Cellular Hydration Serum


Maple Leaf Complex

Cosmetic applications of glucitol-core containing gallotannins from a proprietary phenolic-enriched red maple (Acer rubrum) leaves extract: inhibition of melanogenesis via down-regulation of tyrosinase and melanogenic gene expression in B16F10 melanoma cells


The red maple (Acer rubrum) is a rich source of phenolic compounds which possess galloyl groups attached to different positions of a 1,5-anhydro-d-glucitol core. While these glucitol-core containing gallotannins (GCGs) have reported antioxidant and antiglycative effects, they have not yet been evaluated for their cosmetic applications. Herein, the anti-tyrosinase and anti-melanogenic effects of a proprietary phenolic-enriched red maple leaves extract [Maplifa™; contains ca. 45% ginnalin A (GA) along with other GCGs] were investigated using enzyme and cellular assays. The GCGs showed anti-tyrosinase activity with IC50 values ranging from 101.4 to 1047.3μM and their mechanism of tyrosinase inhibition (using GA as a Electronic supplementary material representative GCG) was evaluated by chelating and computational/modeling studies. GA reduced melanin content in murine melanoma B16F10 cells by 79.1 and 56.7% (at non-toxic concentrations of 25 and 50μM, respectively), and its mechanisms of anti-melanogenic effects were evaluated by using methods including fluorescent probe (DCFDA), real-time PCR, and western blot experiments. These data indicated that GA was able to: (1) reduce the levels of reactive oxygen species, (2) down-regulate the expression of MITF, TYR, TRP-1, and TRP-2 gene levels in a timedependent manner, and (3) significantly reduce protein expression of the TRP-2 gene. Therefore, the anti-melanogenic effects of red maple GCGs warrant further investigation of this proprietary natural product extract for potential cosmetic applications.

Source: Hang Ma, Jialin Xu, Nicholas A. DaSilva, Ling Wang, Zhengxi Wei, Liangran Guo, Shelby L. Johnson, Wei Lu, Jun Xu, Qiong Gu, and Navindra P. Seeram. "Cosmetic applications of glucitol-core containing gallotannins from a proprietary phenolic-enriched red maple (Acer rubrum) leaves extract: inhibition of melanogenesis via down-regulation of tyrosinase and melanogenic gene expression in B16F10 melanoma cells" Springer-Verlag Berlin Heidelberg (2017).

Cytoprotective effects of a proprietary red maple leaf extract and its major polyphenol, ginnalin A, against hydrogen peroxide and methylglyoxal induced oxidative stress in human keratinocytes


Phytochemicals from functional foods are common ingredients in dietary supplements and cosmetic products for anti-skin aging effects due to their antioxidant activities. A proprietary red maple (Acer rubrum) leaf extract (Maplifa™) and its major phenolic compound, ginnalin A (GA), have been reported to show antioxidant, anti-melanogenesis, and anti-glycation effects but their protective effects against oxidative stress in human skin cells remain unknown. Herein, we investigated the cytoprotective effects of Maplifa™ and GA against hydrogen peroxide (H2O2) and methylglyoxal (MGO)-induced oxidative stress in human keratinocytes (HaCaT cells). H2O2 and MGO (both at 400 μM) induced toxicity in HaCaT cells and reduced their viability to 59.2 and 61.6%, respectively. Treatment of Maplifa™ (50 μg mL-1) and GA (50 μM) increased the viability of H2O2- and MGO-treated cells by 22.0 and 15.5%, respectively. Maplifa™ and GA also showed cytoprotective effects by reducing H2O2-induced apoptosis in HaCaT cells by 8.0 and 7.2%, respectively. The anti-apoptotic effect of Maplifa™ was further supported by the decreased levels of apoptosis associated enzymes including caspases-3/7 and -8 in HaCaT cells by 49.5 and 19.0%, respectively. In addition, Maplifa™ (50 μg mL-1) and GA (50 μM) reduced H2O2- and MGO-induced reactive oxygen species (ROS) by 84.1 and 56.8%, respectively. Furthermore, flow cytometry analysis showed that Maplifa™ and GA reduced MGO-induced total cellular ROS production while increasing mitochondria-derived ROS production in HaCaT cells. The cytoprotective effects of Maplifa™ and GA in human keratinocytes support their potential utilization for cosmetic and/or dermatological applications.

Source: Chang Liu, Hao Guo, Joel A Dain, Yinsheng Wan, Xing-Hua Gao, Hong-Duo Chen, Navindra P Seeram, and Hang Ma. "Cytoprotective effects of a proprietary red maple leaf extract and its major polyphenol, ginnalin A, against hydrogen peroxide and methylglyoxal induced oxidative stress in human keratinocytes" Food and Function. (2020): 11(6):5105-5114.

Calendula Officinalis (Marigold)

Antioxidant and Skin Anti-Aging Effects of Marigold Methanol Extract


The objective of this study was to evaluate the antioxidant and anti-aging effects of marigold methanol extract (MGME) in human dermal fibroblasts. Total polyphenolic and flavonoid contents in MGME were 74.8 mg TAE (tannic acid equivalent)/g and 85.6 mg RE (rutin equivalent)/g, respectively. MGME (500 μg/mL) increased 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging, and superoxide dismutase (SOD)-like antioxidant activities by 36.5, 54.7, and 14.8%, respectively, compared with the control. At 1,000 μg/mL, these activities increased by 63.7, 70.6, and 20.6%, respectively. MGME (100 μg/mL) significantly increased the synthesis of type 1 procollagen by 83.7% compared with control treatment. It also significantly decreased Matrix Metalloproteinase-2 (MMP-2) activity andMMP-1mRNA expression by 36.5% and 69.5%, respectively; however, it significantly increased laminin-5mRNA expression by 181.2%. These findings suggest that MGME could protect human skin against photo-aging by attenuating oxidative damage, suppressing MMP expression and/or activity as well as by stimulating collagen synthesis.

Source: Chul Ho Kang, Sung Ja Rhie, and Young Chul Kim. "Antioxidant and Skin Anti-Aging Effects of Marigold Methanol Extract" Toxicological Research (2018): 34(1):31-39.

Protective effect of Calendula officinalis extract against UVB-induced oxidative stress in skin: evaluation of reduced glutathione levels and matrix metalloproteinase secretion


Background and purpose: Calendula officinalis flowers have long been employed time in folk therapy, and more than 35 properties have been attributed to decoctions and tinctures from the flowers. The main uses are as remedies for burns (including sunburns), bruises and cutaneous and internal inflammatory diseases of several origins. The recommended doses are a function both of the type and severity of the condition to be treated and the individual condition of each patient. Therefore, the present study investigated the potential use of Calendula officinalis extract to prevent UV irradiation-induced oxidative stress in skin.

Methods: Firstly, the physico-chemical composition of marigold extract (ME) (hydroalcoholic extract) was assessed and the in vitro antioxidant efficacy was determined using different methodologies. Secondly, the cytotoxicity was evaluated in L929 and HepG2 cells with the MTT assay. Finally, the in vivo protective effect of ME against UVB-induced oxidative stress in the skin of hairless mice was evaluated by determining reduced glutathione (GSH) levels and monitoring the secretion/activity of metalloproteinases.

Results and conclusions: The polyphenol, flavonoid, rutin and narcissin contents found in ME were 28.6 mg/g, 18.8 mg/g, 1.6 mg/g and 12.2mg/g, respectively and evaluation of the in vitro antioxidant activity demonstrated a dose-dependent effect of ME against different radicals. Cytoxicity experiments demonstrated that ME was not cytotoxic for L929 and HepG2 cells at concentrations less than or equal to of 15 mg/mL. However, concentrations greater than or equal to 30 mg/mL, toxic effects were observed. Finally, oral treatment of hairless mice with 150 and 300 mg/kg of ME maintained GSH levels close to non-irradiated control mice. In addition, this extract affects the activity/secretion of matrix metalloproteinases 2 and 9 (MMP-2 and -9) stimulated by exposure to UVB irradiation. However, additional studies are required to have a complete understanding of the protective effects of ME for skin.

Source: Yris Maria Fonseca, Carolina Dias Catini, Fabiana T. M. C. Vicentini, Auro Nomizo, Raquel Fernanda Gerlach, and Maria José Vieira Fonseca. "Protective effect of Calendula officinalis extract against UVB-induced oxidative stress in skin: evaluation of reduced glutathione levels and matrix metalloproteinase secretion" Journal of Ethnopharmacology (2010): 127(3):596-601.

Rosa Canina (Rosehip)

A systematic review on the Rosa canina effect and efficacy profiles


Rose hip, rose hip and seed and rose hip seed, all were negatively monographed by the German Commission E due to insufficient evidence of effects and effectiveness. Therefore a comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of Rosa canina L. to reevaluate its usefulness in traditional medicine. For various preparations of rose hip and rose hip and seed, antioxidative and antiinflammatory effects have been demonstrated. Lipophilic constituents are involved in those mechanisms of action. The proprietary rose hip and seed powder Litozin has been employed successfully in a number of exploratory studies in patients suffering from osteoarthritis, rheumatoid arthritis and low back pain. However, the sizes of the clinical effects for the different indications need to be determined to assure clinical significance. There is also a rationale behind the use of Litozin as part of a hypocaloric diet based on the rose hip probiotic, stool regulating and smooth muscle-relaxing actions, as well as the rose hip seed lipid-lowering, antiobese and antiulcerogenic effects. Further research is needed to clarify the importance of the reported promising experimental effects in clinical use and to characterize the optimum rose hip seed oil preparation for topical use in the treatment of skin diseases.

Source: Cosima Chrubasik, Basil D Roufogalis, Ulf Müller-Ladner, and Sigrun Chrubasik. "A systematic review on the Rosa canina effect and efficacy profiles" Phytotherapy Research (2008): 22(6):725-33.

The effectiveness of a standardized rose hip powder, containing seeds and shells of Rosa canina, on cell longevity, skin wrinkles, moisture, and elasticity


Objective: To evaluate the effects of a rose hip powder (Hyben Vital(®)) made from seeds and shells on cell senescence, skin wrinkling, and aging.

Methods: A total of 34 healthy subjects, aged 35-65 years, with wrinkles on the face (crow's-feet) were subjected to a randomized and double-blinded clinical study of the effects of the rose hip powder, as compared to astaxanthin, a well-known remedy against wrinkles. During the 8-week study, half of the participants ingested the standardized rose hip product, while the other half ingested astaxanthin. Objective measurements of facial wrinkles, skin moisture, and elasticity were made by using Visioscan, Corneometer, and Cutometer at the beginning of the study, after 4 weeks, and after 8 weeks. Evaluation of participant satisfaction of both supplements was assessed using questionnaires. In addition, the effect of the rose hip preparation on cell longevity was measured in terms of leakage of hemoglobin through red cell membranes (hemolytic index) in blood samples kept in a blood bank for 5 weeks. Significance of all values was attained with P≤0.05.

Results: In the double-blinded study, the rose hip group showed statistically significant improvements in crow's-feet wrinkles (P<0.05), skin moisture (P<0.05), and elasticity (P<0.05) after 8 weeks of treatment. A similar improvement was observed for astaxanthin, with P-values 0.05, 0.001, and 0.05. Likewise, both groups expressed equal satisfaction with the results obtained in their self-assessment. The rose hip powder further resulted in increased cell longevity of erythrocyte cells during storage for 5 weeks in a blood bank.

Conclusion: Results suggest that intake of the standardized rose hip powder (Hyben Vital(®)) improves aging-induced skin conditions. The apparent stabilizing effects of the rose hip product on cell membranes of stored erythrocyte cells observed in this study may contribute to improve the cell longevity and obstructing skin aging.

Source: L. Phetcharat, K. Wongsuphasawat, and K. Winther. "The effectiveness of a standardized rose hip powder, containing seeds and shells of Rosa canina, on cell longevity, skin wrinkles, moisture, and elasticity" Clinical Interventions in Aging (2015): 10:1849-56.

Aloe Barbadensis

Aloe Vera: A Short Review


Aloe vera is a natural product that is now a day frequently used in the field of cosmetology. Though there are various indications for its use, controlled trials are needed to determine its real efficacy. The aloe vera plant, its properties, mechanism of action and clinical uses are briefly reviewed in this article.

Active components with its properties: Aloe vera contains 75 potentially active constituents: vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids and amino acids.

  1. Vitamins: It contains vitamins A (beta-carotene), C and E, which are antioxidants. It also contains vitamin B12, folic acid, and choline. Antioxidant neutralizes free radicals.
  2. Enzymes: It contains 8 enzymes: aliiase, alkaline phosphatase, amylase, bradykinase, carboxypeptidase, catalase, cellulase, lipase, and peroxidase. Bradykinase helps to reduce excessive inflammation when applied to the skin topically, while others help in the breakdown of sugars and fats.
  3. Minerals: It provides calcium, chromium, copper, selenium, magnesium, manganese, potassium, sodium and zinc. They are essential for the proper functioning of various enzyme systems in different metabolic pathways and few are antioxidants.
  4. Sugars: It provides monosaccharides (glucose and fructose) and polysaccharides: (glucomannans/polymannose). These are derived from the mucilage layer of the plant and are known as mucopolysaccharides. The most prominent monosaccharide is mannose-6-phosphate, and the most common polysaccharides are called glucomannans [beta-(1,4)-acetylated mannan]. Acemannan, a prominent glucomannan has also been found. Recently, a glycoprotein with antiallergic properties, called alprogen and novel anti-inflammatory compound, C-glucosyl chromone, has been isolated from Aloe vera gel.
  5. Anthraquinones: It provides 12 anthraquinones, which are phenolic compounds traditionally known as laxatives. Aloin and emodin act as analgesics, antibacterials and antivirals.
  6. Fatty acids: It provides 4 plant steroids; cholesterol, campesterol, β-sisosterol and lupeol. All these have anti-inflammatory action and lupeol also possesses antiseptic and analgesic properties.
  7. Hormones: Auxins and gibberellins that help in wound healing and have anti-inflammatory action.
  8. Others: It provides 20 of the 22 human required amino acids and 7 of the 8 essential amino acids. It also contains salicylic acid that possesses anti-inflammatory and antibacterial properties. Lignin, an inert substance, when included in topical preparations, enhances penetrative effect of the other ingredients into the skin. Saponins that are the soapy substances form about 3% of the gel and have cleansing and antiseptic properties.

Mechanism of actions

  1. Healing properties: Glucomannan, a mannose-rich polysaccharide, and gibberellin, a growth hormone, interacts with growth factor receptors on the fibroblast, thereby stimulating its activity and proliferation, which in turn significantly increases collagen synthesis after topical and oral Aloe vera. Aloe gel not only increased collagen content of the wound but also changed collagen composition (more type III) and increased the degree of collagen cross linking. Due to this, it accelerated wound contraction and increased the breaking strength of resulting scar tissue. An increased synthesis of hyaluronic acid and dermatan sulfate in the granulation tissue of a healing wound following oral or topical treatment has been reported.
  2. Effects on skin exposure to UV and gamma radiation: Aloe vera gel has been reported to have a protective effect against radiation damage to the skin. Exact role is not known, but following the administration of aloe vera gel, an antioxidant protein, metallothionein, is generated in the skin, which scavenges hydroxyl radicals and prevents suppression of superoxide dismutase and glutathione peroxidase in the skin. It reduces the production and release of skin keratinocyte-derived immunosuppressive cytokines such as interleukin-10 (IL-10) and hence prevents UV-induced suppression of delayed type hypersensitivity.
  3. Anti-inflammatory action: Aloe vera inhibits the cyclooxygenase pathway and reduces prostaglandin E2 production from arachidonic acid. Recently, the novel anti-inflammatory compound called C-glucosyl chromone was isolated from gel extracts.
  4. Effects on the immune system: Alprogen inhibit calcium influx into mast cells, thereby inhibiting the antigen-antibody-mediated release of histamine and leukotriene from mast cells. In a study on mice that had previously been implanted with murine sarcoma cells, acemannan stimulates the synthesis and release of interleukin-1 (IL-1) and tumor necrosis factor from macrophages in mice, which in turn initiated an immune attack that resulted in necrosis and regression of the cancerous cells. Several low-molecular-weight compounds are also capable of inhibiting the release of reactive oxygen free radicals from activated human neutrophils.
  5. Laxative effects: Anthraquinones present in latex are a potent laxative. It increases intestinal water content, stimulates mucus secretion and increases intestinal peristalsis.
  6. Antiviral and antitumor activity: These actions may be due to indirect or direct effects. Indirect effect is due to stimulation of the immune system and direct effect is due to anthraquinones. The anthraquinone aloin inactivates various enveloped viruses such as herpes simplex, varicella zoster and influenza. In recent studies, a polysaccharide fraction has shown to inhibit the binding of benzopyrene to primary rat hepatocytes, thereby preventing the formation of potentially cancer-initiating benzopyrene-DNA adducts. An induction of glutathione S-transferase and an inhibition of the tumor-promoting effects of phorbol myristic acetate has also been reported which suggest a possible benefit of using aloe gel in cancer chemoprevention.
  7. Moisturizing and anti-aging effect: Mucopolysaccharides help in binding moisture into the skin. Aloe stimulates fibroblast which produces the collagen and elastin fibers making the skin more elastic and less wrinkled. It also has cohesive effects on the superficial flaking epidermal cells by sticking them together, which softens the skin. The amino acids also soften hardened skin cells and zinc acts as an astringent to tighten pores. Its moisturizing effects has also been studied in treatment of dry skin associated with occupational exposure where aloe vera gel gloves improved the skin integrity, decreases appearance of fine wrinkle and decreases erythema. It also has anti-acne effect.
  8. Antiseptic effect: Aloe vera contains 6 antiseptic agents: Lupeol, salicylic acid, urea nitrogen, cinnamonic acid, phenols and sulfur. They all have inhibitory action on fungi, bacteria and viruses.

Clinical uses: The clinical use of aloe vera is supported mostly by anecdotal data. Though most of these uses are interesting, controlled trials are essential to determine its effectiveness in all the following diseases.

Uses based on scientific evidence: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven.

Conditions: Seborrheic dermatitis, psoriasis vulgaris, genital herpes, skin burns, diabetes (type 2), HIV infection, cancer prevention, ulcerative colitis wound healing (results of aloe on wound healing are mixed with some studies reporting positive results and others showing no benefit or potential worsening, pressure ulcers, mucositis, radiation dermatitis, acne vulgaris, lichen planus, frostbite, aphthous stomatitis, and constipation.

Source: Amar Surjushe, Resham Vasani, and D G Saple. "Aloe Vera: A Short Review" Indian Journal of Dermatology. (2008): 53(4): 163–166.

The Effect of Aloe Vera Clinical Trials on Prevention and Healing of Skin Wound: A Systematic Review


Background: Aloe vera is an herbaceous and perennial plant that belongs to the Liliaceae family and used for many medicinal purposes. The present study aimed to systematically review clinical trials regarding the effect of Aloe vera on the prevention and healing of skin wounds.

Methods: To identify all related published studies, we searched SID, IRANDOC, Google Scholar, PubMed, MEDLINE, Scopus, Cochrane Library, and ScienceDirect databases in both the English and Persian languages from 1990 to 2016. The keywords used were Aloe vera, wound healing, and prevention. All clinical trials using Aloe vera gel, cream, or derivatives that included a control group with placebo or comparison with other treatments were included in the study. The PRISMA checklist (2009) was used to conduct the review.

Results: In total, 23 trials that met the inclusion criteria were studied. The results of the studies showed that Aloe vera has been used to prevent skin ulcers and to treat burn wounds, postoperative wounds, cracked nipples, genital herpes, psoriasis, and chronic wounds including pressure ulcers.

Conclusion: Considering the properties of Aloe vera and its compounds, it can be used to retain skin moisture and integrity and to prevent ulcers. It seems that the application of Aloe vera, as a complementary treatment along with current methods, can improve wound healing and promote the health of society.

Source: Davood Hekmatpou, Fatemeh Mehrabi, Kobra Rahzani, and Atefeh Aminiyan. "The Effect of Aloe Vera Clinical Trials on Prevention and Healing of Skin Wound: A Systematic Review" Iranian Journal of Medical Sciences (2019): 44(1):1-9.

Tremella Fuciformis

Tremella fuciformis polysaccharides inhibit UVA-induced photodamage of human dermal fibroblast cells by activating up-regulating Nrf2/Keap1 pathways


Background: UVA radiation can cause skin oxidative stress. Tremella fuciformis polysaccharides (TFPS) are the main active ingredient in Tremella. Previous studies have shown that TFPS have protective effects on UVA-induced oxidative stress cells, but the specific protective mechanism has not been clarified.

Objective: This study aims to explore the potential protective mechanism of Tremella fuciformis polysaccharides on UVA-induced damage to human dermal fibroblasts cells.

Methods: We evaluated the protective ability of TFPS against UVA-induced damage by detecting cell survival rate, the content of reactive oxygen species (ROS) and malondialdehyde (MDA) in the cells, and the scavenging activity of ABTS free radicals, as well as the enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the Nrf2-Keap-1 pathway protein and gene were measured to study the protective mechanism of TFPS from photodamage.

Results: TFPS pretreatment can reduce the oxidative stress of UVA-treated human dermal fibroblasts cells. After TFPS pretreatment, the content of ROS and MDA in the cell decreased significantly and the total antioxidant activity was increased. Among them, the active of CAT, SOD, and GSH-Px in the cells increased significantly. TFPS can also protect fibroblasts by up-regulating Nrf2 and down-regulating Keap1 expression. Finally, it was also found that TFPS pretreatment increased the content of collagen I, elastin, and hyaluronic acid (HA) in skin fibroblasts treated with UVA.

Conclusion: These results indicate that a certain concentration of TFPS can effectively alleviate skin damage caused by UVA, and they may be used as an effective component of cosmetics.

Source: Hao Fu, ShiQuan You, Dan Zhao, Quan An, Jiachan Zhang, Changtao Wang, Dongdong Wang, and Meng Li. "Tremella fuciformis polysaccharides inhibit UVA-induced photodamage of human dermal fibroblast cells by activating up-regulating Nrf2/Keap1 pathways" Journal of Cosmetic Dermatology (2021): 20(12):4052-4059.

Tremella fuciformis polysaccharide suppresses hydrogen peroxide-triggered injury of human skin fibroblasts via upregulation of SIRT1


Tremella fuciformispolysaccharide (TFPS), which is the extract of Tremella fuciformis Berk, has previously been demonstrated to exhibit potent anti-oxidative, anti-inflammatory and anti-aging effects. However, the mechanisms underlying these protective and therapeutic effects remain to be elucidated. The aim of the present study was to investigate the protective effects of TFPS on hydrogen peroxide-induced injury of human skin fibroblasts and to elucidate the aforementioned underlying mechanisms. A hydrogen peroxide-induced human skin fibroblast injury model was firstly established. MTT and reactive oxygen species (ROS) production assays, in addition to terminal deoxynucleotidyl transferase dUTP nick end labeling, reverse transcription-quantitative polymerase chain reaction and western blotting, were performed to investigate the protective effects of TFPS. Hydrogen peroxide decreased human skin fibroblast viability with a concurrent increase in ROS generation and cell apoptosis. Treatment with 0–400 µg/ml TFPS alone for up to 48 h did not result in alteration in cell viability. Notably, TFPS pre-treatment reduced oxidative stress and cell apoptosis in hydrogen peroxide-treated skin fibroblasts. In addition, there was profound inhibition of p16, p21, p53 and caspase-3 expression, and activation of extracellular-signal regulated kinase and Akt serine/threonine kinase 1, following TFPS pre-treatment. Furthermore, it was revealed that TFPS additionally protected fibroblasts via the upregulation of SIRT1 expression, and this was abrogated by the SIRT1 inhibitor niacinamide. These results indicated that TFPS alleviated hydrogen peroxide-induced oxidative stress and apoptosis in skin fibroblasts via upregulation of SIRT1 expression, indicating that TFPS may act as a potential therapeutic agent for oxidative-stress-associated skin diseases and aging.

Source: Tao Shen, Chao Duan, Beidong Chen, Meng Li, Yang Ruan, Danni Xu, Doudou Shi, Dan Yu, Jian Li, and Changtao Wang. "Tremella fuciformis polysaccharide suppresses hydrogen peroxide-triggered injury of human skin fibroblasts via upregulation of SIRT1" Molecular Medicine Reports" (2017): 16(2): 1340–1346.

Hamamelis Virginiana (Witch Hazel)

Anti-inflammatory effect of hamamelis lotion in a UVB erythema test


Background: Although Hamamelis virginiana has long been used in the traditional treatment of skin diseases, there are few controlled clinical studies defining the extent of its anti-inflammatory action.

Objective: The anti-inflammatory efficacy of pH5 Eucerin aftersun lotion with 10% hamamelis distillate, the vehicle and a prior aftersun formulation were tested in 30 healthy volunteers using a modified UVB erythema test as model of inflammation.

Methods: Four UVB doses ranging from 1 to 2 MED were evaluated in each subject. Test fields on the back were treated occlusively for 48 h following irradiation. Chromametry and visual scoring were used to determine the degree of erythema in the treated fields and an untreated, irradiated control field 7, 24 and 48 h after irradiation.

Results: Erythema suppression ranged from approximately 20% of 7 h to 27% at 48 h in the hamamelis fields. A suppression of 11-15% was recorded in the fields treated with the other lotions. Significant differences were noted between hamamelis and these lotions.

Conclusion: These data provide evidence for an anti-inflammatory action of the aftersun lotion with 10% hamamelis and support the usefulness of the UVB erythema test with multiple UV doses for the testing of nonsteroidal anti-inflammatory agents.

Source: B. J. Hughes-Formella, K. Bohnsack, F. Rippke, G. Benner, M. Rudolph, I. and Tausch, J. Gassmueller. "Anti-inflammatory effect of hamamelis lotion in a UVB erythema test" Dermatology (1998): 196(3):316-22.

Highly galloylated tannin fractions from witch hazel (Hamamelis virginiana) bark: electron transfer capacity, in vitro antioxidant activity, and effects on skin-related cells


Witch hazel ( Hammamelis virginiana) bark is a rich source of both condensed and hydrolizable oligomeric tannins. From a polyphenolic extract soluble in both ethyl acetate and water, we have generated fractions rich in pyrogallol-containing polyphenols (proanthocyanidins, gallotannins, and gallates). The mixtures were highly active as free radical scavengers against ABTS, DPPH (hydrogen donation and electron transfer), and HNTTM (electron transfer). They were also able to reduce the newly introduced TNPTM radical, meaning that they included some highly reactive components. Witch hazel phenolics protected red blood cells from free radical-induced hemolysis and were mildly cytotoxic to 3T3 fibroblasts and HaCat keratinocytes. They also inhibited the proliferation of tumoral SK-Mel 28 melanoma cells at lower concentrations than grape and pine procyanidins. The high content in pyrogallol moieties may be behind the effect of witch hazel phenolics on skin cells. Because the most cytotoxic and antiproliferative mixtures were also the most efficient as electron transfer agents, we hypothesize that the final putative antioxidant effect of polyphenols may be in part attributed to the stimulation of defense systems by mild prooxidant challenges provided by reactive oxygen species generated through redox cycling.

Source: Sonia Touriño, Daneida Lizárraga, Anna Carreras, Sonia Lorenzo, Vanessa Ugartondo, Montserrat Mitjans, María Pilar Vinardell, Luis Juliá, Marta Cascante, and Josep Lluís Torres. "Highly galloylated tannin fractions from witch hazel (Hamamelis virginiana) bark: electron transfer capacity, in vitro antioxidant activity, and effects on skin-related cells" Chemical Research in Toxicology (2008): 21(3):696-704.

Trametes Versicolor (Turkey Tail)

Enzymatic hydrolysates obtained from Trametes versicolor polysaccharopeptides protect human skin keratinocyte against AAPH-induced oxidative stress and inflammatory


Background: Polysaccharopeptides (PSPs) extracted from Trametes versicolor show antitumor, anti-inflammatory, and immunomodulation effects. According to our previous report, the enzymatic hydrolysates obtained from T versicolor PSPs by 80 U/mL β-1,3-D-glucanase (PSPs-EH80) did not change the functional groups of PSPs but enhanced their antioxidative activities. However, the mechanism elevating the antioxidant and anti-inflammatory effect of PSPs-EH80 is not clear.

Aims: This research focused on the protective mechanism(s) of PSPs-EH80 against free radical and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative damage in human keratinocyte (HaCaT) cells.

Methods: We evaluated the anti-inflammatory potential of PSPs-EH80 by assessing its free radical-induced oxidative damage. Using the HaCaT cell as the experimental system, we tested the protective effects of PSPs-EH80 on a model of AAPH-induced cellular oxidative damage through the assessment of cell survival rate. Heme oxygenase 1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase were determined using MTT assays and Western blotting.

Results: We demonstrated that PSPs-EH80 significantly enhanced keratinocyte viability, and augmented the antioxidant HO-1 expressions through upregulation of the Nrf2, compared with PSPs. Furthermore, PSPs-EH80 significantly reduced AAPH-induced COX-2 expressions through downregulation of the ERK, p38, and NF-κB signaling pathways.

Conclusion: The PSPs-EH80 exhibits a stronger antioxidant and anti-inflammatory capacity than PSPs. Therefore, PSPs-EH80 could be effective for attenuating free radical-induced oxidative damage in human skin and can be applied widely in the fields of cosmetics and medicine.

Source: Chun-Hsu Chou, Ming-Shiun Tsai, Hsin-Yu Lu, Chao-Kai Chang, Kuan-Chen Cheng, Mei-Hsin Jhan, and Chang-Wei Hsieh. "Enzymatic hydrolysates obtained from Trametes versicolor polysaccharopeptides protect human skin keratinocyte against AAPH-induced oxidative stress and inflammatory" Journal of Cosmetic Dermatology (2019): 18(6):2011-2018.

The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro


Background: The medicinal mushroom Trametes versicolor (Tv, Turkey Tail) is often prepared for consumption as a powder from the fungal mycelium and the fermented substrate on which it grew. The goal for this study was to evaluate the immune-modulating properties of the mycelium versus the fermented substrate, to document whether an important part of the immune-activating effects resides in the metabolically fermented substrate.

Methods: Tv mycelium was cultured on rice flour. The mycelium and the fermented substrate were mechanically separated, dried, and milled. The initial substrate served as a control. Aqueous fractions were extracted and passed through 0.22-μm filters. The remaining solids were passed through homogenization spin columns without filtration. The aqueous and solid fractions of the initial substrate (IS), the fermented substrate (FS), and theTrametes versicolor mycelium (TvM) were tested for immune-activating and modulating activities on human peripheral blood mononuclear cell cultures, to examine expression of the CD69 activation marker on lymphocytes versus monocytes, and on the T, NKT, and NK lymphocyte subsets. Culture supernatants were tested for cytokines using Luminex arrays.

Results: Both aqueous and solid fractions of TvM triggered robust induction of CD69 on lymphocytes and monocytes, whereas FS only triggered minor induction of CD69, and IS had no activating effect. The aqueous extract of TvM had stronger activating effects than the solid fraction. In contrast, the solid fraction of IS triggered a reduction in CD69, below levels on untreated cells.

Both aqueous and solid fractions of FS triggered large and dose-dependent increases in immune-activating pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10), anti-viral cytokines interferon-gamma (IFN-γ) and Macrophage Inflammatory Protein-alpha (MIP-1α), as well as Granulocyte-Colony Stimulating Factor (G-CSF) and Interleukin-8 (IL-8). TvM triggered more modest cytokine increases. The aqueous extract of IS showed no effects, whereas the solid fraction showed modest effects on induction of cytokines and growth factors.

Conclusion: The results demonstrated that the immune-activating bioactivity of a mycelial-based medicinal mushroom preparation is a combination of the mycelium itself (including insoluble beta-glucans, and also water-soluble components), and the highly bioactive, metabolically fermented substrate, not present in the initial substrate.

Source: Kathleen F. Benson, Paul Stamets, Renee Davis, Regan Nally, Alex Taylor, Sonya Slater, and Gitte S. Jensen. "The mycelium of the Trametes versicolor(Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro". BMC Complementary Medicine and Therapies (2019): 19: 342.


Glycerol and the skin: holistic approach to its origin and functions


Glycerol is a trihydroxy alcohol that has been included for many years in topical dermatological preparations. In addition, endogenous glycerol plays a role in skin hydration, cutaneous elasticity and epidermal barrier repair. The aquaporin-3 transport channel and lipid metabolism in the pilosebaceous unit have been evidenced as potential pathways for endogenous delivery of glycerol and for its metabolism in the skin. Multiple effects of glycerol on the skin have been reported. The diverse actions of the polyol glycerol on the epidermis include improvement of stratum corneum hydration, skin barrier function and skin mechanical properties, inhibition of the stratum corneum lipid phase transition, protection against irritating stimuli, enhancement of desmosomal degradation, and acceleration of wound-healing processes. Even an antimicrobial effect has been demonstrated. Topical application of glycerol-containing products improves skin properties in diseases characterized by xerosis and impaired epidermal barrier function, such as atopic dermatitis. The increase of epidermal hydration by glycerol is critical in skin conditions aggravated by dry and cold environmental conditions, e.g. winter xerosis. This paper provides a review on effects of glycerol on the skin, the mechanisms of its action, and the potential applications of glycerol in dermatology.

Source; J. W. Fluhr, R. Darlenski,and C. Surber. "Glycerol and the skin: holistic approach to its origin and functions" British Journal of Dermatology (2008): 159(1):23-34.

The 24-hour skin hydration and barrier function effects of a hyaluronic 1%, glycerin 5%, and Centella asiatica stem cells extract moisturizing fluid: an intra-subject, randomized, assessor-blinded study


Introduction: Moisturizing products are commonly used to improve hydration in skin dryness conditions. However, some topical hydrating products could have negative effects on skin barrier function. In addition, hydrating effects of moisturizers are not commonly evaluated up to 24 hours after a single application. Hyaluronic acid (HA) and glycerin are very well-known substances able to improve skin hydration. Centella asiatica extract (CAE) could exert lenitive, anti-inflammatory and reepithelialization actions. Furthermore, CAE could inhibit hyaluronidase enzyme activity, therefore prolonging the effect of HA. A fluid containing HA 1%, glycerin 5% and stem cells CAE has been recently developed (Jaluronius CS [JCS] fluid).

Study aim: To evaluate and compare the 24-hour effects of JCS fluid on skin hydration and on transepidermal water loss (TEWL) in healthy subjects in comparison with the control site.

Subjects and methods: Twenty healthy women, mean age 40 years, were enrolled in an intra-subject (right vs left), randomized, assessor-blinded, controlled, 1-day trial. The primary end points were the skin hydration and TEWL, evaluated at the volar surface of the forearm and in standardized conditions (temperature- and humidity-controlled room: 23°C and 30% of humidity) using a corneometer and a vapometer device at baseline, 1, 8 and 24 hours after JCS fluid application. Measurements were performed by an operator blinded for the treatments.

Results: Skin hydration after 24 hours was significantly higher (P=0.001; Mann–WhitneyUtest) in the JCS-treated area in comparison with the control site. JCS induced a significant (P=0.0001) increase in skin hydration at each evaluation time (+59% after 1 hour, +48% after 8 hours and +29% after 24 hours) in comparison with both baseline (P=0.0001) and non-treated control site (P=0.001). TEWL after 24 hours was significantly lower (P=0.049; Mann–WhitneyUtest) in the JCS-treated area in comparison with the control site (13±4 arbitrary units [AU] vs 16±6 AU). JCS fluid significantly reduced post-stripping TEWL in comparison with baseline after 1, 8 and 24 hours (−52%, −32% and −48%, respectively). In the control site, TEWL was not reduced in comparison with baseline values at each time point’s evaluation.

Conclusion: A single application of JCS significantly improves skin hydration for up to 24 hours at the same time as improving skin barrier function.

Source: Massimo Milani and Adele Sparavigna." The 24-hour skin hydration and barrier function effects of a hyaluronic 1%, glycerin 5%, and Centella asiatica stem cells extract moisturizing fluid: an intra-subject, randomized, assessor-blinded study" Clinical, Cosmetic and Investigational Dermatology (2017): 10: 311–315.

Sodium Alginate

Sodium alginate-based composites as a collagen substitute for skin bioengineering


The skin is a combination of two different types of tissue-epithelial and connective (mesenchymal). The outer protective layer of the skin, the epidermis, consists of multiple layers of keratinocytes residing on the basement membrane that separates them from the underlying dermis, which consists of a well-vascularized fibrous extracellular matrix seeded mainly by fibroblasts and mesenchymal stromal cells. These skin features suggest that the development of a fibroblast-friendly porous scaffold covered with a flat dense sheath mimicking the basement membrane, and sufficient to support keratinocyte attachment, would be a reasonable approach in the generation of clinically relevant skin substitutes useful for reconstructive dermatology and burn treatment. Therefore, we developed a procedure to obtain biocompatible composite bilayer scaffolds comprising a spongy dermis-like body (supporting vascularization and appropriate fibroblast and multipotent stromal cell activity) fused with a film-like cover (supporting keratinocyte attachment, growth and differentiation). The sodium alginate (SA), an algae-derived biopolymer, has been used as a base component for these scaffolds while collagen (CL) and fibrinogen (FG) were used as minor additives in variable concentrations. The slow rates of composite SA-based scaffold biodegradation were achieved by using Ba2+as cross-linking cations. By manipulating the SA/CL/FG ratio we managed to obtain sponge scaffolds with highly interconnected porous structures, with an average pore size ranging from 60 to 300 μm, and sufficient tensile strength (3.12-5.26 MPa). The scaffolds biocompatibility with the major human skin cell types was confirmed by seeding the scaffold sponge compartment with primary skin fibroblasts and subcutaneous adipose-derived stromal cells while the film side biocompatibility was tested using primary human keratinocytes. The obtained results have shown that bilayer alginate-based scaffolds have biological and mechanical properties comparable with CL scaffolds but surpass them in cost efficiency and vascularization ability in the subcutaneous implantation model in laboratory mice.

Source: Elena V. Solovieva, Anastasiya Yu Teterina, Olga I. Klein, Vladimir S. Komlev, Andrey A. Alekseev, and Andrey A. Panteleyev. "Sodium alginate-based composites as a collagen substitute for skin bioengineering" Biomedical Materials (Bristol, England) (2020): 16(1):015002.

Fibrinogen-modified sodium alginate as a scaffold material for skin tissue engineering


In search for a new pro-angiogenic scaffold material suitable for skin bioengineering and grafting therapy, we have fabricated a number of composite sodium alginate (AG)-fibrinogen (FG) sponge scaffolds using the freeze-drying approach. Thrombin was added to drive FG/fibrin conversion, while ε-aminocapronic acid (εAc) was used as antifibrinolytic component. The slow rates of scaffold biodegradation were achieved by using Ca2+and Mg2+cations as cross-linking agents. The novel thrombin-modified AG-FG scaffolds with highly interconnected porous structure were evaluated using scanning electron microscopy, tensile testing and pycnometric analysis. The scaffolds were characterized by high porosity and tensile strength, possessing average pore size from about 60 to 300 μm depending on AG/FG ratio and fibrin stabilization. The biocompatibility of thrombin-modified scaffolds with a different AG/FG ratio was tested on human cells with potential applicability to skin tissue engineering: immortalized epidermal keratinocytes (N-TERT), primary skin fibroblasts, endothelial cells (HUVEC) and subcutaneous adipose-derived stromal cells. The scaffolds with low (15%) FG content have shown the highest adhesiveness and survival rates for all types of cells, as compared to the scaffolds with higher FG content. In unstabilized scaffolds, the addition of FG did not stimulate the aortic ring sprouting. At the same time, fibrin stabilization by εAc resulted in significant increase of aortic ring sprouting and more efficient formation of microvascular network. Altogether, obtained results suggest that thrombin-modified alginate sponges can be successfully used as a grafting material by itself to promote skin healing and regeneration and also as a scaffold for three-dimensional bioequivalent construction.

Source: Elena V. Solovieva, Anastasiya Yu Teterina, Olga I. Klein, Vladimir S. Komlev, Andrey A. Alekseev, and Andrey A. Panteleyev. "Fibrinogen-modified sodium alginate as a scaffold material for skin tissue engineering" Biomedical Materials (Bristol, England) (2018): 13(2):025007.

Citrus Aurantium Dulcis (Orange) Peel

Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin


Limonene has demonstrated efficacy in preclinical models of breast and colon cancers. The principal sources of d-limonene are the oils of orange, grapefruit, and lemon. The present case-control study was designed to determine the usual citrus consumption patterns of an older Southwestern population and to then evaluate how this citrus consumption varied with history of squamous cell carcinoma (SCC) of the skin. In this Arizona population, 64.3% and 74.5% of the respondents reported weekly consumption of citrus fruits and citrus juices, respectively. Orange juice (78.5%), orange (74.3%), and grapefruit (65.3%) were the predominant varieties of citrus consumed. Peel consumption was not uncommon, with 34.7% of all subjects reporting citrus peel use. We found no association between the overall consumption of citrus fruits [odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.73-1.32] or citrus juices (OR = 0.97, 95% CI = 0.71-1.31) and skin SCC. However, the most striking feature was the protection purported by citrus peel consumption (OR = 0.66, 95% CI = 0.45-0.95). Moreover, there was a dose-response relationship between higher citrus peel in the diet and degree of risk lowering. This is the first study to explore the relationship between citrus peel consumption and human cancers. Our results show that peel consumption, the major source of dietary d-limonene, is not uncommon and may have a potential protective effect in relation to skin SCC. Further studies with large sample sizes are needed to more completely evaluate the interrelationships between peel intake, bioavailability of d-limonene, and other lifestyle factors.

Source: I. A. Hakim, R. B. Harris, and C. Ritenbaugh. "Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin" Nutrition and Cancer (2000): 37(2):161-8.

Orange peel extract, containing high levels of polymethoxyflavonoid, suppressed UVB-induced COX-2 expression and PGE2 production in HaCaT cells through PPAR-γ activation


Ultraviolet light (UV) induces an inflammatory response in the skin by cyclooxygenase (COX)-2 expression and prostaglandin (PG) E2 production. Citrus peel has been used as a natural medicine. It contains polymethoxyflavonoids (PMFs) as a major ingredient, which have anti-inflammatory activity. We obtained orange peel extract containing high levels of PMFs. The extract suppressed UVB-induced COX-2 expression and PGE2 production in HaCaT cells. Furthermore, it was found that this extract acted as a peroxisome proliferator-activated receptor (PPAR)-γ agonist. The suppression of UVB-induced COX-2 expression by this extract was inhibited by GW 9662 and T0070907, which are both PPAR-γ antagonists. It is therefore suggested that orange peel extract, containing high levels of PMFs, suppresses UVB-induced COX-2 expression and PGE2 production through PPAR-γ. Hence, these extracts could provide useful protection against or alleviation of UV damage.

Source: Norihiro Yoshizaki, Takahiro Fujii, Hitoshi Masaki, Takeshi Okubo, Kunio Shimada, and Ron Hashizume. "Orange peel extract, containing high levels of polymethoxyflavonoid, suppressed UVB-induced COX-2 expression and PGE2 production in HaCaT cells through PPAR-γ activation" Experimental Dermatology (2014): 23 Suppl 1:18-22.

  1. https://slideheaven.com/cosmetic-applications-of-glucitol-core-containing-gallotannins-from-a-proprietar.html
  2. https://pubmed.ncbi.nlm.nih.gov/32356551/
  3. https://pubmed.ncbi.nlm.nih.gov/29371999/
  4. https://pubmed.ncbi.nlm.nih.gov/20026397/
  5. https://pubmed.ncbi.nlm.nih.gov/18384191/
  6. https://pubmed.ncbi.nlm.nih.gov/26604725/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763764/
  8. https://pubmed.ncbi.nlm.nih.gov/30666070/
  9. https://pubmed.ncbi.nlm.nih.gov/33686752/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561887/
  11. https://pubmed.ncbi.nlm.nih.gov/9621139/
  12. https://pubmed.ncbi.nlm.nih.gov/18311930/
  13. https://pubmed.ncbi.nlm.nih.gov/31033173/
  14. https://pubmed.ncbi.nlm.nih.gov/18510666/
  15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560567/
  16. https://pubmed.ncbi.nlm.nih.gov/33245048/
  17. https://pubmed.ncbi.nlm.nih.gov/28972200/
  18. https://pubmed.ncbi.nlm.nih.gov/11142088/
  19. https://pubmed.ncbi.nlm.nih.gov/25234831/