• Sacha inchi Research

    BMC Genomics. 2012 Dec 20;13:716. doi: 10.1186/1471-2164-13-716.

    Transcriptome analysis of Sacha Inchi (Plukenetia volubilis L.) seeds at two developmental stages.

    Wang X1, Xu R, Wang R, Liu A.



    Sacha Inchi (Plukenetia volubilis L., Euphorbiaceae) is a potential oilseed crop because the seeds of this plant are rich in unsaturated fatty acids (FAs). In particular, the fatty acid composition of its seed oil differs markedly in containing large quantities of α-linolenic acid (18C:3, a kind of ω-3 FAs). However, little is known about the molecular mechanisms responsible for biosynthesis of unsaturated fatty acids in the developing seeds of this species. Transcriptome data are needed to better understand these mechanisms.


    In this study, de novo transcriptome assembly and gene expression analysis were performed using Illumina sequencing technology. A total of 52.6 million 90-bp paired-end reads were generated from two libraries constructed at the initial stage and fast oil accumulation stage of seed development. These reads were assembled into 70,392 unigenes; 22,179 unigenes showed a 2-fold or greater expression difference between the two libraries. Using this data we identified unigenes that may be involved in de novo FA and triacylglycerol biosynthesis. In particular, a number of unigenes encoding desaturase for formation of unsaturated fatty acids with high expression levels in the fast oil accumulation stage compared with the initial stage of seed development were identified.


    This study provides the first comprehensive dataset characterizing Sacha Inchi gene expression at the transcriptional level. These data provide the foundation for further studies on molecular mechanisms underlying oil accumulation and PUFA biosynthesis in Sacha Inchi seeds. Our analyses facilitate understanding of the molecular mechanisms responsible for the high unsaturated fatty acids (especially α-linolenic acid) accumulation in Sacha Inchi seeds.

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     Rejuvenation Res. 2005 Spring;8(1):46-57.

    Gerontomodulatory and youth-preserving effects of zeatin on human skin fibroblasts undergoing aging in vitro.

    Rattan SI1, Sodagam L.

    Our studies have shown that zeatin, (6-[4-hydroxy-3-methyl-but-2-enylamino]adenine), a cytokinin plant growth factor, has gerontomodulatory, youth preserving and anti-aging effects on serially passaged human adult skin fibroblasts undergoing aging in vitro. There were no immediate negative or toxic effects in terms of cell attachment, cell proliferation, cell survival, cytoskeletal organization, and cellular growth by treatment with zeatinconcentrations between 1 and 200 microM. During long-term treatment, cells could be maintained throughout their replicative lifespan in the presence of 40, 80, and 200 microM zeatin, but the optimal concentration of zeatin's anti-aging and youth preserving effects was found to be 80 microM. Life-long serial passaging of human skin  fibroblasts in the presence of zeatin resulted in the prevention of cell enlargement, reduction of intracellular debris, prevention of actin polymerization, and enhancement of cellular ability to decompose hydrogen peroxide and to cope with ethanol and oxidative stresses. Most importantly, anti-aging and beneficial effects of zeatin were observed without any induction of additional cell proliferation or an increase in the maximum proliferative capacity, thus ruling out any potentially harmful and carcinogenic effects.


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  • Moringa Research

    Moringa oleifera: a food plant with multiple medicinal uses.

    Anwar F1, Latif SAshraf MGilani AH.

    ytother Res. 2007 Jan;21(1):17-25.



    Moringa oleifera Lam (Moringaceae) is a highly valued plant, distributed in many countries of the tropics and subtropics. It has an impressive range of medicinal uses with high nutritional value. Different parts of this plant contain a profile of important minerals, and are a good of protein, vitamins, beta-carotene, amino acids and various phenolics. The Moringa plant provides a rich and rare combination of zeatin, quercetin, beta-sitosterol, caffeoylquinic acid and kaempferol. In addition to its compelling water purifying powers and high nutritional value, M. oleifera is very important for its medicinal value. Various parts of this plant such as the leaves, roots, seed, bark, fruit, flowers and immature pods act as cardiac and circulatory stimulants, possess antitumor, antipyretic, antiepileptic, anti-inflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, cholesterol lowering, antioxidant, antidiabetic, hepatoprotective, antibacterial and antifungal activities, and are being employed for the treatment of different ailments in the indigenous system of medicine, particularly in South Asia. This review focuses on the detailed phytochemical composition, medicinal uses, along with pharmacological properties of different parts of this multipurpose tree.

    Anti-fungal activity of crude extracts and essential oil of Moringa oleifera Lam.

    Chuang PH1, Lee CWChou JYMurugan MShieh BJChen HM.

    Bioresour Technol. 2007 Jan;98(1):232-6. Epub 2006 Jan 6.



    Investigations were carried out to evaluate the therapeutic properties of the seeds and leaves of Moringa oleifera Lam as herbal medicines. Ethanol extracts showed anti-fungal activities in vitro against dermatophytes such as Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis. GC-MS analysis of the chemical composition of the essential oil from leaves showed a total of 44 compounds. Isolated extracts could be of use for the future development of anti-skin disease agents.


    Evaluation of the polyphenol content and antioxidant properties of methanol extracts of the leaves, stem, and root barks of Moringa oleifera Lam.


    Atawodi SE1, Atawodi JCIdakwo GAPfundstein BHaubner RWurtele GBartsch HOwen RW.

    [PubMed - indexed for MEDLINE]

    J Med Food. 2010 Jun;13(3):710-6. doi: 10.1089/jmf.2009.0057.



    Medicinal plants have been shown to have both chemopreventive and/or therapeutic effects on cancer and other diseases related to oxidative damage. Moringa oleifera Lam., known in the Hausa and Igala languages of Nigeria as "Zogale" and "Gergedi," respectively, and drumstick in English, is a plant that is used both as food and in folkloric medicine in Nigeria and elsewhere. Different parts of the plant were analyzed for polyphenol content as well as in vitro antioxidant potential. The methanol extract of the leaves of M. oleifera contained chlorogenic acid, rutin, quercetin glucoside, and kaempferol rhamnoglucoside, whereas in the root and stem barks, several procyanidin peaks were detected. With the xanthine oxidase model system, all the extracts exhibited strong in vitro antioxidant activity, with 50% inhibitory concentration (IC(50)) values of 16, 30, and 38 microL for the roots, leaves, and stem bark, respectively. Similarly, potent radical scavenging capacity was observed when extracts were evaluated with the 2-deoxyguanosine assay model system, with IC(50) values of 40, 58, and 72 microL for methanol extracts of the leaves, stem, and root barks, respectively. The high antioxidant/radical scavenging effects observed for different parts of M. oleifera appear to provide justification for their widespread therapeutic use in traditional medicine in different continents. The possibility that this high antioxidant/radical scavenging capacity may impact on the cancer chemopreventive potential of the plant must be considered.


    Chemical composition and biological activity of the essential oil from leaves of Moringa oleifera Lam. cultivated in Mozambique.

    Marrufo T1, Nazzaro FMancini EFratianni FCoppola RDe Martino LAgostinho ABDe Feo V.

    olecules. 2013 Sep 9;18(9):10989-1000. doi: 10.3390/molecules180910989.

     moringa powder


    The antioxidant capacity and antimicrobial activity of the essential oil of Moringa oleifera (Moringaceae) grown in Mozambique was investigated. The chemical composition was studied by means of GC and GC-MS analysis. Hexacosane (13.9%), pentacosane (13.3%) and heptacosane (11.4%) were the main components. Ultra High Performance Chromatography-DAD analysis detected the flavonoids quercetin (126 μg/g) and luteolin (6.2 μg/g). The essential oil exhibited a relatively low free radical scavenging capacity. The antimicrobial activity of the essential oil was assayed against two Gram-positive strains (Bacillus cereus, Staphylococcus aureus), two Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa), and five fungal strains of agro-food interest (Penicillium aurantiogriseum, Penicillium expansum, Penicillium citrinum, Penicillium digitatum, and Aspergillus niger spp.). B. cereus and P. aeruginosa, as well as the fungal strains were sensitive to the essential oil.


    Chemomodulatory effect of Moringa oleifera, Lam, on hepatic carcinogen metabolising enzymes, antioxidant parameters and skin papillomagenesis in mice.

    Bharali RTabassum JAzad MR.

    Department of Biotechnology, Gauhati University, Guwahati 781014, Assam, India.


    Asian Pac J Cancer Prev. 2003 Apr-Jun;4(2):131-9.



    The modulatory effects of a hydro-alcoholic extract of drumsticks of Moringa oliefera Lam at doses of 125 mg/kg bodyweight and 250 mg/ kg body weight for 7 and 14 days, respectively, were investigated with reference to drug metabolising Phase I (Cytochrome b(5) and Cytochrome p(450) ) and Phase II (Glutathione-S- transferase) enzymes, anti-oxidant enzymes, glutathione content and lipid peroxidation in the liver of 6-8 week old female Swiss albino mice. Further, the chemopreventive efficacy of the extract was evaluated in a two stage model of 7,12 - dimethylbenz(a)anthracene induced skin papillomagenesis. Significant increase (p<0.05 to p<0.01) in the activities of hepatic cytochrome b(5), cytochrome p(450), catalase, glutathione peroxidase ( GPx ), glutathione reductase (GR), acid soluble sulfhydryl content (-SH ) and a significant decrease ( p<0.01 ) in the hepatic MDA level were observed at both dose levels of treatment when compared with the control values. Glutathione-S- transferase ( GST )activity was found to be significantly increased (p<0.01 ) only at the higher dose level. Butylated hydroxyanisol (BHA ) fed at a dose of 0.75% in the diet for 7 and 14 days (positive control ) caused a significant increase (p<0.05 to p<0.01) in the levels of hepatic phase I and phase II enzymes, anti- oxidant enzymes, glutathione content and a decrease in lipid peroxidation. The skin papillomagenesis studies demonstrated a significant decrease (p<0.05 ) in the percentage of mice with papillomas, average number of papillomas per mouse and papillomas per papilloma bearing mouse when the animals received a topical application of the extract at a dose of 5mg/ kg body weight in the peri-initiation phase 7 days before and 7 days after DMBA application, Group II ), promotional phase (from the day of croton oil application and continued till the end of the experiment, Group III ) and both peri and post initiation stages (from 7 days prior to DMBA application and continued till the end of the experiment, Group IV) compared to the control group (Group I ). The percentage inhibition of tumor multiplicity has been recorded to be 27, 72, and 81 in Groups II, III, and IV, respectively. These findings are suggestive of a possible chemopreventive potential of Moringa oliefera drumstick extract against chemical carcinogenesis.


    Moringa oleifera Lam. (Moringaceae) grown in Nigeria: In vitro antisickling activity on deoxygenated erythrocyte cells.

    Adejumo OEKolapo ALFolarin AO.

    Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Olabisi Onabanjo University, Sagamu, Nigeria.

    Pharm Bioallied Sci. 2012 Apr;4(2):118-22. doi: 10.4103/0975-7406.94812.

    Phytochemical screening revealed the presence of saponins, free anthraquinones, and alkaloids.


    moringa leaf

    Moringa oleifera: a food plant with multiple medicinal uses.

    Anwar FLatif SAshraf MGilani AH.

    Phytother Res. 2007 Jan;21(1):17-25.

    Department of Chemistry, University of Agriculture, Faisalabad-38040, Pakistan.



    Moringa oleifera Lam (Moringaceae) is a highly valued plant, distributed in many countries of the tropics and subtropics. It has an impressive range of medicinal uses with high nutritional value. Different parts of this plant contain a profile of important minerals, and are a good of protein, vitamins, beta-carotene, amino acids and various phenolics. The Moringa plant provides a rich and rare combination of zeatin, quercetin, beta-sitosterol, caffeoylquinic acid and kaempferol. In addition to its compelling water purifying powers and high nutritional value, M. oleifera is very important for its medicinal value. Various parts of this plant such as the leaves, roots, seed, bark, fruit, flowers and immature pods act as cardiac and circulatory stimulants, possess antitumor, antipyretic, antiepileptic, antiinflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, cholesterol lowering, antioxidant, antidiabetic, hepatoprotective, antibacterial and antifungal activities, and are being employed for the treatment of different ailments in the indigenous system of medicine, particularly in South Asia. This review focuses on the detailed phytochemical composition, medicinal uses, along with pharmacological properties of different parts of this multipurpose tree.


    Profiling glucosinolates and phenolics in vegetative and reproductive tissues of the multi-purpose trees Moringa oleifera L. (horseradish tree) and Moringa stenopetala L.


    Bennett RNMellon FAFoidl NPratt JHDupont MSPerkins LKroon PA.

    J Agric Food Chem. 2003 Jun 4;51(12):3546-53.


    Phytochemicals, Nutrition Division, Institute of Food Research, Norwich Research Park, Colney Lane, Norwich, Malawi.



    Moringa species are important multi-purpose tropical crops, as human foods and for medicine and oil production. There has been no previous comprehensive analysis of the secondary metabolites in Moringa species. Tissues of M. oleifera from a wide variety of s and M. stenopetala from a single were analyzed for glucosinolates and phenolics (flavonoids, anthocyanins, proanthocyanidins, and cinnamates). M. oleifera and M. stenopetala seeds only contained 4-(alpha-l-rhamnopyranosyloxy)-benzylglucosinolate at high concentrations. Roots of M. oleifera and M. stenopetala had high concentrations of both 4-(alpha-l-rhamnopyranosyloxy)-benzylglucosinolate and benzyl glucosinolate. Leaves from both species contained 4-(alpha-l-rhamnopyranosyloxy)-benzylglucosinolate and three monoacetyl isomers of this glucosinolate. Only 4-(alpha-l-rhamnopyranosyloxy)-benzylglucosinolate was detected in M. oleifera bark tissue. M. oleifera leaves contained quercetin-3-O-glucoside and quercetin-3-O-(6' '-malonyl-glucoside), and lower amounts of kaempferol-3-O-glucoside and kaempferol-3-O-(6' '-malonyl-glucoside). M. oleifera leaves also contained 3-caffeoylquinic acid and 5-caffeoylquinic acid. Leaves of M. stenopetala contained quercetin 3-O-rhamnoglucoside

    (rutin) and 5-caffeoylquinic acid. Neither proanthocyanidins nor anthocyanins were detected in any of the tissues of either species.


    Kaempferol, a potential cytostatic and cure for inflammatory disorders.

    Rajendran P1, Rengarajan T1, Nandakumar N2, Palaniswami R3, Nishigaki Y1,Nishigaki I4.

    Eur J Med Chem. 2014 Oct 30;86:103-12. doi: 10.1016/j.ejmech.2014.08.011. Epub 2014 Aug 5.1NPO-International Laboratory of Biochemistry, 1-166, Uchide, Nakagawa-ku, Nagoya 454-0926, Japan.
    2Department of Microbiology, Immunology and Genetics, Ben Gurion University of the Negev, Beer Sheva 84105, P.O.B. 653, Israel.
    3Department of Applied Zoology and Biotechnology, Vivekananda College, Affiliated to Madurai Kamaraj University, Thiruvedakam West, Madurai 625234, India.
    4NPO-International Laboratory of Biochemistry, 1-166, Uchide, Nakagawa-ku, Nagoya 454-

    0926, Japan. Electronic address:



    Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g., tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries, and grapes) and in plants or botanical products commonly used in traditional medicine (e.g., Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Its anti-oxidant/anti-inflammatory effects have been demonstrated in various disease models, including those for encephalomyelitis, diabetes, asthma, and


    carcinogenesis. Moreover, kaempferol act as a scavenger of free radicals and superoxide radicals as well as preserve the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase, and glutathione-S-transferase. The anticancer effect of this flavonoid is mediated through different modes of action, including anti-proliferation, apoptosis induction,

    cell-cycle arrest, generation of reactive oxygen species (ROS), and anti-metastasis/anti-angiogenesis activities. In addition, kaempferol was found to exhibit its anticancer activity through the modulation of multiple molecular targets including p53 and STAT3, through the activation of caspases, and through the generation of ROS. The anti-tumor effects of kaempferol have also been investigated in tumor-bearing mice. The combination of kaempferol and conventional chemotherapeutic drugs produces a greater therapeutic effect than the latter, as well as reduces the toxicity of the latter. In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of kaempferol with a focus on its molecular targets and the possible use of this flavonoid for the treatment of inflammatory diseases and cancer.

    Copyright © 2014. Published by Elsevier Masson SAS.



    Therapeutic Potential of Moringa oleifera Leaves in Chronic Hyperglycemia and Dyslipidemia: A Review.

    Mbikay M.

    Chronic Disease Program, Ottawa Hospital Research Institute Ottawa, ON, Canada.

    Front Pharmacol. 2012 Mar 1;3:24. doi: 10.3389/fphar.2012.00024. eCollection 2012.



    Moringa oleifera (M. oleifera) is an angiosperm plant, native of the Indian subcontinent, where its various parts have been utilized throughout history as food and medicine. It is now cultivated in all tropical and sub-tropical regions of the world. The nutritional, prophylactic, and therapeutic virtues of this plant are being extolled on the Internet. Dietary consumption of its part is therein promoted as a strategy of personal health preservation and self-medication in various diseases. The enthusiasm for the health benefits of M. oleifera is in dire contrast with the scarcity of strong experimental and clinical evidence supporting them. Fortunately, the chasm is slowly being filled. In this article, I review current scientific data on the corrective potential of M. oleifera leaves in chronic hyperglycemia and dyslipidemia, as symptoms of

    diabetes and cardiovascular disease (CVD) risk. Reported studies in experimental animals and humans, although limited in number and variable in design, seem concordant in their support

    for this potential. However, before M. oleifera leaf formulations can be recommended as medication in the prevention or treatment of diabetes and CVD, it is necessary that the scientific basis of their efficacy, the therapeutic modalities of their administration and their possible side effects be more rigorously determined.



    CHLOROPHYLL:  Moringa is one of the few foods that contain chlorophyll together with so many other nutrients. Chlorophyll is often referred to as the ‘blood of plants.” Studies have shown that it supports liver function and detoxification of the body.

    BETA-SITOSTEROL:  Beta-sitosterol is a specific plant sterol which has been shown to reduce blood cholesterol levels and also improve other blood lipid levels, bringing them to a more normal range.  Plant sterols like beta-sitosterol are also proven to be very beneficial in preventing and treating prostate enlargement due to aging, and have been found to reduce the growth of prostate and colon cancer cells.  Beta-sitosterol also boosts the immune system, has anti-inflammatory properties, helps normalize blood sugar, supports the pancreas, helps to heal ulcers and can alleviate cramps.

    moringa seeds 

    ZEATIN:  Biochemical analysis has revealed that the Moringa leaves and leaf powder contain unusually high amounts of plant hormones named cytokinins, such as zeatin and the related dihyrozeatin.  Scientists have found zeatin in very low concentrations in plants, with zeatin concentrations varying between .00002 mcg/g material to .02 mcg/g.  The zeatin concentration in Moringa leaves gathered from various parts of the world was found to be very high, between 5 mcg and 200 mcg/g material, or thousands of times more concentrated than most plants studied so far.  

    Cytokinins function as plant hormones, which are naturally occurring growth promoters and factors that delay the process of aging in many plants.  In cultured human cells, cytokinins have proven to delay biochemical modifications associated with aging.  Zeatin has potent antioxidant properties, and has been shown to protect the skin and increase the activity of known anti-oxidant enzymes that naturally fight aging.  It has also been shown to protect animals against neuronal toxicity induced by age specific factors, and in the laboratory setting, to inhibit cancer cell growth and induce their differentiation back into normal cells.  

    LUTEIN:  Moringa has extraordinary amounts of lutein.  100 g of leaves contain more than 70 mg, while the recommended daily amount for the best protective antioxidant activity is 5 – 20 mg for an adult.  Lutein promotes healthy eyes by reducing the risk of macular degeneration.  

    CAFFEOYLQUINIC ACIDS:  Moringa leaves contain 0.5 – 1% caffeoylquinic acids, coming very close to the content that makes artichokes famous.  Caffeoylquinic acids are antioxidants considered to be choleretic (bile increasing which helps to digest dietary fats), hepatoprotective (effective against hepatitis and other liver diseases), cholesterol-reducing, and diuretic. 

    NOTE:  Complex mixtures of naturally occurring antioxidants from plants are the most effective and beneficial protectors against oxidation and aging.  Moringa contains many other antioxidants including alpha carotene, xanthins, kaempferol, quercetin, and rutin.


    Effect of dehydration methods on retention of carotenoids, tocopherols, ascorbic acid and antioxidant activity in Moringa oleifera leaves and preparation of a RTE product.

    Saini RK1, Shetty NP1, Prakash M2, Giridhar P1.

    Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysore, 570 020 India.
    2Sensory Science Department, CSIR-Central Food Technological Research Institute, Mysore, 570 020 India.

    J Food Sci Technol. 2014 Sep;51(9):2176-82. doi: 10.1007/s13197-014-1264-3. Epub 2014 Jan 30.



    Fresh leaves of M. oleifera plants were analysed for nutritionally important phytoconstituents and feasible commercially used dehydration method were evaluated to preserve these in dehydrated leaves. Trans-lutein, trans-β-carotene and trans-zeaxanthin were found as the major carotenoids in fresh leaves, accounting for 36.9, 18.2 and 5.5 mg/100 g FW, respectively. Similarly, high amounts of ascorbic acid, α-tocopherol and total phenolic content (271.0, 36.9 and 512.0 mg/100 g FW), respectively were recorded in leaves. α-tocopherol was the most stable vitamin under all drying conditions (86.4 % retention during oven drying), compare to other studied phytoconstituents. Cabinet tray drying was found as efficient as lyophilisation to retain maximum content of total carotenoids (60.1 %), trans-β-carotene (90.1 %), 13-cis-lutein (93.2 %), and DPPH activity, however, lutein (51.3 %) and ascorbic acid (97.8 %) was best preserved by lyophilisation. During dehydration, significant trans to cis isomerization of β-carotene and lutein was also recorded. A ready to eat (RTE) chutney powder (adjunct) was developed from dehydrated leaves. The product was evaluated using Quantitative Descriptive Analysis and was accepted with a high overall quality score. The present investigation explores the nutritional potential of M. oleifera leaves and suitable methods of drying that could be useful for processed food formulation.



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  • MSM research for skin:

    MSM research for skin:

    MSM improves rosacea: Combined effects of silymarin and methylsulfonylmethane in the management of rosacea: clinical and instrumental evaluation.

    Berardesca E1Cameli NCavallotti CLevy JLPiérard GEde Paoli Ambrosi G.

    J Cosmet Dermatol. 2008 Mar;7(1):8-14. doi: 10.1111/j.1473-2165.2008.00355.x.



    skin benefits for msm




    This study aims to evaluate a topical treatment based on silymarin/methylsulfonilmethane (S-MSM) to improve erythematous-telangiectactic rosacea.



    Forty-six patients affected by stage I-III rosacea entered this double-blind, placebo-controlled study. Subjects were treated for 1 month. Clinical and instrumental evaluations were done at baseline, after 10 and 20 days, and at the end of the study. Itching, stinging, erythema, and papules were investigated clinically as well as hydration and erythema instrumentally with capacitance and color measurements.



    A statistically significant improvement was observed in many clinical and instrumental parameters investigated (P < 0.001). In particular, improvement of skin redness, papules, itching, hydration, and skin color occurred.



    The combination of silymarin and S-MSM can be useful in managing symptoms and condition of rosacea skin, especially in the rosacea subtype 1 erythemato-telangiectatic phase. The action can be considered multicentric and multiphase because of the direct modulating action on cytokines and angiokines normally involved and up-regulated in the case of such skin condition.

    Clinical and instrumental evaluation of skin improvement after treatment with a new 50% pyruvic acid peel.

    Berardesca E1Cameli NPrimavera GCarrera M.

    Dermatol Surg. 2006 Apr;32(4):526-31.





    Pyruvic acid is an alpha-keto acid that presents keratolytic, antimicrobial, and sebostatic properties as well as the ability to stimulate new collagen production and elastic fibers formation. Because of its low pKa and its small dimension, it penetrates rapidly and deeply through the skin, so far as to be considered a potent chemical peel agent. It has proven its efficacy for the treatment of many dermatological conditions such as acne, superficial scarring, photodamage, and pigmentary disorders. Pyruvic acid application usually induces intense burning, and the postpeeling period is characterized by erythema, desquamation, and, sometimes, crusting.



    The aim of the study is to assess the efficacy and tolerability of 50% pyruvic acid in a new non-erythematogenic formulation (pyruvic acid 50%, dimethyl isosorbide, propylene glycol, ethyl alcohol, dimethyl sulfone, ethyl lactate, water) for the treatment of photodamage, superficial scarring, and melasma.


    Twenty subjects affected by photodamage, superficial scarring, and melasma, but otherwise healthy, entered the study. Four peeling sessions were performed once every 2 weeks. The patients were evaluated clinically and by means of several noninvasive methods in order to monitor the following parameters: hydration, color (erythema and pigmentation), elasticity, skin smoothness, skin roughness, scaliness, and wrinkles.



    The patients did not report any discomfort either during the peeling session or during the postpeeling period, without any impact on their social life. We did not observe any case of persistent erythema as well as any case of postinflammatory hyperpigmentation. Instrumental evaluations showed a significant reduction in the degree of pigmentation in patients with melasma, a significant increase in skin elasticity, and an improvement of the degree of wrinkling in all the patients.



    This innovative formulation of 50% pyruvic acid peel has been shown to be safe and effective to treat photodamage, melasma, and superficial scarring, allowing the patients to carry out regularly their working life as well as their social life. Furthermore, the results have been evaluated by means of noninvasive devices, which have permitted one to quantify the improvements.

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    Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks.

    Darbre PD1Harvey PW.

    J Appl Toxicol. 2008 Jul;28(5):561-78. doi: 10.1002/jat.1358.



    This toxicology update reviews research over the past four years since publication in 2004 of the first measurement of intact esters of p-hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been confirmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not only in vitro but also in vivo using healthy human subjects. Using a wide variety of assay systems in vitro and in vivo, the oestrogen agonist properties of parabens together with their common metabolite (p-hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co-formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to


    influence development of malignant melanoma which has also recently been shown to be influenced by oestrogenic stimulation.


    Significance of the detection of esters of p-hydroxybenzoic acid (parabens) in human breast tumours.

    Harvey PWEverett DJ.

    J Appl Toxicol. 2004 Jan-Feb;24(1):1-4.



    This issue of Journal of Applied Toxicology publishes the paper Concentrations of Parabens in Human Breast Tumours by Darbre et al. (2004), which reports that esters of p-hydroxybenzoic acid (parabens) can be detected in samples of tissue from human breast tumours. Breast tumour samples were supplied from 20 patients, in collaboration with the Edinburgh Breast Unit Research Group, and analysed by high-pressure liquid chromatography and tandem mass spectrometry. The parabens are used as antimicrobial preservatives in underarm deodorants and antiperspirants and in a wide range of other consumer products. The parabens also have inherent oestrogenic and other hormone related activity (increased progesterone receptor gene expression). As oestrogen is a major aetiological factor in the growth and development of the majority of human breast cancers, it has been previously suggested by Darbre that parabens and other chemicals in underarm cosmetics may contribute to the rising incidence of breast cancer. The significance of the finding of parabens in tumour samples is discussed here in terms of 1). Darbre et al's study design, 2). what can be inferred from this type of data (and what can not, such as the cause of these tumours), 3). the toxicology of these compounds and 4). the limitations of the existing toxicology database and the need to consider data that is appropriate to human exposures.


    Concentrations of parabens in human breast tumours.

    Darbre PD1Aljarrah AMiller WRColdham NGSauer MJPope GS.

    J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.


    Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which thehuman population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.


    Endocrine disrupters and human health: could oestrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women?

    Harvey PW1Darbre P.

    J Appl Toxicol. 2004 May-Jun;24(3):167-76.



    In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or


    lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected inhuman breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of: data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, becauseexposure to oestrogenic chemicals through application of body care products (unlike diffuse environmental chemical exposures) should be amenable to evaluation, quantification and control. The exposure issues are clear and the exposed population is large, and these factors should provide the necessary impetus to investigate this potential issue of public health.


    Parabens, oestrogenicity, underarm cosmetics and breast cancer: a perspective on a hypothesis.

    Harvey PW.

    J Appl Toxicol. 2003 Sep-Oct;23(5):285-8.



    A recent review by Darbre (2003) published in this journal (J. Appi. Toxicol. 23: 89-95) has attracted public and scientific interest that requires perspective, particularly on the use of esters of p-hydroxybenzoic acid (parabens) as preservatives in underarm cosmetics. Although parabens are generally regarded as safe, recent reports suggest


    that they are oestrogenic in a variety of in vitro (including MCF7 and ZR-75-1 human breast cancer cell lines) and in vivo tests for oestrogenicity (uterotrophic assays in both rat and mouse). There are also recent reports of adverse reproductive and developmental outcomes in rodent toxicity studies. Of interest is the lack of activity by the oral route but clear activity by the subcutaneous and topical routes, which is of some relevance to the use of underarm cosmetics. There would seem to be a case now to supplement these emerging toxicity data with longer-term regulatory standard tests examining other oestrogenic endpoints and at least to consider these findings in more up-to-date risk assessments specific for cosmetic use. Further, there are few data on the use of underarm cosmetics and the risk of breast cancer, and although one recent retrospective interview-based study found no association there is a need for more thorough investigation taking into account the type of chemicals used. Darbre has forwarded a hypothesis and called for further work to establish whether or not the use of underarm cosmetics (particularly containing oestrogenic formulants) contributes to the rising incidence of breast cancer. It would seem prudent to conduct this work because the current database is sparse and the effects of long-term low-level exposures to weakly oestrogenic chemicals on humanhealth, particularly their application to the underarm and the risks of breast cancer, are unknown. The role of oestrogens in breast cancer, however, is undisputed.




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    Retinol lotion reduces the fine wrinkles from natural aging of skin, University of Michigan study finds.  

    One of the researchers is Cho with the Seoul National University in South Korea. In addition to Kang and Voorhees, authors of the study were lead author Reza Kafi, M.D.; Heh Shin Kwak, M.D.; Wendy E. Schumacher, B.S.; Soyun Cho, M.D., Ph.D.; Valerie N. Hanft, M.D.; Ted A. Hamilton, M.S.; Anya L. King, M.S.; Jacqueline D. Neal, B.S.E.; James Varani, Ph.D.; and Gary J. Fisher, Ph.D. All of the authors were at the University of Michigan Department of Dermatology when they participated in the study. Kafi and Kwak now are at Stanford Medical School, and Cho is with the Seoul National University in South Korea.


    “In the past, it was everyone believed that retinoids would treat only photoaging, or damage from exposure to sun. This is the first systematic, double-blind study showing that it improves any kind of aging – photoaging as well as natural aging,” says co-author John J. Voorhees, M.D., the Duncan and Ella Poth Distinguished Professor and chair of the Department of Dermatology at the U-M Medical School. “You can rub it anywhere, and it will help to treat the signs of aging.” RETINOL (retinoids) IS THE REASON AMG EYE SERUM IS SO POPULAR. 


    Improvement of naturally aged skin with vitamin A (retinol).

    Kafi R1, Kwak HS, Schumacher WE, Cho S, Hanft VN, Hamilton TA, King AL, Neal JD, Varani J, Fisher GJ, Voorhees JJ, Kang S.

    Arch Dermatol. 2007 May;143(5):606-12.





    To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin.


    Randomized, double-blind, vehicle-controlled, left and right arm comparison study.


    Academic referral center.


    The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities.


    Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks.


    Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas.


    After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (-1.64 [95% CI, -2.06 to -1.22] vs -0.08 [95% CI, -0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle.


    Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

    Triple nanoemulsion potentiates the effects of topical treatments with microencapsulatedretinol and modulates biological processes related to skin aging.

    Afornali A1, Vecchi Rd1, Stuart RM2, Dieamant G3, Oliveira LL4, Brohem CA5, Feferman IH6, Fabrício LH7, Lorencini M8.

    An Bras Dermatol. 2013 Nov-Dec;88(6):930-6. doi: 10.1590/abd1806-4841.20132208.





    The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage.

    natural retinol  


    To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging.


    Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR).


    A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging.


    This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.


    N-retinoyl-D-glucosamine, a new retinoic acid agonist, mediates topical retinoid efficacy with no irritation on photoaged skin.

    Kambayashi H1, Odake Y, Takada K, Funasaka Y, Ichihashi M, Kato S.

    r J Dermatol. 2005 Dec;153 Suppl 2:30-6.





    Chronic ultraviolet (UV) radiation from sunlight induces wrinkle formation. Retinoic acid (RA) can markedly improve wrinkles, although RA does have some side-effects, such as skin irritation. As the efficacy and cytotoxicity of RA has been traced to its free carboxylic acid, we synthesized a new molecule, N-retinoyl-D-glucosamine (GRA), in which a glucosamine has been attached to the polar end group of all-trans retinoic acid.


    To analyse the effect of topical GRA in wrinkle repair and anti-irritation in photoaged mice compared with topical RA, as well as to determine retinoic acid receptor (RAR) and retinoid X receptor (RXR) transactivation activity in vitro.


    Hairless mice were irradiated with 60 mJ cm-2 of UVB for 10 weeks, and then topically treated with 0.05% GRA or 0.05% RA for 8 weeks. An in vitro transcriptional assay was performed and the activity of GRA in 293 cells transfected with RAR-alpha or RXR-alpha expression plasmid and luciferase reporter plasmid then determined.



    Topical GRA and RA brought about almost complete disappearance of the wrinkles caused by UVB irradiation. The two ligands promoted both a wide repair zone histologically, and the expression of type 1 collagen in the skin. In contrast, topical GRA treatment did not produce irritation such as erythema or roughness, or alteration of transepidermal water loss values, compared with RA. In the in vitro luciferase assay, GRA resulted in significant dose-dependent RAR transactivation activity in a 100 times higher concentration range than RA. GRA did not mediate RXR transactivation activity at all.


    Topical GRA appears to be able to repair photoaged skin damage without any of the irritation caused by topical RA, probably via RAR transactivation activity.


    Marked improvement induced in photoaged skin of hairless mouse by ER36009, a novel RARgamma-specific retinoid, but not by ER35794, an RXR-selective agonist.

    Sakuta T1, Kanayama T.

    Int J Dermatol. 2006 Nov;45(11):1288-95.





    Photoaging (premature skin aging) results largely from repeated exposure of the skin to ultraviolet (UV) radiation from the sun. Topical all-trans retinoic acid (RA), the only agent that has been approved for the treatment of photoaging, has been shown to reverse this process. In this study, we evaluated the pharmacologic effects of novel synthetic retinoids, ER36009 and ER35794, on murine wrinkles induced by UVB. ER36009 is a specific agonist of retinoic acid receptor (RAR)gamma, the most abundant RAR subtype in the skin, while ER35794 is a potent retinoid X receptor (RXR)-selective agonist.


    After a 10-week exposure to escalating doses of UVB irradiation, the animals were treated three times per week with ER36009 (0.0001%, 0.00025%, 0.0005%), ER35794 (0.025%, 0.05%, 0.1%), RA (0.05%) or acetone (control) for 3 weeks.


    ER36009 exerted a dose-dependent wrinkle-effacing effect, and 0.0005% ER36009-treated skin was significantly different from the control. ER36009 also significantly and dose-dependently increased both epidermal thickness and the area of the dermal repair zone defined by newly synthesized collagen. The effect of 0.0005% ER36009 on photodamaged skin was superior to that of 0.05% RA. In contrast, ER35794 was inactive in this model, though this compound exhibited lower local toxicity than other retinoids.



    These data indicate that RARgamma, but not RXR, plays an important role in the improvement of the signs of photoaging, and so a specific RARgamma agonist might be superior to an RAR pan-agonist for clinical treatment. We conclude that ER36009 is a candidate for a potent anti-skin-aging agent.



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