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    Bakuchiol and astaxanthin:a new weapon for sun protection?

    2022-10-02 02:26:15DominaPetric
    Food and Health 2022年3期

    Domina Petric

    1 Department of Clinical pharmacology and toxicology,University Hospital Center Split,Split,Croatia.

    Background

    Exposure to sunlight must be very well balanced because on the one hand,it is essential for the production of vitamin D,but on the other hand,it can be very harmful to the skin (increased risk for skin carcinogenesis and accelerated photoaging).Exposure to ultraviolet B radiation is a significant determinant of vitamin D status.During exposure to sunlight,the solar UVB photons (290-315 nm) are absorbed by 7-dehydrocholesterol in the skin and converted to previtamin D(3),which then undergoes a rapid transformation within the plasma membrane to vitamin D(3).During the winter at latitudes above circa 35 degrees,there is a minimal previtamin D(3)production in the skin [1].Because of that,the prophylactic intake of vitamin D as a pharmacological preparation during the winter at latitudes above 35 degrees is beneficial.Vitamin D status is not only determined by exposure to UVB and limited sources in food,but small effects of polymorphisms in the genes for key proteins involved in vitamin D production and metabolism are also present.The halflife of 25(OH)D is affected by calcium intake.Fat tissue has a function as a reservoir for the parent vitamin D,which is released during the reductions in adiposity.Skeletal muscle might also be an important site of 25(OH)D sequestration,protecting this metabolite from degradation by the liver,because of what exercise is usually associated with better vitamin D status [2].It has been known that excessive exposure to sunlight might trigger skin-related carcinogenesis,especially malignant melanoma development.Therefore,various sunscreens have been used for the prevention of carcinogenesis,as well as for the prevention of accelerated photoaging.Classic sunscreens sometimes contain toxic chemicals,which can paradoxically increase the risk of skin cancer instead of lowering that risk.It is especially the case with para-amino benzoic acid (PABA) and its derivatives,which are present in some sunscreens as ultraviolet B filters.The presence of PABA in sunscreen increases the likelihood of UV radiation-related damage of DNA,which then increases the possibility of skin cancer carcinogenesis.Derivatives of benzophenone,such as benzophenone-2 (BP2) and oxybenzone (benzophenone-3,BP3),are known to be bioaccumulative and toxic,and may be found in some sunscreens.Ethanolamine compounds can also be found in sunscreen,although the European Commission prohibits the use of diethanolamine (DEA)in cosmetics,because the interaction of DEA with other ingredients causes the formation of carcinogenic nitrosamines.Homosalate is found in some sunscreens with sun protecting factor (SPF),although it is known to be a potential endocrine disruptor,affecting androgen and progesterone systems.It is also known that homosalate may enhance the absorption of pesticides in the body.Results of experiments using homosalate in human breast cancer cells showed an increased rate of cell growth and multiplication of 3.5 times.Heavy metals (lead,arsenic,mercury,aluminum,zinc,chromium,iron) can also be found in some sunscreens.Octinoxate is used as a UV filter for various cosmetic products,including sunscreens.Studies have shown that octinoxate may increase the rate of estrogensensitive cell proliferation.Styrene acrylates copolymer and related styrene-based polymers,which are regarded as possible human carcinogens,might also be found in sunscreens with SPF >30.Titanium dioxide,which is considered as a possible human carcinogen by International Agency for Research on Cancer (IARC),can be found in some sunscreens [3-11].To to support the campaign for safer cosmetics,including preparations used for sun protection,it is of great importance to explore new and safer options.With that said,the author here summarizes available up-to-date evidence of the potential sun-protective function of bakuchiol and astaxanthin,intending to explore further,potentially safer and effective possibilities for sun-protection,skin cancer prevention and photoaging slowdown.

    Bakuchiol

    Bakuchiol is an extract derived from the leaves and seeds of the babchi plant (Psoralea corylifolia) [12].It has been marketed for the additional treatment of acne,melasma,photoaging slowdown and for the treatment of hyperpigmentation.Studies have shown functional similarities to retinoids without the limiting side effects,such as erythema,burning,stinging and increased photosensitivity [13].Bakuchiol is a phytochemical with cutaneous antiaging effects when applied topically.Results of a study (Dhaliwal et al,2019)demonstrated that bakuchiol is comparable with retinol in its ability to improve photoaging,but is better tolerated.Unlike retinol,which can increase photosensitivity,bakuchiol can decrease it [14].Results of another study (Kim et al,2016) reported the chemo-preventive properties of bakuchiol,which acts by inhibiting epidermal growth factor (EGF)-induced neoplastic cell transformation.Bakuchiol also decreased viability and inhibited anchorage-independent growth of A431 human epithelial carcinoma cells.It reduced A431 xenograft tumor growth in the vivo mouse model.Using kinase profiling,the authors identified hematopoietic cell kinase (Hck),B lymphocyte kinase (Blk) and p38 mitogen-activated protein kinase (MAPK) as targets of bakuchiol,which directly bound to each kinase in an ATPcompetitive manner.Bakuchiol also inhibited EGF-induced signaling pathways downstream of Hck,Blk and p38 MAPK,including the mitogen-activated protein kinase/extracellular signal-regulated kinases (MEK/ERKs),p38 mitogen-activated protein kinase/mitogenand stress-activated protein kinase 1 (p38 MAPK/MSK1) and AKT/p70S6K (a protease cascade signaling pathway related to cell proliferation,with phosphorylation as the activation mode) pathways.These findings indicate that bakuchiol exhibits potent anticancer activity [15],but more research is mandatory to further explore bakuchiol’s potential chemo-preventive properties.Results of a clinical trial involving 60 females (1/3 eczema/atopic dermatitis,1/3 rosacea,1/3 cosmetic intolerance syndrome) showed that bakuchiol as a natural anti-aging moisturizer is well tolerated and effective in individuals with sensitive skin [16].These results signal that bakuchiol might also be used as an additional treatment for eczema,atopic dermatitis,rosacea and cosmetic intolerance syndrome.Results of a study in which comparative gene expression profiling of bakuchiol and retinol were used,showed that bakuchiol could function as a functional analogue of retinol without any structural similarities with retinoids.Researchers also tested bakuchiol as a finished skin care product in a clinical case study by twice-a-day facial application.They found that,after 12 weeks of treatment,there was a significant improvement in lines and wrinkles,pigmentation,elasticity,firmness and overall reduction in photo-damage,but without usual retinol-associated undesirable effects [17],meaning that bakuchiol might be a safer option for photoaging slowdown and as an anti-aging moisturizer in comparison with retinol.In another study,human dermal fibroblasts were treated with active compounds of bakuchiol and vanilla tahitensis extract (VTE),and exposed to an acute dose of UVA,followed by analysis using confocal microscopy.UVA induced a significant increase in interleukin-8 (IL-8) and p16 expression with marked morphological changes in fibroblasts.Treatment with bakuchiol or VTE alone prevented both actin network alteration and IL-8 upregulation.Bakuchiol and VTE also demonstrated synergistic protection against IL-8 and p16 overexpression.Serum application prevented glycosaminoglycan(GAG) loss at the dermo-epidermal junction and increased dermal GAG in UVA-exposed skin explants.Researchers also performed an open-label clinical trial in women applying the serum twice daily for 56 days,followed by the assessment of skin remodeling by FaceScan,and skin firmness evaluation using Dynaskin and clinical scoring.Results showed a reduction of face ptosis (11%),a reduction of skin deformation (24%),firming effect was positive,and skin radiance was improved (29%).The authors concluded that the combination of bakuchiol and VTE demonstrated anti-aging efficacy [18].This study shows that bakuchiol has local anti-inflammatory potential(immunoregulating of IL-8 expression) further explaining its effectiveness as a sun-protecting agent.

    Considering results of above mentioned preclinical and clinical studies signaling the possible sun-protective,chemo-preventive and anti-aging properties of bakuchiol,further research on the use of bakuchiol as a new sun-protective agent might be relevant.In addition,bakuchiol might also be explored as an additional treatment for acne,rosacea,hyperpigmentation and a skin chemo-preventive cosmeceutical preparation.It might also be helpful for the prevention and slowdown of photoaging.In comparison to retinol,which is known to be very effective against acne,bakuchiol does not increase the photosensitivity.Therefore,it is suitable for use all year round,while topical retinol should not be used in summertime,and when used,it can only be used before bedtime provided that the cream with SPF is applied in the morning.Bakuchiol can be used twice daily,and there is no need for SPF preparations usage.It has been known that retinoids are teratogenic,and although there is no firm evidence that topical retinoid application significantly increases endogenous levels,possible teratogenic effects of topical retinoid preparations,especially with prolonged use,cannot be completely ruled out.

    Astaxanthin

    Astaxanthin is a xanthophyll carotenoid.There is evidence in the available scientific literature that astaxanthin might exert clinical benefit on skin homeostasis thanks to its photoprotective,antioxidant and anti-inflammatory effects [19].Because of its anti-inflammatory,immune-modulating and DNA repair properties,the use of astaxanthin as a nutraceutical product has been encouraged for skin health maintenance and prevention of skin damage [20].Results of a 10-week double-blind placebo-controlled study on 23 healthy Japanese participants,who were divided into the astaxanthin group(4 mg peroral daily) and placebo group,showed that the astaxanthin group had increased minimal erythema dose (MED) in comparison with the placebo group.The astaxanthin group also had a reduced loss of skin moisture in the irradiated area compared with the placebo group.Authors concluded that astaxanthin might possess a protective function against UV-induced skin deterioration [21].In addition to possible skin-protective function,it has been reported that astaxanthin can inhibit low-density lipoprotein (LDL) oxidation,increase high-density lipoprotein (HDL)-cholesterol (“good cholesterol”) and adiponectin levels in clinical studies.Available upto-date evidence also suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular diseases [22].It has been shown that anti-inflammation mechanisms of astaxanthin include multiple signaling pathways: phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT),nuclear factor erythroid 2-related factor 2 (Nrf2),nuclear factor kappa B (NF-κB),extracellular signal-regulated kinase 1/2 (ERK1/2),c-Jun N-terminal kinase (JNK),p38 MAP kinase (p38 MAPK),and Janus kinase 2/signal transducer and activator of transcription proteins-3(JAK-2/STAT-3) [23].

    Although clinical evidence is scarce,astaxanthin could exert sunprotective function when taken as a nutraceutical during the sunbathing season,but more research is mandatory.In addition,some evidence showed that astaxanthin might also have beneficial effects on lipid profile (inhibition of LDL oxidation,increase of HDL levels).Therefore,it might be suitable as an atherosclerosispreventing nutraceutical.

    Conclusion

    Insolation is associated with both positive effects (vitamin D production,beneficial psychological effects) and negative effects (in the context of excessive ultraviolet radiation exposure: increased risk for skin carcinogenesis,accelerated photoaging),and therefore,various strategies are needed in order to mitigate the negative effects.In addition to avoiding sunbathing during a time when the ultraviolet index is high (especially between 11 a.m.and 3 p.m.in summertime)and the use of sunscreens with sun protective factors,but without incriminated toxic chemicals,such as PABA,BP-2,BP-3,DEA,homosalate,octinoxate,heavy metals,titanium dioxide and styrene acrylates copolymer,bakuchiol as face moisturizer and astaxanthin as a nutraceutical product should be further investigated as a potential new weapon against sun-related skin damage.Available evidence in the scientific literature suggests that topical application of bakuchiol might be associated with beneficial dermatological effects,including the decrease in photosensitivity,slowdown of photoaging,sunprotective function,and even chemo-preventive properties.In addition,bakuchiol has shown some effectiveness as the (additional)treatment of acne,rosacea,melasma and hyperpigmentation.Unlike retinol,which is known to be very effective against acne,bakuchiol does not increase the photosensitivity.Therefore,it can be used all year round,twice daily,while retinol should not be used during the sunbathing season.It has also been known that all retinoids are teratogenic when used orally,but although there is no firm evidence that topical retinoid application significantly increases endogenous levels,possible teratogenic effects of prolonged use of topical retinoid preparations cannot completely be ruled out.Astaxanthin,as a potent antioxidant,has been already marketed as a nutraceutical product for sun protection,used ideally during the sunbathing season at a peroral dose of 4 mg daily.The synergistic sun-protective effects using cosmeceutical preparation containing bakuchiol and astaxanthin capsules at the same time during the sunbathing season were never investigated,although there might be such an effect,and further studies on this subject might show interesting results.In summary,both bakuchiol and astaxanthin show promising sun-protective effects,but more research is mandatory.

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