Thursday, April 17, 2014

Asthma in Folate points of view

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients, polluted environment as well as intake foods  triggering the inflammatory allergens.

Folate, also known as folic acid, vitamin B9, is a water soluble vitamin, found abundantly in leafy vegetables, citrus fruits, beans, whole grain, etc. The vitamin plays an important role in synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in certain biological reactions, production of red blood cells for anemia prevention.

1. Serum levels of folate
 Scientific studies, linking serum levels of folate associated to risk of asthma have produced inconsistent results. The study by Ain Shams University showed that serum folate levels are significantly lower among atopics, and correlate inversely with the degree of atopy  among asthmatics(1). Other researchers suggested that low serum folate and impaired folate metabolism may be a potential risk factors for development of asthma and atopic disease, according to The Capital Region of Denmark, in a random sample of 6784 persons from a general population aged 30-60 years participated in a health examination in 1999-2001, low levels of serum of folate were associated with self-reported doctor-diagnosed asthma and attacks of shortness of breath, but not with lung function or atopy(2). The Johns Hopkins School of Medicine study also indicated that the effects of serum levels of folate were associated inversely associated with high total IgE levels, atopy, and wheeze(3).

2. The effects of folate in maternal intake
Folic acid supplementation has an established role in early pregnancy for preventing neural tube defects, but its causes of childhood asthma and asthmatic symptoms in epidemiological studies have been inconclusive results. According to the University of Western Australia, maternal folic acid exposure may be associated to childhood asthma and wheeze(4). Other in the study of pre-natal FACSs exposure population showed a small increased risk of early wheeze, but no adverse association of respiratory or allergic outcomes(5). In the study using the data from an Australian prospective birth cohort study (n = 557) from 1998 to 2005. At 3.5 years and 5.5 years, 490 and 423 mothers and children participation, researchers at the The University of Adelaide, indicated the correlation of the supplementation with folate in pregnancy and incidence of childhood allergic asthma through epigenetic mechanisms and also associated with poorer respiratory outcomes in young children(6).

Since the search of the effect of folate intake in reduced risk and treatment of asthma have produced limitation of result, we concluded that folate deficiency or low levels of folate may be associated to increased risk of early onset of the disease, but multi centers and large sample size studies are necessary to improve its validation. Overdoses of folate may cause stomach problems, sleep problems, skin reactions, seizures, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Study of folate status among Egyptian asthmatics by Farres MN1, Shahin RY, Melek NA, El-Kabarity RH, Arafa NA.(PubMed)
(2) Atopy, asthma, and lung function in relation to folate and vitamin B(12) in adults by Thuesen BH1, Husemoen LL, Ovesen L, Jørgensen T, Fenger M, Gilderson G, Linneberg A.(PubMed)
(3) Higher serum folate levels are associated with a lower risk of atopy and wheeze by Matsui EC1, Matsui W.(PubMed)
(4) Folic acid in pregnancy - is there a link with childhood asthma or wheeze? by Sharland E1, Montgomery B, Granell R.(PubMed)
(5) Maternal use of folic acid supplements during pregnancy, and childhood respiratory health and atopy by Bekkers MB1, Elstgeest LE, Scholtens S, Haveman-Nies A, de Jongste JC, Kerkhof M, Koppelman GH, Gehring U, Smit HA, Wijga AH.(PubMed)
(6) Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study by Whitrow MJ1, Moore VM, Rumbold AR, Davies MJ.(PubMed)

Wednesday, April 16, 2014

Asthma in Vitamin K points of view

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients, polluted environment as well as intake foods  triggering the inflammatory allergens.
Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.
Epidemiological studies focusing vitamin K in reduced risk and treatment of asthma have been inconclusive(a)(b)(c).

Menaquinone (vitamin K2), a variant of vitamin K, in a double blind study of 191 patients with bronchial asthma, showed an effective rate of 90.9% in mild patients, 86.7% in moderate patients, and 72.7% in severe patients(1). Other researchers suggested that treatment of menaquinone for long periods in patients with bronchial asthma indicated a significant inhibition of the disease(2). The data base of PubMed showed limitation in quantity of the research, we, therefore make no conclusion of the effectiveness of the vitamin in reduced risk and treatment of asthma. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.
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References
(a) Maternal intake of vitamins A, E and K in pregnancy and child allergic disease: a longitudinal study from the Danish National Birth Cohort by Maslova E, Hansen S, Strøm M, Halldorsson TI, Olsen SF.(PubMed)
(b) Fat-soluble vitamins and atopic disease: what is the evidence? by Litonjua AA.(PubMed)
(c) [Antioxidant and fat intake in patients with polinic asthma].[Article in Spanish] by de Luis DA1, Izaola O, Aller R, Armentia A, Cuéllar L.(PubMed)
(1) Menaquinone (vitamin K2) therapy for bronchial asthma. II. Clinical effect of menaquinone on bronchial asthma by Kimur I, Tanizaki Y, Sato S, Saito K, Takahashi K.(PubMed)
(2) Menaquinone (vitamin K2) therapy for bronchial asthma. I. Mechanism of action menaquinone on allergic reactions by Kimura I, Tanizaki Y, Sato S, Saito K, Takahashi K.(PubMed)

Tuesday, April 15, 2014

Asthma in Vitamin E points of view

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients, polluted environment as well as intake foods  triggering the inflammatory allergens.
 Vitamin E,  a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(2), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..
General consensus suggestion of increased dietary vitamin E intake is associated with a reduced incidence of asthma, due its antioxidant status, but epidemiological studeies, linking vitamin E inreduced risk and treatment of asthma have not been conclusive(a)(b)(c)(d)(e).

1. Serum levels of vitamin E
Serum levels of vitamin in asthmatic patients may be correlated to the occurrence of the diseases. The University of Tampere study of in five European rural settings with Children of 1133 mothers recruited during pregnancy, showed no associated of with allergies or asthma by 6 years of age regardless the concentration of vitamin E(1). and the study of the Yamaguchi University, also indicated no correlation of levels of vitamin E and asthma in the a total of Of 2796 students attending schools in Shunan, Japan, in 2006.(1a). The University of Medical Sciences study indicated other wise as treatment of fluticasone and vitamin E (50mg/day) showed an significantly increased of Serum level of Vitamin E, with improved FEV1 and FEV1/FVC ratio(2). The study of acute asthmatic attack in children, showed a high degree of reactive oxygen species formation causing considerable oxidative stress with the high level of oxidants Serum malondialdehyde (MDA) and low level of antioxidants(vitamin C, vitamin E and uric acid)(3). Researchers at the Oslo University Hospital, in the study of children of 7-12 yr with asthma (n = 50) and no asthma (controls) (n = 52)indicated that schoolchildren with asthma and rhinitis had reduced levels of the major serum antioxidant albumin, and poorly controlled asthma was associated with decreased vitamin E and transferrin levels(4).


2. The effects
The Northwestern University study indicated the opposing regulatory effects as allergic inflammation is inhibited by supplementation with the purified natural vitamin E isoform α-tocopherol but elevated by the isoform γ-tocopherol when administered at physiological tissue concentrations(5)(6). But according to University of North Carolina School of Medicine, γ-tocopherol (GT) significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and macrophage expression of CD206, CD36 and CD86 in allergic asthmatics through downregulation of both innate and adaptive immune response elements, and atopic status(7).  The composition containing 623 mg of gamma-tocopherol, 61.1 mg of d-alpha-tocopherol, 11.1 mg of d-beta-tocopherol (11.1 mg), and 231 mg of d-sigma-tocopherol capsule in Phase I human dosing study showed the decreased systemic oxidative stress, increased serum levels of gamma-tocopherol, and inhibited monocyte responses to LPS without any adverse health effects(8). In Ovalbumin (OVA)-sensitized Brown Norway rats, treatment of gamma-tocopherol (gammaT), inhibited the pathogenesis of both AR and asthma inflammatory pathways(9). Suggestion of oxidant stress and diminished antioxidant defenses may be a cause of asthmatic disease(10) and uncontrolled asthma and severe asthma pattern have impaired antioxidant defences and are thus most susceptible to the damaging effects of oxidative stress(11). 1500 IU of natural-source d-α-tocopheryl acetate daily for at least 16 weeks in volunteered asthmatic patient, showed to inhibited oxidant stress, through  modulation of allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo(12).

Taking altogether, Aγ-tocopherol, a variant of vitamin E, may be effective in reduced risk and treatment of asthmatic disorder, but further large sample and in multi centers studies are necessary to validate it claims. Over doses of vitamin E supplement can cause symptoms of blurred vision, weakness, dizziness, nausea, diarrhea, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(a) Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial by Pearson PJ1, Lewis SA, Britton J, Fogarty A(PubMed)
(b) Effects of vitamin E on mitochondrial dysfunction and asthma features in an experimental allergic murine model by Mabalirajan U1, Aich J, Leishangthem GD, Sharma SK, Dinda AK, Ghosh B.(PubMed)
(c) Diet and asthma: vitamins and methyl donors by Han YY1, Blatter J1, Brehm JM1, Forno E1, Litonjua AA2, Celedón JC3.(PubMed)
(d) Asthma, allergy, and responses to methyl donor supplements and nutrients by Sharma S1, Litonjua A(PubMed)
(e) Vitamin e supplementation, lung functions and clinical manifestations in children with moderate asthma: a randomized double blind placebo- controlled trial by Ghaffari J1, Farid Hossiani R, Khalilian A, Nahanmoghadam N, Salehifar E, Rafatpanah H.(PubMed)
(1) Serum vitamin E concentrations at 1 year and risk of atopy, atopic dermatitis, wheezing, and asthma in childhood: the PASTURE study by Nwaru BI1, Virtanen SM, Alfthan G, Karvonen AM, Genuneit J, Lauener RP, Dalphin JC, Hyvärinen A, Pfefferle P, Riedler J, Weber J, Roduit C, Kaulek V, Braun-Fahrländer C, von Mutius E, Pekkanen J; PASTURE study group.(PubMed)
(1a) Association of serum carotenoids and tocopherols with atopic diseases in Japanese children and adolescents by Okuda M1, Bando N, Terao J, Sasaki S, Sugiyama S, Kunitsugu I, Hobara T.(PubMed)
(2) Vitamin e supplementation, lung functions and clinical manifestations in children with moderate asthma: a randomized double blind placebo- controlled trial by Ghaffari J1, Farid Hossiani R, Khalilian A, Nahanmoghadam N, Salehifar E, Rafatpanah H.(PubMed)
(3) Antioxidant status in acute asthmatic attack in children by Al-Abdulla NO1, Al Naama LM, Hassan MK.(PubMed)
(4) Altered oxidative state in schoolchildren with asthma and allergic rhinitis by Bakkeheim E1, Mowinckel P, Carlsen KH, Burney P, Carlsen KC.(PubMed)
(5) Vitamin E isoforms as modulators of lung inflammation by Abdala-Valencia H1, Berdnikovs S, Cook-Mills JM.(PubMed)
(6) Two faces of vitamin E in the lung by Cook-Mills JM1, Abdala-Valencia H, Hartert T.(PubMed)
(7) Effects of ex vivo γ-tocopherol on airway macrophage function in healthy and mild allergic asthmatics by Geiser M1, Lay JC, Bennett WD, Zhou H, Wang X, Peden DB, Alexis NE.(PubMed)
(8) In vivo gamma-tocopherol supplementation decreases systemic oxidative stress and cytokine responses of human monocytes in normal and asthmatic subjects by Wiser J1, Alexis NE, Jiang Q, Wu W, Robinette C, Roubey R, Peden DB.(PubMed)
(9) Gamma-tocopherol prevents airway eosinophilia and mucous cell hyperplasia in experimentally induced allergic rhinitis and asthma by Wagner JG1, Jiang Q, Harkema JR, Ames BN, Illek B, Roubey RA, Peden DB.(PubMed)
(10) Oxidative stress and antioxidant status in Saudi asthmatic patients by Al-Afaleg NO1, Al-Senaidy A, El-Ansary A.(PubMed)
(11) Reduced circulating antioxidant defences are associated with airway hyper-responsiveness, poor control and severe disease pattern in asthma by Wood LG1, Gibson PG.(PubMed)
(12) Natural-source d-α-tocopheryl acetate inhibits oxidant stress and modulates atopic asthma in humans in vivo by Hoskins A1, Roberts JL 2nd, Milne G, Choi L, Dworski R.(PubMed)

Monday, April 14, 2014

Asthma in Vitamin D points of view

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients, polluted environment as well as intake foods  triggering the inflammatory allergens.
Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.

1. Serum of vitamin D
Epidemiological studies, linking the levels of serum 25-OH vitamin D with asthma may be inconclusive. The study of included 4,999 adults aged 30-60 years in 1999-2001. 3,032 of those included at baseline also participated at a follow-up examination 5 years later and 3,727 answered a 10 year follow-up questionnaire, showed no association of serum serum 25-OH vitamin D and the risk of asthma in Danish adults(1)(1a). Some researchers in the study of general Korean population suggested that vitamin D-insufficiency may have an increased likelihood of atopic dermatitis, but not asthma, allergic rhinitis, or IgE sensitization(2)(2a). But the study by Royal Brompton Hospital, London indicated otherwise in the study of relationships between serum vitamin D, lung function, and pathology in children with severe, therapy-resistant asthma (STRA)(3)(4) and 25 hydroxy vitamin D insufficiency is associated with bronchial asthma(4a) On the other hand, the study of iMayo Clinic indicated the correlation between serum 25(OH)D concentrations and positive pneumococcal antibody levels in all subjects regardless of asthma(5).

2. The benefits
According to the study by Universitätsmedizin Berlin, oral administration of vitamin D in vitamin D deficiency induced asthma, showed an increased expression of CD38 on B cells and a decreased T-cell-dependent proinflammatory cytokine production in doses of(6). In support to above study, Vitamin D found to decreaed inflammatory cytokine production from T-cell subsets implicated in asthma, according to Florida Atlantic University(7). In patient with in patients with steroid-resistant (SR) and steroid-sensitive (SS) asthma, oral administration of vitamin D, although exerted its anti-inflammatory and corticosteroid-enhancing effects in monocytes of patients with SR asthma and patients with SS asthma, the responses to corticosteroids in patients with SR asthma remained significantly lower than those in patients with SS asthma(8). Other in the study of the effect of vitamin D in severe therapy-resistant asthma (STRA) patients, showed an positive effect of 1α,25-dihydroxyvitamin D3, the active form of vitamin D in culture enhanced dexamethasone-induced IL-10 (Defective IL-10 expression causes a significantly diminished levels of anti-inflammatory interleukin (IL)-10))without marked effects on IL-13 or IL-17A production(9). Patients with severe asthma exhibited increased levels of TH17 cytokines.The study of King's College London, also suggested that 1,25(OH)2D3 inhibits TH17 cytokine production in all patients with moderate-to-severe asthma(10), enhances the frequency of Treg cells(11)and upregulates CD200 on peripheral human CD4+ T cells(12).

Taking altogether, without going into reviews,  vitamin D used conjunction with other anti asthma medicine and its the active form 1α,25-dihydroxyvitamin D3, may be associated to reduced risk and treatment of asthmatic diseases.  Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) The association of serum 25-OH vitamin D with atopy, asthma, and lung function in a prospective study of Danish adults by Thuesen BH1, Skaaby T, Husemoen LL, Fenger M, Jørgensen T, Linneberg A.(PubMed)
(1a) Vitamin d in pediatric inpatients with respiratory illnesses by Iqbal S1, Mosenkis EV, Jain P, Wiles A, Lerner J, Benton AS, Chamberlain JM, Freishtat RJ, Teach SJ.(PubMed)
(2) Low vitamin D levels are associated with atopic dermatitis, but not allergic rhinitis, asthma, or IgE sensitization, in the adult Korean population by Cheng HM1, Kim S2, Park GH3, Chang SE4, Bang S5, Won CH4, Lee MW4, Choi JH4, Moon KC(PubMed)
(2a) Vitamin D with asthma and COPD: not a false hope? A systematic review and meta-analysis By Zhang LL1, Gong J2, Liu CT3.(PubMed)
(3) Childhood asthma and vitamin D deficiency in Turkey: is there cause and effect relationship between them? Uysalol M1, Mutlu LC, Saracoglu GV, Karasu E, Guzel S, Kayaoglu S, Uzel N.(PubMed)
(4) Relationship between serum vitamin D, disease severity, and airway remodeling in children with asthma by Gupta A1, Sjoukes A, Richards D, Banya W, Hawrylowicz C, Bush A, Saglani S.(PubMed)
(4a) Serum 25 Hydroxy Vitamin D Insufficiency Associated with Bronchial Asthma in Lucknow, India by Awasthi S1, Vikram K.(PubMed)
(5) Serum 25-hydroxyvitamin D is associated with enhanced pneumococcal antibody levels in individuals with asthma by Lee J1, Zhao H, Fenta Y, Kita H, Kumar R, Juhn YJ.(PubMed)
(6) Oral vitamin D increases the frequencies of CD38+ human B cells and ameliorates IL-17-producing T cells by Drozdenko G1, Heine G, Worm M.(PubMed)
(7) Effect of vitamin D on T-helper type 9 polarized human memory cells in chronic persistent asthma by Keating P1, Munim A2, Hartmann JX2.(PubMed)
(8) Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma by Zhang Y1, Leung DY2, Goleva E3.(PubMed)
(9) Defective IL-10 expression and in vitro steroid-induced IL-17A in paediatric severe therapy-resistant asthma by Gupta A1, Dimeloe S, Richards DF, Chambers ES, Black C, Urry Z, Ryanna K, Xystrakis E, Bush A, Saglani S, Hawrylowicz CM.(PubMed)
(10) Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion by Nanzer AM1, Chambers ES, Ryanna K, Richards DF, Black C, Timms PM, Martineau AR, Griffiths CJ, Corrigan CJ, Hawrylowicz CM.(PubMed)
(11) The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+ CD4+ T cells by Urry Z1, Chambers ES, Xystrakis E, Dimeloe S, Richards DF, Gabryšová L, Christensen J, Gupta A, Saglani S, Bush A, O'Garra A, Brown Z, Hawrylowicz CM.(PubMed)
(12) 1α,25-dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells by Dimeloe S1, Richards DF, Urry ZL, Gupta A, Stratigou V, Farooque S, Saglani S, Bush A, Hawrylowicz CM.(PubMed)

Sunday, April 13, 2014

Asthma in Vitamin C points of view

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients and polluted environment.
Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.
Epidemiological studies, linking vitamin C in reduced risk and treatment of asthma have been inconclusive(a)(b)(c)(d).

The study of the effects of antioxidant nutritional status with allergic rhinitis (AR) in Korean schoolchildren aged 6-12 years, in a total of 4,554 children in Seoul, Korea, showed  a positive effect of Vitamin C intake negatively associated with an increased risk of AR symptoms(1). Accordin got the Rabin Medical Center, vitamin C also enhanced the protective effect on the hyperreactive airways of patients with exercise-induced asthma (EIA)(2). Oxidative stress mediated by reactive oxygen species is known to contribute to the inflammatory process of bronchial asthma. According to Dr. Ruprai RK., in the study of the oxidative stress plasma malondialdehyde and ascorbic acid (Vitamin C) showed an oxidative imbalance in asthmatic patients and antioxidant supply may have a beneficial impact on the free radical induced injury and improvement of respiratory reserve in Asthmatics(3)(4). In Saudi asthmatic patients, King Saud University study showed to exhibit oxidative stress and defective antioxidant status and suggested these may be primary causative factor in the pathogenesis of asthma(5).
In mega doses, vitamin C in asthmatic patients also Vitamin C decreased airway hyperreactivity to methacholine, inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration(6).

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References
(a) Vitamin C supplementation for asthma by Kaur B1, Rowe BH, Arnold E.(PubMed)
(b) Vitamin C supplementation for asthma by Ram FS1, Rowe BH, Kaur B(PubMed)
(c) Vitamin C for asthma and exercise-induced bronchoconstriction by Milan SJ1, Hart A, Wilkinson M.(PubMed)
(d) Vitamin C and common cold-induced asthma: a systematic review and statistical analysis by Hemilä H.(PubMed)
(1) Association of antioxidants with allergic rhinitis in children from seoul by Seo JH1, Kwon SO, Lee SY, Kim HY, Kwon JW, Kim BJ, Yu J, Kim HB, Kim WK, Jang GC, Song DJ, Shim JY, Oh SY, Hong SJ.(PubMed)
(2) Blocking effect of vitamin C in exercise-induced asthma by Cohen HA1, Neuman I, Nahum H.(PubMed)
(3) Plasma oxidant-antioxidants status in asthma and its correlation with pulmonary function tests by Ruprai RK.(PubMed)
(4) Antioxidant status in acute asthmatic attack in children by Al-Abdulla NO1, Al Naama LM, Hassan MK.(PubMed)
(5) Oxidative stress and antioxidant status in Saudi asthmatic patients by Al-Afaleg NO1, Al-Senaidy A, El-Ansary A.(PubMed)
(6) Mega-dose vitamin C attenuated lung inflammation in mouse asthma model by Jeong YJ1, Kim JH, Kang JS, Lee WJ, Hwang YI.(PubMed)








Saturday, April 12, 2014

Asthma in Vitamin A points of view

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients and polluted environment.
Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Epidemiological studies linking vitamin A in reduced risk and treatment of asthma have been inconclusive(a)(b)(c)(d)(e), but according to the University G. D'Annunzio, and Respiratory Pathophysiology Center, dietary supplementation or adequate intake of lycopene and vitamin A rich foods may be beneficial in asthmatic subjects(f).

1. Retinols
Serum vitamin A concentrations was found significantly lower in asthmatic subjects than healthy control subjects and administration of all-trans retinoic acid, ATRA dramatically attenuated airway inflammation through inhibiting Th2 and Th17 differentiation and/or functions. according to the Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(1). ORMDL3 is a candidate gene of childhood onset asthma, and high-transcript of ORMDL3 is associated with the development of asthma. According to Nanjing Medical University, all-trans retinoic acid (ATRA) is an active metabolite of Vitamin A, reduced the risk od asthma through maintained airway epithelial integrity, inhibited asthma effector cells differentiation, modulates immune response, possibly via facilitates ORMDL3 production probable through PKA/CREB(2). Also in all-trans retinoic acid, ATRA, the Tehran University of Medical Sciences study suggested that ATRA diverted the human immune response in neutral conditions (without adding polarizing cytokines) by increasing FOXP3+ cells and decreasing RORγt+ cells(3). In rats with asthma, ATRA  was found to alleviate airway hyperresponsiveness and airway remodeling possibly through decreasing the protein expression of MMP-9(4). The study at 1Inserm U700 and Université Paris 7, in a mouse model of ovalbumin (OVA)-induced T helper (Th) 2-type responses and airway remodeling, indicated a effectiveness of liposomally encapsulated ATRA (Lipo-ATRA) in exacerbates allergic immune and inflammatory responses, most likely through promoting Th2 development(5).
Unfortunately, according to Johns Hopkins University, even though animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma, but vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency(6). 

2. Carotenoids (beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin) Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects. In the study of the effect of vitamin intake among asthmatic subject, researchers at the Hung Kuang University, found that nutritional supplement therapy including beta carotene may improve dysregulated oxidant and antioxidant status, inflammation and immune responses, pulmonary function, and health-related quality of life in patients with mild to moderate allergic asthma(7). The John Hunter Hospital study of asthmatic subjects with airway hyper-responsiveness (AHR), indicated a reduced levels of beta-carotene and alpha-tocopherol compared with those without AHR, possibly due to impaired antioxidant defences and are thus most susceptible to the damaging effects of oxidative (8). Other researchers suggested that the imbalance of antioxidants found in asthmatic patients may be the possible causes od the disease(9) and modifying the dietary intake of carotenoids alters clinical asthma outcomes with improvements evident only through increased whole foods intake, not supplements(10)
But according to the study of Yamaguchi University, there was no significant association for asthma in Japanese youth(11) and the study of a total of 423 children from a rural area of Thailand, in a Health Interview for Asthma Control questionnaire, showed no correlation of dietary intake of carotenoids between asthmatic and non-asthmatic children(12).

Taking altogether, Using vitamin A in prevention and treatment of asthmatic patient remains controversial. According to the study in summarization of the important of vitamin A in treatment of asthma suggested that excessive intake of vitamin A may increase the risk or severity of asthma in industrialized countries whereas vitamin A deficiency continues to increase mortality from infectious diseases in developing countries(12).

But  study summarized the important of vitamin A in treatment of asthma suggested that excessive intake of vitamin A may increase the risk or severity of asthma in industrialized countries whereas vitamin A deficiency continues to increase mortality from infectious diseases in developing countries(13). Overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(a) Diet and asthma: vitamins and methyl donors by Han YY1, Blatter J1, Brehm JM1, Forno E1, Litonjua AA2, Celedón JC3.(PubMed)
(b) Maternal intake of vitamins A, E and K in pregnancy and child allergic disease: a longitudinal study from the Danish National Birth Cohort by Maslova E, Hansen S, Strøm M, Halldorsson TI, Olsen SF.(PubMed)
(c) Nutritional supplements and plasma antioxidants in childhood asthma by Fabian E1, Pölöskey P, Kósa L, Elmadfa I, Réthy LA.(PubMed)
(d) Nutritional supplement therapy improves oxidative stress, immune response, pulmonary function, and quality of life in allergic asthma patients: an open-label pilot study by Guo CH1, Liu PJ, Lin KP, Chen PC(PubMed)
(e) Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study by Mai XM1, Langhammer A, Chen Y, Camargo CA Jr.(PubMed)
(f) Plasma lycopene and antioxidant vitamins in asthma: the PLAVA study by Riccioni G1, Bucciarelli T, Mancini B, Di Ilio C, Della Vecchia R, D'Orazio N.(PubMed)
(1) All-trans retinoic acid attenuates airway inflammation by inhibiting Th2 and Th17 response in experimental allergic asthma by Wu J1, Zhang Y, Liu Q, Zhong W, Xia Z.(PubMed)
(2) All-trans retinoic acid modulates ORMDL3 expression via transcriptional regulation by Zhuang LL1, Huang BX, Feng J, Zhu LH, Jin R, Qiu LZ, Zhou GP.(PubMed)
(3) Effect of all-trans retinoic acid (ATRA) on viability, proliferation, activation and lineage-specific transcription factors of CD4+ T cells by Bidad K1, Salehi E, Oraei M, Saboor-Yaraghi AA, Nicknam MH.(PubMed)
(4) [Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma].[Article in Chinese] by Li WK1, Li Y, Zhong LL.(PubMed)
(5) Liposomal retinoic acids modulate asthma manifestations in mice by Maret M1, Ruffie C, Periquet B, Campo AM, Menevret M, Phelep A, Dziewiszek K, Druilhe A, Pretolani M.(PubMed)
(6) Supplementation with vitamin A early in life and subsequent risk of asthma by Checkley W1, West KP Jr, Wise RA, Wu L, LeClerq SC, Khatry S, Katz J, Christian P, Tielsch JM, Sommer A.(PubMed)
(7) Nutritional supplement therapy improves oxidative stress, immune response, pulmonary function, and quality of life in allergic asthma patients: an open-label pilot study by Guo CH1, Liu PJ, Lin KP, Chen PC.(PubMed)
(8) Reduced circulating antioxidant defences are associated with airway hyper-responsiveness, poor control and severe disease pattern in asthma by Wood LG1, Gibson PG.(PubMed)
(9) Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD by Ochs-Balcom HM1, Grant BJ, Muti P, Sempos CT, Freudenheim JL, Browne RW, McCann SE, Trevisan M, Cassano PA, Iacoviello L, Schünemann HJ.(PubMed)
(10) Manipulating antioxidant intake in asthma: a randomized controlled trial by Wood LG1, Garg ML, Smart JM, Scott HA, Barker D, Gibson PG.(PubMed)
(11) Association of serum carotenoids and tocopherols with atopic diseases in Japanese children and adolescents by Okuda M1, Bando N, Terao J, Sasaki S, Sugiyama S, Kunitsugu I, Hobara T.(PubMed)
(12) Carotenoid intake and asthma prevalence in Thai children by Rerksuppaphol S1, Rerksuppaphol L.(PubMed)
(13) Vitamin A deficiency decreases and high dietary vitamin A increases disease severity in the mouse model of asthma by Schuster GU1, Kenyon NJ, Stephensen CB.(PubMed)

Friday, April 11, 2014

Skin Lightening (whitening) in herbs, Foods and Antioxidants Points of View

 Kyle J. Norton(Draft Article)

Human skin pigmentation is the result of natural selection evolved to prevent damage to skin through regulation of ultraviolet radiated penetration depending to the production of melanin in the skin cells.
1. Hypo-pigment
a. Vitiligo is defined as a condition of destruction of cells that give your skin its color, causing white patches on your skin.
b. Albinism is a congenital disorder causes of complete or partial absence of pigment in the skin, hair and eyes duas a result of restriction of the skin cells from producing melanin
2.Hyper pigment is a result of over production of pigments of certain cells in the skin, causing skin darkening in some area, such as tan or brown patches, commonly on the facial skin
3. Skin discoloring is a result of discoloring your skin in specific spots or very widespread
4. Chloasma is the appearance of brown patches of pigmentation on the forehead, cheeks, and neck
due to hormonal change during pregnancy.
5. Melasma happens to women who have fluctuation of hormones, are taking birth control pills and certain medications. with brownish-grayish patches on the skin, most often on the cheek.
Epidemiological studies, linking herbal medicine in skin lighting may have produced certain interest results(a)(b)(c).
A. The herbs
1. Ampelopsis japonica (Bai Lian)
Bai Lian is also known as Japanese Ampelopsis Root, the bitter, sweet, acrid and cool herb has been used in TCM to redice infection and to treat carbuncles, sores, scalding injuries, dysentery with blood, intestine pain, hemorrhoids as it clears Heat, expels toxins, resolves ulcers, promotes muscle regeneration, etc, by promoting the function of liver channel.
Ampelopsis japonica  may process the property in treating skin hyperpigmentation disorders, such as melisma. According to the study at the Macao Polytechnic Institute,  Linderagalactone c and (+)-n-methyllaurotetanine found in  Ampelopsis japonica  exhibited the strongest prospects in topical formulations, throguh high predicted tyrosinase binding scores and displayed good skin permeation properties in Surflex-Dock and the QSAR-based Dermal Permeability Coefficient Program (DERMWIN) and Skin Irritation Corrosion Rules Estimation Tool (SICRET) implemented in Toxtree.(1). The screening of 50 extracts from traditional Chinese medicines (TCM) used for tyrosinase activity-inhibiting agents, Ampelopsis japonica showed similar or greater ratio of cell growth IC(50) to cellular tyrosinase IC(50) when compared with other herbs(2).

2. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgo biloba, one of the potent herb showed more advanced binding energies than the gold standard whitening agents, arbutin and kojic acid(1). Glycol extracts of ginkgo boiloba(F1A+M), may process of arbutin diffusion from the produced hydrogel formulations. According to Uniwersytet Medyczny w Łodzi, formulation containing glycol extract of ginkgo processed the most effective in arbutin release to the acceptor fluid through a semipermeable membrane (3). Other herbal extracts were also found to have a similar effect in promoting the process of arbutin release, including rosemary, sage and nettle(4).

3. Spicebush Root (Wu Yao)
Wu Yao is also known as Spicebush Root. The acrid and warm herb has been used in TCM  as   increased metabolism, antibiotic, anti-viral agent andto harmonize peristalsis of digestive tract, release intestinal gas, etc., as it moves Qi, warms the Kidneys. calms pain, etc. by enhancing the functions of lung, spleen, kidney and bladder.channels.
The study at Macao Polytechnic Institute, in the finding of herbal medicine used as tyrosinase inhibitors and for treatment of skin hyperpigmentation disorders, showed a promising result of
Spicebush Root's chemical constituents in tyrosinase binding scores and displayed good skin permeation properties and minimal potential for skin sensitization and irritation(5). Other study at the Institute of Chinese Materia Medica of Shanghai University of Traditional Chinese Medicine, found that Spicebush Root consists appreciable antityrosinase activity with more than 50% inhibition against mushroom tyrosinase activity(6).

4. Chinese gall (Wu Bei zi)
Wu Bei Zi is also known as Chinese Gall. The  sour, tart and cold herb has been used in TCM to treat chronic cough, chronic diarrhea with or without infection, spermatorrhea, night sweating, bleeding not during menses, etc., as it restrains Lungs, moves Fire downwards, strengthens the Intestines andthe Essence, prevents sweating, stops bleeding, etc. by enhancing the functions of lung, large intestine and kidney channels.
Chinese gall extract in the testing against mushroom tyrosinase activity inhibition, using ultraviolet A (UVA) or alpha-melanocyte-stimulating hormone (alpha-MSH) to stimulate B16 cells showed a promising effect in inhibition of melanin biosynthesis associated with hyperpigmentation in a dose-dependent manner, according to National Chiayi University(7). In Mouse melanocyte cell lines, water extract of Galla Chinensis, showed to exhibit higher depigmentation activity and caused lower tyrosinase activity(8).

5. Sargassum polycystum(Brown seaweed)
Sargassum polycystum, a type of brown seaweed, has been used for the treatment of skin-related disorders in traditional medicine. The ethanolic crude extract from Sargassum polycystum showed significant inhibition of melanogenesis through down activated cellular tyrosinase activity in B16F10 cells(9).

6. Nardostachys chinensis(Gan Song)
gan Song also known as Nardostachyos Root and Rhizome. The herb has been used in traditional Chinese medicine to treat melasma and lentigines, move Qi, calm pain, eliminate stagnation and invigorates the Spleen. According to Pusan National University, the active 20% methanol chromatographic fraction from the ethyl acetate layer (PPNC) showed to suppressed the melanin synthesis s, through stimulated MEK/ERK phosphorylation and PI3K/Akt signaling with suppressing cAMP levels and subsequently stimulating MITF and TRPs down-regulation(10).

7. Cuscuta japonica(Tu Si Zi)
Tu Si Zi is also known as Dodder Seed. The acrid, sweet and  neutral herb has been used in TCM to treat  psychological disorder, calm the fetus, prevent miscarriage, etc. as it tonifies kidneys, liver and spleen, improves yin, etc. by enhancing the functions of liver and kidney channels.
According to Pusan National University, the aqueous fraction from Semen cuscutae (AFSC) showed a marked reduction of melanin synthesis and tyrosinase activity in α-MSH-stimulated B16F10 cells through inhibited p38 MAPK phosphorylation with suppressed cAMP levels and subsequently down-regulate MITF and TRP expression(11).

8. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in trditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
Curcumin, a major chemical constituents of turmeric, showed to suppressed alpha-MSH-stimulated melanogenesis probably through involved the down-regulation of MITF and its downstream signal pathway through the activation of MEK/ERK or PI3K/Akt(12). Other sudy conducted by Pusan National University, also showed partial purification from C. longa (PPC)  reduced melanin synthesis via MITF and its downstream signal pathway including tyrosinase and TRPs in alpha-MSH-induced melanogenesis, through activation of the MEK/ERK or Akt(13).

9. Fermenting red ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng(RG), wild ginseng, American ginseng (root).
Fermented red ginseng (FRG), increased contents of ginsenoside metabolites, such as Rg3, Rg5, Rk1, compound K, Rh1, F2, Rg2, and flavonoids content showed to increased anti-wrinkle efficacy, whitening efficacy, and reduced toxicological potency compared to RG(13a)

B. The foods
1. Long Yan (Longan)
Long Yan is also known as longan. The slightly sweet and neutral herb (fruit) has been used in TCM as notification after illnesses, neurasthenia, forgetfulness, palpitation, insomnia, etc. as it tonifies Heart and Spleen, benefits Qi and Blood, etc. Longan seeds containing high levels of  polyphenolic compounds such as corilagin, gallic acid and ellagic acid, may be potential sources of potent natural dietary antioxidants in the application as a new natural skin-whitening agent(14), through its higher antioxidant and antityrosinase activities(15).

2. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Green tea polyphenol may be used as a natural ingredient with excellent physiological functions for the human skin through cosmetic or food composition(16). Other study of the effects of tea polysaccharides (TPS) and polyphenols (TPP) on skin, showed to exhibit the moisture absorption and retention, sunscreen, promoting the proliferation of fibroblast cells, and tyrosinase inhibitory effect(17).

3. Cinnamon
Cinnamon is a spice derived from the inner bark of tree, native to South East Asia, of over 300 species of the genus Cinnamomum, belonging to the family Lauraceae.. The herb has been use in herbal and traditional medicine as anti-fungal and bacteria level to improve reproductive organ, prevent flatulence and intestinal cramping, treat indigestion, diarrhea, bad breath, headache, migraine, etc.
The essential oil extracted from Cinnamomum cassia Presl (CC-EO) and its major component, cinnamaldehyde, possess potent anti-tyrosinase and anti-melanogenic activities through theirs antioxidant activities and  may be a potential source of skin-whitening agents(18)

4. Red Onion((Allium cepa)
The onion is a plants in the genus Allium, belongs to the family Alliaceae, a close relation of garlic. It It is often called the "king of vegetables" because of its pungent taste and found in a large number of recipes and preparations spanning almost the totality of the world's cultures. Depending on the variety, an onion can be sharp, spicy, tangy, pungent, mild or sweet.
Quercetin 4'-O-β-D-glucopyranoside was isolated from the dried skin of A. cepa. showed tyrosinase inhibitory activity as it possesses ingredients with potential for skin-whitening cosmetics(19).

5. Ginger
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
[6]-Gingerol, an active component of ginger not only (25-100 µM) effectively suppressed murine tyrosinase activity and decreases the amount of melanin, but also decreased the intracellular reactive oxygen species (ROS) level in a dose-dependent manner(20). the University of Malaya, in the study of the effects of [8]-Gingerol, another active component of Zinger, found that  [8]-gingerol (5-100μM) not only effectively suppressed intracellular tyrosinase activity and decreased the amount of melanin in B16F10 and B16F1 cells, but also fectively decreased intracellular reactive species (RS) and reactive oxygen species (ROS) levels at the same dose manner, probably through down-regulation of both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways or through its antioxidant properties(21).

6.  Pomegranate
Pomegranates is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.
Pomegranate extract (PE) containing 90% ellagic acid administered orally, inhibited UV-induced skin pigmentation on the back of brownish guinea pigs with  skin-whitening effect was similar between guinea pigs fed with PE and those fed with L-ascorbic acid(21a) and moderate effect in human skin(21b).

C. The Antioxidants
C.1. Free radical scavengers
Suggestions of antioxidants, may be next potential agent in inhibition of tyrosinase activity and reduction of the melanin content in cells(22)(22a)
1. Vitamin C,
Vitamin C also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.
Ascorbic acid (AA) has been well known as a skin whitening agent, according to the Mahidol University, AA showed to inhibit UVA-mediated catalase (CAT) inactivation, glutathione (GSH) depletion, oxidant formation and NO production through suppression of eNOS and iNOS mRNA via its antioxidant defense(23). In the comparison of orchid extracts and 3% vitamin C derivative formulated, researchers at the Osaka National Hospital, National Hospital Organizationfound that the orchid-rich plant extracts possess efficacy similar to vitamin C derivative in whitening the skin as well as melasma and lentigo senilis on the face of Japanese women(24). Other study suggested that topical application of the composition of L(+) lactic acid supplemented with ascorbic acid (1%) produced a whitening effect and a modest preferential lightening of age spots which becomes apparent after three months, through demonstrated clinically by the test panelists, and trained clinicians, and with objective instrumental methods(25).

2. Vitamin E
Vitamin E,  a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(26), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..
The study in comparison of the effects of vitamin E analogues (d-alpha-, dl-alpha-, d-beta-, d-gamma-, and d-delta-tocopherols, d-alpha- and dl-alpha-tocopheryl acetates) and 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMC) on melanogenesis in mouse B16 melanoma cells, showed a positive effects of d-beta-tocopherol and d-gamma-tocopherol, 2 variants of vitamin E, in skin whitening with lower skin toxicity, as well as improved skin pigmentation such as skin spots and freckles caused by UV exposure(27). According to Kobe University School of Medicine, alpha-Tocopheryl ferulate (alpha-TF), a compound containing alpha-T (a variant of vitamin E) and ferulic acid exhibited an efficient whitening effects, through suppressed melanogenesis and inhibited biological reactions induced by reactive oxygen species(28)(29).

C.2. The antioxidants
1. Resveratrol
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc.
Piceatannol, a derivative of resveratrol exerted its antimelanogenic action through the combined effect of antioxidative property
and suppressed RS generation while increasing the GSH/GSSG ratio(30). According to 1Johnson &
Johnson Skin Research Center, resveratrol may be a potential cosmetic skin whitening agent through
reduced microphthalmia-associated transcription factor and tyrosinase promoter activities(31).

4. Glutathione
Glutathione (GSH), an antioxidants plays an important role in protecting cells against the free radicals
and ixidative stress, may be a potential agent in the management of hyperpigmentation(32). According
to the Chulalongkorn University, orally administered glutathione, 500 mg per day for 4 weeks, was found
effectively in reduced melanin indices consistently in all subjects(33) and may be used in the treatment
of pigmentary disorders.(34). Other study also indicated the effectiveness of  glutathione in regulatesing
 melanocytotoxicity and depigmenting potency of N-acetyl-4-S-CAP in black and yellow mice(35)


Taken altogether, although with scattered data, the herbs, foods, and antioxidants indicated above may potent in exhibition of the depigment and lightening (whitening) effects, through inhibited, and biological reactions induced by reactive oxygen species and suppressed melanogenesis and intracellular tyrosinase activity. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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References
(a) Tyrosinase modulation by five Rwandese herbal medicines traditionally used for skin treatment by Kamagaju L1, Morandini R, Bizuru E, Nyetera P, Nduwayezu JB, Stévigny C, Ghanem G, Duez P.(PubMed)
(b) An ethnobotanical survey of medicinal plants used in Rwanda for voluntary depigmentation by Kamagaju L1, Bizuru E, Minani V, Morandini R, Stévigny C, Ghanem G, Duez P.(PubMed)
(c) Tyrosinase inhibition by extracts and constituents of Sideroxylon inerme L. stem bark, used in South Africa for skin lightening by Momtaz S1, Mapunya BM, Houghton PJ, Edgerly C, Hussein A, Naidoo S, Lall N.(PubMed))
(1) In silico prediction of the cosmetic whitening effects of naturally occurring lead compounds by Fong P1, Tong HH.(PubMed)
(2) Screening of Chinese herbal medicines for antityrosinase activity in a cell free system and B16 cells by Ye Y1, Chou GX, Mu DD, Wang H, Chu JH, Leung AK, Fong WF, Yu ZL(PubMed)
(3) [Glycol plant extracts in the prescription of topical skin-whitening hydrogels].[Article in Polish] by Piechota-Urbańska M1, Berner-Strzelczyk A.(PubMed)
(4) [The effect of dry standardized plant extracts on the process of arbutin release from topical preparations produced on Carbopol base].[Article in Polish] by Piechota-Urbańska M.(PubMed)
(5) In silico prediction of the cosmetic whitening effects of naturally occurring lead compounds by Fong P1, Tong HH.(PubMed)
(6) Screening of Chinese herbal medicines for antityrosinase activity in a cell free system and B16 cells by Ye Y1, Chou GX, Mu DD, Wang H, Chu JH, Leung AK, Fong WF, Yu ZL.(PubMed)
(7) Melanogenesis inhibition by gallotannins from Chinese galls in B16 mouse melanoma cells by Chen LG1, Chang WL, Lee CJ, Lee LT, Shih CM, Wang CC.(PubMed)
(8) Depigmentation of melanocytes by the treatment of extracts from traditional Chinese herbs: a cell culture assay by Zhong S1, Wu Y, Soo-Mi A, Zhao J, Wang K, Yang S, Jae-Ho Y, Zhu X.(PubMed)
(9) Inhibitory effects of Sargassum polycystum on tyrosinase activity and melanin formation in B16F10 murine melanoma cells by Chan YY1, Kim KH, Cheah SH(PubMed)
(10) Partially purified components of Nardostachys chinensis suppress melanin synthesis through ERK and Akt signaling pathway with cAMP down-regulation in B16F10 cells by Jang JY1, Kim HN, Kim YR, Choi WY, Choi YH, Shin HK, Choi BT.(PubMed)
(11) Aqueous fraction from Cuscuta japonica seed suppresses melanin synthesis through inhibition of the p38 mitogen-activated protein kinase signaling pathway in B16F10 cells by Jang JY1, Kim HN, Kim YR, Choi YH, Kim BW, Shin HK, Choi BT.(PubMed)
(12) Curcumin suppresses alpha-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells by Lee JH1, Jang JY, Park C, Kim BW, Choi YH, Choi BT.(PubMed)
(13) Partially purified Curcuma longa inhibits alpha-melanocyte-stimulating hormone-stimulated melanogenesis through extracellular signal-regulated kinase or Akt activation-mediated signalling in B16F10 cells by Jang JY1, Lee JH, Jeong SY, Chung KT, Choi YH, Choi BT.(PubMed)
(13a) Fermenting red ginseng enhances its safety and efficacy as a novel skin care anti-aging ingredient: in vitro and animal study by Lee HS1, Kim MR, Park Y, Park HJ, Chang UJ, Kim SY, Suh HJ.(PubMed)
(14) Evaluation of free radical scavenging and antityrosinase activities of standardized longan fruit extract by Rangkadilok N1, Sitthimonchai S, Worasuttayangkurn L, Mahidol C, Ruchirawat M, Satayavivad J.(PubMed)
(15) Enhanced antioxidant and antityrosinase activities of longan fruit pericarp by ultra-high-pressure-assisted extraction by rasad KN1, Yang B, Shi J, Yu C, Zhao M, Xue S, Jiang Y.(PubMed)
(16) Physiological activity of irradiated green tea polyphenol on the human skin by An BJ1, Kwak JH, Son JH, Park JM, Lee JY, Park TS, Kim SY, Kim YS, Jo C, Byun MW.(PubMed)
(17) Protective effects of tea polysaccharides and polyphenols on skin by Wei X1, Liu Y, Xiao J, Wang Y.(PubMed)
(18) Cinnamomum cassia essential oil inhibits α-MSH-induced melanin production and oxidative stress in murine B16 melanoma cells by Chou ST1, Chang WL, Chang CT, Hsu SL, Lin YC, Shih Y.(PubMed)
(19) Tyrosinase inhibitory effect of quercetin 4'-O-β-D-glucopyranoside from dried skin of red onion (Allium cepa) by Arung ET1, Wijaya Kusuma I, Shimizu K, Kondo R.(PubMed)
(20) Inhibitory effect of [6]-gingerol on melanogenesis in B16F10 melanoma cells and a possible mechanism of action by Huang HC1, Chiu SH, Chang TM.(PubMed)
(21) [8]-Gingerol inhibits melanogenesis in murine melanoma cells through down-regulation of the MAPK and PKA signal pathways by Huang HC1, Chou YC, Wu CY, Chang TM.(PubMed)
(21a) Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation by Yoshimura M1, Watanabe Y, Kasai K, Yamakoshi J, Koga T.(PubMed)
(21b) Effects of oral administration of ellagic acid-rich pomegranate extract on ultraviolet-induced pigmentation in the human skin by Kasai K1, Yoshimura M, Koga T, Arii M, Kawasaki S.(PubMed)
(22) Biofunctional Constituents from Liriodendron tulipifera with Antioxidants and Anti-Melanogenic Properties by Li WJ1, Lin YC, Wu PF, Wen ZH, Liu PL, Chen CY, Wang HM.(PubMed)
(22a) The effects of areca catechu L extract on anti-inflammation and anti-melanogenesis by Lee KK1, Choi JD.(PubMed)
(23) Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system by Panich U1, Tangsupa-a-nan V, Onkoksoong T, Kongtaphan K, Kasetsinsombat K, Akarasereenont P, Wongkajornsilp A.(PubMed)
(24) \Whitening efficacy of plant extracts including orchid extracts on Japanese female skin with melasma and lentigo senilis by Tadokoro T1, Bonté F, Archambault JC, Cauchard JH, Neveu M, Ozawa K, Noguchi F, Ikeda A, Nagamatsu M, Shinn S.(PubMed)
(25) The effects of topical l(+) lactic Acid and ascorbic Acid on skin whitening by Smith WP.(PubMed)
(26) Traber MG. Vitamin E. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006;396-411.
(27) Comparison of the inhibitory effects of vitamin E analogues on melanogenesis in mouse B16 melanoma cells by Kamei Y1, Otsuka Y, Abe K.(PubMed)
(28) The depigmenting effect of alpha-tocopheryl ferulate on human melanoma cells by Funasaka Y1, Chakraborty AK, Komoto M, Ohashi A, Ichihashi M.(PubMed)
(29) Depigmenting effect of alpha-tocopheryl ferulate on normal human melanocytes by Funasaka Y1, Komoto M, Ichihashi M.(PubMed)
(30) Piceatannol inhibits melanogenesis by its antioxidative actions by Yokozawa T1, Kim YJ.(PubMed)
(31) Modulation of microphthalmia-associated transcription factor gene expression alters skin pigmentation by Lin CB1, Babiarz L, Liebel F, Roydon Price E, Kizoulis M, Gendimenico GJ, Fisher DE, Seiberg M.(PubMed)
(32) Natural ingredients for darker skin types: growing options for hyperpigmentation by Alexis AF Blackcloud P.(PubMed)
(33) Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study by Arjinpathana N1, Asawanonda P.(PubMed)
(34) Glutathione as a depigmenting agent: an overview by Villarama CD1, Maibach HI.(PubMed)
(35) Glutathione plays a key role in the depigmenting and melanocytotoxic action of N-acetyl-4-S-cysteaminylphenol in black and yellow hair follicles by Alena F1, Dixon W, Thomas P, Jimbow K.(PubMed)