Herbal Topical Treatment

biomedicines
Review
New Herbal Biomedicines for the Topical Treatment
of Dermatological Disorders
Julia Hoffmann, Fabian Gendrisch, Christoph Mathis Schempp and Ute Wölfle *
Research Center Skinitial, Department of Dermatology, Medical Center, University of Freiburg, Hauptstr. 7,
D-79104 Freiburg, Germany; julia.hoffmann@uniklinik-freiburg.de (J.H.);
fabian.gendrisch@uniklinik-freiburg.de (F.G.); christoph.schempp@uniklinik-freiburg.de (C.M.S.)
* Correspondence: ute.woelfle@uniklinik-freiburg.de; Tel.: +49-0761-27068250; Fax: +49-0761-27068290

Received: 8 January 2020; Accepted: 6 February 2020; Published: 8 February 2020
Abstract: Herbal extracts and isolated plant compounds play an increasing role in the treatment of
skin disorders and wounds. Several new herbal drugs, medicinal products and cosmetic products for
the treatment of various skin conditions have been developed in recent years. In this nonsystematic
review, we focus on herbal drugs that were tested in controlled clinical studies or in scientifically
sound preclinical studies. The herbal biomedicines are intended to treat atopic dermatitis (St. John’s
wort, licorice, tormentil, bitter substances, evening primrose), psoriasis (araroba tree, lace flower,
barberry bark, indigo, turmeric, olibanum, St. John’s wort), actinic keratosis (birch bark, petty spurge),
herpes simplex (lemon balm, sage and rhubarb), rosacea (green tea, licorice, tormentil) and acne
vulgaris (tea tree oil, green tea, hop), or to improve photo protection (green tea, Dyer’s weed, cocoa
tree, carotinoids, licorice), aesthetic dermatology (licorice, pine bark, gotu kola) and wound healing
(birch bark, onion).
Keywords: atopic dermatitis; acne; actinic keratoses; psoriasis; rosacea; wound healing
1. Introduction
Herbal therapies have been used for the treatment of skin conditions for centuries. Several plant
compounds are still used in topical treatments, such as salicylic acid from willow bark from Salix spp.
(for desquamation), 8-methoxypsoralen from Ammi visnaga (L.) Lam. (for photochemotherapy), and
tannins from oak bark, black tea or hamamelis bark (for oozing eczema). Traditionally used medical
plants were evaluated and documented in 300 monographs by Commission E at the German institute
for drugs and medicinal products (BfArm) between 1976 and 1993. About 30% of these plants received
a negative evaluation. The positive monographs contained 25 plants with relevance for dermatological
treatments. They include well-known medical plants such as chamomile, which hazel and marigold.
However, most of these plants only achieved a low level of evidence for their efficacy, because only
a few high quality clinical studies have been performed [1,2]. During the last years the therapeutic
potential of medical plants traditionally used in dermatology has been explored, and some of them
have been developed and approved as drug or medical device for the treatment of skin disorders.
Furthermore, an increasing number of herbal products have been developed in the field of medical
cosmetics, often called “cosmeceuticals”. This review highlights the most exciting new experimental
and clinical studies with herbal drugs and cosmeceuticals for skin disorders. Literature was searched in
actual plant reviews focusing on special skin diseases. We focused predominantly on controlled clinical
studies with a sufficiently high level of evidence. However, this is not purely a systematic evidence
based review, because we have also included scientifically confirmed effects of plant extracts with
promising new treatment options for dermatologists. In this way we could point to new auspicious
treatment strategies, although clinical studies are still missing or under preparation. The quality of the
Biomedicines 2020, 8, 27; doi:10.3390/biomedicines8020027 www.mdpi.com/journal/biomedicines

Biomedicines 2020, 8, 27 2 of 21
clinical studies was classified as “levels of evidence” (LOE) A to D according to the proposal of the UK
National Health Service [3]. Level A represents the highest level with randomized, controlled clinical
studies and cohort studies. Level B includes conclusive retrospective or analytical cohort studies,
research results, and case control studies, as well as follow-up studies of level A. Level C includes case
reports or follow-up studies of level B and level D is assigned to expert opinions without scientific
background, pure laboratory research or mechanisms of action. The outline of the paper is arranged
according to dermatological conditions and at the end of this article, the main findings are summarized.
2. Atopic Dermatitis
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Dermatologists often
prescribe glucocorticoids to the patients, but patients and parents of children with AD worry about the
side effects of glucocorticoids, especially in long term therapy. They ask for herbal therapies because
they expect similar effectivity and fewer side effects. A comprehensive, evidence-based review on
clinical studies with herbal products for AD has been published recently [4]. Some of the studies are
highlighted here.
2.1. St. John’s Wort (Hypericum perforatum (L.))

St. John’s wort is traditionally used as hypericum oil for the treatment of wounds and burns.
The lipophilic phloroglucin derivative hyperforin displays antibacterial, anti-inflammatory and
keratinocyte differentiation-promoting properties [5]. The efficacy of a hyperforin-rich ointment
standardized to 1.5% hyperforin has been investigated in a randomized, placebo-controlled half side
comparison pilot study in 21 AD patients. The treatment was performed twice daily over a period of
4 weeks [6] (LOE-A).
2.2. Licorice (Glycyrrhiza glabra (L.))

The anti-inflammatory effect of licorice (Glycyrrhiza glabra L. and Glycyrrhiza uralensis Fisch. ex
DC.) is well studied and summarized in an actual review [7]. Most studies were performed with the
triterpenes glycyrrhizin and glycyrrhetinic acid of licorice on skin [7–10]. However, other ingredients,
such as the flavonoid isoliquiritigenin [11] and the chalcone licochalcone A [12–14] display also
anti-inflammatory effects. A hydrophilic ointment with 2% glycyrrhetinic acid as the main active
ingredient was tested in a randomized, placebo-controlled study on 281 adult subjects with mild to
moderate AD. The application was performed three times daily in the affected areas. After five weeks
the verum was significantly superior to the vehicle (placebo) (80% vs 10% improvement) [15] (LOE-A).
In a placebo controlled study with 26 adults a cream with Licochalcone A as anti-inflammatory
ingredient showed anti-inflammatory effects superior to placebo [16] (LOE-A). Furthermore it has
been shown that a herbal composition with glycyrrhizinic acid (0.6%) and licorice extract (0.1%
Glycyrrhiza uralensis root extract) as main active ingredients displays anti-inflammatory effects in
a placebo-controlled double-blind UV-erythema test study 48 h after irradiation and cream application.
The licorice-based product was as effective as 1% hydrocortisone acetate [17]. Besides, it reduced the
severity score in 10 patients with AD treated twice daily over 2 weeks in a non-interventional pilot
study [17] (LOE-B).
2.3. Tormentil (Potentilla erecta (L.))

Tannins from black tea (Camellia sinensis (L.) Kuntze), witch hazel (Hamamelis virginiana L.) and
oak bark (Quercus spp.) have been empirically used in dermatology since ancient times. Tannins are
used as wet-lipid wraps or local baths for the treatment of acute, oozing eczema. A cream containing
2% tannins from the rhizome of tormentil (Potentilla erecta (L.) Raeusch.) displayed a corticoid-like
vasoconstrictive effect in an occlusive patch test after 48 h [18]. It also displayed placebo-controlled
anti-inflammatory properties comparable to hydrocortisone in the UV-erythema test (LOE-A) and
was effective in the treatment of 24 patients suffering from mild to moderate AD. The application was
performed twice daily over 2 weeks, and was not placebo controlled [19] (LOE-B).
2.4. Bitter Substances

Bitter substances have been used as appetizing and digestion promoting agents since Ayurvedic
medicine 5000 years ago. Only recently the molecular structure of bitter taste receptors (TAS2Rs)
has been elucidated, and it was shown that TAS2Rs are also expressed in human epidermis [20].
Bitter compounds such as salicin from willow bark (from Salix spp.) and amarogentin from Gentiana
lutea (L.) bind to the bitter taste receptors of the skin, eventually leading to calcium influx and the
enhanced expression of skin barrier-constituting proteins such as filaggrin [20]. Bitter compounds also
stimulated the synthesis of lipids in keratinocytes. In a placebo-controlled, double-blind half-side
comparison with 33 volunteers 5% gentian extract significantly increased the lipid content of the
epidermal stratum corneum on the volar forearm. In this body region skin lipids are nearly exclusively
produced by keratinocytes [21]. The application occurred twice a day for 4 weeks. After 2 weeks of
treatment, a significant increase in the lipid content could already be observed (LOE-B). Interestingly,
the predilection sites of AD (flexures of the arms and knees) correspond to skin regions in which
the lipids are exclusively formed by keratinocytes and not by sebaceous glands. Therefore, topical
treatment with bitter agents is especially helpful in dry and atopic skin with reduced synthesis of
epidermal lipids.
2.5. Evening Primrose (Oenothera biennis (L.))

The oil obtained from evening primrose seeds is beneficial for AD due to its high content of
γ-linolenic acid. It is used both internally and in topical products. Only a few high-quality studies have
investigated the effect of evening primrose oil in AD. A recent meta-analysis of the existing literature
concludes that there is a moderate effect of evening primrose oil on itching, scaling and crusting in
AD [22] (LOE-A).
3. Psoriasis Vulgaris
Herbal products are also used for the topical treatment of psoriasis. Psoriasis is a chronic,
immune-mediated skin disease that shows red and scaly patches on the skin that itch or burn. Three
systematic reviews have evaluated the use of herbal therapies in psoriasis [23–25].
3.1. Araroba Tree (Vataireopsis araroba (Aguiar) Ducke)

The most potent topical treatment for psoriasis is the anthracen derivative dithranol (synonym:
anthralin). It was obtained from chrysarobin, extracted from the bark of the araroba tree that grows in
the rain forests of the Amazon. Dithranol inhibits the release of pro-inflammatory cytokines and the
proliferation of keratinocytes. A randomized controlled multicenter study on 106 psoriasis patients
with chronic psoriasis plaques demonstrated significant better therapeutic effectivity for dithranol
short contact treatments (15–45 min) with stepwise increasing concentrations of dithranol (up to 5%)
once daily for 12 weeks as compared to the standard treatment calcipotriol ointment (50 µg/g twice
daily) [26] (LOE-A).
3.2. Lace Flower (Ammi majus(L.) and Ammi visnaga (L.))

The furanocoumarins 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP) are isolated
for therapeutic use from Ammi majus (L.) and Ammi visnaga (L.) Lam. The psoralens are phototoxic
substances that are photo-activated by long-wave ultraviolet A (UVA) radiation and may cause severe
phototoxic skin reactions. In the therapeutic setting of PUVA therapy (psoralen plus UVA) they
inhibit keratinocyte proliferation and display immunosuppressive effects that are used to treat severe
inflammatory skin conditions, i.e., psoriasis. Several clinical studies confirmed the efficacy of systemic
PUVA [27] (LOE-A), bath PUVA [28] (LOE-A) and cream PUVA therapy (0.1% 8-MOP) [29] in psoriasis
(LOE-A).
3.3. Barberry Bark (Mahonia aquifolium (Pursh) Nutt.)

The barberry Mahonia aquifolium is a shrub indigenous to Northern America. It was used for
centuries by Native Americans to treat psoriasis. Tinctures and ointments from Mahonia bark are available
as traditional drugs in Northern America and Europe. Recently, a randomized placebo-controlled
double-blind study in 200 psoriasis patients demonstrated the efficacy and safety of a 10% Mahonia
ointment in the treatment of psoriasis. The application was done twice daily for 12 weeks [30] (LOE-A).
3.4. Indigo (Baphicacanthus cusia, Brem.)

‘Indigo naturalis‘ is an important remedy in Traditional Chinese Medicine (TCM). It is a blue
powder obtained from the plant Baphicacanthus cusia by grinding, fermentation and addition of lime.
In a randomized placebo-controlled study 42 patients suffering from chronic plaque psoriasis were
treated once daily with a 10% indigo containing ointment for 12 weeks. The indigo naturalis used
contained 1.4% indigo and 0.16% indirubin. Treatment with indigo improved symptoms by 81%, while
the improvement with placebo was only 26% [31] (LOE-A). As a side effect, four patients showed itching.
Because Indigo naturalis causes long lasting blue staining of skin and clothes, Taiwanese researchers
developed a patented uncolored Indigo naturalis extract [32]. Several studies with Indigo extract have
been performed in psoriasis. A recently published randomized, double-blind, placebo-controlled study
in 100 psoriasis patients showed a dose-dependent efficacy of Indigo extract applied twice a day over
8 weeks. Indigo extract (200 µg/g) reduced the PASI by 70%, and Indigo extract (50 µg/g) reduced the
PASI by 50%. Side effects in some patients were nasopharyngitis, infections of the upper respiratory
tract and local erythema. Severe side effects were not observed [33] (LOE-A). Punch biopsies obtained
before treatment and after 8 weeks of treatment revealed a normalization of skin morphology and
downregulation of the pro-inflammatory key cytokine in psoriasis, IL-17 [33]. All studies with Indigo
extract were performed on Asian patients. Whether the effect of Indigo naturalis is comparable in
Caucasians cannot be assessed.
3.5. Turmeric (Curcuma longa (L.))

Turmeric plays an important role in TCM and in Aryuvedic Medicine. In vitro, turmeric and
its major active ingredient curcumin display anti-inflammatory, antimicrobial and anti-oxidative
properties [34]. During the last years some laboratory and clinical studies have investigated the
therapeutic potential of curcumin in psoriasis. Curcumin may improve psoriasis by inhibition of
phosphorylase kinase [35,36], downregulation of pro-inflammatory cytokines such as IL-17 and TNF-α,
as well as improvement of the epidermal barrier by inducing the expression of involucrin and filaggrin
in vitro [37]. However, randomized placebo-controlled studies with turmeric and curcumin in psoriasis
are missing so far [38].
3.6. Olibanum (Boswellia Serrata, Triana & Planch.)

Olibanum containing ointments were recommended in the Greco-Roman period by Hippocrates,
Galen and Dioscorides for the treatment of various skin disorders such as psoriasis, burns, warts,
bleeding and wounds. Recently, 200 patients with mild to moderate psoriasis were treated three times
daily for 12 weeks with an olibanum ointment containing 5% 3-O-Acetyl-11-keto-β-boswellic acid in
an open label application study. The PASI was significantly reduced, as well as serum biomarkers
such as leukotrien B4, TNF-α, VEGF and PGE2 (LOE-B). Thirteen patients (6.5%) developed contact
dermatitis [39].
3.7. St. John’s Wort (Hypericum perforatum (L.))

Psoriatic keratinocytes show increased cell proliferation, disturbed cell differentiation, an inflammatory
phenotype and reduced expression of cationic channels such as TRPC6. Hyperforin—the major lipophilic
active ingredient of St. John’s wort—displays in vitro pronounced anti-inflammatory effects and stimulates
calcium influx into psoriasis keratinocytes, activates TRPC6 expression, reduces cell proliferation and
promotes proper cell differentiation [40]. A placebo-controlled single-blind pilot study with 5% St. John’s
wort extract on 10 psoriasis patients revealed a significant improvement of the erythema, extension and
thickness of the psoriasis plaques. The treatment was performed twice daily [41] (LOE-B). Similarly,
a recently published placebo-controlled, double-blind half-side comparison in 20 patients with mild to
moderate plaque psoriasis with 5% St. John’s wort extract showed a significant reduction of the PASI and
the lesional TNF-α expression [42] (LOE-B).
4. Herpes Simplex
The herpes simplex virus (HSV) can cause blisters and sores in almost any part of the skin. These
sores usually occur either around the mouth and nose, or on the genitals and buttocks. Several extracts
were described with antiviral activity [43] including licorice extract [44] and Boswellia serrata oleo
gum [45]. However clinical studies using these plant products are still missing. Here, we focused on
plants with clinical evidence against herpes simplex infection.
4.1. Lemon Balm (Melissa officinalis (L.))

Lemon balm cream was tested in 66 patients with recurrent herpes simplex labialis in a randomized
double-blind, placebo-controlled study. The application of the test cream (1% dried Melissa officialis
extract) was four times daily for 5 days. The lesions cleared significantly faster with lemon balm cream,
and the patients had less blisters and pain [46] (LOE-A).
4.2. Sage (Salvia officinalis (L.)) and rhubarb (Rheum palmatum (L.))
A randomized, placebo-controlled study investigated the combination of sage and rhubarb extract
in 149 patients with herpes simplex labialis. The patients were treated topically with either acyclovir
(50 mg/g), sage extract (23 mg/g), or the combination of sage and rhubarb extract (23 mg/g each).
The combined sage-rhubarb cream was superior to sage alone, and was as effective as acyclovir [47]
(LOE-A).
5. Actinic Keratosis
Actinic keratoses (AK) represent in situ squamous cell carcinomas that form on sun-damaged skin
and appear clinically as thick, scaly or crusty skin. Several plant extracts were tested against actinic
keratosis; however, the results were mostly not promising (e.g., for St John’s wort [48].
5.1. Birch Bark (Betula spp.)

Birch bark contains 87% triterpenes, mainly betulin. A betulin oleogel is produced by mixing
a standardized dry extract from birch bark with vegetable oil. In a multicenter, placebo-controlled,
randomized study with betulin oleogel, 165 patients were treated topically for 3 months and showed
no positive effect. However, two thirds of the patients had actinic keratosis grade 3 [49] (LOE-A).
In contrast in a non-randomized, non-placebo controlled study with 28 patients with actinic keratosis
grade 1 or 2 it could be demonstrated that a therapy with betulin cream (betulin oleogel with additional
water) was as effective as cryotherapy [50] (LOE-B). The same result was achieved with betulin oleogel
in a prospective, randomized, monocentric study with 45 patients with early grades of AK [51] (LOE-B).
Histological and experimental studies suggest a differentiation-promoting effect as main mechanism of
action of betulin in early grades of actinic keratosis [51,52].
5.2. Petty Spurge (Euphorbia peplus (L.))

The latex of the lactiferous petty spurge contains toxic diterpene esters such as ingenol mebutate.
A randomized double-blind, placebo-controlled study evaluated the efficacy of 0.025% and 0.05%
ingenol mebutate gel compared to placebo in 200 patients with actinic keratoses. The topical products
were applied once daily for three days. Both ingenol mebutate concentrations were highly effective
(75% and 100% clearing, versus 0% clearing with placebo). Ingenol mebutate induces a localized
necrosis of the treated skin, followed by an inflammatory response, crusting and subsequent clearing
of the treated area. Scar formation was not observed [53] (LOE-A). These results were confirmed in
another randomized double-blind, placebo-controlled study [54] (LOE-A). Ingenol mebutate gel was
approved in 2013 as a prescription drug (150 µg/g gel and 500 µg/g gel).
6. Photoprotection and Esthetic Dermatology

Numerous plants contain photo-protective antioxidants and ultraviolet (UV) absorbing
polyphenols (catechins and flavonoids), and carotinoids. These compounds may protect the skin from
sunburn, skin ageing and the development of skin cancer, that are at least in part mediated by reactive
oxygen species (ROS). A systematic review from 2014 summarizes topically and orally provided plant
compounds for improved protection from sunlight [55]. Plant extracts are also used for multiple
cosmetic indications. A review published in 2010 highlights controlled clinical studies for different
cosmetic indications as well as for photo protection [2].
6.1. Green Tea (Non-Fermented Camellia sinensis (L.))

Green tea extracts contain high amounts of oligomeric proanthocyanidins such as catechin,
epicatechin and epigallocatechin-3-gallate, that are potent antioxidants with photo-protective properties.
They reduce oxidative stress induced by UV radiation and inhibit various cytokines and mediators
involved in skin carcinogenesis [56] (LOE-D). Some studies have shown that green tea extract may
prevent UV-induced inflammation when applied topically or systemically [57]. However, in vivo
studies confirming that green tea may prevent skin cancer are still missing.
6.2. Dyer’s Weed (Reseda luteola (L.))

Flavonoids such as quercetin, rutin and luteolin are potent antioxidants. Dyer’s weed (is
particularly rich in luteolin. It has been shown that Dyer’s weed extracts and luteolin display
prominent anti-oxidant and anti-inflammatory effects in skin cells [58]. Additionally, luteolin absorbs
UVA radiation and protects skin cells from UVB-induced DNA -damage [59,60]. In a randomized,
placebo-controlled, double-blind study with 40 healthy volunteers a Dyer’s weed extract containing
2.5% luteolin reduced UVB-induced erythema to a similar extent as 1% hydrocortisone [61] (LOE-A).
It has been recently shown that oxidative stress also plays a critical role in the induction of irritant
and allergic contact dermatitis [62]. An ointment containing a combination of luteolin, tocopherol and
ubichinone with a high radical protecting factor may protect the skin from skin irritation induced
by alkali, acid, alcohol, soap, detergents and disinfection. This protective effect has been proven in
the repetitive washing test in a placebo-controlled, double-blind study with 25 volunteers. As active
ingredients, the antioxidant cream contained 0.1% Dyer’s weed extract, 0.1% tocopherol and 0.05%
ubiquinone. 15 min prior to the washings, 200 µL of the test ointment was applied. The test was
performed 3 times daily on 7 consecutive days. The antioxidant ointment significantly reduced
erythema and transepidermal water loss and improved skin hydration in the washing test [63]
(LOE-A).
6.3. Cocoa Tree (Theobroma cacao (L.))

Cocoa powder contains a mixture of flavanols and tannins, mainly catechin and epicatechin.
In a randomized comparative double-blind study the photo-protective effect of cocoa consumption
on UV-induced skin erythema was assessed in 24 female volunteers. The volunteers ingested cocoa
with a high (326 mg/d) or a strongly reduced flavanol content (27 mg/d) dissolved in 100 mL water
over 12 weeks. Subsequently, a UV-erythema test was performed in all subjects. It was shown that
only the flavanol-rich cocoa preparation reduced the UV-erythema. Moreover, the consumption of the
flavanol-rich cocoa drink significantly increased skin firmness and hydration [64] (LOE-A).
6.4. Carotinoids
The effect of the plant-derived carotinoids β-carotene and lycopene on UV-induced skin erythema
was assessed in a randomized placebo-controlled, double-blind parallel group study with 36 volunteers.
On a daily basis, the subjects orally received either 24 mg β-carotene, or a carotinoid mix with 8 mg
of β-carotene, lutein and lycopene respectively, or placebo. Skin erythema was measured at the
beginning, after 6 weeks and after 8 weeks. Both the carotinoid mix and β-carotene significantly
reduced UV-erythema after 8 weeks compared to the placebo [65] (LOE-A). Similarly, a controlled
study with lycopene showed a significant reduction of the UV-erythema after 12 weeks [66] (LOE-B).
A diet supplementation with a tomato paste containing high concentration in lycopene (16 mg
lycopene) was tested in 20 women for 12 weeks in a randomized, controlled, single-blinded study.
The assessing investigator was unaware of supplement allocation. A reduced UV-induced MMP-1
(Matrix-Metallo-Proteinase-1) production and protection from mitochondrial DNA-damage was shown
in skin samples [67] (LOE-B).
6.5. Citrus Fruits (Citrus spp.)

A case-control study with 470 participants showed that the consumption of citrus peel was
associated with a lower risk to develop squamous cell carcinoma (SCC) (LOE-C) [68].
6.6. Coffee Plants (Coffea spec.)

A prospective observatory study from the “Nurses’ Health Study and Health professionals” with
173229 patients showed that those patients with the highest quintile of caffeine intake compared with
those in the lowest quintile had reduces Basal Cell Carcinoma (BCC) risk [69] (LOE-B). A case-control
study compared 166 patients with BCC to 158 patients not showing BCC. No significant effect of coffee
drinking could be shown on BCC risk [70] (LOE-B).
6.7. Licorice (Glycyrrhiza glabra (L.))

The root of licorice contains many different biologically active compounds [7]. The steroid saponin
β-glycyrrhetinic acid is the best studied anti-inflammatory compound of licorice. In a randomized,
placebo-controlled, double-blind intra-individual comparison study, the effect of an ointment with 2.5%
β-glycyrrhetinic acid on the subcutaneous fat tissue of the thigh was investigated in 18 female volunteers.
When applied twice daily over 4 weeks, the ointment with β-glycyrrhetinic acid significantly reduced
the circumference of the thigh compared to the non-treated or placebo-treated contralateral thigh.
The authors hypothesized that topically applied β-glycyrrhetinic acid is absorbed by the skin and
may reduce subcutaneous depots of fat tissue through interaction with the local 11-hydroxysteroid
dehydrogenase, eventually inhibiting adipocyte growth and maturation [71] (LOE-A).
Licorice extracts are also traditionally used for depigmentation purposes. It has been shown
that the lipophilic compound glabridin inhibits the enzyme tyrosin kinase and melanogenesis in
melanocytes in animal experiments. The application of an ointment with 0.5% glabridin reduced
UVB-induced pigmentation on guinea pig skin [72] (LOE-D).
Some studies have investigated the photo-protective properties of the flavonoid licochalcone A
present in licorice roots. In HaCaT keratinocytes licochalcone A upregulated various anti-inflammatory
and cyto-protective enzymes [13]. UVA-treated human dermal fibroblasts containing licochalcone
A showed higher glutathion levels and a reduced concentration of UV-generated reactive oxygen
species [12] (LOE-D). These in vitro data are supported by a double-blind, placebo-controlled in vivo
study with 22 healthy volunteers that were treated with either licochalcone A or the vehicle on
their volar forearms twice daily for two weeks. The test areas were then irradiated with UVA, and
luminescence of the skin was measured with ultra-weak photon emission detection. In the licochalcone
A treated skin area, the generation of UVA-induced photons was significantly lower than on the
placebo-treated area [12] (LOE-A).
6.8. Pine Bark (Pinus pinaster, Ailton)

A standardized polyphenol extract obtained from the bark of Pinus pinaster (Syn.: P. maritima)
with antioxidant properties has potent photo-protective and pigmentation modulating properties [73].
The effect of pine bark extract on melasma hyperpigmentation was investigated in an open label clinical
study on 30 women with melasmatic hyperpigmentations. The subjects received 25 mg pine bark
extract three times daily over four weeks. The degree and area of pigmentation was reduced in 80% of
the test persons [74] (LOE-B).
6.9. Gotu Kola (Centella asiatica (L.) Urban)

Centella asiatica contains a variety of pentacyclic triterpenoids, including asiaticoside, brahmoside,
asiatic acid, and madecassic acid. Other constituents include centellose, centelloside, and madecassoside.
A cream with Centella asiatica-extract, tocopherol and a collagen-elastin hydrolysate was tested in
a randomized placebo-controlled, double-blind study on 80 pregnant women. The cream was applied
daily from the end of the 12th week of pregnancy until delivery. The active cream was significantly
superior to the placebo with regard to the number and severity of stretch marks [75] (LOE-A).
Another vehicle-controlled half-side comparison study investigated the effect of a cream containing
0.1% asiaticoside on periocular wrinkles in 27 women. The women applied the creams twice daily
over 12 weeks. Silicone imprints revealed a significantly superior reduction of the crow’s feet wrinkles
with the asiaticoside cream compared to placebo [76] (LOE-B).
7. Wound Healing
Wound healing is a natural physiological response to tissue injury and involves a complex
interplay between numerous cell types (keratinocytes, fibroblasts and immune cells), cytokines and the
vascular system to stop bleeding, kill bacteria and initiate re-epithelialization. Most herbal remedies
traditionally used for wound healing have not been investigated in controlled clinical studies [77].
In contrast, the wound-healing properties of a betulin rich extract from the bark of white birches have
been thoroughly investigated. This extract allows the production of a solid phase stabilized emulsion
without conventional emulsifiers or preservatives [78] and will be described in more detail.
7.1. Birch Bark (Betula spp.)

The wound healing properties of betulin have been elucidated at the molecular level and positively
affect all three phases of wound healing (the inflammatory phase as well as migration and differentiation
phase of keratinocytes) [79]. The first clinical evidence for the wound healing properties of betulin
was achieved in a split thickness wound study with the topical application of a water-free betulin
oleogel [80]. Subsequently, several multicentric, controlled, randomized clinical studies on superficial
wounds and second degree burns were performed with betulin oleogel [81–83] (LOE-A). In 2016, the
European Medical Agency (EMA) approved betulin oleogel as a drug for the topical treatment of
superficial wounds and burns [84].
7.2. Onion (Allium cepa (L.))

A systematic review published in 2017 on anti-scarring agents mentions many positive outcomes
in scarring management with onion extract [85].
In a randomized placebo controlled study on 58 subjects that underwent small surgical procedures
of the skin, such as excision of skin tumors or punch biopsies, the effect of onion extract on scar
formation was investigated. After initial primary wound healing for three weeks, the patients received
onion extract or placebo twice daily for 10 weeks. Onion extract significantly improved redness,
smoothness, texture and general appearance of the scars compared to placebo [86] (LOE-A).
8. Rosacea
Rosacea is an inflammatory skin disease of the face affecting both sebaceous glands and small
superficial skin vessels. Different clinical forms of rosacea include an erythematous, papulopustulous
and telangiectatic variant. A recent systematic review analyzed the efficacy of herbal medicinal
products for the treatment of rosacea [87].
8.1. Green Tea (Non-Fermented Camellia sinensis (L.))

Green tea extract contains high amounts of oligomeric proanthocyanidins such as epigallocatechin-
3-gallate (EGCG)—a potent antioxidant with photo-protective properties. It has been shown that
EGCG inhibits the expression of the vascular endothelial growth factor VEGF and the hypoxia-induced
factor 1α (HIF-1α) that both stimulate angiogenesis in the skin. In a very small randomized, double
blind, vehicle controlled split face trial four volunteers used a 2.5% EGCG containing cream twice
daily over 6 weeks. However, no reduction in skin erythema could be detected, neither clinically nor
histologically [88] (LOE-D). However, larger clinical studies are needed to determine if EGCG has
a clinically relevant effect. As sun exposure is a trigger factor of rosacea, green tea products might have
a relevant therapeutic role via their photo-protective effects.
8.2. Licorice Root (Glycyrrhiza inflata, Batalin)

An open label study with 62 volunteers showed that licochalcone A, a flavonoid from licorice root,
incorporated in different vehicles significantly reduces erythema in rosacea when applied once daily
over 8 weeks. When combined topically with the antibiotic metronidazole it was also well tolerated
in 25 patients [89] (LOE-B). The combination of licochalcone A with trans-4-t-butylcyclohexanol,
an inhibitor of the cation channel TRPV1, was also investigated. The TRPV1 channel in the skin
is known to mediate sensation of pain, itch and warmth. In keratinocytes stimulation of TRPV1
results in increased Ca2+ -influx, which induces finally cell death and disruption of the epidermal
barrier [90]. In an open, not placebo controlled, international multi-center study 1221 patients with
sensitive skin prone to redness and rosacea were treated with this combination. An improvement of
the studied symptoms (e.g., redness and erythema) could be shown after 4 weeks with applications
twice a day [90] (LOE-B). The product was well tolerated. However the used concentration of
trans-4-t-butylcyclohexano and licochalcone A was not mentioned in the publication.
8.3. Bitter Wood (Simarouba amara Aubl.)

In a recent review on herbal products for rosacea [87] a 4% extract from Simarouba amara was the
only herbal product that reduced telangiectasia. In a study with 30 patients suffering from rosacea
a topical gel with Simarouba amara-extract was applied twice daily over 6 weeks. All clinical parameters
such as flush, erythema, telangiectasia, papules and pustules were significantly reduced after 6 weeks.
No side effects such as pruritus, edema or stinging were observed. The clinical overall improvement
was similar to conventional standard treatments such as metronidazole or azelaic acid. However, no
control group was included in this study [91] (LOE-B).
8.4. Tormentil (Potentilla erecta (L.))

Although no clinical trials with tormentil have been conducted in rosacea, recent studies point to
a potent vasoconstrictory effect of tormentil that might be useful in treating telangiectasia in rosacea.
In a randomized, prospective, placebo controlled double blind patch test with 40 healthy volunteers 1%
hydrocortisone and a tormentil extract containing the ellagitannin agrimoniin displayed both a similar
blanching effect, that means a paling of the skin [18] (LOE-B). The exact mechanism responsible for the
blanching effect is not entirely clear, but local vasoconstriction of smooth muscle cells and consecutive
blood flow reduction seem to be involved in this phenomenon [92]. Tormentil-extract displays this
vasoconstrictive property at least partly by radical scavenging of NO, an important vasodilator of
dermal blood vessels and by inhibition of the endothelial NO-syntase (eNOS) that is constitutively
active. Because of its vasoconstrictive effect PE might be beneficial to treat rosacea erythematosa
(LOE-C). Facial reddening in rosacea is at least partly mediated by formation of NO via iNOS that
is induced by endogenous or exogenous factors such as demodex mites. Sauermann and colleagues
showed that the treatment of rosacea with the topical NO inhibitor L-NAME (1% L-NAME cream,
applied twice daily for 3 weeks) resulted in a significant reduction of erythema in rosacea patients [93]
(LOE-B). However, a clinical study to prove that tormentil extract indeed reduces the facial reddening
in rosacea is still missing.
9. Acne Vulgaris
Acne vulgaris is characterized by hyperactive sebaceous glands, epidermal hyperproliferation and
perifollicular inflammation. The most important pathogens linked to acne-prone skin are for example
Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). Botanical and phytochemical
options for acne vulgaris therapy are summarized in a systematic review published in 2014 [94].
9.1. Tea Tree (Melaleuca alternifolia (Maiden & Betche) Cheel)

In a single-blind, randomized study 5% tee tree oil was compared to 5% benzoyl peroxide on
124 acne patients in topical application. After 3 months of treatment signs and symptoms had markedly
improved with both preparations. There were no differences between the two therapies [95] (LOE-B).
A vehicle-controlled, randomized, double-blind study with 60 acne patients confirmed the efficacy of
a gel containing 5% tea tree oil when applied twice daily over 45 days [96] (LOE-A).
9.2. Green Tea (non-fermented Camellia sinensis (L.))

It could be shown that epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea,
displays apoptotic, sebosuppressive and anti-inflammatory effects on human sebocytes. Furthermore
it displays antibacterial effects on P. acnes [97]. EGCG significantly improved acne in an 8-week
randomized, split-face, clinical trial with 35 patients that were treated with 1% or 5% EGCG solution
twice daily [97] (LOE-A). The efficacy of a lotion with 2% green tea extract was demonstrated in
a prospective, non-randomized study on 20 patients with acne using the preparation twice daily for
6 weeks [98] (LOE-B).
9.3. Hop (Humulus lupulus (L.))

Hop extract shows anti-oxidative and anti-inflammatory effects. In the microdilution test hop
extract inhibited the growth of P. acnes and S. aureus already at a concentration of 3.1 and 9.4 µg/mL
respectively. In addition, a gel formulation with 0.3% hop extract (w/w) showed antibacterial activity
in the agar diffusion test against P. acnes and S. aureus (inhibition zone value: 5.5 mm and 3 mm,
respectively) (LOE-C). Therefore, hop extract might be an alternative treatment option for acne-prone
skin [99] and should be tested in clinical studies.
10. Conclusions
Botanical compounds such as salicylic acid, methoxsalen and chrysarobin have been traditionally
used and still play an important role in the treatment of psoriasis. Recently, the alkaloid indirubin from
indigo has been shown to be effective against psoriasis in randomized clinical trials. Glycyrrhetinic acid
and licochalcone A from licorice have been shown to be effective in the treatment of atopic dermatitis.
The toxicBiomedicines
diterpene ester
2019, ingenol
7, x FOR mebutate from petty spurge has been approved as a highly 11
PEER REVIEW effective
of 23
prescription drug for the treatment of superficial epithelial skin cancer (actinic keratoses). Only recently,
betulin-oleogel obtained from birch bark has been approved as a drug for the topical treatment L R of
superficialDisease
wounds and burns. Plant These examples
Compound
illustrate that Treatment O e that
botanical compounds and extracts
Biomedicines 2019, 7, x FOR PEER REVIEW 11 of 23
are summarized in Table 1 have a great potential to be developed as prescription or over-the-counter
E f
drugs in dermatology.
Biomedicines 2019, 7, x FOR PEER REVIEW Hyperforin L 11 of
R 23
Disease Plant Compound Treatment O e
TableSt. Summary
1. John’s wort of herbal compounds for the treatment ofwith
- Ointment skin1.5%
diseases. L R
E f
Disease Plant
(Hypericum Compound Treatment
hyperforin twice daily for 4 OAL e6
Hyperforin
Disease Plant
perforatum (L.)) Compound weeks Treatment EO f Ref
E
St. John’s wort Hyperforin - Ointment with 1.5%
Hyperforin
(Hypericum hyperforin twice daily for 4 A 6
St. John’s wort Glycyrrhetinic acid - -Ointment withointment
Hydrophilic 1.5% with
perforatum
St. John’s wort(L.)) weeks
- Ointment with 1.5%
(Hypericum
(Hypericum perforatum hyperforin
2% twice
glycyrrhetinic
hyperforin twicedaily
acidfor
daily 4
three
for AAA 615[6]
(L.))
perforatum (L.)) 4
weeks weeks
times daily for 5 weeks
Glycyrrhetinic acid -- Hydrophilic

Cream with ointment
0.6% with
glycyrrhizinic
2% glycyrrhetinicacidacid
andthree A 15
Glycyrrhetinicacid
acid - Hydrophilic ointment with
Glycyrrhetinic - licorice
Hydrophilic
extractointment with
times daily for 5(0.1%
2% glycyrrhetinic acid three
weeks A [15]
2% glycyrrhetinic
times for 5acid
dailyuralensis
Glycyrrhiza weeksthree
root A 15
Licorice - Cream with 0.6%
- Cream
times daily with 50.6%
for daily
weeks
(Glycyrrhiza extract) twice
glycyrrhizinic
glycyrrhizinic acid for
and2 licorice B
acidand 17
- weeks
Cream
extractwith
(0.1%0.6%
Glycyrrhiza B [17]
glabra (L.)) licorice extract (0.1%
Licorice uralensis rootacid
extract)
glycyrrhizinic and twice
glabra (L.))
(GlycyrrhizaLicorice Licochalcone A Glycyrrhiza
daily for 2uralensis
weeks root
licorice extract (0.1%
Atopic (Glycyrrhiza Licochalcone A extract) twice daily for 2 B 17
Atopic Glycyrrhiza uralensis root
dermatitis Licorice weeks
- Cream with < 1%
dermatitis glabra (L.)) - Cream
extract) with
twice < 1%
daily for 2 BAA 1716
(Glycyrrhiza Licochalcone A [16]
licochalcone
licochalconeAA
glabra (L.)) weeks
Atopic
Licochalcone A
dermatitis - Cream with
- Cream < 1%
with 2% tannins from
Atopic A 16
Biomedicines 2019, 7, x FOR PEER REVIEW the rhizome
licochalcone
- Cream withAof 2%tormentil
tannins from for 48 BB [18]
1218
of 23
dermatitis Tormentil h in anwith
- Cream UV-erythema
< 1% test
Tannins the rhizome of tormentil for 48 A 16
(Potentilla erecta (L.)) - Cream with 2% tannins from
licochalcone A
Tormentil h the
in anrhizome of tormentil
UV-erythema test twice B [19]
Evening daily for 2 weeks
(Potentilla erecta Tannins - Cream with 2% tannins from B 18
Atopic primrose - -Meta-analysis
Cream with 5% forgentain
the use of
(L.)) Primrose oil - Cream
the rhizome
extract with of2%
twice tannins
tormentil
daily from
for 4for
weeks48 A 22
dermatitisBitter substances
(Oenothera Gentian extract primrose
- the
Cream
increases oil
with 2%
inof tannins from
volunteers BB 18[21]
Tormentil rhizome
h in an UV-erythema testtormentil twice
biennis (L.)) the epidermal
rhizome lipids
of that are
tormentil for 48
(Potentilla erecta Tannins daily
reducedfor 2in
weeks
atopic dermatitis B 19
Tormentil h in an UV-erythema test
Atopic Evening primrose
(L.)) - Meta-analysis
- Cream for the use
with 2% tannins from of
Primrose oil A [22]
dermatitis (Oenothera bienniserecta
(Potentilla (L.)) Tannins
Dithranol primrose
- Cream oil 5% gentain
with
the rhizome of tormentil twice
(L.)) Dithranol -Cream
Daily twice
- extract short
with 2% treatments
tannins
daily (15 -
from
for 4 weeks
Araroba tree daily for 2short
- Daily weeks treatments (15 - B 19
45 rhizome
the min) with inof dithranol
tormentil cream
Bitter substances
Araroba tree
(Vataireopsis
Gentian extract increases
45 min) with dithranol twice
volunteers cream B 21
Psoriasis (Vataireopsis araroba ofof
daily stepwise
stepwise
for 2with rising
weeks rising BAA 1926
[26]
-epidermal
Cream lipids that are
5% gentain
vulgaris araroba
(Aguiar) (Aguiar)
Ducke) concentrations up to 5% for
concentrations
reduced
extract in atopic
twice updermatitis
daily to 5%
for for 12
4 weeks
Ducke) 12 weeks
- weeks
Cream with 5% gentain
Bitter substances Gentian extract increases in volunteers B 21
extract twice daily for 4 weeks
epidermal lipids that are
Bitter substances 8-methoxypsoralen
Gentian extract increases in volunteers BA 2127
reduced
- Oral 8-MOPin atopic PUVAdermatitis
(0.6
(8-MOP) epidermal lipids that are
mg/kg) twice per week
reduced in atopic dermatitis
- Bath PUVA with 5 mg/l
A 28
8-MOP 4 times per week
Lace flower - Cream PUVA with 0.1%
(Ammi majus (L.) 8-MOP 12 treatments
and A 29
Ammi visnaga 5-methoxypsoralen
(L.)) (5-MOP)
Dithranol
8-methoxypsoralen - Daily short treatments (15 - A 27
Araroba tree - Oral 8-MOP PUVA (0.6
Dithranol
(8-MOP) 45 min) with dithranol cream
(Vataireopsis mg/kg) twice per week (15 -
-ofDaily shortrising
stepwise treatments A 26
Araroba tree
araroba (Aguiar) - 45
Bath PUVA
min) withwith 5 mg/l
dithranol
concentrations up to 5%cream
for 12 A 2812 of 21
Biomedicines 2020, 8, 27 (Vataireopsis
Ducke) 8-MOP
of stepwise rising week
4 times per A 26
weeks
araroba (Aguiar)
Lace flower - concentrations
Cream PUVA withup to0.1%
5% for 12
(AmmiDucke)
majus (L.)
Table 1. Cont.
8-methoxypsoralen 8-MOP
weeks 12 treatments A 27
and - Oral 8-MOP PUVA (0.6 A 29
(8-MOP)
5-methoxypsoralen mg/kg) twice per week L
Ammi visnaga 8-methoxypsoralen AO 27
Disease Plant Compound Treatment Ref
(5-MOP) -- Oral
Bath 8-MOP
PUVA with PUVA (0.6
5 mg/l
(L.)) (8-MOP) E
A 28
Psoriasis 8-methoxypsoralen (8-MOP) - mg/kg)
8-MOP
- Oral
Oral 4twice
times
8-MOP
5-MOP
per
perweek
PUVA
PUVA week
(1.2 A [27]
vulgaris Lace flower (0.6
-- Bath mg/kg)
PUVA twice
with 5per week
mg/l A 27
mg/kg) twice per week0.1%
Cream PUVA with
A 28
(Ammi majus (L.) - Bath 4PUVA
8-MOP timeswith 5 mg/L
per week
8-MOP A [28]
8-MOP124 treatments
times per week A 29
Laceand
flower - Cream PUVA with 0.1%
Lace flower - Cream PUVA with 0.1%
(Ammi(Ammi
majusmajus
(L.) (L.) 5-methoxypsoralen A [29]
Ammi visnaga 8-MOP1212treatments
8-MOP treatments
and and (5-MOP) (5-MOP) A 29
(L.)) 5-methoxypsoralen
Ammi visnaga (L.))
Psoriasis Ammi visnaga 5-methoxypsoralen
Barberry bark - Oral 5-MOP PUVA (1.2
vulgaris (5-MOP) - Oral 5-MOPointment
PUVA (1.2 A 27
(L.))
(Mahonia - mg/kg)
10% Mahonia
twice per week twice A [27]
Psoriasis Mahonia ointment mg/kg) twice per week A 30
aquifolium - Oralfor
daily 5-MOP
12 weeks PUVA (1.2
Biomedicines
vulgaris 2019, 7, x FOR PEER REVIEW A 13 27
of 23
(Pursh) Nutt.) mg/kg) twice per week
Barberry bark
Biomedicines(Mahonia
2019, 7, x aquifolium
FOR PEER REVIEW - 10% Mahonia ointment twice
Mahonia ointment A 13 of 23
[30]
Indigo naturalis containing daily for 12 weeks
(Pursh) Nutt.) bark
Barberry - Indigo ointment (50 µg/g
Indigo naturalis
indigo containing
and indirubin and 200 µg/g indigo extract)
(Mahonia Indigo - 10% Mahonia ointment twice
Indigo indigo andextract
Mahonia indirubin
ointment - 10% indigo ointment (1.4% A
A 33
30
Barberry bark
aquifolium applied
-daily
Indigofor twice
12 daily
ointment
weeks over
(50 8
µg/g
(Baphicacanthus - 10%and
indigo indigo ointment
0.16% (1.4%
indirubin) A 31
(Mahonia
(Pursh) Nutt.) weeks
and
- 10%200 µg/g
Mahonia
indigo indigo extract)
ointment
and 0.16% twice
indirubin) A [31]
cusia Brem.) Indigo extract
Mahonia ointment daily forfor
daily 1212
weeks
weeks A
A 33
30
aquifolium
Indigo applied
daily fortwice daily over 8
12 weeks
(Baphicacanthus cusia weeks
Psoriasis (Pursh) Nutt.) Curcumin
Brem.) Indigo naturalis containing
vulgaris - Indigo ointment (50 µg/g and
indigo and indirubin - No randomized
Turmeric 200 µg/g indigo extract)
Indigo IndigoIndigo extract
Curcumin
naturalis containing - applied
10% indigo ointment
twice
placebo-controlleddaily (1.4%
over
studies
A [33]
(Curcuma longa
(Baphicacanthus 8 weeks
indigo and 0.16% indirubin) A 31
indigo and indirubin available, only
- No randomized in vitro studies
(L.))
Turmeric
Indigo
cusia Brem.) Curcumin -daily
10% indigo
- Nofor 12 ointment
randomized
weeks (1.4%
or in vivo studies using mice
placebo-controlled
Turmeric (Curcuma
(Curcuma longa placebo-controlledstudies
studies
(Baphicacanthus indigo and 0.16% indirubin) A 31
Psoriasis longa (L.)) available,only
available, onlyininvitro
vitro studies
studies
(L.))
cusia Brem.) daily
or infor 12 studies
vivo weeks using mice
vulgaris 3-O-Acetyl-11-keto- or in vivo studies using mice
3-O-Acetyl-11-keto-
- Olibanum ointment
Psoriasis β-boswellic
β-boswellic acid
acid
Olibanum - Olibanum
containing 5%ointment
vulgaris 3-O-Acetyl-11-keto-
Olibanum containing 5%
(Boswellia serrata, 3-O-Acetyl-11-keto-β-boswelli
- Olibanum ointment B 39
(Boswellia serrata, β-boswellic acid 3-O-Acetyl-11-keto-β-boswellic B [39]
Triana &Olibanum
TrianaPlanch)
& Planch) acid three
ccontaining times
acid three5% daily for 12
12 weeks
(Boswellia serrata, weeks
3-O-Acetyl-11-keto-β-boswelli B 39
Triana & Planch) c acid three times daily for 12
St. John’s wort - 5% St. John’s wort extract
weeks B [41]
(Hypericum perforatum St. John’s wort extract - 5% St. daily
twice John’sfor
wort extract
4 weeks B 41
(L.))
St. John’s wort - 5%daily
twice St. John’s wort extract
for 4 weeks B [42]
once daily for 4 weeks
(Hypericum St. John’s wort extract - 5% St. John’s wort extract B 41
- Cream containing 1% dried
Lemon balm (L.))
perforatum -twice
5% St. John’s
St. John’s wort Lemon balm extract daily
Melissa for wort
officialis extract
4 weeks
extract applied A [46]
(Melissa officinalis (L.))
4 times daily for
once daily for 4 weeks 5 days B 42
(Hypericum St. John’s wort extract
- Treatment with cream
Herpes perforatum (L.)) - 5% St. John’s
containing wort
sage extract
extract (23
simplex Sage
mg/g)
once or combination
daily for 4 weeks of sage B 42
(Salvia officinalis (L.))
Sage and rhubarb extract and rhubarb extract (23 mg/g A [47]
and Rhubarb
Lemon balm each) until
- Cream healing1%
containing (7.6dried
days
(Rheum palmatum (L.))
with sage and 6.7 with
(Melissa Lemon balm extract Melissa officialis extract applied
combination) A 46
officinalis
Lemon balm (L.)) 4- Cream
times daily for 5 days
containing 1% dried
(Melissa Lemon balm extract Melissa officialis extract applied A 46
Herpes officinalis (L.)) 4 times daily for 5 days
simplex - Treatment with cream
Sage
containing sage extract (23
Herpes (Salvia officinalis
mg/g) or combination
- Treatment with creamof sage
simplex (L.))
Sageand
Sage and rhubarb extract and rhubarbsage
containing extract (23 (23
extract mg/g A 47
Rhubarb
(Salvia officinalis
each)
mg/g)until healing (7.6of
or combination days
sage
(Rheum
(L.)) and
Sage and rhubarb extract with sage andextract
and rhubarb 6.7 with
(23 mg/g A 47
Betulin - Treatment with betulin
oleogel for 3 months without
A 49
Birch bark effect in high grade actinic
Biomedicines
Biomedicines 2019, 7, x FOR PEER REVIEW
2020, 8, 27 B 1450
of
1323
of 21
(Betula spp.) keratoses- Birch bark ointment
Biomedicines 2019, 7, x FOR PEER REVIEW B 1451of 23
Betulin (betulin oleogel)
- Treatment withfor 2 months-
betulin
Betulin1. Cont.
Table Betulin
oleogel oleogel for
for 3 with
- Treatment months3 months
without
betulin
Actinic A 49
Birch bark Ingenol mebutate -effect
oleogel
Gel with in for
high grade
3 months
0.025% oractinic
without
0.05% L
keratoses B
AO
A 50
49Ref
53
Disease Biomedicines Plant
2019, 7, x7,FOR PEER
PEERREVIEW Compound Treatment
Biomedicines 2019,
(Betula
Birch xbark
FOR
spp.) REVIEW keratoses-
effect inmebutate
ingenol Birch
high gradebark for 314 of1423of 23
ointment
actinic
daily
BE
B 51
50
(Betula
Petty spp.)
spurge Betulin
Betulin (betulin
keratoses-
days - Treatmentoleogel)
Birch with forbetulin
bark 2 ointment
months-
Betulin - Treatment
- Treatment with
withbetulin
betulin B 51
oleogel
-Betulin
(betulin for
oleogel 3without
months
forfor30.01% without
2months
(Euphorbia peplus oleogelGel
oleogel forwith 3oleogel)
0.0025%,
3 months
for months without months-
or A [49]
Actinic effect in high grade actinic A A49 49
(L.)) Birchbark
Birch bark effect
0.05%
effect inin
Betulinhigh grade
oleogel
ingenol
high gradeactinic
foror3 0.05%
mebutate
actinic months
on
keratoses Ingenol mebutate - Gel with
keratoses 0.025% B 50
ActinicBirch bark (Betula spp.)spp.)
(Betula keratoses- Birch bark ointment B 50A 53
(Betula spp.) keratoses-
two - Birch Birch
consecutive
bark bark ointment
days
ointment orfor
on
(betulin
B 3 51
Ingenol mebutate ingenol
- Gel withmebutate
0.025% daily
or 0.05% B 51A B [50]
keratoses (betulin oleogel) for 2 months-
oleogel) forfor28 months A 54
53
(betulin
day 1 oleogel)
and day 2 months-
Actinic Petty spurge days
ingenol
Betulin oleogelmebutate
for 3 months daily for 3
Actinic Betulin- Betulin
oleogeloleogel
for 3 monthsfor 3 months B [51]
keratoses Actinic(Euphorbia
Petty spurgepeplus Epigallocatechin-3-gallate
Ingenol mebutate - Gel-days
Gel
with with
0.025%0.0025%,
or 0.05% 0.01% or
keratoses Ingenol
Ingenol mebutate
mebutate - Gel with 0.025%
- Gel with 0.025% or 0.05% or 0.05%
A 53
keratoses ingenol mebutate daily for 3 0.01%
(L.)) peplus
(Euphorbia ingenol
0.05%
- Gel with mebutate
ingenol mebutate
0.0025%, dailyon for
orA 53 A [53]
GreenPetty
tea spurge ingenol
- 13mg/cm mebutate daily for 3
Petty spurge days days skin of
2
(L.))
Petty spurge two
days0.05% consecutive
ingenol mebutate days or on
(Euphorbia peplus
(Camellia (L.)) peplus
sinensis
(Euphorbia - Gel with 0.0025%,
0.01% or 0.01% or
epigallocatechin-3-gallate
- Gel with 0.0025%, A
D 54
56
(Euphorbia peplus day
two
- Gel0.05% 1 and day
consecutive
with 0.0025%, 8 days or onon
0.01%
(L.)) 0.05% ingenol ingenol
mebutate on or
mebutate
(L.)) before UV exposure AA 54[54]
(L.)) Epigallocatechin-3-gallate two 0.05%
daytwo consecutive
ingenol
1 and
consecutive mebutate
day
days 8 ondays
or on or on
two
day 1 and day
consecutive
8
days or on
A 54
Epigallocatechin-3-gallate day 1 and day 8
A 54
Epigallocatechin-3-gallate day 1 and day2 8
Green tea Epigallocatechin-3-gallate - 1 mg/cm skin of
Luteolin
Epigallocatechin-3-gallate
(Camellia
Greensinensis
tea epigallocatechin-3-gallate
- 1 mg/cm 2 skin of
2 skin of 2
D 56
Green tea - 1 mg/cm- 1 mg/cm skin of
Green tea
(L.))
(Camellia sinensis
(Camellia sinensis before UV exposure
epigallocatechin-3-gallate D 56 DD 56[56]
(Camellia sinensis Green
(L.))tea - 1 mg/cm2 skin of
(L.)) before before
-before
Dyer’s
UV UV exposure
weed
exposure extract
(L.))
(Camellia sinensis UV exposure
epigallocatechin-3-gallate D 56A 61
(L.)) containing
before 2.5% luteolin
UV exposure
Photo- Luteolin
Luteolin
Luteolin
Dyer’s weed Luteolin
protection
(Reseda luteola Luteolin
and esthetic - Dyer’s
- Dyer’s weed weed
extract extract
- Dyer’s weed extract A 61 A
(L.)) containing 2.5% luteolin A 61[61]
dermatology -containing
containing
Dyer’s 2.5%
weed 2.5% luteolin
luteolin
extract
- Cream
- Dyer’s weed with 0.1%
extract Dyer's A 61
Dyer’s weed
Photo- A 61
Photo- (Reseda luteolaDyer’s(L.)) weed containing
containing
weed 2.5%2.5%
extract, luteolin
luteolin
0.1% tocopherol
protection
Dyer’s(Reseda
weedluteola Dyer`s weed extract A 63
protection
Photo- Photo-
and esthetic and 0.05% ubiquinone three
(Reseda Dyer’s weed
Dyer’s luteola
weed(L.)) - Cream with 0.1% Dyer’s
and protection
Biomedicines 2019, 7, x FOR PEER REVIEW
dermatology
esthetic
protection times
- Cream daily
with 0.1%for 70.1%
Dyer's daystocopherol 15 of 23
(Reseda luteola weed extract,
and esthetic (L.))
(Reseda luteola Dyer’s weed extract A [63]
dermatology
and esthetic and 0.05%
weed extract, ubiquinone three
0.1% tocopherol
(L.)) Dyer`s weed extract - Cream with 0.1% Dyer'sA 63
dermatology (L.)) β-carotene and times
0.05%
- Cream
daily
ubiquinone
with
for 7 days
three
0.1% Dyer's
dermatology
Biomedicines 2019, 7, x FOR PEER REVIEW Flavanol weed
- Cream extract,
with 0.1% tocopherol
Dyer's 15 of 23
Flavanol times daily for 7 days
weed extract, 0.1% tocopherol
Dyer`s weed extract A 63
Dyer`s weed extract and
weed 0.05%
extract, ubiquinone
0.1% threeA
tocopherol 63
Photo- - -Ingestion
and 0.05% of
ubiquinone cocoa with
three high
Cocoa tree Dyer`s weed extract
β-carotene -24Ingestion
mg β-carotene of cocoa orally
withdaily
high A 63
protection Flavanol times
anddaily
times daily
0.05% 7for 7 days three
for ubiquinone
days A 65
Cocoa tree (326 (326mg/d)
mg/d)
for up to 8 weeks or low
or low (27 mg/d)
(27 mg/d)
and esthetic (Theobroma cacao A A 64[64]
(Theobroma cacao (L.)) times
- Ingestion
flavanol daily
flavanol
of cocoa
content for
content
with7indays
in
high water
water over
over
dermatology Cocoa tree
(L.))
Biomedicines 2019, 7, x FOR PEER REVIEW 12
(326 -mg/d) weeks
24 mg β-carotene
or low (27 mg/d) orally daily 15 of 23
(Theobroma cacao Flavanol
Flavanol 12 weeks A 64
flavanol content in water over
A 65
(L.)) for up to
- Ingestion of 8 weeks
cocoa with high
Carotinoids Flavanol
β-carotene - Ingestion of cocoa with high
12 weeks
Cocoa tree Lycopene
Cocoa tree β-carotene (326 - 10 mgorlycopene
mg/d) low (27 mg/d) daily for 12
(Theobroma cacao (326 mg/d) or
- Ingestion low (27
of cocoa mg/d)
with A
high 64 B 66
(Theobroma cacao
Cocoa tree - 24 content
flavanol
weeks mg β-carotenein water over orally daily A 64[65]
(L.)) A
Carotinoids 12flavanol
(326formg
-weeks
24 mg/d)content
to 8orweeks
up β-carotene low in(27water
mg/d)
orally over
daily
(L.)) cacao
(Theobroma Lycopene AA 64
65
12- 10 mg lycopene
weeks
flavanol indaily for 12
Carotinoids for upmg
- -Tomato
10 tocontent
8lycopene
weeks
paste
water over
daily for16
containing B 66
(L.)) Lycopene
12weeks
weeks B [66]
12 weeks
mg lycopene daily for 12
- Tomato paste containing 16 B 67
weeks
Carotinoids - mg lycopene
Tomato pastedaily for
containing 16 B [67]
Lycopene 12 weeks
Limonene -mg10 lycopene
mg lycopene dailydaily for 12
for 12
Limonene B
B 66
67
weeks
weeks
- Regular citrus fruit
Citrus fruits Limonene - Regular citrus fruit
Citrus fruits
(Citrus
(Citrus spp.)spp.) -consumption
consumption
Tomato pastewith with ororwithout
containing without
16 CC 68
[68]
peel
peellycopene daily for 12
mg
Photo- Citrus fruits B 67
weeks
consumption with or without C 68
protection (Citrus spp.)
Limonene peel
and esthetic Caffeine
Photo-
dermatology
protection - Regular citrus fruit
Citrus plants
Coffee fruits - Observatorywith
studies on B 69
and esthetic Caffeine consumption or without C 68
(Citrus spec.)
(Coffea spp.) caffeine intake B 70
dermatology peel
Photo-
mg lycopene daily for 12
B 67
Limonene mg lycopene daily for 12
weeks
B 67
weeks
Limonene
Citrus fruits Limonene
consumption with or without C 68
Biomedicines 2020, 8, 27 (Citrus spp.) - Regular citrus fruit 14 of 21
Citrus fruits peel
- Regular citrus
consumption fruit
with or without C 68
Photo- Citrus fruits
(Citrus spp.)
consumption with or without
peel C 68
protection (Citrus spp.) Table 1. Cont.
Photo- peel
andPhoto-
esthetic Caffeine
protection L
dermatology
protection
Disease Plant Compound Treatment O Ref
and esthetic Caffeine
E
and esthetic
dermatology Coffee plants Caffeine - Observatory studies on B 69
Caffeine
dermatology (Coffea spec.) caffeine intake B 70
Coffee plants - Observatory studies on B 69
Coffee spec.)
(Coffea plants - Observatory
caffeine intake studies on BBB 69
70
Coffee plants - Observatory studies on [69]
(Coffea spec.)spec.)
(Coffea caffeineintake
caffeine intake BB [70]
70
Biomedicines 2019, 7, x FOR PEER REVIEW β-glycyrrhetinic acid 16 of 23
β-glycyrrhetinic
Licochalcone Aacid
β-glycyrrhetinic acid - Ointment with 2.5%
β-glycyrrhetinic
Licochalcone acid
A
-β-glycyrrhetinic
9 µM LicochalconeacidAtwice
in in A 71
- Ointment with 2.5% D 12
- Ointment
- 9 µM
daily with 2.5%
Licochalcone
over 4 weeks A in in
vitro experiments-
- β-glycyrrhetinic
Ointment with acid Ointment
2.5%
β-glycyrrhetinic acidtwice
twice AD
A 71
[71]
12
Licorice vitro
dailyexperiments-
containing
over 4 weeks Ointment
licochalcone A
β-glycyrrhetinic
daily over 4 weeksacid twice A 71
A 12
(Glycyrrhiza containing
twice licochalcone
daily4for 2 weeks A
daily over weeks A 12
Licorice Glabridin
glabra (L.)) twice daily for 2 weeks
Licorice
(Glycyrrhiza Glabridin
Glabridin
(Glycyrrhiza
glabra (L.))
Licorice Glabridin - Ointment with 0.5%
Photo- glabra (L.)) - Ointment with 0.5% DD 72
(Glycyrrhiza glabra (L.)) [72]
protection glabridin
-glabridin ononguinea
guinea
of 25pigpigskin
skin
Biomedicines 2019, 7, xPine
FOR bark
PEER REVIEW Oral ingestion
- Ointment with 0.5%
mg pine 16 of 23
and esthetic Pine bark - Oral ingestion of 25 mg pine D 72
(Pinus pinaster Pine bark extract bark extractwith
- Ointment three0.5%
times daily B 74
dermatology glabridin on guinea pig skin
(Pinus pinaster Licochalcone
Pine A
bark extract bark D 72
Ailton) for 30extract
glabridindayson three times daily
guinea pig skin
B 74
Photo- Licochalcone A - 9 µM Licochalcone A in
Ailton) -for
9 µM30 days
Licochalcone A in in D [12]
Photo- in vitro experiments D 12
protection vitro experiments- Ointment
protection
and esthetic - Ointmentlicochalcone
containing A
containing
and esthetic
dermatology licochalcone A twice daily for AA 12
[12]
-twice
Cream with
daily
2 weeks forCentella
2 weeksasiatica
dermatology - Cream with Centella asiatica
extract applied daily from the
Gotu kola extract - Oral ingestion of 25 mg pine A 75
Pine bark extract applied daily from the
Pine bark extract end barkof extract
the 12ththree
week of daily
times B [74]
(Pinus pinaster Ailton) Gotu kola extract A 75
for 30 days
end of the until
12th week of
pregnancy delivery
Gotu kola - Cream with Centella asiatica
Pine bark pregnancy
- extract
Oral ingestionuntil delivery
appliedof 25 mg
daily pine
from the
Gotu
(Centella kola
asiatica Gotu kola extract A [75]
(Pinus pinaster Pine bark extract end of the 12th week
bark extract three times daily of B 74
Asiaticoside
(Centella
(L.) asiatica
Urban) pregnancy until delivery
Ailton) Asiaticoside for 30 days
Gotu kola
(L.) Urban) Asiaticoside
Photo- - Cream containing 0.1%
(Centella asiatica (L.)
protection Urban) - Cream containing
asiaticoside 0.1%
twice daily for 12 B 76
- Cream containing 0.1%
and esthetic asiaticoside
asiaticosidetwice
weeks twicedaily
dailyfor
for12 BB 76
[76]
dermatology 12 weeks
-weeks
Cream with Centella asiatica
extract applied daily from the
GotuBetulin
kola extract - Wounds including A 75
end of the 12th week second
of
Betulin
Betulin - Wounds
degree burns including
anddelivery second
- Wounds
pregnancy including
until second
Gotu kola degreeburns
degree burnsand
split-thickness and graft
skin
Birch bark split-thickness skin graft
Birch bark asiatica
(Centella split-thickness
wounds skin graft
Birch bark woundswereweretreated
treatedwith
with A [81]
(Betula
(Betula spp.)spp.) Asiaticoside A 81
Wound (L.) Urban) betulin
wounds oleogel
were (containing
treated
betulin oleogel (containing with
healing (Betula spp.) 10% betulin) till wound A 81
betulin
10% oleogel
betulin) tillto(containing
wound
- closure
Cream or up
containing 28 0.1%
days
Wound 10% betulin)
closure or up till28
to wound
days
asiaticoside twicetwice
- Onion extract dailydaily
for 12
for B 76
Wound
healing Onion closure or after
up toinitial
28 days
Onion extract 10
weeksweeks primary A [86]
healing (Allium cepa (L.)) wound healing
- Onion extract twice daily for
Onion
Onion extract - Onion
10 weeksextract
after twiceprimary
initial daily for A 86
Onion Betulin - Wounds including second
(Allium cepa (L.))
Onion extract 10 weeks
wound after initial primary
healing A 86
(Allium cepa (L.)) degree burns and
wound healing
split-thickness skin graft
Birch bark
wounds were treated with
(Betula spp.) A 81
betulin oleogel (containing
10% betulin) till wound
Wound closure or up to 28 days
Licochalcone A - Licochalcone A in different B 89
vehicles applied daily for 8
weeks
Biomedicines 2020, 8, 27 Licorice root 15 of 21
- Treatment with licochalcone
(Glycyrrhiza
A and
inflata Batalin) Table 1. Cont. trans-4-t-butylcyclohexanol
Biomedicines 2019, 7, x FOR PEER REVIEW (TRPV1 inhibitor) twice a day L 17 of 23
DiseaseRosacea Plant Compound for 4 weeks Treatment BO 90Ref
Epigallocatechin-3-gallate E
Green - Cream containing 2.5%
Green - Cream containing 2.5%
Bitter-wood
tea(Camellia - Gel containing 4%
epigallocatechin Simarouba
gallate twice D 88
- Cream containing 2.5%
Green tea(Camellia
tea(Camellia epigallocatechin gallate twice D 88
(Simarouba
sinensis amara Bitter-wood extract epigallocatechin
amara extract twicegallate twice
daily for 6 BD 91[88]
sinensis (L.))(L.)) daily for 6 weeks
sinensis (L.)) dailyfor
daily for66weeks
weeks
Aubl.) weeks
Licochalcone A - Licochalcone A in different B 89

Licochalcone A - -Licochalcone
LicochalconeAAinindifferent
different B 89
Licochalcone A vehicles
vehiclesapplied
applieddaily
dailyforfor
8 B [89]
vehicles
8 weeksapplied daily for 8
Rosacea Licorice root weeks
Licorice
Tormentil
(Glycyrrhiza root
inflata - weeks
- Treatment
Tormentil with licochalcone
extract (5%)
Licorice root - Treatment
A and with licochalcone
Batalin)
(Glycyrrhiza
(Potentilla erecta Tormentil extract - Treatment with licochalcone
applied topically once for 48 h C 18
(Glycyrrhiza A trans-4-t-butylcyclohexanol
and B [90]
inflata(L.))
Batalin) toA(TRPV1
and inhibitor)
volunteers twice
in a patch a day
test
inflata Batalin) trans-4-t-butylcyclohexanol
for 4 weeks
trans-4-t-butylcyclohexanol
Bitter-wood (TRPV1 inhibitor) twice
- Gel containing a day
4% Simarouba
Rosacea (Simarouba amara Bitter-wood extract (TRPV1 inhibitor)
amara extract twice
twice dailya for
day B [91]
Rosacea for 4 weeks B 90
Aubl.) - for
Gel containing
6 weeks
4 weeks 5% Melaleuca BB 95
90
Tea tree - Tormentil
alternifolia oil extract
applied(5%)
topically
Tormentil
Tormentil extract applied topically once for 48 h C [18]
erecta (L.))
(Potentilla(Melaleuca forto3volunteers
months in a patch test
Bitter-wood - Gel containing 4% Simarouba
Bitter-wood
alternifolia Tea tree oil - -Gel
Gelcontaining
containing4% 5%Simarouba
Melaleuca
(Simarouba amara Bitter-wood extract amara extract twice daily for 6 B 91
(Simarouba
Tea(Maiden
tree amara
& Bitter-wood extract alternifolia
- amara oil applied
extract twice
Gel containing topically
daily
5% Melaleucafor 6 BB [95]
91
Aubl.)
(Melaleuca alternifolia weeks
for 3 months
Aubl.)
Betche) Cheel) Tea tree oil weeks
alternifolia oil applied twice
(Maiden & Betche) - Gel containing 5% Melaleuca
Acne daily for 45 days
alternifolia oil applied twice AA 96[96]
Cheel)
vulgaris daily for 45 days
- Treatment with 1% or 5%
Green tea
Tormentil - Tormentil extract
- Treatment (5%)or 5%
with 1%
Tormentil epigallocatechin-3-gallate
- epigallocatechin-3-gallate
Tormentil extract (5%)
Green tea
(Camellia
Acne (Potentillasinensis
erecta Tormentil extract applied topically once for 48 h AA
C 97[97]
18
(Camellia(Potentilla
sinensis (L.))
erecta Tormentil extract solution
applied twice
solution daily
twice for
daily
topically once 8 48 h
for
for C 18
vulgaris (L.))
(L.)) to8volunteers
weeks in a patch test
(L.)) weeks
to volunteers in a patch test
- Lotion with 2% Camellia

Green tea extract - Gel containing
sinensis extract5%
twiceMelaleuca
daily for B B 95[98]
- Gel containing 5% Melaleuca B 95
Tea tree 6 weeks oil applied topically
alternifolia
Hop Tea tree alternifolia oiland
applied topically
(Humulus (Melaleuca
lupulus (L.)) for- 3.1 µg/mL
3 months 9.4 µg/mL of
(Melaleuca Humulus
for 3 months lupulus extract
alternifolia Tea
Hoptree oil
extract in vitro [99]
C
alternifolia Tea tree oil - Gel containing5% 0.3% Humulus
(Maiden & - Gel containing Melaleuca
(Maiden & - lupulus extract in
Gel containing 5% vitro
Melaleuca
Betche) Cheel) alternifolia oil applied twice
Acne Betche) Cheel) alternifolia oil applied twice
Acne daily for 45 days A
96
vulgaris daily for 45 days A
96
Author Contributions:
vulgaris Writing—originalEpigallocatechin-3-gallate
draft preparation, review and editing (J.H., U.W.), writing—review and
editing (F.G., C.M.S.), Table 1 preparationEpigallocatechin-3-gallate
(F.G.). All authors have read and agreed to the published version of
the manuscript. - Treatment with 1% or 5%
Green tea - Treatment with 1% or 5%
Funding: For this review Green
no externaltea epigallocatechin-3-gallate
(Camellia sinensisfunding was received. epigallocatechin-3-gallate A 97
(Camellia sinensis solution twice daily for 8 A 97
Conflicts of Interest: U.W. and (L.)) C.S. hold a patent on the topical use of bitter taste receptor
solution twice daily for 8 agonist and have
performed contract research for (L.))Birken AG, Cassella Med, Weleda and WALA.
weeks
weeks
References
1. Reuter, J.; Wölfle, U.; Weckesser, S.; Schempp, C. Which plant for which skin disease? Part 1: Atopic
dermatitis, psoriasis, acne, condyloma and herpes simplex. J. Dtsch. Dermatol. Ges. 2010, 8, 788–796.
[CrossRef] [PubMed]
2. Reuter, J.; Wölfle, U.; Korting, H.C.; Schempp, C. Which plant for which skin disease? Part 2: Dermatophytes,
chronic venous insufficiency, photoprotection, actinic keratoses, vitiligo, hair loss, cosmetic indications.
J. Dtsch. Dermatol. Ges. 2010, 8, 866–873. [CrossRef] [PubMed]
3. Oxford Centre for Evidence-Based Medicine. Levels of Evidence and Grades of Recommendation, 2009.
Available online: http://www.cebm.net/index.aspx?o=1025#levels (accessed on 26 March 2010).
4. Vieira, B.L.; Lim, N.R.; Lohman, M.E.; Lio, P.A. Complementary and Alternative Medicine for Atopic
Dermatitis: An Evidence-Based Review. Am. J. Clin. Dermatol. 2016, 17, 557–581. [CrossRef] [PubMed]
5. Wölfle, U.; Seelinger, G.; Schempp, C.M. Topical application of St. John’s wort (Hypericum perforatum).
Planta Med. 2014, 80, 109–120.
6. Schempp, C.M.; Windeck, T.; Hezel, S.; Simon, J.C. Topical treatment of atopic dermatitis with St. John’s wort
cream–a randomized, placebo controlled, double blind half-side comparison. Phytomedicine Int. J. Phytother.
Phytopharm. 2003, 10 (Suppl. S4), 31–37. [CrossRef]
7. Yang, R.; Wang, L.; Yuan, B.; Liu, Y. The Pharmacological Activities of Licorice. Planta Med. 2015, 81,
1654–1669. [CrossRef]
8. Lee, Y.M.; Hirota, S.; Jippo-Kanemoto, T.; Kim, H.R.; Shin, T.Y.; Yeom, Y.; Lee, K.K.; Kitamura, Y.; Nomura, S.;
Kim, H.M. Inhibition of histamine synthesis by glycyrrhetinic acid in mast cells cocultured with Swiss 3T3
fibroblasts. Int. Arch. Allergy Immunol. 1996, 110, 272–277. [CrossRef]
9. Afnan, Q.; Adil, M.D.; Nissar-Ul, A.; Rafiq, A.R.; Amir, H.F.; Kaiser, P.; Gupta, V.K.; Vishwakarma, R.;
Tasduq, S.A. Glycyrrhizic acid (GA), a triterpenoid saponin glycoside alleviates ultraviolet-B
irradiation-induced photoaging in human dermal fibroblasts. Phytomedicine Int. J. Phytother. Phytopharm.
2012, 19, 658–664. [CrossRef]
10. Farrukh, M.R.; Nissar, U.-A.; Kaiser, P.J.; Afnan, Q.; Sharma, P.R.; Bhushan, S.; Tasduq, S.A. Glycyrrhizic acid
(GA) inhibits reactive oxygen Species mediated photodamage by blocking ER stress and MAPK pathway in
UV-B irradiated human skin fibroblasts. J. Photochem. Photobiol. B 2015, 148, 351–357. [CrossRef]
11. Yu, H.; Li, H.; Li, Y.; Li, M.; Chen, G. Effect of isoliquiritigenin for the treatment of atopic dermatitis-like skin
lesions in mice. Arch. Dermatol. Res. 2017, 309, 805–813. [CrossRef]
12. Kühnl, J.; Roggenkamp, D.; Gehrke, S.A.; Stäb, F.; Wenck, H.; Kolbe, L.; Neufang, G. Licochalcone A
activates Nrf2 in vitro and contributes to licorice extract-induced lowered cutaneous oxidative stress in vivo.
Exp. Dermatol. 2015, 24, 42–47. [CrossRef] [PubMed]
13. Song, N.R.; Kim, J.-E.; Park, J.S.; Kim, J.R.; Kang, H.; Lee, E.; Kang, Y.-G.; Son, J.E.; Seo, S.G.; Heo, Y.S.; et al.
Licochalcone A, a polyphenol present in licorice, suppresses UV-induced COX-2 expression by targeting
PI3K, MEK1, and B-Raf. Int. J. Mol. Sci. 2015, 16, 4453–4470. [CrossRef] [PubMed]
14. Sulzberger, M.; Worthmann, A.-C.; Holtzmann, U.; Buck, B.; Jung, K.A.; Schoelermann, A.M.; Rippke, F.;
Stäb, F.; Wenck, H.; Neufang, G.; et al. Effective treatment for sensitive skin: 4-t-butylcyclohexanol and
licochalcone A. J. Eur. Acad. Dermatol. Venereol. 2016, 30 (Suppl. S1), 9–17. [CrossRef] [PubMed]
15. Abramovits, W.; Boguniewicz, M.; Adult Atopiclair Study Group. A multicenter, randomized,
vehicle-controlled clinical study to examine the efficacy and safety of MAS063DP (Atopiclair) in the
management of mild to moderate atopic dermatitis in adults. J. Drugs Dermatol. 2006, 5, 236–244. [PubMed]
16. Angelova-Fischer, I.; Rippke, F.; Richter, D.; Filbry, A.; Arrowitz, C.; Weber, T.; Fischer, T.W.; Zillikens, D.
Stand-alone Emollient Treatment Reduces Flares After Discontinuation of Topical Steroid Treatment in Atopic
Dermatitis: A Double-blind, Randomized, Vehicle-controlled, Left-right Comparison Study. Acta Derm.
Venereol. 2018, 98, 517–523. [CrossRef] [PubMed]
17. Seiwerth, J.; Tasiopoulou, G.; Hoffmann, J.; Wölfle, U.; Schwabe, K.; Quirin, K.-W.; Schempp, C.M.
Anti-Inflammatory Effect of a Novel Topical Herbal Composition (VEL-091604) Consisting of Gentian Root,
Licorice Root and Willow Bark Extract. Planta Med. 2019, 85, 608–614. [CrossRef]
18. Wölfle, U.; Hoffmann, J.; Haarhaus, B.; Rao Mittapalli, V.; Schempp, C.M. Anti-inflammatory and
vasoconstrictive properties of Potentilla erecta—A traditional medicinal plant from the northern hemisphere.
J. Ethnopharmacol. 2017, 204, 86–94. [CrossRef]
19. Hoffmann, J.; Wölfle, U.; Schempp, C.M.; Casetti, F. Tannins from Potentilla officinalis display antiinflammatory
effects in the UV erythema test and on atopic skin. J. Dtsch. Dermatol. Ges. 2016, 14, 917–922.
20. Wölfle, U.; Elsholz, F.A.; Kersten, A.; Haarhaus, B.; Müller, W.E.; Schempp, C.M. Expression and functional
activity of the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes. Skin Pharmacol. Physiol.
2015, 28, 137–146. [CrossRef]
21. Wölfle, U.; Haarhaus, B.; Seiwerth, J.; Cawelius, A.; Schwabe, K.; Quirin, K.-W.; Schempp, C.M. The Herbal
Bitter Drug Gentiana lutea Modulates Lipid Synthesis in Human Keratinocytes In Vitro and In Vivo. Int. J.
Mol. Sci. 2017, 18, 1814. [CrossRef]
22. Morse, N.L.; Clough, P.M. A meta-analysis of randomized, placebo-controlled clinical trials of Efamol evening
primrose oil in atopic eczema. Where do we go from here in light of more recent discoveries? Curr. Pharm.
Biotechnol. 2006, 7, 503–524. [CrossRef] [PubMed]
23. Farahnik, B.; Sharma, D.; Alban, J.; Sivamani, R.K. Topical Botanical Agents for the Treatment of Psoriasis:
A Systematic Review. Am. J. Clin. Dermatol. 2017, 18, 451–468. [CrossRef] [PubMed]
24. Gamret, A.C.; Price, A.; Fertig, R.M.; Lev-Tov, H.; Nichols, A.J. Complementary and Alternative Medicine
Therapies for Psoriasis: A Systematic Review. JAMA Dermatol. 2018, 154, 1330–1337. [CrossRef] [PubMed]
25. Herman, A.; Herman, A.P. Topically Used Herbal Products for the Treatment of Psoriasis—Mechanism of
Action, Drug Delivery, Clinical Studies. Planta Med. 2016, 82, 1447–1455. [CrossRef] [PubMed]
26. Van de Kerkhof, P.C.M.; van der Valk, P.G.M.; Swinkels, O.Q.J.; Kucharekova, M.; de Rie, M.A.; de Vries, H.J.C.;
Damstra, R.; Oranje, A.P.; de Waard-van der Spek, F.B.; van Neer, P.; et al. A comparison of twice-daily
calcipotriol ointment with once-daily short-contact dithranol cream therapy: A randomized controlled
trial of supervised treatment of psoriasis vulgaris in a day-care setting. Br. J. Dermatol. 2006, 155, 800–807.
[CrossRef] [PubMed]
27. Markham, T.; Rogers, S.; Collins, P. Narrowband UV-B (TL-01) phototherapy vs oral 8-methoxypsoralen
psoralen-UV-A for the treatment of chronic plaque psoriasis. Arch. Dermatol. 2003, 139, 325–328. [CrossRef]
[PubMed]
28. Vongthongsri, R.; Konschitzky, R.; Seeber, A.; Treitl, C.; Hönigsmann, H.; Tanew, A. Randomized, double-blind
comparison of 1 mg/L versus 5 mg/L methoxsalen bath-PUVA therapy for chronic plaque-type psoriasis.
J. Am. Acad. Dermatol. 2006, 55, 627–631. [CrossRef]
29. Amornpinyokeit, N.; Asawanonda, P. 8-Methoxypsoralen cream plus targeted narrowband ultraviolet B for
psoriasis. Photodermatol. Photoimmunol. Photomed. 2006, 22, 285–289. [CrossRef]
30. Bernstein, S.; Donsky, H.; Gulliver, W.; Hamilton, D.; Nobel, S.; Norman, R. Treatment of mild to moderate
psoriasis with Reliéva, a Mahonia aquifolium extract–a double-blind, placebo-controlled study. Am. J. Ther.
2006, 13, 121–126. [CrossRef]
31. Lin, Y.-K.; Chang, C.-J.; Chang, Y.-C.; Wong, W.-R.; Chang, S.-C.; Pang, J.-H.S. Clinical assessment of patients
with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using indigo naturalis.
Arch. Dermatol. 2008, 144, 1457–1464. [CrossRef]
32. Lin, Y.-K.; See, L.-C.; Huang, Y.-H.; Chang, Y.-C.; Tsou, T.-C.; Lin, T.-Y.; Lin, N.-L. Efficacy and safety of Indigo
naturalis extract in oil (Lindioil) in treating nail psoriasis: A randomized, observer-blind, vehicle-controlled
trial. Phytomedicine Int. J. Phytother. Phytopharm. 2014, 21, 1015–1020. [CrossRef] [PubMed]
33. Lin, Y.-K.; See, L.-C.; Huang, Y.-H.; Chi, C.-C.; Hui, R.C.-Y. Comparison of indirubin concentrations in indigo
naturalis ointment for psoriasis treatment: A randomized, double-blind, dosage-controlled trial. Br. J.
Dermatol. 2018, 178, 124–131. [CrossRef] [PubMed]
34. Antiga, E.; Bonciolini, V.; Volpi, W.; Del Bianco, E.; Caproni, M. Oral Curcumin (Meriva) Is Effective as
an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris.
BioMed Res. Int. 2015. [CrossRef] [PubMed]
35. Heng, M.C.; Song, M.K.; Harker, J.; Heng, M.K. Drug-induced suppression of phosphorylase kinase
activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical
parameters. Br. J. Dermatol. 2000, 143, 937–949. [CrossRef]
36. Reddy, S.; Aggarwal, B.B. Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase.
FEBS Lett. 1994, 341, 19–22. [CrossRef]
37. Varma, S.R.; Sivaprakasam, T.O.; Mishra, A.; Prabhu, S.; Rafiq, M.; Rangesh, P. Imiquimod-induced
psoriasis-like inflammation in differentiated Human keratinocytes: Its evaluation using curcumin. Eur. J.
Pharmacol. 2017, 813, 33–41. [CrossRef]
38. Nardo, V.D.; Gianfaldoni, S.; Tchernev, G.; Wollina, U.; Barygina, V.; Lotti, J.; Daaboul, F.; Lotti, T. Use of
Curcumin in Psoriasis. Open Access Maced. J. Med. Sci. 2018, 6, 218–220. [CrossRef]
39. Muhammed, M.; Nagabhushanam, K.; Sankarab, N.; Sood, R.; Kumar Karri, S. Clinical evaluation of AKBBA
in the management of psoriasis. Clin. Dermatol. 2014, 2, 17–24. [CrossRef]
40. Leuner, K.; Kraus, M.; Woelfle, U.; Beschmann, H.; Harteneck, C.; Boehncke, W.-H.; Schempp, C.M.;
Müller, W.E. Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired
differentiation and enhanced proliferation. PLoS ONE 2011, 6, e14716. [CrossRef]
41. Najafizadeh, P.; Hashemian, F.; Mansouri, P.; Farshi, S.; Surmaghi, M.S.; Chalangari, R. The evaluation of the
clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: A pilot
study. Australas. J. Dermatol. 2012, 53, 131–135. [CrossRef]
42. Mansouri, P.; Mirafzal, S.; Najafizadeh, P.; Safaei-Naraghi, Z.; Salehi-Surmaghi, M.H.; Hashemian, F. The
impact of topical Saint John’s Wort (Hypericum perforatum) treatment on tissue tumor necrosis factor-alpha
levels in plaque-type psoriasis: A pilot study. J. Postgrad. Med. 2017, 63, 215–220. [PubMed]
43. Hassan, S.T.S.; Masarčíková, R.; Berchová, K. Bioactive natural products with anti-herpes simplex virus
properties. J. Pharm. Pharmacol. 2015, 67, 1325–1336. [CrossRef] [PubMed]
44. Fukuchi, K.; Okudaira, N.; Adachi, K.; Odai-Ide, R.; Watanabe, S.; Ohno, H.; Yamamoto, M.; Kanamoto, T.;
Terakubo, S.; Nakashima, H.; et al. Antiviral and Antitumor Activity of Licorice Root Extracts. Vivo Athens
Greece 2016, 30, 777–785. [CrossRef] [PubMed]
45. Goswami, D.; Mahapatra, A.D.; Banerjee, S.; Kar, A.; Ojha, D.; Mukherjee, P.K.; Chattopadhyay, D. Boswellia
serrata oleo-gum-resin and β-boswellic acid inhibits HSV-1 infection in vitro through modulation of NF-κB
and p38 MAP kinase signaling. Phytomedicine Int. J. Phytother. Phytopharm. 2018, 51, 94–103. [CrossRef]
46. Koytchev, R.; Alken, R.G.; Dundarov, S. Balm mint extract (Lo-701) for topical treatment of recurring herpes
labialis. Phytomedicine Int. J. Phytother. Phytopharm. 1999, 6, 225–230. [CrossRef]
47. Saller, R.; Büechi, S.; Meyrat, R.; Schmidhauser, C. Combined herbal preparation for topical treatment of
Herpes labialis. Res. Complement. Nat. Class Med. 2001, 8, 373–382.
48. Kacerovská, D.; Pizinger, K.; Majer, F.; Smíd, F. Photodynamic therapy of nonmelanoma skin cancer with
topical hypericum perforatum extract–a pilot study. Photochem. Photobiol. 2008, 84, 779–785. [CrossRef]
49. Pflugfelder, A.; Andonov, E.; Weide, B.; Dirschka, T.; Schempp, C.; Stockfleth, E.; Stratigos, A.;
Krüger-Krasagakis, S.; Bauer, J.; Garbe, C.; et al. Lack of activity of betulin-based Oleogel-S10 in the
treatment of actinic keratoses: A randomized, multicentre, placebo-controlled double-blind phase II trial.
Br. J. Dermatol. 2015, 172, 926–932. [CrossRef]
50. Huyke, C.; Reuter, J.; Rodig, M.; Kersten, A.; Laszczyk, M.; Scheffler, A.; Nashan, D.; Schempp, C. Treatment
of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study.
J. Dtsch. Dermatol. Ges. 2009, 7, 128–133.
51. Huyke, C.; Laszczyk, M.; Scheffler, A.; Ernst, R.; Schempp, C.M. Treatment of actinic keratoses with birch
bark extract: A pilot study. J. Dtsch. Dermatol. Ges. 2006, 4, 132–136. [CrossRef]
52. Woelfle, U.; Laszczyk, M.N.; Kraus, M.; Leuner, K.; Kersten, A.; Simon-Haarhaus, B.; Scheffler, A.; Martin, S.F.;
Müller, W.E.; Nashan, D.; et al. Triterpenes promote keratinocyte differentiation in vitro, ex vivo and in vivo:
A role for the transient receptor potential canonical (subtype) 6. J. Investig. Dermatol. 2010, 130, 113–123.
[CrossRef]
53. Anderson, L.; Schmieder, G.J.; Werschler, W.P.; Tschen, E.H.; Ling, M.R.; Stough, D.B.; Katsamas, J.
Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and
0.05% for actinic keratosis. J. Am. Acad. Dermatol. 2009, 60, 934–943. [CrossRef]
54. Siller, G.; Gebauer, K.; Welburn, P.; Katsamas, J.; Ogbourne, S.M. PEP005 (ingenol mebutate) gel, a novel agent
for the treatment of actinic keratosis: Results of a randomized, double-blind, vehicle-controlled, multicentre,
phase IIa study. Australas. J. Dermatol. 2009, 50, 16–22. [CrossRef]
55. Chen, A.C.; Damian, D.L.; Halliday, G.M. Oral and systemic photoprotection. Photodermatol. Photoimmunol.
Photomed. 2014, 30, 102–111. [CrossRef]
56. Katiyar, S.K.; Afaq, F.; Perez, A.; Mukhtar, H. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment
of human skin inhibits ultraviolet radiation-induced oxidative stress. Carcinogenesis 2001, 22, 287–294.
[CrossRef]
57. Katiyar, S.K.; Ahmad, N.; Mukhtar, H. Green tea and skin. Arch. Dermatol. 2000, 136, 989–994. [CrossRef]
58. Seelinger, G.; Merfort, I.; Schempp, C.M. Anti-oxidant, anti-inflammatory and anti-allergic activities of
luteolin. Planta Med. 2008, 74, 1667–1677. [CrossRef]
59. Wölfle, U.; Esser, P.R.; Simon-Haarhaus, B.; Martin, S.F.; Lademann, J.; Schempp, C.M. UVB-induced DNA
damage, generation of reactive oxygen species, and inflammation are effectively attenuated by the flavonoid
luteolin in vitro and in vivo. Free Radic. Biol. Med. 2011, 50, 1081–1093. [CrossRef]
60. Wölfle, U.; Heinemann, A.; Esser, P.R.; Haarhaus, B.; Martin, S.F.; Schempp, C.M. Luteolin prevents solar
radiation-induced matrix metalloproteinase-1 activation in human fibroblasts: A role for p38 mitogen-activated
protein kinase and interleukin-20 released from keratinocytes. Rejuvenation Res. 2012, 15, 466–475. [CrossRef]
61. Casetti, F.; Jung, W.; Wölfle, U.; Reuter, J.; Neumann, K.; Gilb, B.; Wähling, A.; Wagner, S.; Merfort, I.;
Schempp, C.M. Topical application of solubilized Reseda luteola extract reduces ultraviolet B-induced
inflammation in vivo. J. Photochem. Photobiol. B 2009, 96, 260–265. [CrossRef]
62. Martin, S.F.; Esser, P.R.; Weber, F.C.; Jakob, T.; Freudenberg, M.A.; Schmidt, M.; Goebeler, M. Mechanisms of
chemical-induced innate immunity in allergic contact dermatitis. Allergy 2011, 66, 1152–1163. [CrossRef]
[PubMed]
63. Schempp, C.M.; Meinke, M.C.; Lademann, J.; Ferrari, Y.; Brecht, T.; Gehring, W. Topical antioxidants protect
the skin from chemical-induced irritation in the repetitive washing test: A placebo-controlled, double-blind
study. Contact Dermat. 2012, 67, 234–237. [CrossRef]
64. Heinrich, U.; Neukam, K.; Tronnier, H.; Sies, H.; Stahl, W. Long-term ingestion of high flavanol cocoa
provides photoprotection against UV-induced erythema and improves skin condition in women. J. Nutr.
2006, 136, 1565–1569. [CrossRef] [PubMed]
65. Heinrich, U.; Gärtner, C.; Wiebusch, M.; Eichler, O.; Sies, H.; Tronnier, H.; Stahl, W. Supplementation with
beta-carotene or a similar amount of mixed carotenoids protects humans from UV-induced erythema. J. Nutr.
2003, 133, 98–101. [CrossRef]
66. Aust, O.; Stahl, W.; Sies, H.; Tronnier, H.; Heinrich, U. Supplementation with tomato-based products increases
lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema.
Int. J. Vitam. Nutr. Res. 2005, 75, 54–60. [CrossRef]
67. Rizwan, M.; Rodriguez-Blanco, I.; Harbottle, A.; Birch-Machin, M.A.; Watson, R.E.B.; Rhodes, L.E. Tomato
paste rich in lycopene protects against cutaneous photodamage in humans in vivo: A randomized controlled
trial. Br. J. Dermatol. 2011, 164, 154–162. [CrossRef]
68. Hakim, I.A.; Harris, R.B.; Ritenbaugh, C. Citrus peel use is associated with reduced risk of squamous cell
carcinoma of the skin. Nutr. Cancer 2000, 37, 161–168. [CrossRef]
69. Song, F.; Qureshi, A.A.; Han, J. Increased caffeine intake is associated with reduced risk of basal cell carcinoma
of the skin. Cancer Res. 2012, 72, 3282–3289. [CrossRef]
70. Corona, R.; Dogliotti, E.; D’Errico, M.; Sera, F.; Iavarone, I.; Baliva, G.; Chinni, L.; Gobello, T.; Mazzanti, C.;
Puddu, P.; et al. Risk factors for basal cell carcinoma in a Mediterranean population. Arch. Dermatol. 2001,
137, 1162–1168. [CrossRef]
71. Armanini, D.; Nacamulli, D.; Francini-Pesenti, F.; Battagin, G.; Ragazzi, E.; Fiore, C. Glycyrrhetinic acid, the
active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application.
Steroids 2005, 70, 538–542. [CrossRef]
72. Yokota, T.; Nishio, H.; Kubota, Y.; Mizoguchi, M. The inhibitory effect of glabridin from licorice extracts on
melanogenesis and inflammation. Pigment. Cell Res. 1998, 11, 355–361. [CrossRef] [PubMed]
73. Grether-Beck, S.; Marini, A.; Jaenicke, T.; Krutmann, J. French Maritime Pine Bark Extract (Pycnogenol® )
Effects on Human Skin: Clinical and Molecular Evidence. Skin Pharmacol. Physiol. 2016, 29, 13–17. [CrossRef]
74. Ni, Z.; Mu, Y.; Gulati, O. Treatment of melasma with Pycnogenol. Phytother. Res. PTR 2002, 16, 567–571.
[CrossRef] [PubMed]
75. Mallol, J.; Belda, M.A.; Costa, D.; Noval, A.; Sola, M. Prophylaxis of Striae gravidarum with a topical
formulation. A double blind trial. Int. J. Cosmet. Sci. 1991, 13, 51–57. [CrossRef] [PubMed]
76. Lee, J.; Jung, E.; Lee, H.; Seo, Y.; Koh, J.; Park, D. Evaluation of the effects of a preparation containing
asiaticoside on periocular wrinkles of human volunteers. Int. J. Cosmet. Sci. 2008, 30, 167–173. [CrossRef]
77. Pazyar, N.; Yaghoobi, R.; Rafiee, E.; Mehrabian, A.; Feily, A. Skin wound healing and phytomedicine:
A review. Skin Pharmacol. Physiol. 2014, 27, 303–310. [CrossRef]
78. Laszczyk, M.; Jäger, S.; Simon-Haarhaus, B.; Scheffler, A.; Schempp, C.M. Physical, chemical and
pharmacological characterization of a new oleogel-forming triterpene extract from the outer bark of
birch (betulae cortex). Planta Med. 2006, 72, 1389–1395. [CrossRef]
79. Ebeling, S.; Naumann, K.; Pollok, S.; Wardecki, T.; Vidal-Y-Sy, S.; Nascimento, J.M.; Boerries, M.; Schmidt, G.;
Brandner, J.M.; Merfort, I. From a traditional medicinal plant to a rational drug: Understanding the clinically
proven wound healing efficacy of birch bark extract. PLoS ONE 2014, 9, e86147. [CrossRef]
80. Metelmann, H.-R.; Brandner, J.M.; Schumann, H.; Bross, F.; Fimmers, R.; Böttger, K.; Scheffler, A.; Podmelle, F.
Accelerated reepithelialization by triterpenes: Proof of concept in the healing of surgical skin lesions.
Skin Pharmacol. Physiol. 2015, 28, 1–11. [CrossRef]
81. Barret, J.P.; Podmelle, F.; Lipový, B.; Rennekampff, H.-O.; Schumann, H.; Schwieger-Briel, A.; Zahn, T.R.;
Metelmann, H.-R.; BSH-12 and BSG-12 Study Groups. Accelerated re-epithelialization of partial-thickness
skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program. Burns 2017,
43, 1284–1294. [CrossRef]
82. Frew, Q.; Rennekampff, H.-O.; Dziewulski, P.; Moiemen, N.; BBW-11 Study Group; Zahn, T.; Hartmann, B.
Betulin wound gel accelerated healing of superficial partial thickness burns: Results of a randomized,
intra-individually controlled, phase III trial with 12-months follow-up. Burns 2019, 45, 876–890. [CrossRef]
[PubMed]
83. Scheffler, A. The Wound Healing Properties of Betulin from Birch Bark from Bench to Bedside. Planta Med.
2019, 85, 524–527. [CrossRef] [PubMed]
84. European Medicines Agency (EMA). Assessment Report of the Committee for Medicinal Products for
Human Use (CHMP) on Episalvan, International Non-Proprietary Name: Birch Bark Extract. Available
online: https://www.ema.europa.eu/en/medicines/human/EPAR/episalvan (accessed on 20 November 2019).
85. Fang, Q.-Q.; Chen, C.-Y.; Zhang, M.-X.; Huang, C.-L.; Wang, X.-W.; Xu, J.-H.; Wu, L.-H.; Zhang, L.-Y.;
Tan, W.-Q. The Effectiveness of Topical Anti-scarring Agents and a Novel Combined Process on Cutaneous
Scar Management. Curr. Pharm. Des. 2017, 23, 2268–2275. [CrossRef] [PubMed]
86. Draelos, Z.D. The ability of onion extract gel to improve the cosmetic appearance of postsurgical scars.
J. Cosmet. Dermatol. 2008, 7, 101–104. [CrossRef] [PubMed]
87. Fisk, W.A.; Lev-Tov, H.A.; Clark, A.K.; Sivamani, R.K. Phytochemical and Botanical Therapies for Rosacea: A
Systematic Review. Phytother. Res. PTR 2015, 29, 1439–1451. [CrossRef]
88. Domingo, D.S.; Camouse, M.M.; Hsia, A.H.; Matsui, M.; Maes, D.; Ward, N.L.; Cooper, K.D.; Baron, E.D.
Anti-angiogenic effects of epigallocatechin-3-gallate in human skin. Int. J. Clin. Exp. Pathol. 2010, 3, 705–709.
89. Weber, T.M.; Ceilley, R.I.; Buerger, A.; Kolbe, L.; Trookman, N.S.; Rizer, R.L.; Schoelermann, A. Skin tolerance,
efficacy, and quality of life of patients with red facial skin using a skin care regimen containing Licochalcone
A. J. Cosmet. Dermatol. 2006, 5, 227–232. [CrossRef]
90. Jovanovic, Z.; Angabini, N.; Ehlen, S.; Mokos, Z.B.; Subotic, M.; Neufang, G. Efficacy and Tolerability of
a Cosmetic Skin Care Product with Trans-4-t-butylcyclohexanol and Licochalcone A in Subjects with Sensitive
Skin Prone to Redness and Rosacea. J. Drugs Dermatol. 2017, 16, 605–610.
91. Ferrari, A.; Diehl, C. Evaluation of the efficacy and tolerance of a topical gel with 4% quassia extract in the
treatment of rosacea. J. Clin. Pharmacol. 2012, 52, 84–88. [CrossRef]
92. Sudhapriyadhars, G. Topical glucocorticoid—A review. J. Pharm. Sci. Res. 2014, 6, 244–246.
93. Sauermann, G.; Jaspers, S.; Hoppe, U.; Salzer, B.; Steinkraus, V. Influence of NO-synthase antagonists in
rosacea patients. J. Investig. Dermatol. 1997, 4, 657.
94. Fisk, W.A.; Lev-Tov, H.A.; Sivamani, R.K. Botanical and phytochemical therapy of acne: A systematic review.
Phytother. Res. PTR 2014, 28, 1137–1152. [CrossRef] [PubMed]
95. Bassett, I.B.; Pannowitz, D.L.; Barnetson, R.S. A comparative study of tea-tree oil versus benzoylperoxide in
the treatment of acne. Med. J. Aust. 1990, 153, 455–458. [CrossRef] [PubMed]
96. Enshaieh, S.; Jooya, A.; Siadat, A.H.; Iraji, F. The efficacy of 5% topical tea tree oil gel in mild to moderate
acne vulgaris: A randomized, double-blind placebo-controlled study. Indian J. Dermatol. Venereol. Leprol.
2007, 73, 22–25. [PubMed]
97. Yoon, J.Y.; Kwon, H.H.; Min, S.U.; Thiboutot, D.M.; Suh, D.H. Epigallocatechin-3-gallate improves acne in
humans by modulating intracellular molecular targets and inhibiting P. acnes. J. Investig. Dermatol. 2013,
133, 429–440. [CrossRef]
98. Elsaie, M.L.; Abdelhamid, M.F.; Elsaaiee, L.T.; Emam, H.M. The efficacy of topical 2% green tea lotion in
mild-to-moderate acne vulgaris. J. Drugs Dermatol. 2009, 8, 358–364.
99. Weber, N.; Biehler, K.; Schwabe, K.; Haarhaus, B.; Quirin, K.-W.; Frank, U.; Schempp, C.M.; Wölfle, U.
Hop Extract Acts as an Antioxidant with Antimicrobial Effects against PropionibacteriumAcnes and
Staphylococcus Aureus. Molecules 2019, 24, 223. [CrossRef]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Herbal Topical Treatment

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Herbal Topical Treatment

Uploaded by

Copyright:

Available Formats

biomedicines

Biomedicines 2020, 8, 27; doi:10.3390/biomedicines8020027 www.mdpi.com/journal/biomedicines

2.1. St. John’s Wort (Hypericum perforatum (L.))

2.2. Licorice (Glycyrrhiza glabra (L.))

2.3. Tormentil (Potentilla erecta (L.))

2.4. Bitter Substances

2.5. Evening Primrose (Oenothera biennis (L.))

3.1. Araroba Tree (Vataireopsis araroba (Aguiar) Ducke)

3.2. Lace Flower (Ammi majus(L.) and Ammi visnaga (L.))

3.3. Barberry Bark (Mahonia aquifolium (Pursh) Nutt.)

3.4. Indigo (Baphicacanthus cusia, Brem.)

3.5. Turmeric (Curcuma longa (L.))

3.6. Olibanum (Boswellia Serrata, Triana & Planch.)

3.7. St. John’s Wort (Hypericum perforatum (L.))

4.1. Lemon Balm (Melissa officinalis (L.))

5.1. Birch Bark (Betula spp.)

5.2. Petty Spurge (Euphorbia peplus (L.))

6. Photoprotection and Esthetic Dermatology

6.1. Green Tea (Non-Fermented Camellia sinensis (L.))

6.2. Dyer’s Weed (Reseda luteola (L.))

6.3. Cocoa Tree (Theobroma cacao (L.))

6.5. Citrus Fruits (Citrus spp.)

6.6. Coffee Plants (Coffea spec.)

6.7. Licorice (Glycyrrhiza glabra (L.))

6.8. Pine Bark (Pinus pinaster, Ailton)

6.9. Gotu Kola (Centella asiatica (L.) Urban)

7.1. Birch Bark (Betula spp.)

7.2. Onion (Allium cepa (L.))

8.1. Green Tea (Non-Fermented Camellia sinensis (L.))

8.2. Licorice Root (Glycyrrhiza inflata, Batalin)

8.3. Bitter Wood (Simarouba amara Aubl.)

8.4. Tormentil (Potentilla erecta (L.))

9.1. Tea Tree (Melaleuca alternifolia (Maiden & Betche) Cheel)

9.2. Green Tea (non-fermented Camellia sinensis (L.))

9.3. Hop (Humulus lupulus (L.))

Glycyrrhetinic acid -- Hydrophilic

Ammi visnaga 5-methoxypsoralen

Licochalcone A - Licochalcone A in different B 89

- Lotion with 2% Camellia

You might also like