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Effect of hesperidin on B16 and HaCaT cell lines irradiated by narrowband-UVB light
Abstract
Objective: To investigate the effects of hesperidine on B16 and HaCat cell lines irradiated by Narrowband-UVB light. Methods: MTT, NaOH assay, Takahashi technique were applied to measure the proliferation of B16 and HaCaT cells, the synthesis of melanin, and the tyrosinase activity of B16 cell respectively. The expression of CXC receptor 2 (CXCR2) on keratinocytes was analyzed by flow cytometry. To detect the contents of transforming growth factor-β1 (TGF-β1), enzyme linked immunosorbent assay was applied. Results: The findings indicated that hesperidine at the concentrations of 50-600 mg/L did not affect the proliferation of B16 and HaCaT cells. At the doses of 200 mg/L and over, hesperidine inhibited the tyrosinase activity and melanogenesis in B16 cells. The levels of TGF-β 1 in the supernatant of cultured keratinocytes presented as "wave shape" according to hesperidine contents. The expression of CXCR2 in the normal cultured keratinocytes did not change with different concentrations of hesperidine. However, the expression of CXCR2 in the cultured cells irradiated by narrowband-UVB light was increased obviously. When 200-600 mg/L hesperidine were added to the media, in which the cultured keatinocytes would be irradiated by Narrowband-UVB light later, the expression of CXCR2 decreased markedly in a dose-dependent manner, especially, when the dosage of hesperidine was 600 mg/L. Conclusions: Hesperidine has various biological effects, with gentle effectiveness, and without cytotoxicity. It is a potent plant extract for whitening and photoprotection.
... It appears that hesperidin can also attenuate UVA-induced damage to fibroblasts. Because hesperidin is hydrolyzed to hesperetin by the gut microbiota and absorbed by passive transport in the large intestine [36], some studies use hesperetin instead of hesperidin. Bae et al. [37] reported that treatment of UVA-irradiated human fibroblasts with 0.1% Citrus unshiu peel extract, containing hesperetin (metabolite of hesperidin), decreased expression levels of -galactosidase, matrix metalloproteinase-1, and the number of senescent cells. ...
... In contrast, other studies demonstrated that hesperidin did not affect melanin production in B16F10 murine melanoma cells [47][48][49]. However, most of other studies showed that both citrus extract and hesperidin inhibited melanogenesis in both murine B16-F10 melanoma cells and human melanocytes [36,44,[50][51][52][53]. For example, treatments with 50 M hesperidin for 48-72 hr induced 60% reduction in melanin content in murine B16-F10 melanoma cells and ≈30% reduction in human melanocytes [50]. ...
... Upregulation of expression levels of tyrosinase, TRPs, and MITF can increase melanin production [117,118]. A number of studies demonstrated that hesperidin decreased expression levels and activity of tyrosinase, TRPs, and MITF in both B16 mouse melanoma cells and human melanocytes [36,[50][51][52]. Moreover, hesperidin could activate adrenergic receptor, leading to induction of aggregation of melanophores in B. melanostictus, suggesting that hesperidin-induced skin lightening is mediated by adrenergic receptor [119]. ...
Hesperidin is a bioflavonoid, with high concentration in citrus fruits. In addition to its well-known benefits for cardiovascular function, type II diabetes, and anti-inflammation, recent studies have demonstrated multiple benefits of hesperidin for cutaneous functions, including wound healing, UV protection, anti-inflammation, antimicrobial, antiskin cancer, and skin lightening. In addition, hesperidin enhances epidermal permeability barrier homeostasis in both normal young and aged skin. The mechanisms by which hesperidin benefits cutaneous functions are attributable to its antioxidant properties, inhibition of MAPK-dependent signaling pathways, and stimulation of epidermal proliferation, differentiation, and lipid production. Because of its low cost, wide availability, and superior safety, hesperidin could prove useful for the management of a variety of cutaneous conditions.
... Jest bioflawonoidem naturalnie obecnym w skórce i owocach cytrusowych. Właściwości rozjaśniające hesperydyny zostały udowodnione w wielu badaniach [26][27][28][29]. ...
... Zhang i wsp. [26] potwierdzili zdolność hesperydyny do hamowania syntezy melaniny bez efektów cytotoksyczności dla komórek. Badanie in vitro na komórkach czerniaka B16 i ludzkich pierwotnych melanocytach wykazało, że hesperydyna hamuje tyrozynazę w sposób zależny od dawki. ...
Melanogenesis is a process catalyzed by tyrosinase enzyme leading to synthesis of two types of pigment in the skin: black-brown eumelanin and red-yellow pheomelanin. Pheomelanin is synthesized in the second stage of melanosome maturation, while eumelanin-synthesizing melanosomes are inactive. The black-brown pigment is produced in the third stage of melanosome development. The last, fourth stage of melanosome maturation is characterized by low tyrosinase activity, which reflects the low pigment production in the skin. The process of skin pigment production (melanogenesis) is mainly regulated by solar radiation, hormones and other endo- and exogenous factors. Over- stimulated melanogenesis leads to unsightly hyperpigmentation of the skin. Some substances used
in cosmetics have the ability to regulate melanogenesis and lower melanin levels.
The active ingredients on active melanocytes include: azelaic acid and azeoglycin, ferulic acid, ascorbic acid, kojic acid, tranexamic acid, extract of common daisy, licorice root extract, soybean extract, milk thistle extract, white mulberry extract, turmeric and bitter melon leaves extract, aloe extract as well as sericin, hesperidin and niacinamide.
The literature also emphasizes the possibility of influencing inactive melanocytes, such ingredients include vitamin A and its derivatives, hydroquinone, arbutin, Chinese tea and ashwagandha. Each of the described active ingredients is characterized by a different activity and partially different mechanism of action, which is based mainly on the inhibition of the activation of enzymes involved in melanogenesis (tyrosine and TRP-1 and TRP-2 proteins) mainly by: blocking the expression of MITF and binding to copper ions in the active site for tyrosinase. Active substances with a brightening effect applied externally to the skin are effective in hyperpigmentation therapies in which there is an increased amount of eumelanin in melanosomes, an increased activity of melanocytes and an increased transfer of melanin to keratinocytes.
The aim of the study was a literature review of the most frequently described active ingredients of natural origin with properties that lighten skin discoloration, paying attention to the potential effectiveness of selected active substances and their mechanism of action with reference to the melanogenesis process.
... Other flavonoids' dermatological relevance involves the treatment of skin aging; for example, kaempferol can delay skin aging by opposing collagenases, elastases, and hyaluronidase enzymes that damage the extracellular matrix, as well as decrease the erythema developed after UVB irradiation [209,210]. A study by Zhang et al. 2008 reported that hesperidin is able in a dose-dependent manner to inhibit melanin synthesis [211]. Also, it protects against UVAinduced damage of fibroblasts and oxidative damage of collagen [212]. ...
... Other flavonoids' dermatological relevance involves the treatment of skin aging; for example, kaempferol can delay skin aging by opposing collagenases, elastases, and hyaluronidase enzymes that damage the extracellular matrix, as well as decrease the erythema developed after UVB irradiation [209,210]. A study by Zhang et al. 2008 reported that hesperidin is able in a dose-dependent manner to inhibit melanin synthesis [211]. Also, it protects against UVAinduced damage of fibroblasts and oxidative damage of collagen [212]. ...
The concept of beauty and cosmetics is as ancient as mankind and civilization where everyone is obsessed with looking charming and young. A cosmetic is defined by the US Food and Drug Administration as the preparation used for cleaning, perfuming, and improving the appearance of the human body. Plants have emerged as the best source of cosmetic ingredients that meet the characteristics of efficiency and safety, thus increasingly replacing synthetic ingredients. Accordingly, there is a growing demand for naturally based cosmetics worldwide and an ever-growing interest in understanding their molecular and mechanistic aspects. In this chapter, we discussed the role of plants in cosmetology and skin care and how the various chemical structures exert biological activities on the skin of human.
... It has been reported that aloesin and hesperidin can not only effectively inhibit tyrosinase activity but also inhibit melanin formation on B16F10 and on normal human melanocytes [45,46]. Furthermore, aloesin and hesperidin can significantly improve skin hyperpigmentation in vivo in 15 days and in one week, respectively [45,46]. ...
... It has been reported that aloesin and hesperidin can not only effectively inhibit tyrosinase activity but also inhibit melanin formation on B16F10 and on normal human melanocytes [45,46]. Furthermore, aloesin and hesperidin can significantly improve skin hyperpigmentation in vivo in 15 days and in one week, respectively [45,46]. In this study, Ac-P4 has exhibited the great potential on reducing hyperpigmentation. ...
We investigated the kinetics of 4N-acetyl-pentapeptides, Ac-P1, Ac-P2, Ac-P3, and Ac-P4, regarding inhibition of mushroom tyrosinase activity. The peptides sequences of Ac-P1, Ac-P2, Ac-P3, and Ac-P4 were Ac-RSRFK, Ac-KSRFR, Ac-KSSFR, and Ac-RSRFS, respectively. The 4N-acetyl-pentapeptides were able to reduce the oxidation of l-DOPA by tyrosinase in a dose-dependent manner. Of the 4N-acetyl-pentapeptides, only Ac-P4 exhibited lag time (80 s) at a concentration of 0.5 mg/mL. The tyrosinase inhibitory effects of Ac-P4 (IC50 0.29 mg/mL) were more effective than those of Ac-P1, Ac-P2, and Ac-P3, in which IC50s were 0.75 mg/mL, 0.78 mg/mL, and 0.81 mg/mL, respectively. Kinetic analysis demonstrated that all 4N-acetyl-pentapeptides were mixed-type tyrosinase inhibitors. Furthermore, 0.1 mg/mL of Ac-P4 exhibited significant melanogenesis inhibition on B16F10 melanoma cells and was more effective than kojic acid. The melanogenesis inhibition of Ac-P4 was dose-dependent and did not induce any cytotoxicity on B16F10 melanoma cells.
... Hesperidin merupakan senyawa yang terdapat dalam tanaman sitrus seperti lemon, jeruk, jeruk nipis, dan anggur (Liu et al., 2013;Ye et al., 2015;Omidbaigi dan Nasiri, 2004;Levaj et al., 2009;Agcam et al., 2014;Abad-Gracia et al., 2012). Hesperidin dapat menurunkan ekspresi dan aktivitas tirosinase, tyrosinase-related protein (TRP), MITF pada sel-sel melanoma B16 tikus dan melanosit manusia (Zhang et al., 2008;Lee et al., 2015;Kim et al., 2013;Kiefer et al., 2010). Selain itu, hesperidin juga dapat mengaktivasi reseptor alpha adrenergik (Galgut dan Ali, 2012). ...
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.
... These findings suggested that orally administered PE may be used as an effective inhibitory agent [47]. Zhang et al. [48], investigated the effects of hesperidin on B16 and HaCat cell lines, it was found hesperidin inhibited the tyrosinase activity and melanogenesis in B16 cells. Hesperidin has various biological effects, with gentle effectiveness, and without cytotoxicity. ...
Cutaneous pigmentation plays critical role in determining the color of skin along with photo protection of skin from dreadful effects of ultraviolet radiations. Conversely, abnormal accumulation of melanin is responsible for hyper pigmentary disorders such as melasma, senile lentigines and freckles. Because of the visible nature of dermatologic diseases, they have a considerable psychosomatic effect on affected patients. Tyrosinase inhibitors are molecules that interrelate in some way with the enzyme to prevent it from working in the normal manner. Past many decades witnessed the quest for the development of natural tyrosinase inhibitors due to imperative role played by tyrosinase in the process of melanogenesis and fungi or fruit enzymatic browning. Mechanism of pigmentation is characterized by the intact process of the synthesis of specialized black pigment within melanosomes. Melanin is synthesized by a cascade of enzymatic and chemical reactions. For this reason, melanin production is mainly controlled by the expression and activation of tyrosinase. In the current article, we discussed tyrosinase inhibitors from the natural sources, which can be an essential constituent of cosmetics products and depigmenting agents for the treatment of hyperpigmentory disorders.
... Yamakoshi et al. [81] have reported the oral administration of a proanthocyanidin rich extract from grape seeds for one year reduced effectively the hyperpigmentation of women with chloasma. Ellagic acid is a natural polyphenol that is widely found in fruits and vegetables and the main active ingredient of fruit rinds of pomegranate, showed inhibitory activity in the process of melanogenesis by inhibition of the proliferation of melanocytes and melanin synthesis by tyrosinase in melanocytes [82]. ...
Skin pigmentation is an important human phenotypic trait that gives special aesthetic hue to individuals and also protective covering against solar ultra violet radiations, but excessive pigment production and uneven distribution, appear as serious undesirable hyperpigmentory anomalies. To overcome this, various therapeutic agents and skin-lightening cosmetics are in big demand across Asia, and the quest for fairness has led to identification of many new ingredients. The mechanisms underlying pigmentation has been researched extensively and the knowledge are being updated regularly. To understand the etiology of normal and uneven skin pigmentation, first part of the review serves us basic updated information regarding the normal process of melanogenesis and strict coherent attributes that monitor the skin pigmentation control machinery. While the later part of the review focuses on some abnormal hyperpigmentory anomalies, their mode of action at the cellular level and various approaches that exploit the natural botanicals for their permanent and cost effective treatment.
... Studies by Zhu and colleagues have demonstrated hesperidin's potent ability to inhibit melanin synthesis without cytotoxicity. This work found dose-dependent inhibition of tyrosinase activity (vs control) of hesperidin in melanoma B16 cells and human primary melanocytes (Figure 1, Zhang et al., 2008). In addition, hesperidin was found to protect against UVA-induced damage of fibroblasts and oxidative damage of collagen (Proteggente et al., 2003). ...
Both physicians and dermatology patients are searching for long-term topical skin care solutions (both cosmetic and cosmeceutical) to address problems presented by skin hyperpigmentation. Specifically, some women often express a desire to "lighten" skin tone by achieving improved visible tone, reduction in yellowness (or sallow tone), and reduction in the appearance of hyperpigmented spots ("age" or "sun" spots). Traditional depigmenting agents, such as hydroquinone, corticosteroids, and kojic acid, although highly effective, can raise several safety concerns (for example, ochronosis, atrophy, carcinogenesis, and other local or systemic side effects) with long-term exposure. An understanding of the benefits of natural and botanical extracts provides opportunities to develop new products to address pigmentation problems. Active compounds isolated from plants, such as arbutin, aloesin, gentisic acid, flavonoids, hesperidin, licorice, niacinamide, yeast derivatives, and polyphenols, inhibit melanogenesis without melanocytotoxicity by different mechanisms. This review presents an overview of trends in the application of plant extracts as topical treatments for hyperpigmentation disorders. It highlights some of the most relevant natural extracts, providing in vitro screening results and relevant available clinical study trial findings supporting their efficacy.
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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