A novel triterpene extract from mistletoe induces rapid apoptosis in murine B16.F10 melanoma cells.

The European mistletoe Viscum album L. is a plant used for remedies in cancer treatment. The benefit of commonly used aqueous extracts is controversial but the plant contains water insoluble triterpene acids providing interesting anticancer properties. Triterpene extracts (TE) from plants and single triterpenoids such as oleanolic acid (OA) or betulinic acid (BA) are known for their cytotoxic effects on cancer cell lines in vitro. We report here cytotoxic effects of a novel OA-rich triterpene extract from mistletoe (V. album L., Santalaceae) solubilized by 2-hydroxypropyl-ß-cyclodextrin (2-HP-ß-CD) on B16.F10 mouse melanoma cells. The 2-HP-ß-CD solubilized triterpene extract (STE) was highly cytotoxic by causing DNA fragmentation, followed by loss of membrane integrity and intracellular adenosine-5'-triphosphate (ATP). Blocking the caspase machinery by inhibitors aborted DNA fragmentation and delayed the cytotoxic effects but did not prevent cell death. The solubilization by 2-HP-ß-CD allows a solvent-free application of triterpene extracts in the in vitro setting. These findings suggest the use of STE from mistletoe as a solvent-free anticancer drug for preclinical animal experiments and clinical trials.

Antimicrobial activity against bacteria with dermatological relevance and skin tolerance of the essential oil from Coriandrum sativum L. fruits.

The aim of this work was to determine the antibacterial activity of essential coriander oil (ECO) on bacteria with dermatological relevance and to assess the skin tolerance of antimicrobial effective ECO concentrations. Essential coriander oil was tested on clinical isolates of different bacteria species, all of which may cause superficial skin infections. Antimicrobial susceptibility testing was performed using a standardized macrodilution test. Essential coriander oil showed good antibacterial activity towards the majority of the bacterial strains tested, including Streptococcus pyogenes (Lancefield group A) and methicillin resistant Staphylococcus aureus (MRSA), with mean minimal inhibitory concentrations of 0.04% v/v and 0.25% v/v, respectively. The skin tolerance of a cream and a lotion containing 0.5% and 1.0% ECO was assessed in 40 healthy volunteers using the occlusive patch test. No skin irritation could be observed by sensitive photometric assessment in any of the volunteers. Because of its activity against Streptococcus pyogenes, Staphylococcus aureus and MRSA combined with excellent skin tolerance, ECO might be useful as an antiseptic for the prevention and treatment of skin infections with Gram-positive bacteria.

Dermocosmetics for dry skin: a new role for botanical extracts.

Dry skin is associated with a disturbed skin barrier and reduced formation of epidermal proteins and lipids. During recent years, skin-barrier-reinforcing properties of some botanical compounds have been described. Searching the PubMed database revealed 9 botanical extracts that specifically improve skin barrier and/or promote keratinocyte differentiation in vivo after topical application. The topical application of Aloe vera (leaf gel), Betula alba (birch bark extract), Helianthus annuus (sunflower oleodistillate), Hypericum perforatum (St. John's wort extract), Lithospermum erythrorhizon (root extract), Piptadenia colubrina (angico-branco extract) and Simarouba amara (bitter wood extract) increased skin hydration, reduced the transepidermal water loss, or promoted keratinocyte differentiation in humans in vivo. The topical application of Rubia cordifolia root extract and rose oil obtained from Rosa spp. flowers stimulated keratinocyte differentiation in mouse models. The underlying mechanisms of these effects are discussed. It is concluded that some botanical compounds display skin-barrier-reinforcing properties that may be used in dermocosmetics for dry skin. However, more investigations on the mode of action and more vehicle-controlled studies are required.

Reseda luteola L. extract displays antiproliferative and pro-apoptotic activities that are related to its major flavonoids.

Reseda luteola L. has been used as a dye due to its high luteolin content since ancient times. However, no pharmacological studies have been performed with Reseda extracts so far. Here, we have assessed antiproliferative and apoptosis-inducing effects of the Reseda extract RF-40. It contains 40% flavonoids, primarily luteolin, but also luteolin-7-O-glucoside and apigenin. RF-40 and the isolated flavonoids dose-dependently inhibited cell proliferation and induced apoptotic oligonucleosomes in PHA-stimulated peripheral blood mononuclar cells. These effects were not due to cytotoxicity as shown with a luminometric ATP assay. Dose-response curves of RF-40 and the isolated flavonoids were similar, with luteolin being the most effective isolated flavonoid. Comparison of RF-40 to its major flavonoids revealed that the pharmacological effects of the extract can mostly be attributed to luteolin. We conclude that Reseda extract is an interesting raw material not only for dyeing purposes but also for further pharmacological investigation.

Topical application of solubilized Reseda luteola extract reduces ultraviolet B-induced inflammation in vivo.

We investigated the skin tolerance and anti-inflammatory potential of a nanoparticular solubilisate of a luteolin-rich Reseda extract (s-RE) in two independent studies in vivo. Reseda luteola extract containing 40% flavonoids was solubilized with polysorbate, resulting in product micelles with a diameter of 10 (+/-1.5)nm. Standardized inflammation was induced by irradiating test areas on the back of healthy volunteers with defined doses of ultraviolet B (UVB). In the first study different concentrations of s-RE were tested in 10 volunteers to evaluate dose-dependency of anti-inflammatory effects of s-RE. In the second randomized, double-blind, placebo-controlled study a defined concentration of s-RE (2.5%w/w) was tested in 40 volunteers in comparison to the vehicle (glycerol) and hydrocortisone (1%w/w). s-RE dose-dependently reduced UVB-induced erythema when applied 30 min before irradiation. To a lesser extent, topical application of s-RE after irradiation also reduced UVB-induced erythema. s-RE was as effective as hydrocortisone, whereas the vehicle had no effect. Occlusive application of s-RE on non-irradiated test sites did not cause any skin irritation. Due to excellent skin tolerance combined with potent anti-inflammatory properties s-RE bears potential especially for the prevention but also for the treatment of inflammatory skin conditions such as UV-induced erythema.

Skin tolerance of a new bath oil containing St. John's wort extract.

BACKGROUND: Dry and atopic skin requires skin care with lipid-rich emollients and moisturizing bath or shower oils. However, it has been shown recently that some bath oils may even impair the skin barrier. OBJECTIVE: To investigate the skin-irritating potential of a new bath oil containing a lipophilic St. John's wort (Hypericum perforatum) extract. METHODS: In this single-center, randomized, double-blind, prospective study, 3 bath oils together with positive and negative controls were applied under occlusion on test areas on the volar forearms of 18 volunteers (visit 1). After 24 h, the tapes were removed, and the test areas were evaluated by a visual score and the instrumental measurement of skin erythema and transepidermal water loss (TEWL) using a Mexameter and a Tewameter (visit 2). The test substances were applied a second time, and the measurements were performed after another 24 h (visit 3). RESULTS: The positive control, 1% vol/vol sodium lauryl sulfate (SLS), caused a significant increase in skin erythema and TEWL. In contrast, distilled water as a negative control did not influence these parameters. The new bath oil containing St. John's wort extract and 1 of the other 2 commercial products were not different from the water control. The third bath oil displayed a skin-irritating effect similar to SLS. CONCLUSION: The results of this study confirm the different skin-irritating potential of bath oils and demonstrate good skin tolerance of the new bath oil containing St. John's wort extract.

Investigation of the anti-inflammatory potential of Aloe vera gel (97.5%) in the ultraviolet erythema test.

BACKGROUND: Aloe vera is a natural product that is frequently used in soothing skin care products such as aftersun lotions. In the present study we aimed to explore the anti-inflammatory potential of a highly concentrated A. vera gel in the UV erythema test in vivo. METHODS: 40 volunteers with skin types II and III were included in the randomized, double-blind, placebo-controlled, phase III monocenter study. Test areas on the back were irradiated with the 1.5-fold minimal erythema dose of UVB. Subsequently, the test areas were treated occlusively on 2 subsequent days with A. vera gel (97.5%), the positive controls (0.25% prednicarbate, 1% hydrocortisone in placebo gel and 1% hydrocortisone cream) and a placebo gel. Erythema values were determined photometrically after 24 and 48 h. RESULTS: A. vera gel (97.5%) significantly reduced UV-induced erythema after 48 h, being superior to 1% hydrocortisone in placebo gel. In contrast, 1% hydrocortisone in cream was more efficient than A. vera gel. CONCLUSIONS: In this study after 48 h the A. vera gel (97.5%) displayed some anti-inflammatory effects superior to those of 1% hydrocortisone in placebo gel. The A. vera gel tested here might be useful in the topical treatment of inflammatory skin conditions such as UV-induced erythema.

Usnea barbata extract prevents ultraviolet-B induced prostaglandin E2 synthesis and COX-2 expression in HaCaT keratinocytes.

Usnea barbata and its major constituent usnic acid are potent antimicrobial agents. Here, we have investigated anti-inflammatory properties of an U. barbata extract (UBE) containing 4% usnic acid in an ultraviolet-B (UVB) model with HaCaT keratinocytes. UVB irradiation induced PGE(2) production and COX-2 expression in a time and dose-dependent manner. UBE inhibited PGE(2) production at a half-maximal concentration of 60 microg/ml (2.4 microg/ml usnic acid) that did not affect the UVB-induced upregulation of COX-2, suggesting an effect on enzyme activity rather than on protein expression. The inhibition of PGE(2) production by UBE was not due to cytotoxicity. Besides its known antimicrobial properties, UBE displays specific UVB protective effects that might be useful in the topical treatment of UVB-mediated inflammatory skin conditions.

Screening of plant extracts for antimicrobial activity against bacteria and yeasts with dermatological relevance.

There is cumulative resistance against antibiotics of many bacteria. Therefore, the development of new antiseptics and antimicrobial agents for the treatment of skin infections is of increasing interest. We have screened six plant extracts and isolated compounds for antimicrobial effects on bacteria and yeasts with dermatological relevance. The following plant extracts have been tested: Gentiana lutea, Harpagophytum procumbens, Boswellia serrata (dry extracts), Usnea barbata, Rosmarinus officinalis and Salvia officinalis (supercritical carbon dioxide [CO2] extracts). Additionally, the following characteristic plant substances were tested: usnic acid, carnosol, carnosic acid, ursolic acid, oleanolic acid, harpagoside, boswellic acid and gentiopicroside. The extracts and compounds were tested against 29 aerobic and anaerobic bacteria and yeasts in the agar dilution test. U. barbata-extract and usnic acid were the most active compounds, especially in anaerobic bacteria. Usnea CO2-extract effectively inhibited the growth of several Gram-positive bacteria like Staphylococcus aureus (including methicillin-resistant strains - MRSA), Propionibacterium acnes and Corynebacterium species. Growth of the dimorphic yeast Malassezia furfur was also inhibited by Usnea-extract. Besides the Usnea-extract, Rosmarinus-, Salvia-, Boswellia- and Harpagophytum-extracts proved to be effective against a panel of bacteria. It is concluded that due to their antimicrobial effects some of the plant extracts may be used for the topical treatment of skin disorders like acne vulgaris and seborrhoic eczema.

[Topical treatment of atopic dermatitis with Hypericum cream. A randomised, placebo-controlled, double-blind half-side comparison study]. / Behandlung der subakuten atopischen Dermatitis mit Johanniskraut-Creme. Eine randomisierte, placebokontrollierte Doppelblindstudie im Halbseitendesign.

BACKGROUND: Recent investigations suggest an anti-inflammatory and antibacterial effect of hyperforin, which is a major constituent of Hypericum perforatum L. (Saint John's wort). OBJECTIVE: In a half-side comparison study we assessed the efficacy of a cream containing Hypericum extract standardized to 1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for the treatment of subacute atopic dermatitis. The study design was a prospective randomized placebo-controlled double-blind single center study. METHODS: In twenty one patients suffering from mild to moderate atopic dermatitis (mean SCORAD 44.5) the treatment with verum or placebo was randomly allocated to the left or right site of the body, respectively. The patients were treated twice daily over a period of four weeks. Eighteen patients completed the study. The severity of the skin lesions on the left and right site was determined by means of a modified SCORAD-index (primary endpoint). RESULTS: The intensity of the eczematous lesions improved on both sites of treatment. However, the Hypericum cream was significantly superior to the vehicle at all clinical visits (days 7, 14, 28) (p<0.05). Skin colonization with Staphylococcus aureus was reduced by both verum and placebo, showing a trend to better antibacterial activity of the Hypericum cream (p=0.064). Skin tolerance and cosmetic acceptability was good or excellent with both the Hypericum cream and the vehicle (secondary endpoints). CONCLUSION: Hypericum cream was significantly superior to its vehicle in the topical treatment of mild to moderate atopic dermatitis. The therapeutic efficacy of the Hypericum cream should be evaluated in further studies with larger patient cohorts, in comparison to standard therapeutic agents (i.e. corticosteroids).

[St. John's wort (Hypericum perforatum L.). A plant with relevance for dermatology]. / Johanniskraut (Hypericum perforatum L.). Eine Pflanze mit Relevanz für die Dermatologie.

Saint John's wort (Hypericum perforatum L.) is a herbal remedy that is effective in the treatment of mild to moderate depression. In traditional folk medicine, oily extracts of St. John's wort are used for topical treatment of wounds, burns and myalgia. The lipophilic phloroglucin-derivative hyperforin has antibacterial and antiinflammatory effects. These effects could be of relevance in topical treatment of infected wounds and other dermatoses, but no studies have been conducted so far. The naphtodianthrone hypericin is a photodtodynamic active substance that kills tumor cells via the induction of apoptosis. Hypericin also displays antiviral activity in vitro. In vivo, intravenous or oral treatment with hypericin of HIV-infected subjects did not result in a reduction of the virus load. Most of the patients treated with hypericin experienced phototoxicity. Similar phototoxic symptoms ("hypericism") have been observed in grazing animals ingesting large amounts of St. John's wort. In contrast, antidepressant medication with St. John's wort usually does not produce phototoxic symptoms. Recent pharmacokinetic studies suggest that the phototoxic threshold level of hypericin is not reached with dosages used for the oral treatment of depression. However, very recent reports demonstrated interactions of St. John's wort with other drugs such as digoxin, indinavir and cyclosporin. Blood levels of these drugs were dramatically decreased by St. John's wort. This should be considered in the treatment of skin conditions with antiviral drugs or cyclosporin.

[Plant-induced toxic and allergic dermatitis (phytodermatitis)]. / Durch Pflanzen ausgelöste toxische und allergische Dermatitis (Phytodermatitis).

Herbal products are being used increasingly for medical or cosmetic purposes. Many cosmetics contain plant extracts for fragrance. Sensitizing plants in cosmetics are tea tree oil, arnica, chamomile, yarrow, citrus extracts, common ivy, aloe, lavender, peppermint, and others. However, the sensitizing potential of these plants varies. Most of the sensitizing substances are sesquiterpene lactones or terpenes. The present paper reviews the various forms of phytodermatitis, including irritant plant dermatitis, phototoxic and photo-allergic dermatitis, allergic dermatitis, and airborne contact dermatitis.

Effect of topical application of Hypericum perforatum extract (St. John's wort) on skin sensitivity to solar simulated radiation.

St. John's wort (Hypericum perforatum) is a tradional folk remedy that is used for the topical treatment of superficial wounds, scars and burns. A characteristic metabolite of St. John's wort is the photodynamic active plant pigment hypericin. It is known that hypericin may cause a severe photodermatitis called hypericism when higher amounts of St. John's wort are ingested orally. To date, no reports on the photosensitizing capacity of topical application of St. John's wort are available. Here, we investigated the effects of Hypericum oil (hypericin 110 microg/mL) and Hypericum ointment (hypericin 30 microg/mL) on skin sensitivity to solar simulated radiation. Sixteen volunteers of the skin types II and III were tested on their volar forearms with solar simulated radiation for photosensitizing effects of Hypericum oil (n=8) and Hypericum ointment (n=8). The minimal erythema dose (MED) was determined by visual assessment, and skin erythema was evaluated photometrically. With the visual erythema score, no change of the MED could be detected after application of either Hypericum oil or Hypericum ointment (P>0.05). With the more sensitive photometric measurement, an increase of the erythema-index after treatment with the Hypericum oil could be detected (P< or =0.01). The results do not provide evidence for a severe phototoxic potential of Hypericum oil and Hypericum ointment, detectable by the clinically relevant visual erythema score. However, the trend towards increased photosensitivity detected with the more sensitive photometric measurement could become relevant in fair-skinned individuals, in diseased skin or after extended solar irradiation.

Topical application of St John's wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells.

St John's wort (Hypericum perforatum) is a traditional herbal medicine that is used for the topical treatment of superficial wounds, burns and dermatitis. The characteristic metabolites of St John's wort are the photodynamic active plant pigment hypericin and the phloroglucin-derivative hyperforin. To date, no studies on immunomodulatory properties of topical preparations of St John's wort have been performed. Here, we investigated the alloantigen presenting function of human epidermal cells (EC) exposed to Hypericum ointment in vivo in a mixed EC lymphocyte reaction (MECLR). The effect of Hypericum ointment was compared with the immunosuppressive effect of solar-simulated radiation (SSR). Subsequently, we tested purified hyperforin in vivo and in vitro in a MECLR to evaluate its possible contribution to the effect of the Hypericum ointment. Furthermore, we assessed the effect of hyperforin on the proliferation of peripheral blood mononuclear cells (PBMC) in vitro. Compared with untreated skin, treatment with Hypericum ointment resulted in a significant suppression of the MECLR (P

[Comparison of balneophototherapy and UVA/B mono-phototherapy in patients with subacute atopic dermatitis]. / Vergleichsstudie Solebäder plus UVA/B versus UVA/B- Monotherapie bei Patienten mit subakuter atopischer Dermatitis.

In a controlled prospective study we compared the efficacy of combined salt water bath and UVA/B phototherapy to a UVA/B mono-phototherapy in patients with subacute atopic dermatitis (AD). The patients in the balneophototherapy group (n=16) were treated with baths containing 3-5% of the synthetic salt Psori-sal(trade mark), followed immediately by UVA/B irradiation, while the other treatment arm (n=12) received UVA/B phototherapy alone. After 20 treatments the balneophototherapy group showed a statistically significant (p

Hypericin levels in human serum and interstitial skin blister fluid after oral single-dose and steady-state administration of Hypericum perforatum extract (St. John's wort).

The photodynamically active plant pigment hypericin, a characteristic metabolite of Hypericum perforatum (St. John's wort), is widely used as an antidepressant. When administered orally, phototoxic symptoms may limit the therapeutic use of hypericin-containing drugs. Here we describe the high-performance liquid chromatographic (HPLC) detection of hypericin and semiquantitative detection of pseudohypericin in human serum and skin blister fluid after oral single-dose (1 x 6 tablets) or steady-state (3 x 1 tablet/day, for 7 days) administration of the Hypericum extract LI 160 in healthy volunteers (n = 12). Serum levels of hypericin and pseudohypericin were always significantly higher than skin levels (p 100 ng/ml).

Salt water bathing prior to UVB irradiation leads to a decrease of the minimal erythema dose and an increased erythema index without affecting skin pigmentation.

The combination of salt water baths and solar radiation is known as an effective treatment for patients with psoriasis and atopic dermatitis. To determine whether increased susceptibility to UVB radiation may contribute to this therapeutic effect we have studied the effect of bathing the skin in salt water prior to UVB irradiation. Twelve subjects were phototested on the volar aspects of their forearms with increasing doses of UVB radiation. One forearm was exposed to 5% salt water prior to irradiation. The minimal erythema dose (MED) was determined and the erythema index and skin pigmentation were assessed by photometric measurement. The combination of salt water bath and irradiation yielded a significant decrease of the MED when compared to UVB alone (median 90 mJ/cm2 vs 130 mJ/cm2, P < 0.01). Analysis of variance showed a significant influence of salt water bath on erythema (P < 0.05) but not on skin pigmentation. Within the MED test area the erythema index of the salt water exposed forearms was elevated significantly (P < 0.05) while skin pigmentation was not affected. Thus, bathing the skin in salt water leads to a decreased threshold level for the elicitation of UVB-induced erythema and a selective increase of the erythemal response. This sensitization to the effects of shortwave UVB radiation may increase immunosuppressive effects of UVB radiation and may lead to an increased efficacy of UVB phototherapy. However, there is also an increased sunburn risk when salt water baths are followed by exposure to UV radiation.

[Effect of various salt solutions on ultraviolet B-induced erythema and pigmentation]. / Der Einfluss verschiedener Salzlösungen auf die Ultraviolett-B-vermittelte Induktion von Erythem und Pigmentierung.

The combination of saltwater baths and subsequent ultraviolet irradiation is an effective treatment for psoriasis and atopic dermatitis. The aim of the present study was to determine the photosensitizing properties of two commercially available bath salts, original salt from the Dead Sea and sodium chloride. To address this issue, test areas on the volar aspects of the forearms were soaked with salt solutions for 15 minutes prior to ultraviolet-B (UVB) irradiation. The salt concentrations tested were 1%, 3% 5% and 15%. Tap water followed by UVB and UVB alone served as controls. Erythema was determined by visual and photometric measurement, and delayed tanning was assessed by colorimetry. Erythema obtained by wetting the skin prior to UVB irradiation was more pronounced than erythema induced by UVB alone. The most prominent erythema was yielded by tap water + UVB. The salts had a differing photosensitizing capacity and the strongest erythema was produced by the 5% solutions. There was only a moderate influence on delayed tanning by bathing the skin prior to irradiation. The results from the present study indicate that soaking the skin with salt solutions or tap water increases skin sensitivity to subsequent UVB irradiation. This may contribute to the effectiveness of salt water baths followed by UV irradiation and may account for an increased sunburn risk after bathing.