Article

Whitening effect of α-bisabolol in Asian women subjects

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Abstract

Synopsis: Although skin pigmentation, which results from the production and distribution of melanin in the epidermis, is the major physiological defence against solar irradiation, hyperpigmentation is a common and distressing problem caused by various inflammatory skin disorders, such as eczema, allergic contact dermatitis and irritant contact dermatitis. We evaluated the effects of a preparation containing alpha-bisabolol on pigmented skin of a group of subjects. The effectiveness of the active compound, alpha-bisabolol, in a base-cream preparation for the treatment of pigmented skin was tested on 28 female subjects as follows: the cream was applied once a day to the back for 8 weeks. These same women also applied a vehicle control cream to the pigmented skin. The results were evaluated by clinical and biophysical test methods. After 8 weeks of treatment of the alpha-bisabolol-containing cream, there was significant lightening effect in the pigmented skin for the majority of the subjects who tested the cream.

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... Numerous qualities of the substance include analgesic, antiinflammatory, antibacterial, and stomach protecting properties. [17] More recently, Kim et al [18] investigated the depigmenting properties of alpha-bisabolol and found that the substance suppresses melanogenesis produced by alpha-melanocyte-stimulating hormone by reducing intracellular cyclic adenosine monophosphate concentrations. In a double-blind, vehiclecontrolled trial, Lee et al [17] assessed the effects of alpha-bisabolol on hyperpigmented skin in not. ...
... [17] More recently, Kim et al [18] investigated the depigmenting properties of alpha-bisabolol and found that the substance suppresses melanogenesis produced by alpha-melanocyte-stimulating hormone by reducing intracellular cyclic adenosine monophosphate concentrations. In a double-blind, vehiclecontrolled trial, Lee et al [17] assessed the effects of alpha-bisabolol on hyperpigmented skin in not. The authors found a more pronounced whitening impact compared to the vehicle control using a spectrophotometer as an objective measurement technique. ...
... The authors found a more pronounced whitening impact compared to the vehicle control using a spectrophotometer as an objective measurement technique. [17] The study does, however, have some drawbacks, including the fact that neither the clinical evaluation criteria nor the lightening impact was described. Alpha-bisabolol may be used as an additional therapy for the decrease of hyperpigmentation in light of the in vitro and in vivo skin research. ...
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It can be difficult to cure hyperpigmentation, so a larger toolkit is required to help with the development of topical remedies. Hydroquinone is currently the gold standard for treatment. However, it has been linked to a number of negative side effects, including exogenous ochronosis in those with darker skin, skin irritability, and contact dermatitis. Topical cosmetic-pharmaceutical hybrids known as "cosmeceuticals" contain physiologically active chemicals that may enhance skin appearance. They are becoming more and more common substitutes for conventional agents. Phytochemicals, or molecules produced from plants, are cosmeceuticals that have been found to have a wide range of cellular effects for a number of dermatological conditions. The usefulness of plant-derived substances in treating hyperpigmentation disorders is examined in the most recent clinical research in this study.
... Alpha-bisabolol is a sesquiterpene alcohol found naturally in plants such as Matricaria chamomilla, Eremanthus erythropappus, Smyrniopsis aucheri, Salvia runcinata and Vanillosmopsis species 27 . It is known to possess several properties including anti-inflammatory, analgesic, antibiotic as well as gastric protective properties 28 . The depigmenting effect of alpha-bisabolol is attributed to its ability to inhibit α-MSH-induced melanogenesis by blocking the phosphorylation of cAMP response element-binding (CREB) protein 29 . ...
... Hence, bakuchiol could be a better option to retinol due to its similar efficacy in improving photoageing and hyperpigmentation but better tolerated profiles 31 . Table 1 Major results Study limitations Reference 1) Significant improvement (32%) in the MASI score in the liposomal-AGE treatment group compared with the control group (10%) 1) No placebo control group 2) Subjective assessment 19 1) Significant reduction in MASI scores and average melanin index for both herbal mixture cream and arbutin cream 2) Significant reduction in erythema index for herbal mixture cream 1) Herbs not studied independently 2) Criteria for clinical evaluation was not described 20 1) Improved melasma and decreased melasma severity in both groups receiving parsley and hydroquinone 2) No statistically significant difference between both groups from independent t-test 1) No placebo control group 2) Subjective assessment 3) Parsley was applied brewed while hydroquinone was available as a cream 21 1) Significant improvements in the pigmented spots size and spot colour in both groups 2) Average melanin indices in the subjects were almost unchanged 1) Melasma type not specified 2) Phytochemicals were not studied independently 3) Formulation included licorice root extract, which has known to influence pigmentation 22 1) 66.67% of the subjects had an overall good to excellent response in the reduction of melasma 1) No comparative control group 2) Alpha arbutin was studied in combination with laser treatment 3) Criteria for 5-point scale evaluation was not described 25 1) 66.67% of the subjects had shown an improvement in skin discolourations 2) Improvement in skin discolouration is more noticeable for melasma than lentigo solaris 1) Melasma type not specified 26 1) Significant skin lightening effect which improved over time than the vehicle control measured by spectrophotometer 2) No significant difference between the test and control groups for clinical improvements of the skin colour 1) The amount of cream applied depends on the area of the tested region 2) Criteria for clinical evaluation was not described 28 1) Improved melasma with the use of the depigmentation cream 2) Significant improvement after twice daily application while milder effect after twice weekly application 1) No comparative control group 2) Phytochemicals were not studied independently 30 1) Significant reduction in wrinkle surface area and hyperpigmentation for both bakuchiol and retinol 2) Bakuchiol was better tolerated than retinol 1) No placebo control group 2) The amount of cream applied was not fixed 3) Bakuchiol cream was applied twice while retinol cream was applied nightly 31 ...
Article
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Hyperpigmentation disorders caused by excessive melanin synthesis may significantly affect the psychosocial aspect of an individual. Being the current gold standard used for the treatment of hyperpigmentation disorders, hydroquinone is associated with several adverse effects including skin irritation, contact dermatitis, mutagenic to mammalian cells, cytotoxic to melanocytes as well as exogenous ochronosis in darker-complexioned individuals. Botanically derived agents have received increased attention in treating hyperpigmentation as they are perceived to be milder, safer, healthier and more cost-effective. Several herbs, plant extracts and phytochemicals with multitude mechanisms of action have been reported to be effective depigmenting agents with milder side effects. Some of the agents were studied in combination and their hypopigmentation effects may be resulting from synergistic effects of the various components. Mechanisms involved in depigmentation include tyrosinase inhibition, inhibition of α-melanocyte-stimulating hormone-induced melanogenesis and antioxidant properties. Use of plant-derived agents for the treatment of hyperpigmentation disorders is promising with the need for more rigorous clinical studies to support the use of these agents. This review summarizes the use of various plants and bioactive constituents and their effectiveness in the control of pigmentation.
... The compound has multiple properties, including anti-inflammatory, analgesic, antibiotic, and gastric protective agent. 16 More recently, Kim et al 17 With the assistance of a spectrophotometer as an objective measuring tool, the authors observed a stronger whitening effect in comparison to the vehicle control. 16 However, the study has limitations, as the lightening effect was neither detected during clinical evaluation nor was there a description of the clinical evaluation criteria. ...
... 16 More recently, Kim et al 17 With the assistance of a spectrophotometer as an objective measuring tool, the authors observed a stronger whitening effect in comparison to the vehicle control. 16 However, the study has limitations, as the lightening effect was neither detected during clinical evaluation nor was there a description of the clinical evaluation criteria. Based on the in vitro and in vivo skin studies, alpha-bisabolol may be utilized as an adjunctive therapy for the reduction of hyperpigmentation. ...
Article
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Ashley K Clark,1 Raja K Sivamani2 1University of California, Davis School of Medicine, 2Department of Dermatology, University of California – Davis, Sacramento, CA, USA Abstract: Treating hyperpigmentation can be challenging and an expanded arsenal is needed to aid in the improvement of topical treatments. The current gold standard treatment is hydroquinone. However, it has been associated with a number of adverse effects, including skin irritation, contact dermatitis, and exogenous ochronosis in people of darker complexion. Cosmeceuticals are topical cosmetic-pharmaceutical hybrids containing biologically active ingredients that may improve the appearance of skin and are increasingly popular alternatives to standard agents. Among cosmeceuticals, plant derived compounds, known as phytochemicals, have been shown to have a multitude of cellular actions for various dermatological diseases. This review examines the latest clinical studies using plant-derived compounds and their effectiveness in the management of hyperpigmentation disorders. Keywords: phytochemicals, botanical, hyperpigmentation, melasma, lentigines
... Finally, the improved effect of the active ingredients by increasing the delivery effect was confirmed through an in vitro experiment. Delivery test was further conducted using α-bisabolol, which is a representative depigmenting ingredient [45][46][47]. Aliquots were collected from the delivery experiment and then were incubated with the B16F10 melanoma cells to confirm the depigment effect. ...
Article
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Dermal delivery, which delivers drugs and cosmetics through the skin, has attracted significant attention due to its non-invasive and simple administration compared with oral or injectable administration. However, delivery of the ingredients through the skin barrier is difficult because the primary function of the skin is to protect the human body by preventing the invasion of contaminants. Although various techniques have been developed to overcome skin barriers, chemical toxicity, complicated processes, and expensive equipment still remain as obstacles. Moreover, green chemistry, which minimizes or eliminates the use of toxic chemicals, is required in the cosmetic industry. Thus, the development of a new method for dermal delivery is required. In this study, we provide a new method for dermal delivery using nanobubbles (NBs). NBs generated in oil improve the delivery effect of the active ingredients through the high Brownian motion and charge-balancing effect. Franz cell experiments and depigmentation experiments using the B16F10 melanoma cells were conducted to confirm the enhanced delivery effects. The system using NBs will contribute to the advancement of the dermal delivery of drugs and cosmetics.
... Topical formulations containing niacinamide, tranexamic acid, kojic acid, 1,4-diaminobutane dihydrochloride, and bisabolol were provided for hyperpigmentation and hypertrophic scarring; several clinical trials have supported the use of these ingredients for hyperpigmentation and hypertrophic scarring as they are effective and well-tolerated. [30][31][32][33][34][35][36] Post-procedure, IL triamcinolone acetonide and onabotulinumtoxinA injections of the treated keloid minimized the chance of recurrence. This supports other studies that have shown that IL triamcinolone acetonide injections combined with onabotulinumtoxinA injections provide scar improvement and symptomatic control on keloid recurrence. ...
Article
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Introduction Keloid scars are therapeutically challenging and although many treatment options exist, there are no specific guidelines, and few reports have discussed keloids in the umbilical region. Methods Here, we present a successful treatment of a 31-year-old female with a history of a recurrent keloid in the umbilical region. The keloid was treated using intralesional cryotherapy followed by intralesional onabotulinumtoxinA and triamcinolone acetonide injections. Discussion The patient expressed high satisfaction, minimal side effects, and no recurrence. Conclusion Overall, due to the low rate of side effects, high patient satisfaction, and absence of recurrence, this treatment modality should be considered as an option for umbilical keloids. Lay Summary Background to subject: Keloids are a type of scar that are difficult to treat. There are many treatment options available, but there is no single best treatment for keloids that form around the belly button region. Question being asked: Is intralesional cryotherapy with intralesional onabotulinumtoxinA and triamcinolone acetonide injections effective at treating keloids in the belly button region? How the work was conducted: We treated a 31-year-old female with a keloid around the belly button region that returned after prior treatment. The keloid was treated using combination therapy of freezing the keloid from the inside out, which is called intralesional cryotherapy. This was followed by two types of injections, called onabotulinumtoxinA and triamcinolone acetonide, directly into the keloid. What we learned: Overall, due to the low rate of side effects, high patient satisfaction and the keloid not returning, this treatment plan should be considered as an option for keloids in the belly button region. What we did not learn: This treatment may or may not be effective and safe for all patients of all skin types and demographics as this treatment was performed for only one patient.
... Todos os quadros foram produzidos com as informações que identificam os trabalhos elegíveis para a revisão, tais como: a citação dos autores, data de publicação, título do artigo, base de dados, metodologia, objetivo do estudo e suas respectivas conclusões. Lee et al (2010) faz uso do composto na forma de creme 0.5 %, por um período de 2 meses, em pele de mulheres com quadro de hiperpigmentação. Os resultados sugerem que o terpenóide reduz as discromias, e apresenta vantagens adicionais ao que se refere a custos de produção. ...
Article
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O presente trabalho objetivou identificar e sistematizar obras científicas que atribuem ao alfa-bisabolol (BISA) atividades antiflogísticas. Trata-se de uma revisão bibliográfica, cuja seleção dos artigos foi realizada nas bases de dados PubMed, Web of Science e Science Direct. Para fins de coleta de dados foi utilizado as diretrizes PRISMA e o método de Bardin. A estratégia de pesquisa identificou 257 artigos que após triagem foram elegíveis para a revisão 37. Os critérios de inclusão definidos foram: artigos originais, artigos de revisão, pesquisa experimental, ensaios clínicos, in vitro, in vivo e in silico, estudos de meta-análise, na língua inglesa, espanhola e portuguesa. Somente trabalhos com textos completos, acessíveis e na linha do tempo do estudo (janeiro de 2008 a julho de 2021), foram utilizados. Literaturas em duplicata, pagas e que não se relacionavam com o objetivo da pesquisa, foram excluídas. Em relação a abordagem com temáticas específicas temos que: 22 (59.45 %) artigos se referem aos efeitos anti-inflamatório, antioxidante e analgésico do BISA, 1 (2.70 %) publicação de revisão e 14 (37.83 %) investigam as ações do sesquiterpeno sobre o tecido tegumentar. De todos os estudos selecionados 89.18 % (n=33) foram realizados em ambiente laboratorial e apenas 10.82 % (n=4) utilizaram outra fonte metodológica. Atualmente há poucas evidências que relatam estudos seguros em preparações tegumentares que utilizam o BISA. Entretanto, os estudos disponíveis sobre as ações antiflogísticas do BISA, comprovam sua eficácia anti-inflamatória, analgésica e antioxidante. Sendo assim, os autores consideram que o sesquiterpeno apresenta potencial clínico para ser utilizado em processos inflamatórios de distintas etiologias, porém são necessárias maiores investigações.
... Similar activities were reported for isoimperatorin and imperatorin (Lin et al., 2008), glabridin and liquirtin (Amer & Metwalli, 2000;Yokota et al., 1998), alpha-bisabolol (J. Lee et al., 2010). ...
Article
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Hyperpigmentation of the skin refers to a dermatological condition which alters the color of the skin, making it discoloured or darkened. The treatments for hyperpigmentation disorders often take very long to show results and have poor patient compliance. The first‐line treatment for hyperpigmentation involves topical formulations of conventional agents such as hydroquinone, kojic acid, glycolic acid followed by oral formulations of therapeutic agents like tranexamic acid, melatonin, cysteamine hydrochloride. The second‐line approaches include chemical peels and laser therapy given under the observation of expert professionals. However, these therapies pose certain limitations and adverse effects like erythema, skin peeling and drying and require long treatment duration to show visible effects. These shortcomings of the conventional treatments provided scope for further research on newer alternatives for managing hyperpigmentation. Some of these therapies include novel formulations like solid lipid nanocarriers, liposomes, phytochemicals, platelet‐rich plasma, microneedling. This review focuses on elaborating on several hyperpigmentation disorders and their mechanisms, the current, novel and emerging treatment options for management of hyperpigmentation.
... Penggunaan tabir surya spektrum luas perlu dilakukan selama 2 -3 bulan sebelum dilakukan peeling untuk mengurangi risiko HPI sebagai komplikasi kemudian penggunaan krim retinoid pada malam hari 6 minggu sebelum tindakan dapat membantu proses penyembuhan dan penetrasi dari agen yang digunakan untuk peeling. Akan tetapi, penggunaan tretinoin perlu dihentikan 48 jam sebelum tindakan chemical peels pada individu dengan kulit lebih cerah dan 2 -3 minggu sebelum tindakan pada individu dengan kulit lebih gelap untuk mengurangi risiko efek samping chemical peels seperti hiperpogmentasi, hipopigmentasi, atau bekas luka (Soriano dan Grimes, 2006;Singh-Behl dan Tung, 2009 (Choi et al., 2002;Lee et al., 2010;Boissy et al., 2005;Ertam et al., 2008;Yokota et al., 1998;Huang et al., 2010;Usach et al., 2015;Zubair dan Mujtaba, 2009;Handog et al., 2009;Altaei, 2012;Kanlayavattanakul dan Lourith, 2018;Lee et al., 2002;Leyden dan Wallo, 2011;Lu et al., 1996;Maeda dan Fukuda, 1996;Picardo dan Cerrera, 2007;Chae dan Ha, 2011;Waqas et al., 2015). Senyawa yang menurunkan pigmentasi pada tanaman-tanaman tersebut adalah sebagai berikut: ...
Article
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Hiperpigmnetasi pascainflamasi (HPI) merupakan penggelapan warna kulit yang terjadi setelah inflamasi atau cedera pada kulit. HPI sering terjadi pada warna kulit lebih gelap dan dapat menurunkan kepercayaan diri seseorang. Pengobatan konvensional HPI adalah hydroquinone (HQ) topikal yang sering dikombinasikan dengan retinoid. HQ memiliki efek samping berupa dermatitis, perubahan warna kuku, leukoderma permanen, hipopigmentasi, dan okronosis eksogen sedangkan retinoid memiliki efek samping teratogenik. Senyawa fitokimia pada tanaman dapat digunakan sebagai kosmeseutikal herbal untuk terapi alternatif HPI yang lebih aman karena memiliki efek toksisitas minimal. Beberapa kosmeseutikal herbal yang dapat digunakan di antaranya adalah aloesin pada lidah buaya, alpha-bisabolol pada kamomil, arbutin pada tanaman bearberry, ellagic acid pada teh hijau, stroberi, ceri, walnut, anggur, dan geranium, glabridin pada akar manis, polifenol pada teh hijau dan kedelai, vitamin C, silimarin pada Silybum marianum, procyanidin pada Pinus pinaster dan kacang tanah, dan lektin pada gandum, kacang-kacangan, dan berbagai jenis sayuran.
... Penggunaan krim pemutih untuk dapat memberikan efek memerlukan waktu ±8 minggu (Lee et al. 2010). Durasi pemakaian krim pemutih sebelum terjadi komplikasi bervariasi mulai dari 6-60 bulan (Olumide et al. 2008). ...
Article
Konsep cantik di masyarakat salah satunya memiliki kulit putih dengan cara menggunakan produk pemutih dan pencerah kulit. Namun terdapat sejumlah produk pemutih yang mengandung bahan berbahaya. Pemilihan produk pemutih harus diperhatikan dengan baik dan benar. Tujuan penelitian ini adalah untuk mengetahui pengetahuan dan penggunaan masyarakat mengenai produk pemutih dan pencerah, serta hubungan antara tingkat pendidikan dan pengetahuan masyarakat mengenai produk pemutih dan pencerah. Penelitian dilakukan pada bulan September 2019 menggunakan metode survei, rancangan studi cross sectional dengan teknik purposive random sampling. Responden dalam penelitian adalah wanita berusia 16–35 tahun (n=130). Dari hasil penelitian diperoleh bahwa produk pemutih dan pencerah yang paling banyak digunakan adalah produk komersil teregistrasi BPOM dengan persentase 69,2% (92 responden). Tingkat pendidikan pengguna produk pemutih dan pencerah tertinggi adalah tingkat sarjana dan pascasarjana yaitu dengan persentase 64,6% (84 responden). Rata-rata skor yang didapatkan dari 130 responden adalah 3,8. Sebanyak 87 responden (67%) memiliki skor di bawah 4,6 yang dikategorikan memiliki pengetahuan rendah mengenai produk pemutih dan pencerah. Uji korelasi Spearman menujukkan terdapat hubungan antara tingkat pendidikan dengan pengetahuan responden mengenai produk pemutih dan pencerah (p=0,016). Responden dalam penelitian memiliki tingkat pengetahuan rendah mengenai produk pemutih dan pencerah serta terdapat hubungan antara tingkat pendidikan dengan pengetahuan tentang produk pemutih dan pencerah.
... Millions of people beyond the US partake of creams and lotions to lighten their skin; although, this practice is not as common stateside. [11][12][13][14] Even so, pharmacologists have long been aware that drugs can be used to temporarily or permanently change human skin color. ...
Book
A pharmacologist walks you through the science underlying the tragic death of Michael Jackson, focusing on the specific pharmacology of every drug documented to be found at the death scene or historically prescribed to Jackson for his personal use. This highly detailed and well-researched analysis offers an easy-to-read explanation drugs Jackson was reported to have used and why, each drug’s mechanism of action and potential toxicity, and a thorough scientific discussion of the drug that caused his premature death. Blending pop culture, forensic autopsy data, police reports and trial transcripts with the fascinating science of pharmacology, this book entertains and informs the reader with precision and unflinching accuracy.
... The essential oil of Vanillosmopsis arborea Baker (Asteraceae) is rich in (-)-αbisabolol (BISA) which is known to have an analgesic and anti-inflammatory profile (Leite et al., 2011;Leite et al., 2014;Leite et al., 2017). Studies show that this terpene has mutagenic/antimutagenic activity (Carneiro & Oliveira, 2005), inhibits human P450-containing systems (Ganzera, Schneider & Stuppner, 2006), induces apoptosis in cell signaling pathways (Cavalieri, Bergamini, Mariotto, 2009;Magnelli et al., 2010), heals (Villegas et al., 2001), provides gastroprotection (Torrado, Agis & Jimenez, 1995;Rocha et al., 2010), acts as an antioxidant (Braga, Sasso & Fonti, 2009), acts as a skin whitening agent (Lee et al., 2010), and has antitumor (Silva et al., 2010) and antinociceptive activity (Leite et al., 2011;Leite et al 2014;Leite et al., 2017). The antinociceptive effect related to BISA is associated with the reduction in neuronal excitability, involving central mechanisms of pain modulation (Wood et al., 2004), as well as the inhibition of proinflammatory cytokines and other inflammatory mediators (Leite et al., 2011;Leite et al., 2014;Barreto et al., 2016). ...
Article
Background: Vanillosmopsis arborea Baker has recognized economic value owing to the high content of (-)-α-bisabolol (BISA) in the essential oil of its stem (EOVA). The antinociceptive effect of EVOA has already been demonstrated, and β-cyclodextrin (βCD) is known to improve the analgesic effect of various substances. Purpose: Thus, we aimed to evaluate the orofacial antinociceptive effect of a complex containing EOVA-βCD in rodents. Methods: EOVA was obtained by simple hydrodistillation, and the essential oil was complexed with βCD. The animals (n = 6/group) were treated orally with EOVA-βCD (10 or 50 mg/kg), or vehicle (control), and subjected to cutaneous orofacial nociception (formalin, capsaicin, acidic saline or glutamate), corneal (hypertonic saline) or temporomandibular (formalin) tests. The expression of FOS protein was analyzed in the spinal cord. Molecular docking was performed using the 5-HT3 and M2 receptors and BISA. Results: The oral administration of EOVA-βCD reduced nociceptive behaviour. Moreover, EOVA-βCD decreased FOS expression. The molecular docking study indicates that BISA interacts with 5-HT3 and M2 receptors, indicating the potential mechanism of action of the tested compound. Conclusions: Our results indicate that EOVA-βCD possesses orofacial antinociceptive effect, indicating that this complex can be used in analgesic drug development.
... It also has several other pharmacological properties including analgesic, antibiotic, and anti-cancer activities 10 . Due to its fragrance odour and therapeutic effects, α-bisabolol is widely used in dermatological formulations and cosmetic 11 . DPPH is a stable free radical, which has been widely used for testing the free-radical scavenging activity of antioxidants 12 . ...
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The chemical composition of the essential oil obtained by hydro-distillation method from the aerial parts of Leontopodium longifolium Ling was analyzed by gas chromatography-mass spectrometry (GC-MS). Totally, forty-three compounds constituting 96.90 % of the oil were detected. The predominant constituents in the oil were α-bisabolol (28.37 %) and α-bisabolol oxide B (10.66 %). The essential oil showed relatively low antioxidant activity (IC50 = 8.907 mg/ml) in the 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging assay, and showed weak antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa with inhibition diameters from 11 mm to 13 mm in antimicrobial tests using disc agar diffusion method.
... They have properties like anti-inflammatory, anti-septic, analgesic and antiallergic. U.S. Food and drug administration has also approved this compound as safe and already been used in skin care treatments as moisturizer, sunscreen, anti-aging and eye cream etc. [19]. α-bisabolol has also been used to enhance the percutaneous absorption of some other molecules [20]. ...
Article
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The present study targeted to explore the antimicrobial constituents of Picea smithiana. It's essential oil was analyzed by GC-MS and result showed that it has rich content of monoterpene compounds, and α-pinene (38.82%), β-pinene (7.41%), camphene (7.75%), Beta phellandrene (6.35%), a-bisabolol (5.60%), L-bornyl acetate (3.86%), Limonene (3.80%) and α-salinene (3.30%) were the major components. The results showed that the essential oil exhibited good antibacterial activity against Micrococcus luteus, Bacillus subtilis and Pseudomonas alcaligenes and moderate activity against Alcalygens denitrificans, Campylobacter coli, Enterococcus fecalis and Pseudomonas aeruginosa with zone of inhibition ranging from 6-15mm and significant antifungal activity against Bipolaris specifera and Curvularia lunata with IC 50 value 2.29mg/ml and 2.87mg/ml (w/v) respectively. Whereas, both leaf and bark extracts showed comparatively lower antimicrobial activity against most of the test organisms. Two antimicrobial compounds were isolated from Picea smithiana essential oil by using bioautography, preparative TLC methods and identified as alpha-selinene and alpha-bisabolol and GC-MS analysis.
... (-)-a-Bisabolol (BISA) is a sesquiterpene alcohol found in the essential oil of various plant species, among them Matricaria chamomilla L. and Vanillosmopsis are the important species (Kamatou & Viljoen 2010). This sesquiterpene is widely used as an additive in cosmetic products as anti-irritant creams, after sun lotions (Lee et al. 2010), astringent for the skin care, sunscreens and make-up (Spiegel 2012). Recently, Solov astru et al. (2015) reported that a spray containing ozonated oil and BISA could be a new therapeutic option for the adjuvant treatment of venous ulcers. ...
Article
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Context: (-)-α-Bisabolol (BISA) is a sesquiterpene alcohol widely used as scent in cosmetic preparations, perfumes, shampoos, toilet soaps and other toiletries with potential for use in the pharmaceutical area. Objective: To evaluate the corneal antinociceptive efficacy of BISA and to analyze the best solubilizing agent. Materials and methods: Acute corneal nociception was induced by the local application of hypertonic saline (5 M NaCl; 20 μL) to the corneal surface of Swiss mice (n = 8/group) 60 min after topical treatment with solutions or ointment containing BISA (50–200 mg/mL). The number of eye wipes performed with the ipsilateral forepaw was counted for a period of 30 s. Control groups (vehicles) were included. Results: BISA (50, 100 or 200 mg/mL) solubilized with Tween 80 did not reduce the number of eye wipes. Animals treated with the ointment (BISA 50, 100 or 200 mg/mL; p < 0.001), as well the solution containing propylene glycol (BISA 100 mg/mL; p < 0.05), showed significant reduction in the number of nociceptive behaviours. Solutions containing propylene glycol and isopropyl myristate had no effects. Discussion and conclusion: BISA possess corneal antinociceptive activity. Although the ointment presented antinociceptive effect, it is concluded that BISA when associated with propylene glycol has better potential for corneal nociceptive pain since it is more comfortable to use, leading to greater acceptance by patients.
... It had higher values of glutamic acid (1.88%), leucine (1.64%), aspartic acid (1.46%), alanine (1.18%), tryptophan (1.01%), arginine (1.05%) and lower (Carvalhoa et al., 2011;Laporta and Sallum, 2011). α-Bisabolo (12.96%) has antitumor effects against cancer and a significant lightening effect in the pigmented skin (Seki et al., 2011;Lee et al., 2010). α-Caryophyllene (5.58%) and ...
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Premna ligustroides Hemsl. is a traditional plant food material, but the chemical components, functional ingredients of the leaves and its antioxidant activity of ethanol extracts had never been studied. In this study, the moisture, ash, crude fiber, crude fatty, pectin, and amino acid were 8.95 +/- 0.01, 7.76 +/- 0.06, 7.86 +/- 0.10, 12.93 +/- 0.05, 19.21 +/- 0.02, and 15.26 +/- 0.16 g/100 g dry basis, respectively. Total flavonoids content of leaves was 74.35 +/- 0.49 mg/g. Degree of esterification (DE) of the pectin was 66.67 +/- 1.02%, and the unsaturated fatty acids occupied 64.71% of the total fatty acids, 17 amino acids which contained seven essential amino acids were detected. Fifty eight volatile compounds were separated and identified. The extracted flavonoids had higher reducing power than ascorbic acid at the same concentration, and had significant scavenging abilities on hydroxyl radicals, superoxide anion radical, and DPPH radical. The results indicated that the leaves of P ligustroides Hemsl. as a kind of botanical food has a great value of development and utilization.
... In particular, α-bisabolol, kojic acid, β-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate were selected. These nine molecules are already known in the literature for their action as skin lighteners [13][14][15][16][17] and are present in several commercial products. ...
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Multi-target strategies are directed toward targets that are unrelated (or distantly related) and can create opportunities to address different pathologies. The antidermatophytic activities of nine natural skin lighteners: α-bisabolol, kojic acid, β-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate, were evaluated, in comparison with the known antifungal drug fluconazole, on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Nannizzia cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Arthroderma gypseum, Trichophyton rubrum and Trichophyton tonsurans. α-Bisabolol showed the best antifungal activity against all fungi and in particular; against M. gypseum. Further investigations were conducted on this fungus to evaluate the inhibition of spore germination and morphological changes induced by α-bisabolol by TEM.
... Bisabolol is another antioxidant in the product, which has been shown to reduce skin pigmentation. 36 This together with the other ingredients may be helping in the reduction in mottled hyperpigmentation throughout the study. ...
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Background: Cumulative lifetime sun exposure is accepted as having a very important role to play in the expression of the signs of photoaging, which is then superimposed on the intrinsic processes involved in the chronological aging of skin. Many groups have evaluated the effects of emulsion-based products, mostly although not exclusively, on the face using a variety of actives including retinoids and antioxidants. Nevertheless, the effect of a topical anhydrous product on photodamaged skin has not been reported in the literature. Aims: The objective of this study was to clinically evaluate the effect of a vitamin A palmitate and antioxidant-containing oil-based moisturizer on facial, neck, decolletage, arms, and lower leg body sites. Methods: In a randomized, controlled and efficacy grader-blinded clinical study conducted over 12 weeks, while at the same time recording the changes in skin condition for a no-treatment group over the same time period, live clinical expert grading of all body sites and also grading of photographs for the face and neck assessed changes in the signs of photodamage was performed for the treatment and no-treatment groups. Results: Compared to the no-treatment group, and to baseline, the oil improved fine lines, coarse wrinkles, mottled pigmentation, uneven skin tone, roughness, firmness, and clarity of the skin on the face and neck and was also shown to improve crepey skin texture, dryness, scaling and roughness on the decolletage, arms and lower legs at the primary end point at 12 weeks (P < 0.001). Moreover, improvements in a variety of parameters were observed as quickly as 2 weeks. In general, the degree of improvement was greatest in the order legs > arms > decolletage > face > neck. Conclusions: Collectively, these results show the cumulative improvements in the signs of photoaging compared to a no-treatment control group for the oil-based antiaging moisturizer for the first time. The differences in the efficacy of the vitamin A palmiate and antioxidant oil-based moisturizer on different body sites probably reflect the differences in likely photodamage.
... In particular, a-bisabolol decreases intracellular cAMP levels requisite for CREB activation, which in turn downregulates the expression of the MITF or tyrosinase gene . Moreover, a-bisabolol reduces UV irradiation-induced skin pigmentation of Asian women (Lee et al., 2010). In the current study, BISA did not affect the cAMP levels in a-MSH-activated melanocytes but inhibited cAMP-induced PKA activation in cells. ...
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Microphthalmia-associated transcription factor (MITF) is inducible in response to cAMP and has a pivotal role in the melanocyte-specific expression of tyrosinase for skin pigmentation. Here we suggest that the cAMP-binding site of protein kinase A (PKA) is a target in the inhibition of the melanogenic process in melanocytes, as evidenced from the molecular mechanism of small molecules such as bisabolangelone (BISA) and Rp-adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS). BISA is a sesquiterpene constituent of Angelica koreana, a plant of the Umbelliferae family, whose roots are used as an alternative medicine. BISA competitively inhibited cAMP binding to the regulatory subunit of PKA and fitted into the cAMP-binding site on the crystal structure of PKA under the most energetically favorable simulation. In α-melanocyte-stimulating hormone (α-MSH)-activated melanocytes, BISA and Rp-cAMPS nullified cAMP-dependent PKA activation, dissociating catalytic subunits from an inactive holoenzyme complex. They resultantly inhibited cellular phosphorylation of the cAMP-responsive element-binding protein (CREB) or another transcription factor SOX9, thus downregulating the expression of MITF or the tyrosinase gene with decreased melanin production. Taken together, this study defined the antimelanogenic mechanism of BISA or Rp-cAMPS with a notable implication of the cAMP-binding site of PKA as a putative target ameliorating melanocyte-specific hyperpigmented disorder.Journal of Investigative Dermatology advance online publication, 20 December 2012; doi:10.1038/jid.2012.425.
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Background: The current ISO guidelines for minimal erythema dose (MED) determination require assessment of erythema area of UV-irradiated skin sites. However, this parameter has not been adequately quantified in daily practice. The aims of this study were to investigate the dose response on the unprotected skin sites by quantifying the erythema area and intensity and to show the potential for improving the precision and consistency of MEDu determination by developing predictive models. Methods: Standard radiation tests were conducted on the back of 31 healthy Chinese volunteers and the MEDu site of each subject was clinically determined by dermatologists. Images of test sites were captured 24 h after radiation, and the erythema area (%EA) and intensity (∆a*) were measured by image analysis. The data were fitted to a logistic 3P function to obtain dose-response curves, and a set of logit (inverse-logistic) models were then derived. An erythema area threshold of %EA = 52% was established to predict MEDu based on the clinical endpoints defined by ISO 24444:2019. Results: Analysis of the clinically determined MEDu sites revealed wide ranges of %EA (62.3 ± 15% SD) and ∆a* (2.96 ± 0.92 SD). The dose response fitted well to a logistic 3P model (mean R2 = 0.965 and 0.975 for %EA and ∆a*, respectively). Applying the area threshold, values of MEDu were determined by the logit model for the test population, which significantly improved the consistency of MEDu determination (52 ± 0% SD and 2.73 ± 0.61 SD for %EA and ∆a*, respectively). Conclusion: This study demonstrated that the dose response of UV-induced erythema can be quantified and modeled once the erythema area and intensity are measured. The results of this study show the potential to improve the precision and consistency of MEDu determination in an SPF test. The similar potential in photodermatological, therapeutic, and diagnostic applications was also implied.
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Background Melasma is a common disorder of hyperpigmentation that affects populations globally and can adversely affect quality of life. Topical therapies—including hydroquinone and nonhydroquinone‐containing formulations—play a central role in the management of melasma. Methods A literature review was conducted using PubMed and Google Scholar. Search keywords included a combination of the following: “melasma,” “chloasma,” and “topical treatment.” We identified and included seminal and high‐quality peer‐reviewed publications, systematic reviews, randomized controlled trials, case series, case reports, consensus statements, and expert opinions. Results Topical therapies are widely used for the treatment of melasma. Triple combination cream containing hydroquinone, fluocinolone, and tretinoin is the most studied formulation with the strongest evidence among treatment options. Numerous other prescription‐based and nonprescription topical agents, including a growing list of cosmeceuticals, have been used in the treatment of melasma, albeit in smaller studies. Conclusion A growing range of topical agents is available for the treatment of melasma. While larger, more robust studies are warranted, nonhydroquinone cosmeceuticals may be useful adjuncts or alternatives to the gold standard of triple‐combination hydroquinone cream.
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Background: Topical measures are the mainstay treatment of postinflammatory hyperpigmentation (PIH). Numerous studies have assessed the efficacy of topical medications for the treatment of PIH, but few have evaluated the quality of evidence supporting these topical therapies. We performed a systematic review to evaluate the evidence of topical treatments for PIH. Methods: We included English-language studies that evaluated topical medications for PIH. We searched PubMed, MEDLINE, and EMBASE from conception to 29th March 2021. We used the modified Grading of Recommendations, Assessment, Development and Evaluation scale (GRADE) scale to assess quality of evidence. Results: Forty-seven of 1224 studies with 1853 subjects were included. Topical agents with high-quality studies included retinoids, hydroxy acids, corticosteroids, thiamidol, niacinamide and plant-derived products. Sunscreens with SPF30 or greater was recommended in almost every study. Common side effects included desquamation, burning, stinging, dryness, and pruritus. Conclusions: Retinoids, hydroxy acids and broad-spectrum sunscreen were supported by the greatest number of high-quality studies. Ongoing inflammation may be subtle, especially in darker skin phenotypes. Herein, we proposed an evidence-based algorithm for PIH based on the high-quality studies. There is a need to adopt a validated outcome measure for PIH to better compare efficacy between various treatments in future studies.
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Background: Melanin protects against the harmful effects of ultraviolet irradiation to the mammalian skin. However, melanin overproduction causes several esthetic problem like a melasma, freckle, age spot and chloasma. So, the development of anti-melanogenic agents is important for the prevention of serious hyperpigmentation diseases. Methods: This study evaluated the anti-melanogenic effect of sesamolin, a lignan compound isolated from sesame seeds, on melanogenesis induced by 3-isobutyl-1-methylxanthine in B16F10 melanoma cells using zymography, tyrosinase inhibitory activity, western blot, and reverse transcription polymerase chain reaction analysis. Also, docking simulations between sesamolin and tyrosinase were performed using Autodock vina, and the skin irritancy of sesamolin was predicted by quantitative structure-activity relationship (QSAR) analysis. Results: Sesamolin significantly inhibited the expression of melanogenesis-related mRNA levels, as well as proteins such as tyrosinase and tyrosinase-related proteins 1 and 2. Sesamolin inhibitory activity was dose-dependent, and 50 µM sesamolin demonstrated the strongest competitive inhibition against intercellular tyrosinase and melanin synthesis without exerting cytotoxic effects. Tyrosinase docking simulations revealed that sesamolin (-6.5 kcal/mol) bound to the active site of tyrosinase more strongly than the positive control (arbutin, -5.7 kcal/mol). Conclusion: Sesamolin is a good candidate for melanogenic inhibition. However, sesamolin was predicted as a weak sensitizer by Derek EC3 prediction. It is necessary to confirm the safety of sesamolin as a cosmetic material in a biological skin toxicity experiment.
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Knowledge about soil moisture dynamics and their relation with rainfall, evapotranspiration, and soil physical properties is fundamental for understanding the hydrological processes in a region. Given the difficulties of measurement and the scarcity of surface soil moisture data in some places such as Northeast Brazil, modelling has become a robust tool to overcome such limitations. This study investigated the dynamics of soil water content in two plots in the Gameleira Experimental River Basin, Northeast Brazil. For this, Time Domain Reflectometry (TDR) probes and Hydrus-1D for modelling one-dimensional flow were used in two stages: with hydraulic parameters estimated with the Beerkan Estimation of Soil Transfer Parameters (BEST) method and optimized by inverse modelling. The results showed that the soil water content in the plots is strongly influenced by rainfall, with the greatest variability in the dry-wet-dry transition periods. The modelling results were considered satisfactory with the data estimated by the BEST method (Root Mean Square Errors, RMSE = 0.023 and 0.022 and coefficients of determination, R 2 = 0.72 and 0.81) and after the optimization (RMSE = 0.012 and 0.020 and R 2 = 0.83 and 0.72). The performance analysis of the simulations provided strong indications of the efficiency of parameters estimated by BEST to predict the soil moisture variability in the studied river basin without the need for calibration or complex numerical approaches.
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UV radiation (UV) is considered as a complete carcinogen as it is both a mutagen and a non-specific damaging agent. It is the most important risk factor for skin cancer and many other skin disorders like Hyperpigmentation. There is a need of long-term topical skin care treatments (both cosmetic and cosmeceutical) to address problems associated with hyperpigmentation. Synthetic depigmenting agents, such as hydroquinone, mequinol, although highly effective, can raise several safety concerns (for example, ochronosis, cataract, impaired wound healing, desquamation, and other local or systemic side effects) with long-term exposure. The benefits of phytochemicals and natural extracts offer opportunities to develop new formulations to treat pigmentation problems. Cosmeceuticals are topical cosmetic-pharmaceutical preparations containing active ingredients which improve the appearance of skin. Among cosmeceuticals, the phytochemicals have been known to have a multitude of cellular actions for various dermatological diseases. Plant-derived compounds and their effectiveness in the treatment of hyperpigmentation disorders (Melasma) are discussed. Keywords: UV radiation, Hyperpigmentation, Phytochemicals, Cosmeceuticals
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Hyperpigmentation of skin is caused by several factors. UV exposure, in addition to oxidative stress elevates inflammatory mediators stimulating melanogenesis. Herbal derived compounds for improving skin lightness are gaining interest as they are perceived to be milder, safer and healthier than fully synthetic products. This review briefly addresses the causes of skin hyperpigmentation and extensively summarizes the status of herbs currently used in skin lightening cosmetics. The properties of active compounds and their dose rate information is summarized where available, along with human or anamial relevant models for activity testing. This review will be of value to cosmetic formulators and dermatologists who are searching for naturally-derived ingredients for improving skin lightness, in line with consumer preference and expectations.
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Skin color varies among ethnic groups on accounts of genetic background. Within an ethnic group, skin color may also vary according to geographical environments and sun exposure habits. While many reports address skin color differences between ethnic groups, few have compared skin color within as ethnic group. To compare skin color characteristics according to differences in latitude including UV exposure between two Asian populations (Korean and Cantonese [Chinese]). We included 461 healthy female subjects: 317 Korean (age 42.3 ± 7.16) and 144 Cantonese (age 41.5 ± 11.2). Skin phototypes were classified according to the Fitzpatrick classification, and back skin color measured using the Minolta colorimeter. We evaluated the lightness (L*), yellowish (b*) value, individual typology angle (ITA°), and minimal erythema dose (MED). Fitzpatrick phototype ratios were similar in Korean (II: 19.9%, III: 78.9%) and Cantonese (II: 27.1%, III: 72.9%). However, the L* (68.47 ± 2.66 vs. 66.44 ± 2.47), ITA° (41.80 ± 5.51 vs. 40.20 ± 5.79), and b* (20.56 ± 1.71 vs. 19.28 ± 1.97) were significantly higher in Korean than in Cantonese. Korean had a significant lower MED than Cantonese (22.33 ± 2.89 vs. 23.38 ± 6.04). Subjective phototype self-assessment showed similar results in Korean and Cantonese. However, objective skin color parameters differed between the two populations. Koreans, who live at a higher latitude and get relatively little sun exposure, have lighter skin color than the Cantonese and burn easily upon UV exposure. © 2015 Wiley Periodicals, Inc.
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Cellulite is a serious cosmetic concern for most of the 90% of women affected by it. To assess the clinical efficacy of a complex integral anti-cellulite gel. This double-blind, randomized, placebo-controlled study involved 44 healthy women, aged 25-55 years. Subjects had a normal to slightly overweight body mass index and presented slight to moderate cellulite on their thighs, buttocks, and/or hips at baseline. Subjects were randomly assigned to either the treated or placebo group and accordingly applied the active product or placebo on their hips, stomach, buttocks, and thighs, twice daily for 3 months. Skin tonicity, orange-peel aspect, and stubborn cellulite were assessed at day 0, 28, 56, and 84. A self-evaluation questionnaire was completed by all volunteers. At the end of the study, an average of 81% of the subjects applying the active product presented improvement in their cellulite condition versus 32% for the placebo group (all descriptors and sites combined). At day 84, skin tonicity, orange-peel appearance, and stubborn cellulite were improved in a significant manner (P<0.05) over placebo, on all studied areas. Skin tonicity improved on average by +41% for buttocks, +35% for hips, and +31% for thighs. Orange peel appearance was reduced on average by -25% for buttocks, -22% for hips, and -22% for thighs. Stubborn cellulite was reduced on average by -19% for buttocks, -24% for hips, and -22% for thighs. Circumference measurements decreased in a significant manner (P<0.05) over placebo, for the abdomen (average value of -1.1 cm) and thighs (average value of -0.8 cm). The product was well tolerated and perceived by the volunteers themselves as better performing than placebo on all criteria. All results validate the efficacy of the present integral formulation to significantly reduce signs of cellulite and reshape the silhouette.
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Hyperpigmentation disorders are common among those seeking care from dermatologists and primary care physicians. The cosmeceutical and natural product industries are rapidly growing and many botanical agents are purported to improve hyperpigmentation disorders. We sought to review clinical evidence for the use of botanical agents in the treatment of hyperpigmentation. We searched MEDLINE and Embase databases and a total of 26 articles met inclusion criteria. Study methodology was analyzed and the reproducibility of the studies was graded. Several botanical agents appear promising as treatment options but few studies were methodologically rigorous. Several plant extract and phytochemicals effectively lighten signs of epidermal melasma and hyperpigmentation induced by ultraviolet radiation exposure. Results were mixed for treatment of solar lentigines or dermal hyperpigmentation. There were few rigorously designed studies; future research will be critical to further ascertain the discussed results. The subtype of hyperpigmentation is important for treatment prognosis, with dermal hyperpigmentation less responsive to treatment. Botanical extracts may play an integrative role in the treatment of hyperpigmentation and further studies that integrate them with standard therapies are needed. Side effects, including worsened hyperpigmentation, need to be discussed when considering these therapies.
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The number of skin cancers continues to rise, accounting for approximately 40% of all cancers reported in the United States and approximately 9,500 deaths per year. Studies have shown reactive oxygen species (ROS) type free radicals are linked to skin cancer and aging. Therefore, it is important for us to identify agents that have anti-oxidant properties to protect skin against free radical damage. The purpose of this research is to investigate the anti-oxidant properties of bisabolol, silymarin, and ectoin that are components from chamomile, milk thistle, and halophilic bacteria, respectively. We measured the ability of bisabolol, silymarin, and ectoin to modulate the hydrogen peroxide (H2O2)-induced upregulation of ROS free radicals in normal human skin fibroblasts in vitro. Using a flow cytometry-based assay, we demonstrated that varying concentrations of these natural components were able to inhibit upregulation of H2O2-generated free radicals in human skin fibroblasts in vitro. Our results indicate components of chamomile, milk thistle, and halophilic bacteria exhibit anti-oxidant capabilities and warrant further study in clinical trials to characterize their anti-cancer and anti-aging capabilities. J Drugs Dermatol. 2013;12(7):780-784.
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Irregular skin pigmentation may be a substantial contributor to the signs of aging and to a person's lack of psychological well-being. Although a large number of skin-lightening agents are available, the opportunity exists to identify more efficacious agents, agents that target alternative biological mechanisms. Aims: To provide clinical evidence of the skin-lightening effect of the tetrapeptide, Pro-Lys-Glu-Lys (PKEK), on subjects with skin types V-VI living in South Africa. Pro-Lys-Glu-Lys was evaluated in a double-blind and vehicle-controlled clinical study using expert grading of digital images by comparing its effects in subjects with skin types V-VI suffering from facial melasma and postinflammatory hyperpigmentation. This study demonstrated the efficacy of PKEK on subjects with skin types V-VI. On comparing the two treatments, the skin-lightening peptide-containing formulation was significantly superior to the vehicle at 12 weeks on overall appearance (P < 0.05) and evenness of skin tone (P < 0.01). The tetrapeptide, PKEK, has proven skin-lightening benefits on skin discoloration from melasma and postinflammatory hyperpigmentation. These studies have been conducted on subjects with skin types V-VI living in South Africa, but we believe this technology to be suitable for all racial groups.
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Many modalities of treatment for acquired skin hyperpigmentation are available including chemical agents or physical therapies, but none are completely satisfactory. Depigmenting compounds should act selectively on hyperactivated melanocytes, without short- or long-term side-effects, and induce a permanent removal of undesired pigment. Since 1961 hydroquinone, a tyrosinase inhibitor, has been introduced and its therapeutic efficacy demonstrated, and other whitening agents specifically acting on tyrosinase by different mechanisms have been proposed. Compounds with depigmenting activity are now numerous and the classification of molecules, based on their mechanism of action, has become difficult. Systematic studies to assess both the efficacy and the safety of such molecules are necessary. Moreover, the evidence that bleaching compounds are fairly ineffective on dermal accumulation of melanin has prompted investigations on the effectiveness of physical therapies, such as lasers. This review which describes the different approaches to obtain depigmentation, suggests a classification of whitening molecules on the basis of the mechanism by which they interfere with melanogenesis, and confirms the necessity to apply standardized protocols to evaluate depigmenting treatments.
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The first mouse microphthalmia transcription factor (Mitf ) mutation was discovered over 60 years ago, and since then over 24 spontaneous and induced mutations have been identified at the locus. Mitf encodes a member of the Myc supergene family of basic helix-loop-helix zipper (bHLH-Zip) transcription factors. Like Myc, Mitf regulates gene expression by binding to DNA as a homodimer or as a heterodimer with another related family member, in the case of Mitf the Tfe3, Tfeb, and Tfec proteins. The study of Mitf has provided many insights into the biology of melanocytes and helped to explain how melanocyte-specific gene expression and signaling is regulated. The human homologue of MITF is mutated in patients with the pigmentary and deafness disorder Waardenburg Syndrome Type 2A (WS2A). The mouse Mitf mutations therefore serve as a model for the study of this human disease. Mutations and/or aberrant expression of several MITF family member genes have also been reported in human cancer, including melanoma (MITF), papillary renal cell carcinoma (TFE3, TFEB), and alveolar soft part sarcoma (TFE3). Genes in the MITF/TFE pathway may therefore also represent valuable therapeutic targets for the treatment of human cancer. Here we review recent developments in the analysis of Mitf function in vivo and in vitro and show how traditional genetics, modern forward genetics and in vitro biochemical analyses have combined to produce an intriguing story on the role and actions of a gene family in a living organism.
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The number of known mono-, di- and sesquiterpenoids has increased explosively in recent years. While the chemistry of certain monoterpenes and isoprene occupied some of the ablest chemists for many years and led to the foundation of modern organic chemistry (Ruzicka, 1959), the chemistry of cyclopentanoid monoterpenes, sesquiterpenes and diterpenes could not be resolved adequately by classical methods and required the development of newer analytical techniques, especially gas chromato-graphy-mass spectrometry (GC-MS), infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy (Loomis and Croteau, 1973).
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IntroductionClassification and PathophysiologyDiagnosis of Melanin Pigmentary Disorders
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Summary Background Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun-exposed areas of the skin. Its histopathological characteristics are not fully understood. Objectives To characterize the histopathological features of facial melasma skin in comparison with adjacent normal skin. Methods Biopsies were taken from both melasma lesional skin and adjacent perilesional normal skin in 56 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana–Masson, diastase-resistant periodic acid-Schiff, Masson trichrome and Verhoeff–van Gieson stains, and immunostaining for melanocytes. Data on the changes in number of melanocytes and melanin contents of the epidermis were analysed by a computer-assisted image analysis program. The ultrastructure of the skin was also examined. Results The amount of melanin was significantly increased in all epidermal layers in melasma skin. The staining intensity and number of epidermal melanocytes increased in melasma lesions. Lesional skin showed more prominent solar elastosis compared with normal skin. Melanosomes increased in number and were more widely dispersed in the keratinocytes of the lesional skin. Lesional melanocytes had many more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in their cytoplasm. A dihydroxyphenylalanine reaction was apparent in the cisternae and vesicles of the trans-Golgi network in melanocytes from lesional skin. Conclusions Melasma is characterized by epidermal hyperpigmentation, possibly caused both by an increased number of melanocytes and by an increased activity of melanogenic enzymes overlying dermal changes caused by solar radiation.
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Mutations in the mouse microphthalmia (mi) gene affect the development of a number of cell types including melanocytes, osteoclasts and mast cells. Recently, mutations in the human mi gene (MITF) were found in patients with Waardenburg Syndrome type 2 (WS2), a dominantly inherited syndrome associated with hearing loss and pigmentary disturbances. We have characterized the molecular defects associated with eight murine mi mutations, which vary in both their mode of inheritance and in the cell types they affect. These molecular data, combined with the extensive body of genetic data accumulated for murine mi, shed light on the phenotypic and developmental consequences of mi mutations and offer a mouse model for WS2.
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(--)-alpha-Bisabolol has a primary antipeptic action depending on dosage, which is not caused by an alteration of the pH-value. The proteolytic activity of pepsin is reduced by 50 percent through addition of bisabolol in the ratio of 1/0.5. The antipeptic action of bisabolol only occurs in case of direct contact. In case of a previous contact with the substrate, the inhibiting effect is lost.
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TYROSINASE activity is greatly enhanced in cultured Cloudman S91 melanoma cells following addition of melanocyte-stimulating hormone (MSH) to the culture medium1. The increased activity occurs in the G2 phase of the cell cycle2 because membrane receptors for MSH are available only in this phase3. The response to MSH is mediated through cyclic AMP (refs 1-4). It is well documented that many peptide hormones function by activating membrane-bound adenyl cyclase molecules, causing net increases in intracellular cyclic AMP concentrations. These increases in turn have profound effects on cell division, morphology, and the expression of differentiated functions in a wide variety of cells and tissues. Little is known, however, about the levels at which genetic expression is regulated or the molecular intermediates involved in the regulation. For example, it is generally assumed that cyclic AMP-dependent protein kinases are involved in many of the responses because most tissues contain such enzymes5. The regulation of glycogenolysis is the best known example supporting this assumption6-7. But it cannot be taken as fact that in eukaryotes all cyclic AMP-mediated processes are post-translational in nature.
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The intracellular signal pathways that mediate pigmentation in human skin are unknown. We now report that a diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-glycerol (OAG) 25-100 microns strikingly increased the melanin content of cultured human melanocytes in a dose dependent manner without altering growth rate. The pigment increase occurred within 24 h, was accompanied by increased incorporation of the melanin precursor L-3,4-dihydroxyphenyl alanine (DOPA), required new protein synthesis, and was completely blocked by the protein kinase C (PKC) inhibitors H-7 and sphingosine. A PKC-inactive DAG isomer had no effect on melanin per cell. These results implicate protein kinase C and its effector DAG in melanogenesis.
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In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.
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Rabbit anti-tyrosinase antibodies were used to study the abundance, processing, and degradation of tyrosinase in murine (Cloudman) melanoma cells. The polyclonal antibodies precipitated low-molecular-weight (68,000 and 70,000) and high-molecular-weight (78,000 and 80,000) tyrosinases that had a precursor-product relationship. Cells with high basal tyrosinase activity had high levels of newly synthesized tyrosinase. Cells with low tyrosinase activity synthesized less tyrosinase and degraded the enzyme at a faster rate than cells with high tyrosinase activity. Melanotropin (melanocyte stimulating hormone), dibutyryl cyclic adenosine monophosphate, and isobutylmethylxanthine caused an increase in the abundance of newly synthesized tyrosinase that was directly proportional to the increase in enzyme activity. This enzyme was not a phosphoprotein. Other changes in the culture conditions that increased the level of tyrosinase activity increased the abundance of newly synthesized enzyme. It is thus concluded that the level of tyrosinase activity in Cloudman melanoma cells is a direct reflection of the abundance of enzyme protein.
Article
Although melanocyte stimulating hormone (MSH) peptides are known to stimulate pigmentation in man, previous reports suggest that human melanocytes are relatively unresponsive to these peptides in vitro. This may be related to the conditions under which the melanocytes were cultured. Thus, we have re-investigated the in vitro effects of MSH peptides using human melanocytes cultured in the absence of artificial mitogens. Human melanocytes were incubated with alpha-MSH or its potent analogue Nle4Dphe7 alpha-MSH for 3 days. After 18 hours, melanocyte morphology had evolved from mainly bipolar to dendritic in approximately 66% of cultures. Nle4DPhe7 alpha-MSH produced dose-related increases in both tyrosinase activity and melanin content although the degree of response was variable and tyrosinase activity was the relatively more responsive to the peptide. Similar results were obtained with alpha-MSH, but, although the effect on melanin content was similar to that of Nle4DPhe7 alpha-MSH, the effect on tyrosinase activity was less marked. The preliminary EC50 values for the actions of the MSH peptides suggest that they may be equipotent in their actions on human melanocytes. In addition, we have demonstrated that the common melanocyte mitogens 12-O-tetradecanoyl phorbol-13-acetate (TPA) and cholera toxin affect basal melanogenesis and modulate the effects of the MSH peptides. However, not all melanocyte cultures showed melanogenic responses to the MSH peptides. Ability to respond was unrelated to basal levels of tyrosinase activity or melanin content. In at least some cultures, morphological and melanogenic responses appear to be independent of one another.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Mice with mutations at the microphthalmia (mi) locus have some or all of the following defects: loss of pigmentation, reduced eye size, failure of secondary bone resorption, reduced numbers of mast cells, and early onset of deafness. Using a transgenic insertional mutation at this locus, we have identified a gene whose expression is disrupted in transgenic animals. This gene encodes a novel member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein family of transcription factors, is altered in mice carrying two independent mi alleles (mi and miws), and is expressed in the developing eye, ear, and skin, all anatomical sites affected by mi. The multiple spontaneous and induced mutations available at mi provide a unique biological resource for studying the role of a bHLH-ZIP protein in mammalian development.
Article
In B16 melanoma cells, cAMP-induced melanogenesis is inhibited by the tumor promoting phorbol ester, TPA. However, the role of PKC activation or depletion in the inhibition of melanogenesis by TPA remains controversial. In this report, using specific PKC inhibitors, we demonstrated that PKC inhibition does not impair cAMP-induced melanin synthesis and tyrosinase expression. Further, the inhibition of melanogenesis by TPA results from a decrease of the tyrosinase promoter transcriptional activity and this effect is mimicked by over-expression of a constitutively active form of PKC alpha. These findings clearly demonstrate that PKC activation accounts for the inhibition of melanin synthesis by TPA. Additional experiments were undertaken to elucidate the mechanism by which TPA inhibits the tyrosinase gene transcription. Deletions and mutation in the tyrosinase promoter showed that TPA acts on a M-box which is involved in tissue-specific expression and regulation by cAMP of the tyrosinase gene. We showed that TPA decreases the binding of microphthalmia, a basic helix-loop-helix transcription factor, to the M-box. Since microphthalmia, strongly stimulates the transcriptional activity of the promoter we propose that TPA, through PKC activation, decreases microphthalmia binding to the M-box of the tyrosinase promoter, thereby leading to a reduced tyrosinase expression and melanogenesis inhibition.
Article
The enormous variety of pigmentation phenotypes in nature reflects a series of remarkable events that begin in the neural crest and end with the manufacture and distribution of pigment by mature melanocytes located in the epidermis and hair follicles. While the origins of melanoblasts from multipotent precursors in the neural crest is striking in itself, yet more so is the fact that these pioneer melanoblasts manage to undertake and survive their long migration, and in doing so proliferate and maintain their identity before ultimately arriving at their destination and undergoing differentiation. With the application of the powerful combination of genetics and molecular and cell biology the mystery surrounding the genesis of the melanocyte lineage is slowly being unravelled. At its heart is the powerful alliance between signal transduction and transcription that coordinates the program of gene expression that confers on a cell its identity, provides its passport for migration, and instructs it in the arts of survival and timely reproduction. The realization that the proliferation and migration of melanoblasts during development resembles closely the proliferation and metastasis of melanoma, a highly dangerous and increasingly common cancer, serves to highlight the value of the melanocyte system as a model for addressing key issues of general significance in both development and cancer.
Article
In mammalian melanocytes, melanin synthesis is controlled by tyrosinase, the critical enzyme in the melanogenic pathway. A recent report showed that the stimulation of melanogenesis by glycyrrhizin (GR) is because of an increased tyrosinase expression at mRNA and protein levels. But, the molecular events of melanogenesis induced by GR remain to be elucidated. In this study, using B16 melanoma cells, we showed that GR activated activator protein-1 (AP-1) and cyclic response filament "CRE" promoters, but not the nuclear factor-kappaB promoter. In addition, although GR stimulated mitogen-activated protein (MAP) kinase, p42/44(mapk), consistent with GR-induced AP-1 promoter activation, GR-induced melanogenesis was not blocked by PD98059, an MEK1 inhibitor, suggesting that MAPkinase induced by GR does not have a direct effect on the level of melanin content. But, GR-induced melanogenesis was inhibited by an inhibitor of protein kinase A (H-89). This result was further confirmed by the fact that GR induced the phosphorylation of CRE binding protein (CREB) and inhibition of glycogen synthase kinase 3beta phosphorylation as well as the production of cAMP, indicating that GR induces melanogenesis through cAMP signaling. In addition, the fact that GR-induced CRE activation was blocked by H-89 but GR-induced increase of cAMP production was not suggests that GR operates upstream of protein kinase A.
Article
Melanogenesis is one of the characteristic functional activities of melanocyte/melanoma and is regulated via mitogen-activated protein kinase (MAPK) and Akt/protein kinase B (PKB) pathways. Placental total lipid fraction (PTLF), prepared from a hydroalcoholic extract of fresh term human placenta contains sphingolipids and was recently shown to stimulate melanogenesis via up-regulation of the key enzyme tyrosinase in B16F10 mouse melanoma cells. How such lipids mediate their effects on pigmentation and tyrosinase expression is a particularly important aspect of melanogenesis. To study the signaling that leads to tyrosinase expression, we have investigated the roles of the MAPK and Akt/PKB pathways in B16F10 melanoma cells in melanogenesis in response to PTLF. Treatment of cells with PTLF led to the time dependent phosphorylation of p38 MAPK. SB203580, a p38 MAPK inhibitor, completely blocked the PTLF-induced melanogenesis by inhibiting promoter activity and subsequent expression of tyrosinase. Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 a blocker of the Akt signaling pathway, or an inhibitor of MEK (MAPK/ERK Kinase), PD98059 when included along with PTLF was found to potentiate PTLF-induced phosphorylation of p38 MAPK together with tyrosinase expression and melanogenesis. The results suggest that the activation of p38 MAPK plays a crucial role in PTLF-induced B16F10 melanogenesis by up-regulating tyrosinase expression.
The Authors Journal compilation ª 2010 Society of Cosmetic Scientists and the Société Française de
ª 2010 The Authors. Journal compilation ª 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie International Journal of Cosmetic Science, 32, 299–303
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