavex Naturextrakte GmbH, Rehlingen, Germany) and a vehicle cream were applied. The HP extract was free of hypericin.
For the determination of the radical scavenging activity of the cream (RPF determination), HP concentrations of 0.5%, 1.5%, 3.0%, and 5.0% were used.
EPR experiments
EPR spectroscopy is based on the resonant absorption of microwave radiation by paramagnetic species exposed to a
Free radical scavenging effect of hyperforin in cells after UV irradiation
Hyperforin reduced the formation of SSR-induced DCF formation in HaCaT cells from 0.625 to 10 μM, whereas the solvent had no effect (Fig. 1A). The EC50 of hyperforin (0.7 μM or 0.35 μg/ml) was more effective compared to Trolox (EC50:12 μg/ml) and N-acetylcysteine (EC50: 847 μg/ml). No phototoxic effect of hyperforin was observed (Fig. 1B).
Radical scavenging effect of the cream without irradiation
The radical scavenging activity was determined using the radical protection factor (RPF) method, which uses a semi stable radical and measures the amount of
Discussion
Hyperforin, the lipophilic main active ingredient of HP, has anti-bacterial, anti-inflammatory, and differentiation promoting properties [4], [7], [17]. In this paper, we have shown that hyperforin reduces ultraviolet-induced oxidative stress without phototoxic effects in vitro. The half maximal radical scavenging concentration lies at 0.7 μM (0.35 μg/ml), which is similar to the antitumorigenic concentrations of hyperforin that have been described earlier [18]. Compared to previously published
Acknowledgments
We would like to thank Birgit Haarhaus for her excellent technical assistance. The study was partly sponsored by Cassella-med GmbH, the Foundation of Skin Physiology, and the Federal Land of Berlin within the Program to Promote Research, Innovation and Technologies (ProFIT, Grant No. 10148423) for granting subsidies from the innovation promotion fund, with co-financing by the European Fund for Regional Development (ERDF). The competence center skintegral receives funding from the Software AG
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2021, Industrial Crops and ProductsCitation Excerpt :The results showed that radical formation could be reduced by almost 80 % when applying the hyperforin-rich cream onto the skin. A formulation containing 44.3 % hyperforin and free of hypericin was investigated for its in vivo photoprotective and radical protection capacity (Meinke et al., 2012). Assays were also conducted in vitro in HaCaT keratinocytes irradiated with solar simulated radiation, and the results showed that hyperforin (EC50, 0.42 μg mL−1) was much more effective when compared to trolox (EC50, 12 μg mL−1).
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2020, European Journal of Medicinal ChemistryCitation Excerpt :It reduces fibroblast’s migration, proliferation and contraction ability [209]. Application of topical hyperforin cream may stabilize stratum corneum lipids and increase radical protection on the skin without helping with the inflammation in deeper layers [210–213]. Lately, it was also found that the β-cyclodextrin-(hydroxypropyl-β-cyclodextrin-) tetra capped hyperforin facilitates wound closure via enhancement of ATP-Ca2+ signalling in keratinocytes [214].