Article

Camphor Induces Proliferative and Anti-senescence Activities in Human Primary Dermal Fibroblasts and Inhibits UV-Induced Wrinkle Formation in Mouse Skin

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Camphor ((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one), a bicyclic monoterpene, is one of the major constituents of essential oils from various herbs such as rosemary, lavender, and sage. In this study, we investigated the beneficial effects of camphor as a botanical ingredient in cosmetics. Camphor induced the proliferation of human primary dermal fibroblasts in a dose-dependent manner via the PI3K/AKT and ERK signaling pathways. Camphor attenuated the elevation of senescence associated with β-galactosidase (SA-β-gal) activity. Elastase activity decreased, while the total amount of collagen increased, in a dose- and time-dependent manner in human primary dermal fibroblasts treated with camphor. Camphor induced the expression of collagen IA, collagen IIIA, collagen IVA, and elastin in human primary dermal fibroblasts. In addition, posttreatment with 26 and 52 mM camphor for 2 weeks led to a significant reduction in the expression of MMP1 but increases in the expression of collagen IA, IIIA, and elastin in mouse skin exposed to UV for 4 weeks. These posttreatments also reduced the depths of the epidermis and subcutaneous fat layer in UV-exposed mouse skin. Taken together, these findings suggest camphor to be a potent wound healing and antiwrinkle agent with considerable potential for use in cosmeceuticals. Copyright © 2015 John Wiley & Sons, Ltd.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Aldehydes (geranial) have a citrus smell and are contained in lemon essential oils. Camphor, a bicyclic monoterpene, is one of the major constituents of essential oils from rosemary, lavender, and sage [18]. In different parts of pine, the following were found: γ-terpinene and β-pinene-in the needles; limonene-in the bark; α-pinene and limonene-in the pollen [19]. ...
... Low doses of camphor could be beneficial, inducing neurohormesis [25] or anti-tumor activity [26]. Camphor as a component of cosmetics can delay skin aging, decreasing the activity of elastase, elevating collagen expressions, activating proliferation of human primary dermal fibroblasts, and attenuating cellular senescence [18]. It has anti-mutagenic effects in small doses [27]. ...
... Camphor induced the proliferation of primary human skin fibroblasts via PI3K/AKT and ERK signaling pathways. It attenuated an increase of the β-galactosidase (SA-β-gal) activity associated with aging, induced the expression of collagen (IA, IIIA, IVA types) and elastin in primary human dermal fibroblasts [18]. Myrcene ameliorates human skin extrinsic aging via decreasing the production of ROS, MMP-1, MMP-3, and IL-6, and increasing of TGF-1 and type I procollagen secretions. ...
Article
Full-text available
Terpenes and terpenoids are the largest groups of plant secondary metabolites. However, unlike polyphenols, they are rarely associated with geroprotective properties. Here we evaluated the conformity of the biological effects of terpenoids with the criteria of geroprotectors, including primary criteria (lifespan-extending effects in model organisms, improvement of aging biomarkers, low toxicity, minimal adverse effects, improvement of the quality of life) and secondary criteria (evolutionarily conserved mechanisms of action, reproducibility of the effects on different models, prevention of age-associated diseases, increasing of stress-resistance). The number of substances that demonstrate the greatest compliance with both primary and secondary criteria of geroprotectors were found among different classes of terpenoids. Thus, terpenoids are an underestimated source of potential geroprotectors that can effectively influence the mechanisms of aging and age-related diseases.
... Myrcene's effect on cell migration is of a dual nature, with inhibitory effects on oral cancer cell lines [124] and stimulation of cell migration on HaCaT cells [125]. The minor compounds 1,8-cineole [112,126,127], camphor [128] and α-pinene [126] are known to promote wound healing, and thus they may also contribute to the herein reported activity of S. rosmarinifolia. Considering these results, we suggest that the reported activity of S. rosmarinifolia might be attributed to the presence of these compounds. ...
... Nevertheless, the contribution of other minor compounds cannot be ruled out. Indeed, camphor, a monoterpene found in low amounts in the EO of S. rosmarinifolia, prevents the increased activity of senescence-associated β-galactosidase [128]. The anti-aging potential of α-pinene is also known [132]. ...
Article
Full-text available
Fungal infections and the accompanying inflammatory responses are associated with great morbidity and mortality due to the frequent relapses triggered by an increased resistance to antifungal agents. Furthermore, this inflammatory state can be exacerbated during inflammaging and cellular senescence. Essential oils (EO) are receiving increasing interest in the field of drug discovery due to their lipophilic nature and complex composition, making them suitable candidates in the development of new antifungal drugs and modulators of numerous molecular targets. This work chemically characterized the EO from Santolina rosmarinifolia L., collected in Setúbal (Portugal), and assessed its antifungal potential by determining its minimum inhibitory (MIC) and minimum lethal (MLC) concentration in accordance with the Clinical Laboratory Standard Guidelines (CLSI) guidelines, as well as its effect on several Candida albicans virulence factors. The anti-inflammatory effect was unveiled using lipopolysaccharide (LPS)-stimulated macrophages by assessing several pro-inflammatory mediators. The wound healing and anti-senescence potential of the EO was also disclosed. The EO was mainly characterized by β-pinene (29.6%), borneol (16.9%), myrcene (15.4%) and limonene (5.7%). It showed a strong antifungal effect against yeasts and filamentous fungi (MIC = 0.07–0.29 mg/mL). Furthermore, it inhibited dimorphic transition (MIC/16), decreased biofilm formation with a preeminent effect after 24 h (MIC/2) and disrupted preformed biofilms in C. albicans. Additionally, the EO decreased nitric oxide (NO) release (IC50 = 0.52 mg/mL) and pro-IL-1β and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated macrophages, promoted wound healing (91% vs. 81% closed wound) and reduced cellular senescence (53% vs. 73% β-galactosidase-positive cells). Overall, this study highlights the relevant pharmacological properties of S. rosmarinifolia, opening new avenues for its industrial exploitation.
... The most abundant compound found in AN oil extract is camphor (23.7%, Table 1), a terpenoid which has been reported to provide several bene its to skin including wound healing properties and anti-wrinkle activity [10]. Camphene (aka as β-pinene) and p-cymene are two additional terpenes present at 16.2% and 13.9% respectively in AN oil extract. ...
... Based on the data presented here, this can best be explained by the chemical composition of this novel AN oil extract. Via GC-MS analysis we identi ied AN oil extract contains several terpenes including its three most abundant compounds, camphor (~24%), Camphene (aka as β-pinene) (~16%) and p-cymene (~14%), all of which have been previously reported to possess skin protecting properties such as wound healing, anti-aging, anti-oxidant and anti-in lammatory properties [10,11]. The unique blend of skin actives identi ied in AN oil extract are potentially more effective when applied topically to skin given the presence of eucalyptol (~6%), which is a known penetration enhancer [9]. ...
Article
Full-text available
Background: The plant Artemisia annua has been used in traditional Chinese medicine for many years. Rich in bioactive molecules, the A. annua plant is used to extract the anti-malaria compound artemisinin (< 1%), which results in most of the plant being unutilized. One byproduct of artemisinin extraction is artemisia naphtha (AN), which has yet to be studied extensively. Aims: Study the activity of a novel AN oil extract against microbes, pro-inflammatory cytokines, and dermatological endpoints that are key for eczema and acne pathogenesis to determine if an effective A. annua extract for these skin conditions can be developed. Methods: Gas chromatography-mass spectrometry was performed to determine the composition of AN oil. P. acnes, S. aureus, M. furfur, and C. albicans were cultured to determine minimal inhibitory concentration. in vitro studies utilizing keratinocytes and macrophages were treated with AN oil and gene expression measured by quantitative RT-PCR. A 13-subject clinical trial was performed with 1% AN oil Gel to assess its potential benefits for sensitive and acne prone skin. Results: AN oil upregulates filaggrin gene expression and possesses antimicrobial and anti-inflammatory activity inhibiting LPS, S. aureus and "Th2 induced" pro-inflammatory mediator release (IL-6, IL-8 and TSLP). Clinical assessment of 1% AN Gel shows it reduces acne blemishes and the appearance of redness. Conclusion: Previously an underutilized and unpurified byproduct, AN is now the source to develop the first topical AN oil for cosmetic use with an activity profile that suggests it is effective for those with sensitive and/or acne prone skin.
... Regarding isolated compounds, the number of studies reporting their effect was scarce. Indeed, camphor prevents the increased activity of senescence-associated β-galactosidase [87]. On the other hand, 1,8-cineole, the major compound of this essential oil, induced cell senescence [88]. ...
Article
Full-text available
The Salvia L. genus (Lamiaceae) is largely used in the pharmaceutical and food industry. Several species of biological relevance are extensively employed in traditional medicine, including Salvia aurea L. (syn. S. africana-lutea L.), which is used as a traditional skin disinfectant and in wounds as a healing remedy; nevertheless, these properties have not been validated yet. The aim of the present study is to characterise S. aurea essential oil (EO), unveiling its chemical composition and validating its biological properties. The EO was obtained by hydrodistillation and subsequently analysed by GC-FID and GC-MS. Different biological activities were assessed: the antifungal effect on dermatophytes and yeasts and the anti-inflammatory potential by evaluating nitric oxide (NO) production and COX-2 and iNOS protein levels. Wound-healing properties were assessed using the scratch-healing test, and the anti-aging capacity was estimated through the senescence-associated beta-galactosidase activity. S. aurea EO is mainly characterised by 1,8-cineole (16.7%), β-pinene (11.9%), cis-thujone (10.5%), camphor (9.5%), and (E)-caryophyllene (9.3%). The results showed an effective inhibition of the growth of dermatophytes. Furthermore, it significantly reduced protein levels of iNOS/COX-2 and simultaneously NO release. Additionally, the EO exhibited anti-senescence potential and enhanced wound healing. Overall, this study highlights the remarkable pharmacological properties of Salvia aurea EO, which should be further explored in order to develop innovative, sustainable, and environmentally friendly skin products.
... Salicin also suppressed oxidative damage in a collagen-induced arthritis rat model [24]. Moreover, TAS2R10 agonist, camphor ameliorated the SA-β-gal activity in human primary dermal fibroblasts and suppressed ultraviolet (UV)-induced wrinkle in mouse skin [25]. Based on these previous studies, we hypothesized that the bitter taste receptors expressed in human keratinocytes exert anti-aging effects in D-gal-induced aging of HaCaT cells by inhibiting cellular senescence and enhancing wound healing. ...
Article
Background/objectives: Bitter taste receptors are taste signaling pathway mediators, and are also expressed and function in extra-gustatory organs. Skin aging affects the quality of life and may lead to medical issues. The purpose of this study was to better understand the anti-skin aging effects of bitter taste receptors in D-galactose (D-gal)-induced aged human keratinocytes, HaCaT cells. Materials/methods: Expressions of bitter taste receptors in HaCaT cells and mouse skin tissues were examined by polymerase chain reaction assay. Bitter taste receptor was overexpressed in HaCaT cells, and D-gal was treated to induce aging. We examined the effects of bitter taste receptors on aging by using β-galactosidase assay, wound healing assay, and Western blot assay. Results: TAS2R16 and TAS2R10 were expressed in HaCaT cells and were upregulated by D-gal treatment. TAS2R16 exerted protective effects against skin aging by regulating p53 and p21, antioxidant enzymes, the SIRT1/mechanistic target of rapamycin pathway, cell migration, and epithelial-mesenchymal transition markers. TAS2R10 was further examined to confirm a role of TAS2R16 in cellular senescence and wound healing in D-gal-induced aged HaCaT cells. Conclusions: Our results suggest a novel potential preventive role of these receptors on skin aging by regulating cellular senescence and wound healing in human keratinocyte, HaCaT.
... Camphor has been reported to have anti-skin-aging effects as a cosmetic ingredient [17], anti-genotoxic effects at low concentrations [33], and antitumor activity [34]. In this study, we used camphorquinone (CQ), a camphor derivative that is widely used as a photoinitiator, to trigger the polymerization process during dental composite preparation [35]. ...
Article
Full-text available
Terpenoids are a wide class of secondary metabolites with geroprotective properties that can alter the mechanism of aging and aging-related diseases. Camphorquinone (CQ) is a bicyclic monoterpenoid compound that can be efficiently synthesized through the continuous bromination and oxidation reaction of camphor. The purpose of this study is to investigate the effects of CQ on oxidative-stress-induced senescence and its underlying mechanisms. To generate oxidative stress in human bone marrow mesenchymal stem cells (hBM-MSCs) and mice, we used hydrogen peroxide (200 μM twice) and D-galactose (D-Gal) (150 mg/kg for 10 weeks), respectively. Our findings suggest that CQ potentially reduces senescence in hBM-MSCs and mouse heart tissue. In addition, we found that CQ boosted AMPK/SIRT1 activation and autophagy in both models. These results were subsequently verified in hBM-MSCs using compound C (an AMPK inhibitor) but AMPK inhibition by CC did not significantly reduce the SIRT1 and the autophagy markers. CQ treatment also reduced the gene expression of inflammation markers in D-Gal-induced aging mouse heart tissue. Furthermore, we determined that CQ fits all of the pharmacological parameters using the freely available SwissADME Web tool. Collectively, our findings demonstrate that CQ possesses antisenescence and cardioprotective properties, and that oxidative-stress-induced senescence could be suppressed by AMPK/SIRT1 and autophagy mechanisms.
... The lotions and creams containing camphor are famous for relieving skin irritation and itchiness and may help to improve the overall appearance of the skin. In addition, this chemical component is considered as an effective element to treat wounds and ultraviolet light-induced wrinkles, and it is used for anti-aging as well [19]. The concentration of camphor in the studied samples ranged from 17.45% to 34.31%, where a high presence (percentage) of this element was found in the aerial parts of the samples that were collected after the flowering stage of the plant. ...
Article
Full-text available
This study describes the chemical composition, antitumor, antioxidant, and antimicrobial activities of the plant Thymus algeriensis Boiss. Essential oils (EOs) were collected in different periods (before, during, and after flowering stage) from the El-Guetfa region, M’sila, Algeria. The EOs extraction was achieved using three distinguishing techniques: hydro (Clevenger trap), steam, and microwave distillations, targeting different aerial parts of the plant (stems, flowers, and leaves). The EOs chemical components were estimated using GC-FID and GC-MS apparatuses. The resulting yield of the extracted oil was moderate and ranged between 0.84 and 1.53% (wt/vol). In total, eighty-five components were identified, in which the oxygenated monoterpenes family formed the main portion, starting from 40.56 up to 70.66%. The obtained essential oil was dominated by five major components that varied from low to quite moderate percentages: camphor (17.45–32.56%), borneol (11.16–22.2%), camphene (7.53–12.86%), 1.8-cineole (5.16–11.21%), and bornyl acetate (3.86–7.92%). The biological results of this oil pointed out that the EOs extracted from the leaves part exposed a weak radical scavenging activity afterward using two well-known antioxidant assays DPPH (IC50 = 8.37 mg/mL) and ABTS (10.84 mg/mL). Meanwhile, this oil presented strong inhibition activity against colon cancer cell line HCT116 (LC50 = 39.8 microg/mL) and a moderate inhibitory against hepatocellular cancer cells HePG2 (LC50 > 100 microg/mL). In addition, this oil antimicrobial activity was quite important against Micrococcus luteus (M. luteus), Staphylococcus aureus CIP 7625, Escherichia coli ATCC 10536, Saccharomyces cerevisiae ATCC 4226, Candida albicans IPA200, Candida tropicalis (Ct), and Candida glabrata (Cg) after using Amoxicillin and Itraconazole as references.
... Cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum and an antibiotic cocktail (100 µg/ml streptomycin and 100 U/ml penicillin) and incubated at 37˚C under 5% CO 2 . Dermal fibroblasts (13) were cultured in DMEM under similar culture conditions. Cells were sub-cultured upon 80% confluency. ...
Article
Overcoming chemo‑ and radio‑resistance is a major challenge in pancreatic cancer treatment. Therefore, there is an urgent need to discover novel therapeutic approaches to avoid chemo‑ and radio‑resistance in pancreatic cancer. Catechol is a phytochemical found in some fruits and vegetables. A few studies have reported on the potential anticancer effects of pure catechol. The present study aimed to explore the chemo‑ and radio‑sensitizing effects of catechol in Panc‑1 human pancreatic cancer cells. The effects of catechol on Panc‑1 cell proliferation, clonogenic survival, invasion, and migration were assessed using MTT, cell migration, and Transwell invasion assays. The chemo‑ and radio‑sensitizing effects of catechol on Panc‑1 cells were evaluated via MTT assay and flow cytometry. Western blotting was conducted to analyze the expression of proteins involved in several mechanisms induced by catechol in Panc‑1 cells, including growth inhibition, apoptosis, suppression of epithelial‑mesenchymal transition (EMT), and chemo‑ and radio‑sensitizing activities. The results indicated that catechol inhibited proliferation, promoted apoptosis, and suppressed cell migration, invasion, and EMT in Panc‑1 cells in a dose‑dependent manner. Catechol treatment also induced the phosphorylation of AMP‑activated protein kinase (AMPK) with a concomitant reduction in the expression of Hippo signaling pathway components, including Yes‑associated protein, cysteine‑rich angiogenic inducer 61, and connective tissue growth factor. In addition, catechol enhanced the chemosensitivity of Panc‑1 cells to gemcitabine, a commonly used chemotherapy in pancreatic cancer treatment. A combination of catechol and radiation enhanced apoptosis and increased the expression of two radiation‑induced DNA damage markers, p‑ATM and p‑Chk2. Collectively, the present results demonstrated that catechol, a naturally occurring compound, could suppress the proliferation of pancreatic cancer cells, reduce the expression of EMT‑related proteins, and enhance the chemo‑ and radio‑sensitivity of Panc‑1 cells by targeting AMPK/Hippo signaling.
... A recent study has shown the effect of camphor on skin health by inducing fibroblast proliferation, maintaining or recovering collagen and elastin production in UV exposed skin, and preventing thickening of the epidermis and subcutaneous fat layer [38]. ...
... seemed to be a plant whose oil was mainly dependent on camphor. As was already known, bornyl acetate exhibited anti-inflammatory [21][22][23], analgesic, anti-tumor [24], whitening, anti-oxidative [25] and immune-regulatory [26] effects while camphor showed various pharmacological effects including anti-tussive [27], anti-oxidative [28], anti-fungal [29], anti-wrinkle [30] and wound-healing [31] activities. However, no report regarding the pharmacological differences of FAL and FALX. ...
Article
Full-text available
Fructus Amomi (FA) is usually regarded as the dried ripe fruit of Amomum villosum Lour. (FAL) or Amomum villosum Lour. var. xanthioides T. L. Wu et Senjen (FALX.). However, FAL, which always has a much higher price because of its better quality, is often confused with FALX. in the market. As volatile oil is the main constituent of FA, a strategy combining gas chromatography–mass spectrometry (GC-MS) and chemometric approaches was applied to compare the chemical composition of FAL and FALX. The results showed that the oil yield of FAL was significantly higher than that of FALX. Total ion chromatography (TIC) showed that cis-nerolidol existed only in FALX. Bornyl acetate and camphor can be considered the most important volatile components in FAL and FALX., respectively. Moreover, hierarchical cluster analysis (HCA) and principal component analysis (PCA) successfully distinguished the chemical constituents of the volatile oils in FAL and FALX. Additionally, bornyl acetate, α-cadinol, linalool, β-myrcene, camphor, d-limonene, terpinolene and borneol were selected as the potential markers for discriminating FAL and FALX. by partial least squares discrimination analysis (PLS-DA). In conclusion, this present study has developed a scientific approach to separate FAL and FALX. based on volatile oils, by GC-MS combined with chemometric techniques.
... 13 On the other hand, camphor was shown to induce proliferative and anti-senescence activities through the PI3K/AKT and ERK signaling pathways in a dose-dependent manner in human dermal fibroblast cells. 14 Given the significance of camphor in the future of the medical and pharmaceutical industries, possible metabolic, anti-aging, cytotoxic, inhibitory and cancer fighting activities together with the underlying mechanisms are under debate and should be unraveled. Research on camphor toxicity mainly focused on laboratory experiments with cell lines, 13,15 rodents, 11,16,17 and pests. ...
Article
Camphor is one of the monoterpenes widely used in cosmetics, pharmacy and food industry. In this study, we aimed to assess oxidative, cytotoxic and apoptotic effects of camphor in the fission yeast (Schizosaccharomyces pombe), which is a promising unicellular model organism in mechanistic toxicology and cell biology. Since Sod1 is the main radical scavenger in the cell, we used sod1 mutants to understand whether camphor-induced ROS accumulation caused higher cytotoxicity and apoptosis. Camphor exposure (0-2000 mg/L) caused significant cytotoxicity in yeast, particularly in sod1 cells. DCFDA (2,7-dichlorodihydrofluorescein diacetate) fluorescence and NBT (p-nitro-blue tetrazolium chloride) reduction increased (at least 2.5-3-fold in sod1 cells) in correlation with camphor concentrations (800-1200 mg/L), showing higher ROS levels and oxidative stress. Moreover, cells, stained with acridine orange/ethidium bromide, showed apoptotic morphology with nuclear fragmentation and condensation. DAPI (4’,6-diamidino-2-phenylindole) staining was used to validate apoptotic nuclear morphology. Dramatically increased mitochondrial impairment, which was higher in sod1 cells than in wild type cells, was shown by Rhodamine 123 staining. In conclusion, camphor-induced excessive ROS production, which could not be prevented significantly in sod1 mutants, caused dramatic increase in mortality rates due to intrinsic apoptosis revealed by mitochondrial impairment and apoptotic nuclear morphology. The potential effects of camphor on apoptotic cell death and accounting mechanisms were clarified in unicellular eukaryotic model, S. pombe.
... The PI3K/Akt pathway plays roles in cell proliferation, survival, apoptosis, oxidative stress, inflammation, and chemotaxis in response to a variety of stimuli including growth factors and cytokines (Hemmings, 1997;Cantley, 2002;Barthel and Klotz, 2005;Liu et al., 2009;Shi et al., 2016). In human dermal fibroblasts, camphor ((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one) increases the production of collagen (type I, III, and IV) and elastin, and activates the PI3K/Akt and ERK signaling pathways; however, the precise relationship between these two events remains unclear (Tran et al., 2015). As stated, our previous results showed that Lf increases collagen IV expression in human dermal fibroblasts (Ishii et al., 2012). ...
Article
Dermal fibroblasts generate the extracellular matrix component elastin, which is synthesized as tropoelastin (TE) and play a critical role in maintaining skin elasticity. Lactoferrin (Lf), an 80-kDa iron-binding glycoprotein, has biological functions such as antibacterial, antiinflammatory, and anticancer activities. We previously reported that bovine Lf increases TE mRNA expression in human dermal fibroblasts. However, it remains unclear how Lf up-regulates TE expression. Here, we investigated molecular mechanisms underlying this effect. Lf promoted the phosphorylation of Akt1 and extracellular signal-regulated protein kinase (ERK)1/2. As expected, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the MAPK inhibitor U0126 inhibited Lf-induced phosphorylation of Akt1 and ERK1/2, respectively. In contrast, LY294002, but not U0126, inhibited Lf-induced TE expression. Human dermal fibroblasts expressed lipoprotein receptor-related protein 1 (LRP-1) mRNA, and the LRP1 inhibitor receptor-associated protein attenuated Lf-induced increases in TE expression. Furthermore, siRNA-mediated knockdown of LRP-1 significantly suppressed Lf-increased TE expression and Lf-induced Akt1 phosphorylation. Iron-saturated Lf (holo-Lf) increased TE expression and promoted Akt1 phosphorylation, when compared to those parameters in cells treated with iron-free Lf (apo-Lf). Transforming growth factor (TGF)-β1 also increased TE expression. LY294002 inhibited TGF-β1-mediated TE upregulation, whereas TGF-β1 activated Akt2, but not Akt1, phosphorylation. These results indicate that holo-Lf, but not apo-Lf, increases TE expression through LRP-1 in human dermal fibroblasts and suggest that holo-Lf and TGF-β1 enhance TE expression by activating the PI3K/Akt1 and PI3K/Akt2 pathways, respectively.
... The monoterpene 1,8-cineole has been reported to attenuate hydrogen peroxide cytotoxicity [83], while camphor and 1,8-cineole have been identified as anti-inflammatory compounds of a Salvia officinalis infusion applied in human fibroblasts [31]. Furthermore, camphor induced fibroblast proliferation and collagen formation in dermal fibroblasts [102]. ...
Article
Background: The rise of organic electronics represents one of the most prominent technological developments of the last two decades, with its interface with biological systems highlighting new directions of research. The "soft" nature of conducting polymers renders them unique platforms for cell-based microdevices, allowing their implementation in drug discovery, pharmaceutical effect analysis, environmental pollutant testing etc. Methods: Cellular adhesion, proliferation and viability experiments were carried out to verify the biocompatibility of a PEDOT conductive polymer surface. Cyclic voltammetry was employed for estimating the electrocatalytic activity of the renal cell/electrode interface. The nephrotoxicity agent CCl4 and the medicinal plant Salvia officinalis were used on the proposed assembly. Renal cell viability was also assayed through the MTT assay. Results: Renal cells were able to adhere and proliferate on the conducting polymer surface. Electrochemical responses of the polymer exhibited good correlation with cell number and CCl4 concentration. Amelioration of the CCl4-induced renotoxicity by co-incubation with Salvia officinalis extract was demonstrated by both the MTT assay and the electrode's capacitance. Conclusions: A conducting polymer-based bioelectrochemical assembly was established for in vitro mammalian cytotoxicity/cytoprotection assessment, employing renal cell monolayers as the primary transducers for signal generation and biological sensing. General significance: The knowledge on PEDOT mammalian cell biocompatibility and possible applications was expanded. The proposed interdisciplinary approach connects soft electronics with biology and could provide a useful tool for preliminary crude drug screening and bioactivity studies of natural products or plant extracts in vitro.
... The most highly studied intracellular signaling cascades in the context of cancer are the mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways [20]. We were obtained [21], whereby the proliferative effects of camphor were shown to be mediated by the PI3K/AKT/mTOR and MAP kinase pathways-the key signaling pathways involved in the control of cell proliferation. In this same study, camphor-induced phosphorylation of ERK, but not PI3K and AKT, was also reported. ...
Article
Full-text available
The human hair follicle, a mini-organ formed with neuroectodermal-meso-dermal interaction, is a complex structure, in the active steady state (anagen) the dermal papilla can be considered as a ball of extracellular matrix, surrounding specialized fibroblasts. The cross-talk of dermal papilla with neighbouring matrix cells results in the maintenance of hair fibre production. This study aimed to investigate the proliferative potential of the compound TrichotechTM, a phytocomplex obtained from a mixture of essential oils, on cultured human fibroblasts and its ability to modulate the gene expression of FGF-7 and FGF-10. TrichotechTM was shown to enhance fibroblasts proliferation in concentrations of 0.5% to 2.0%, and also increase the percentage of cells in the S/G2/M phases of the cell cycle. TrichotechTM at both 1.0% and 2.0% induced a statistically significant effect on wound healing assay compared to the untreated control. We examined the interaction between cell survival (PI3K/Akt) and mitogenic (Ras/MAPK) signal transduction pathways after TrichotechTM treatment (1.0% and 2.0%) on the fibroblast cell line. TrichotechTM caused phosphorylation of ERK1/2, as well as greater phosphorylation of MEK in comparison with both the untreated control and ERK1/2. PI3K and AKT, however, were not shown to be significantly more phosphorylated following TrichotechTM exposure. To verify the relative expression of mRNA for FGF-7 and FGF-10 genes, a real-time polymerase chain reaction (qPCR) protocol was used. Results show the increase in mRNA expression by fibroblasts after treatment with TrichotechTM. In both concentrations tested, TrichotechTM was found to increase the expression of FGF-7 and FGF-10. Sirius red staining allows for rapid assessment of collagen content, it showed a significant increase in collagen content in treated fibroblasts. Further investigation concerning TrichotechTM could be helpful towards the development of new bioactive phytocomplexes for dermatological and trichological use.
Article
The biomolecules offer different metal-binding sites to form a coordination polymer with structural diversity. The coordination directed one-dimensional metal-biomolecule nanofibers (Cu-Asp NFs) designed using copper as metal ion and aspartate as a ligand for triboelectric nanogenerator (TENG) is reported here. The different characterization techniques reveal the detailed characteristics of the synthesized Cu-Asp NFs. The robust coating of the Cu-Asp NFs is achieved using a simple tape cast coater. The bending and water dipping studies suggest the stability of the coated material. The relative polarity test and Kelvin probe force microscopy (KPFM) reveal the position of Cu-Asp in the triboelectric series. The Cu-Asp NFs and Teflon are used as the active material for the fabrication of freestanding mode (NF-TENG) and contact-separation mode (cNF-TENG) TENG. The NF-TENG generates an output of 200 V and 6 μA. The simple ion deposition technique enhances the voltage, current, and transferred charge of cNF-TENG by 2.5, 8, and 3 times. The use of the material for the single electrode sliding mode device further confirms the coated material's stability and robustness. A selective self-powered thioacetamide sensor is developed with the cNF-TENG, which exhibits a sensitivity of 0.76 v mM-1. Finally, NF-TENG is demonstrated for powering up numerous portable electronics.
Article
This systematic review shows the effectiveness of Matricaria chamomilla for improving health. Original papers and case reports published during 2014–2018 in PubMed, Science Direct and Scopus were included. Most studies were in vitro, performed with extracts, in 2018, and originated from Iran. In vitro assays focused mainly on antimicrobial, antiparasitic and antioxidant activities. In vivo studies specially investigated organ and tissue protective activity of chamomile. Clinical trials have validated some of these in vitro and in vivo pharmacological activities (diabetes mellitus, hypertension and pain). Future preclinical and clinical investigations should be aimed at deeping into pure compounds responsible for activities.
Article
Human skin aging is a progressive process that includes intrinsic aging and extrinsic photodamage, both of which can cause an accumulation of reactive oxygen species (ROS), resulting in dermal fibrosis dysfunction and wrinkle formation. Galangin is a flavonoid that exhibits anti-inflammatory and antioxidative potential. Previous studies have reported that galangin has antioxidative activity against ROS-mediated stress. The aim of the present study is to determine the antiaging effects of galangin on dermal fibroblasts exposed to H2 O2 . In this study, we established a hydrogen peroxide-induced inflammation and aging model using human HS68 dermal fibroblasts. Stimulation of fibroblasts with H2 O2 is associated with skin aging and increased expression of inflammation-related proteins, along with downregulation of collagen I/III formation and expression of antioxidative proteins. Galangin effectively reduced NF-κB activation, the expression of inflammation-related proteins and cell aging. Galangin also reversed H2 O2 -activated cell senescence in HS68 cells. Our results reveal that galangin protects human dermal fibroblasts by inhibiting NF-κB activation, decreases the expression of inflammatory factors and upregulates IGF1R/Akt-related proteins, indicating that galangin may be a potential candidate for developing natural antiaging products that protect skin from damage caused by ROS.
Article
Full-text available
Adams, R. P. 2007. Identification of essential oil components by gas chromatography/ mass spectrometry, 4th Edition. Allured Publ., Carol Stream, IL Is out of print, but you can obtain a free pdf of it at www.juniperus.org
Article
Full-text available
Stewartia koreana (S. koreana) has been used in the treatment of inflammatory diseases, such as acute gastroenteritis and aches, in Korean folk medicine and has been reported to have a number of biological activities, such as anti-inflammatory activity and the promotion of angiogenesis. In this study, we aimed to determine the effects of S. koreana extract (SKE) and its components on dermal fibroblast growth and migration, and to investigate the wound healing activity of the extract in mice. In vitro experiments revealed that the numbers of SKE-treated cells increased by approximately 2.5-‑ and 3.7-fold with 50 and 100 µg/ml of SKE, respectively. 5-bromo-2'-deoxy-uridine (BrdU) incorporation was also increased in the SKE-treated cells by 2.3-fold. SKE promoted the migration of human skin fibroblasts and, among the isolated compounds, hyperin increased the proliferation and migration of the fibroblasts to almost the same degree as SKE. Western blot analysis demonstrated that SKE stimulated the MEK/ERK1/2 and PI3K/Akt signaling pathways. In in vivo experiments, the SKE-treated wound lesions of mice decreased by approximately 7% in diameter after 2 days of treatment with SKE compared with the wound lesions on the 1st day of the experiment. On the 9th day of treatment, the diameter of the lesions was further reduced by approximately 83% in the SKE-treated wound areas compared with the wound areas on the 1st day of treatment. Our results demonstrate that methanol extracts of S. koreana leaves promote the proliferation and migration of skin fibroblasts and possess effective wound healing activity through the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways. Hyperin was identified as an active compound responsible for the stimulation of fibroblast growth and migration.
Article
Full-text available
Photodynamic therapy (PDT) is known to be effective in the photorejuvenation of photoaged skin. However, the molecular mechanisms of rejuvenation by PDT remain elusive. In this study we aimed to understand the molecular events occurring during the photorejuvenation after PDT in dermal fibroblasts in vitro. First, we found that PDT conditions resulted in an increased fibroblasts proliferation and motility in vitro. Under this condition, cells had increased intracellular reactive oxygen species (ROS) production. Importantly, PDT induced a prolonged activation of extracellular-signal-regulated kinase (ERK) with a corresponding increase in matrix metalloproteinase (MMP)-3 and collagen type Iα mRNA and protein. Moreover, inhibition of PDT-induced ERK activation significantly suppressed fibroblast proliferation and expression of MMP-3 and collagen type Iα following PDT. In addition, NAC (an antioxidant) inhibited PDT-induced fibroblast proliferation and ERK activation indicating that prolonged ERK activation and intracellular ROS contribute to the proliferation of fibroblasts and the dermal remodeling process for skin rejuvenation. We also identified increased collagen volume and decreased elastotic materials which are used as markers of photoaging in human skin samples using histochemistry. Results from this study suggest that intracellular ROS stimulated by PDT in dermal fibroblasts lead to prolonged activation of ERK, and eventually fibroblast proliferation and activation. Our data thus reveal a molecular mechanism underlying the skin rejuvenation effect of PDT.Journal of Investigative Dermatology accepted article preview online, 21 January 2013; doi:10.1038/jid.2013.25.
Article
Full-text available
Camphor is prescribed in traditional medicine for the treatment of inflammation-related diseases and skin care products. The present study aims at finding out the effects of Camphor on the endometrium structures of Sprague–Dawley female Rats. 40 animals (3 months old) were divided into 4 subgroups (n = 10), 3 experimental groups were given daily intraperitoneal injection of 5, 10 and 20 mg/kg of Camphor watery solution and the control group was given distilled water. All groups were kept in the same environmental conditions. At the end of 6 weeks, all rats were killed and their uteri were removed for histological analysis. Comparing with the control group, an increase in the body and reproductive system weight, less uterine glands, degeneration of luminal epithelium and enlargement of uterus lumen were recorded. All the treated groups showed an increase in estrogen concentration. Furthermore, the highest dose caused an increase in progesterone concentration. The present study showed that Camphor could alter both hormonal and structural aspect of uterus that ultimately reflected on fertility of exposed animals. [Fatma Al-Qudsi and Sabah Linjawi. Histological and Hormonal Changes in Rat Endometrium under the Effect of Camphor. Life Science Journal 2012; 9(2):348-355]. (ISSN:
Article
Full-text available
Camphor and borneol are wildly distributed in the essential oils of medicinal plants from various parts of the World. Our study has been carried out to evaluate the effect of these two bicyclic monoterpenes on rat thymocytes. Camphor and borneol at concentrations of 0.5 and 5 µg/mL did not induce significant toxicity on the immune system cells, while a significant increase of thymocyte viability was detected when cells were incubated with 50 µg/mL of camphor. A significant increase of cell viability was similarly detected when thymocytes were cultivated with borneol at concentrations of 0.5 and 5 µg/mL. The role of camphor and borneol in reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disturbances in rat thymocytes as well as their potential mechanism(s) of action were also discussed.
Article
Full-text available
In response to nutrient stress, cells start an autophagy program that can lead to adaptation or death. The mechanisms underlying the signaling from starvation to the initiation of autophagy are not fully understood. In the current study we show that the absence or inactivation of PARP-1 strongly delays starvation-induced autophagy. We have found that DNA damage is an early event of starvation-induced autophagy as measured by γ-H2AX accumulation and comet assay, with PARP-1 knockout cells displaying a reduction in both parameters. During starvation, ROS-induced DNA damage activates PARP-1, leading to ATP depletion (an early event after nutrient deprivation). The absence of PARP-1 blunted AMPK activation and prevented the complete loss of mTOR activity, leading to a delay in autophagy. PARP-1 depletion favors apoptosis in starved cells, suggesting a pro-survival role of autophagy and PARP-1 activation after nutrient deprivation. In vivo results show that neonates of PARP-1 mutant mice subjected to acute starvation, also display deficient liver autophagy, implying a physiological role for PARP-1 in starvation-induced autophagy. Thus, the PARP signaling pathway is a key regulator of the initial steps of autophagy commitment following starvation.
Article
Full-text available
Herbs have been used in medicines and cosmetics from centuries. Their potential to treat different skin diseases, to adorn and improve the skin appearance is well-known. As ultraviolet (UV) radiation can cause sunburns, wrinkles, lower immunity against infections, premature aging, and cancer, there is permanent need for protection from UV radiation and prevention from their side effects. Herbs and herbal preparations have a high potential due to their antioxidant activity, primarily. Antioxidants such as vitamins (vitamin C, vitamin E), flavonoids, and phenolic acids play the main role in fighting against free radical species that are the main cause of numerous negative skin changes. Although isolated plant compounds have a high potential in protection of the skin, whole herbs extracts showed better potential due to their complex composition. Many studies showed that green and black tea (polyphenols) ameliorate adverse skin reactions following UV exposure. The gel from aloe is believed to stimulate skin and assist in new cell growth. Spectrophotometer testing indicates that as a concentrated extract of Krameria triandra it absorbs 25 to 30% of the amount of UV radiation typically absorbed by octyl methoxycinnamate. Sesame oil resists 30% of UV rays, while coconut, peanut, olive, and cottonseed oils block out about 20%. A "sclerojuglonic" compound which is forming from naphthoquinone and keratin is the reaction product that provides UV protection. Traditional use of plant in medication or beautification is the basis for researches and making new trends in cosmetics. This review covers all essential aspects of potential of herbs as radioprotective agents and its future prospects.
Article
Full-text available
Mitogen-activated protein kinases (MAPKs) are serine-threonine protein kinases that play the major role in signal transduction from the cell surface to the nucleus. MAPKs, which consist of growth factor-regulated extracellular signal-related kinases (ERKs), and the stress-activated MAPKs, c-jun NH(2)-terminal kinases (JNKs) and p38 MAPKs, are part of a three-kinase signaling module composed of the MAPK, an MAPK kinase (MAP2K) and an MAPK kinase (MAP3K). MAP3Ks phosphorylate MAP2Ks, which in turn activate MAPKs. MAPK phosphatases (MKPs), which recognize the TXY amino acid motif present in MAPKs, dephosphorylate and deactivate MAPKs. MAPK pathways are known to be influenced not only by receptor ligand interactions, but also by different stressors placed on the cell. One type of stress that induces potential activation of MAPK pathways is the oxidative stress caused by reactive oxygen species (ROS). Generally, increased ROS production in a cell leads to the activation of ERKs, JNKs, or p38 MAPKs, but the mechanisms by which ROS can activate these kinases are unclear. Oxidative modifications of MAPK signaling proteins and inactivation and/or degradation of MKPs may provide the plausible mechanisms for activation of MAPK pathways by ROS, which will be reviewed in this paper.
Article
Full-text available
Inflammatory molecules and their transcription factor, nuclear factor kappa-B (NF-kappaB), are thought to play important roles in diabetes-induced cardiac dysfunction. Here, we investigated the effects of pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, in diabetic mice. Obese db/db mice and heterozygous lean mice (n = 8) were allowed free access to drinking water (control) or water containing PDTC (100 mg/kg) for 20 weeks. Left ventricular (LV) function was measured using echocardiography at baseline and at study end. Mice were sacrificed and LV removed for gene expression, biochemical, immunofluorescence, and mitochondrial assays. LV and mitochondrial reactive oxygen species (ROS), superoxide and peroxynitrite were measured using electron spin resonance spectroscopy. Enhanced NF-kappaB activity in db/db mice was associated with increased oxidative stress as demonstrated by increased ROS, superoxide, and peroxynitrite production, and increased NF-kappaB, gp91phox, and Nox1 expression; PDTC ameliorated these effects. Mitochondrial free radical production and structural damage were higher in the db/db group than in the control, db/db PDTC, and PDTC-treated heterozygous animal groups. This study demonstrates that NF-kappaB blockade with PDTC mitigates oxidative stress and improves mitochondrial structural integrity directly, through down-regulation of increased oxygen-free radicals, thereby increasing ATP synthesis and thus restoring cardiac function in type II diabetes.
Article
Full-text available
Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer's disease, Parkinson's disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario.
Article
Full-text available
The hallmark of photoaged skin is solar elastosis, which is probably an end product of elastic fiber degradation. Exposure of human skin to a certain threshold of UV, infrared radiation (IR), and heat leads to an influx of neutrophils. These neutrophils are packed with potent proteolytic enzymes capable of degrading collagen and, particularly, elastic fibers. Neutrophil-derived proteolytic enzymes are held responsible for the extracellular matrix (ECM) damage observed in several non-dermatological conditions. Furthermore, neutrophil elastase, a major product of neutrophils, is strongly associated with solar elastosis in mice. Taken together with our data that show in vivo proteolytic activity of neutrophil-derived elastase and matrix metalloproteinases (MMPs) in UV-exposed skin, we have hypothesized earlier that neutrophils are major contributors to the photoaging process. Although several groups have shown that MMPs are also induced in skin exposed to relatively low doses of UV, IR, and heat, clinical data indicate that high(er) doses of UV, IR, and heat are necessary to induce photoaging or photoaging-like pathology in the skin. Therefore, we propose that MMPs generated by suberythemogenic doses of UV and low doses of IR/heat are involved in cellular processes other than ECM degradation.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 67-72; doi:10.1038/jidsymp.2009.15.
Article
Full-text available
Abnormal repair and dysregulated angiogenesis have been implicated in the pathogenesis of pulmonary fibrosis, but the underlying mechanisms of regulation are not well understood. The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). Exposure of lung fibroblasts to bleomycin, a known inducer of fibrosis, resulted in rapid activation of PI3K/Akt and a parallel increase in fibroblast proliferation and collagen production, characteristics of lung fibrosis. Bleomycin had no significant effect on total Akt protein expression but induced phosphorylation of the protein at threonine 308 and serine 473 positions. Inhibition of this phosphorylation by PI3K inhibitors or by dominant-negative Akt (T308A/S473A) expression abrogated the effects of bleomycin on fibroblast proliferation and collagen production, suggesting the role of PI3K/Akt in the fibrogenic process. Activation of PI3K/Akt by bleomycin also led to transcriptional activation and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor, which contributed to the fibroproliferative and collagen-inducing effects of bleomycin. The fibrogenic effects of bleomycin were dependent on ROS generation, particularly superoxide anion and hydrogen peroxide, which were induced by bleomycin. Inhibition of ROS generation by antioxidant enzymes, catalase and superoxide dismutase mimetic MnTBAP, abrogated the fibrogenic effects of bleomycin as well as its induction of PI3K/Akt and HIF-1alpha activation. Together, our results indicate a novel role of PI3K/Akt in fibrogenesis of human lung fibroblasts and its regulation by ROS, which could be exploited for the treatment of pulmonary fibrosis and related disorders.
Article
Full-text available
The hairless (Hr) gene encodes a transcriptional co-repressor highly expressed in the mammalian skin. In the mouse, several null and hypomorphic Hr alleles have been identified resulting in hairlessness in homozygous animals, characterized by alopecia developing after a single cycle of relatively normal hair growth. Mutations in the human ortholog have also been associated with congenital alopecia. Although a variety of hairless strains have been developed, outbred SKH1 mice are the most widely used in dermatologic research. These unpigmented and immunocompetent mice allow for ready manipulation of the skin, application of topical agents, and exposure to UVR, as well as easy visualization of the cutaneous response. Wound healing, acute photobiologic responses, and skin carcinogenesis have been extensively studied in SKH1 mice and are well characterized. In addition, tumors induced in these mice resemble, both at the morphologic and molecular levels, UVR-induced skin malignancies in man. Two limitations of the SKH1 mouse in dermatologic research are the relatively uncharacterized genetic background and its outbred status, which precludes inter-individual transplantation studies.
Article
Full-text available
Over the years, studies have focused on the transcriptional regulation of oncogenesis. More recently, a growing emphasis has been placed on translational control. The Ras and Akt signal transduction pathways play a critical role in regulating mRNA translation and cellular transformation. The question arises: How might the Ras and Akt signaling pathways affect translation and mediate transformation? These pathways converge on a crucial effector of translation, the initiation factor eIF4E, which binds the 5'cap of mRNAs. This review focuses on the role of eIF4E in oncogenesis. eIF4E controls the translation of various malignancy-associated mRNAs which are involved in polyamine synthesis, cell cycle progression, activation of proto-oncogenes, angiogenesis, autocrine growth stimulation, cell survival, invasion and communication with the extracellular environment. eIF4E-mediated translational modulation of these mRNAs plays a pivotal role in both tumor formation and metastasis. Interestingly, eIF4E activity is implicated in mitosis, embryogenesis and in apoptosis. Finally, the finding that eIF4E is overexpressed in several human cancers makes it a prime target for anticancer therapies.
Article
Full-text available
The MAPK (mitogen-activated protein kinase) pathway is one of the most important and intensively studied signalling pathways. It is at the heart of a molecular-signalling network that governs the growth, proliferation, differentiation and survival of many, if not all, cell types. It is de-regulated in various diseases, ranging from cancer to immunological, inflammatory and degenerative syndromes, and thus represents an important drug target. Over recent years, the computational or mathematical modelling of biological systems has become increasingly valuable, and there is now a wide variety of mathematical models of the MAPK pathway which have led to some novel insights and predictions as to how this system functions. In the present review we give an overview of the processes involved in modelling a biological system using the popular approach of ordinary differential equations. Focusing on the MAPK pathway, we introduce the features and functions of the pathway itself before comparing the available models and describing what new biological insights they have led to.
Article
Full-text available
Replicative senescence limits the proliferation of somatic cells passaged in culture and may reflect cellular aging in vivo. The most widely used biomarker for senescent and aging cells is senescence-associated beta-galactosidase (SA-beta-gal), which is defined as beta-galactosidase activity detectable at pH 6.0 in senescent cells, but the origin of SA-beta-gal and its cellular roles in senescence are not known. We demonstrate here that SA-beta-gal activity is expressed from GLB1, the gene encoding lysosomal beta-D-galactosidase, the activity of which is typically measured at acidic pH 4.5. Fibroblasts from patients with autosomal recessive G(M1)-gangliosidosis, which have defective lysosomal beta-galactosidase, did not express SA-beta-gal at late passages even though they underwent replicative senescence. In addition, late passage normal fibroblasts expressing small-hairpin interfering RNA that depleted GLB1 mRNA underwent senescence but failed to express SA-beta-gal. GLB1 mRNA depletion also prevented expression of SA-beta-gal activity in HeLa cervical carcinoma cells induced to enter a senescent state by repression of their endogenous human papillomavirus E7 oncogene. SA-beta-gal induction during senescence was due at least in part to increased expression of the lysosomal beta-galactosidase protein. These results also indicate that SA-beta-gal is not required for senescence.
Article
Full-text available
Signals received at the cell surface must be properly transmitted to critical targets within the cell to achieve the appropriate biological response. This process of signal transduction is often initiated by receptor tyrosine kinases (RTKs), which function as entry points for many extracellular cues and play a critical role in recruiting the intracellular signaling cascades that orchestrate a particular response. Essential for most RTK-mediated signaling is the engagement and activation of the mitogen-activated protein kinase (MAPK) cascade comprised of the Raf, MEK and extracellular signal-regulated kinase (ERK) kinases. For many years, it was thought that signaling from RTKs to ERK occurred only at the plasma membrane and was mediated by a simple, linear Ras-dependent pathway. However, the limitation of this model became apparent with the discovery that Ras and ERK can be activated at various intracellular compartments, and that RTKs can modulate Ras/ERK signaling from these sites. Moreover, ERK scaffolding proteins and signaling modulators have been identified that play critical roles in determining the strength, duration and location of RTK-mediated ERK signaling. Together, these factors contribute to the diversity of biological responses generated by RTK signaling.
Article
Full-text available
To investigate how extracellular matrix mechanical properties influence cell and matrix patterning in three-dimensional culture. Human corneal fibroblasts were seeded within 30 x 10 mm collagen matrices that were unconstrained (UN), fully constrained (CO) along the long axis by attaching the construct to two immobilized plastic bars, or partially constrained (PC) by allowing linear elastic displacement of one bar. After 24 hours, constructs were labeled with phalloidin and were imaged using fluorescent and reflected light (for collagen) confocal microscopy. Cell morphology and local collagen fibril density and alignment were measured using digital image processing. Corneal fibroblasts in UN matrices were less elongated (UN < PC < CO; P < 0.05) than those in constrained matrices. Cells were aligned parallel to the long axis in the anisotropic region of constrained matrices but were randomly aligned in unconstrained (isotropic) matrices (UN < PC = CO; P < 0.05). Both the local collagen density and the degree of cell/collagen coalignment were higher in constrained matrices (UN < PC < CO; P < 0.05). In regions of higher cell density, additional bands of aligned collagen were often observed between individual cells. These data suggest that cell spreading, alignment, and contractile force generation are directly influenced by the mechanical properties of the surrounding extracellular matrix (ECM). Corneal fibroblasts generally align and compact collagen parallel to the axis of greatest ECM stiffness. Mechanical cross-talk between adjacent cells leads to enhancement of matrix reorganization, and results in additional, more complex matrix patterning.
Article
Full-text available
Acutely transforming retrovirus AKT8 in rodent T-cell lymphoma (Akt) is a serine/threonine kinase that plays important roles in survival, cell-cycle progression, and cell proliferation, and has recently been implicated in collagen regulation. The aim of this study was to determine the role of Akt in collagen deposition by normal dermal fibroblasts, and to determine the sensitivity of cultured systemic sclerosis (SSc) fibroblasts to Akt inhibition. We show that blockade of Akt using pharmacological inhibitors, small interfering RNA (siRNA), and a dominant-negative Akt mutant led to inhibition of the basal type I collagen production. Furthermore, inhibition of Akt upregulated basal matrix metalloproteinase 1 (MMP1) production and reversed the inhibitory effect of transforming growth factor-beta (TGF-beta) on MMP1 gene expression. In addition, SSc fibroblasts were more sensitive to Akt inhibition, with respect to collagen and MMP1 production. These findings suggest that in human dermal fibroblasts, Akt has dual profibrotic effects, increasing collagen synthesis and decreasing its degradation via downregulation of MMP1. Akt could directly contribute to elevated collagen in SSc fibroblasts and it may represent an attractive target for therapy of SSc fibrosis.
Article
Full-text available
The mammalian target of rapamycin (mTOR) is a protein kinase that forms two functionally distinct complexes important for nutrient and growth factor signaling. Both complexes phosphorylate a hydrophobic motif on downstream protein kinases, which contributes to the activation of these kinases. mTOR complex 1 (mTORC1) phosphorylates S6K1, while mTORC2 phosphorylates Akt. The TSC1-TSC2 complex is a critical negative regulator of mTORC1. However, how mTORC2 is regulated and whether the TSC1-TSC2 complex is involved are unknown. We find that mTORC2 isolated from a variety of cells lacking a functional TSC1-TSC2 complex is impaired in its kinase activity toward Akt. Importantly, the defect in mTORC2 activity in these cells can be separated from effects on mTORC1 signaling and known feedback mechanisms affecting insulin receptor substrate-1 and phosphatidylinositol 3-kinase. Our data also suggest that the TSC1-TSC2 complex positively regulates mTORC2 in a manner independent of its GTPase-activating protein activity toward Rheb. Finally, we find that the TSC1-TSC2 complex can physically associate with mTORC2 but not mTORC1. These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation.
Article
Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.
Article
Abstract Reactive oxygen species (ROS) are thought to have effects on T-cell function and proliferation. Low concentrations of ROS in T cells are a prerequisite for cell survival, and increased ROS accumulation can lead to apoptosis/necrosis. The cellular redox state of a T cell can also affect T-cell receptor signaling, skewing the immune response. Various T-cell subsets have different redox statuses, and this differential ROS susceptibility could modulate the outcome of an immune response in various disease states. Recent advances in T-cell redox signaling reveal that ROS modulate signaling cascades such as the mitogen-activated protein kinase, phosphoinositide 3-kinase (PI3K)/AKT, and JAK/STAT pathways. Also, tumor microenvironments, chronic T-cell stimulation leading to replicative senescence, gender, and age affect T-cell susceptibility to ROS, thereby contributing to diverse immune outcomes. Antioxidants such as glutathione, thioredoxin, superoxide dismutase, and catalase balance cellular oxidative stress. T-cell redox states are also regulated by expression of various vitamins and dietary compounds. Changes in T-cell redox regulation may affect the pathogenesis of various human diseases. Many strategies to control oxidative stress have been employed for various diseases, including the use of active antioxidants from dietary products and pharmacologic or genetic engineering of antioxidant genes in T cells. Here, we discuss the existence of a complex web of molecules/factors that exogenously or endogenously affect oxidants, and we relate these molecules to potential therapeutics. Antioxid. Redox Signal. 00, 000-000.
Article
The Ras-extracellular signal-regulated kinase (Ras-ERK) and phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) signaling pathways are the chief mechanisms for controlling cell survival, differentiation, proliferation, metabolism, and motility in response to extracellular cues. Components of these pathways were among the first to be discovered when scientists began cloning proto-oncogenes and purifying cellular kinase activities in the 1980s. Ras-ERK and PI3K-mTOR were originally modeled as linear signaling conduits activated by different stimuli, yet even early experiments hinted that they might intersect to regulate each other and co-regulate downstream functions. The extent of this cross-talk and its significance in cancer therapeutics are now becoming clear.
Article
Please cite this paper as: Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation. Experimental Dermatology 2010; 19: e182–e190. Abstract: Ellagic acid, a polyphenol compound present in berries and pomegranate, has received attention as an agent that may have potential bioactivities preventing chronic diseases. This study examined photoprotective effects of ellagic acid on collagen breakdown and inflammatory responses in UV (ultraviolet)-B irradiated human skin cells and hairless mice. Ellagic acid attenuated the UV-B-induced toxicity of HaCaT keratinocytes and human dermal fibroblasts. Non-toxic ellagic acid markedly prevented collagen degradation by blocking matrix metalloproteinase production in UV-B-exposed fibroblasts. Anti-wrinkle activity of ellagic acid was further investigated in hairless mice exposed to UV-B, in which it attenuated UV-B-triggered skin wrinkle formation and epidermal thickening. Topical application of 10 μmol/l ellagic acid diminished production of pro-inflammatory cytokines IL-1β and IL-6, and blocked infiltration of inflammatory macrophages in the integuments of SKH-1 hairless mice exposed to UV-B for 8 weeks. In addition, this compound mitigated inflammatory intracellular cell adhesion molecule-1 expression in UV-B-irradiated keratinocytes and photoaged mouse epidermis. These results demonstrate that ellagic acid prevented collagen destruction and inflammatory responses caused by UV-B. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies interrupting skin wrinkle and inflammation associated with chronic UV exposure leading to photoageing.
Article
The relations of biological markers of extracellular matrix (plasma elastin peptides and elastase inhibitors) to the clinical history of cardiovascular diseases and risk factors for atherosclerosis were examined in a large population study (the EVA Study) on vascular and cognitive aging performed in 1389 men and women aged 59-71 years. A moderate decrease in elastin peptides was observed in women with a self-reported history of coronary heart disease (P < 0.091) and stroke (P < 0.03) as well as with diabetes (P < 0.043). Similar but non-significant trends were found in men. Furthermore, elastin peptides were significantly and positively correlated to HDL-cholesterol and apolipoprotein A1 in both sexes. On the other hand, elastase inhibitor titers were significantly higher in women than in men. A moderate increase was also found in men (P < 0.097) and women (P < 0.068) with a history of coronary heart disease that reached significance level after pooling both sexes (P < 0.014). Furthermore, elastase inhibitor titers were significantly and positively related to fibrinogen and C reactive protein in either sex. No consistent associations were observed between both biological markers of extracellular matrix and age, blood pressure, body mass index and tobacco or alcohol consumption. These results suggest that a decrease in elastin peptides and an increase in elastase inhibitors might be associated with risk factors of atherogenesis as well as with atherosclerosis-related diseases.
Article
Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging. We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis. A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin. Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.
Article
Type I and type III procollagen are reduced in photodamaged human skin. This reduction could result from increased degradation by metalloproteinases and/or from reduced procollagen synthesis. In the present study, we investigated type I procollagen production in photodamaged and sun-protected human skin. Skin samples from severely sun-damaged forearm skin and matched sun-protected hip skin from the same individuals were assessed for type I procollagen gene expression by in situ hybridization and for type I procollagen protein by immunostaining. Both mRNA and protein were reduced ( approximately 65 and 57%, respectively) in photodamaged forearm skin compared to sun-protected hip skin. We next investigated whether reduced type I procollagen production was because of inherently reduced capacity of skin fibroblasts in severely photodamaged forearm skin to synthesize procollagen, or whether contextual influences within photodamaged skin act to down-regulate type I procollagen synthesis. For these studies, fibroblasts from photodamaged skin and matched sun-protected skin were established in culture. Equivalent numbers of fibroblasts were isolated from the two skin sites. Fibroblasts from the two sites had similar growth capacities and produced virtually identical amounts of type I procollagen protein. These findings indicate that the lack of type I procollagen synthesis in sun-damaged skin is not because of irreversible damage to fibroblast collagen-synthetic capacity. It follows, therefore, that factors within the severely photodamaged skin may act in some manner to inhibit procollagen production by cells that are inherently capable of doing so. Interactions between fibroblasts and the collagenous extracellular matrix regulate type I procollagen synthesis. In sun-protected skin, collagen fibrils exist as a highly organized matrix. Fibroblasts are found within the matrix, in close apposition with collagen fibers. In photodamaged skin, collagen fibrils are shortened, thinned, and disorganized. The level of partially degraded collagen is approximately 3.6-fold greater in photodamaged skin than in sun-protected skin, and some fibroblasts are surrounded by debris. To model this situation, skin fibroblasts were cultured in vitro on intact collagen or on collagen that had been partially degraded by exposure to collagenolytic enzymes. Collagen that had been partially degraded by exposure to collagenolytic enzymes from either bacteria or human skin underwent contraction in the presence of dermal fibroblasts, whereas intact collagen did not. Fibroblasts cultured on collagen that had been exposed to either source of collagenolytic enzyme demonstrated reduced proliferative capacity (22 and 17% reduction on collagen degraded by bacterial collagenase or human skin collagenase, respectively) and synthesized less type I procollagen (36 and 88% reduction, respectively, on a per cell basis). Taken together, these findings indicate that 1) fibroblasts from photoaged and sun-protected skin are similar in their capacities for growth and type I procollagen production; and 2) the accumulation of partially degraded collagen observed in photodamaged skin may inhibit, by an as yet unidentified mechanism, type I procollagen synthesis.
Article
We previously reported that wrinkle formation in the skin following long-term ultraviolet B irradiation is accompanied by decreases in skin elasticity and the curling of elastic fibers in the dermis. We further showed that wrinkles could be repaired by treatment with retinoic acid and that this was concomitant with the recovery of skin elasticity ascribed to the repair of damaged elastic fibers. Those studies suggested that decreasing the tortuosity of dermal elastic fibers is an important factor involved in inhibiting or repairing wrinkle formation. Therefore, it is of particular interest to determine whether the inhibition of elastase activity in vivo would prevent the damage of dermal elastic fibers and might abolish wrinkle formation associated with the loss of skin elasticity. Because the major elastase in the skin under noninflammatory conditions is skin fibroblast elastase, we used a specific inhibitor of that enzyme to assess its biologic role in wrinkle formation. The hind limb skins of Sprague-Dawley rats were irradiated with ultraviolet B at a suberythemal dose three times a week for 6 wk. During that period, 0.1-10.0 mM N-phenetylphosphonyl-leucyl-tryptophane, an inhibitor of skin fibroblast elastase, was applied topically five times a week. N-phenetylphosphonyl-leucyl-tryptophane application at concentrations of 0.1-1.0 mM abolished wrinkle formation in a concentration-dependent manner, with a peak for inhibition at 1.0 mM. This inhibition was accompanied by a continued low tortuosity of dermal elastic fibers and a maintenance of skin elasticity. Measurement of elastase activity after 6 wk of ultraviolet B irradiation demonstrated that whereas phosphoramidon-sensitive elastase activity was significantly enhanced in the ultraviolet B-exposed skin, there was no significant increase in that activity in the ultraviolet B-exposed, N-phenetylphosphonyl-leucyl-tryptophane-treated skin. These findings suggest that skin fibroblast elastase plays an essential part in the degeneration and/or tortuosity of elastic fibers induced by cumulative ultraviolet B irradiation.
Article
Three-dimensional lattices of reconstituted, polymerized type I collagen were subjected to partial hydrolysis by organ culture fluid from human skin or by various matrix metalloproteinases, including matrix metalloproteinase-1 (interstitial collagenase), -2 (72 kDa gelatinase A), -8 (neutrophil collagenase), -9 (92 kDa gelatinase B), or -13 (collagenase 3). Following partial digestion, human dermal fibroblasts were incubated on the enzyme-treated or control lattices and examined for ability to contract the collagen lattice and synthesize type I procollagen. Collagen lattices partially degraded by organ culture fluid were contracted by fibroblasts under conditions in which control collagen lattices were not. On the partially degraded collagen, fibroblasts synthesized reduced amounts of type I procollagen (approximately 70% reduction). Purified matrix metalloproteinases with collagenolytic activity duplicated the effects of the human skin organ culture fluid, although matrix metalloproteinases 8 and 13 were less efficient than matrix metalloproteinase-1 (65% vs 40% and 18% reduction in type I procollagen production for matrix metalloproteinases 1, 8, and 13, respectively). Matrix metalloproteinases 2 and 9 were without effect on intact collagen; however, when collagen lattices were subjected to digestion by a combination of matrix metalloproteinases 1 and 9, fragments produced by matrix metalloproteinase-1 were further degraded by the gelatinase. Collagen contraction and inhibition of procollagen synthesis were both reduced. Matrix metalloproteinase-2 was less effective than matrix metalloproteinase-9 in clearing matrix metalloproteinase-1-generated fragments. Matrix metalloproteinase-2 was also less effective in preventing contraction and inhibiting the downregulation of type I procollagen synthesis. These observations suggest that in the presence of high molecular weight fragments of type I collagen, type I procollagen synthesis is inhibited. As these fragments are processed further, there is less inhibition of type I procollagen production.
Article
UV filters represent new classes of estrogenic [Environ. Health Perspect. 109 (2001) 239] or antiandrogenic [Toxicol. Sci. 74 (2003) 43] chemicals. We tested 3-benzylidene camphor (3-BC), reported as estrogenic in fish [Pharmacol. Toxicol. 91 (2002) 204], and mammalian systems in comparison to 4-methylbenzylidene camphor (4-MBC), shown to be active in rats, and analyzed binding to estrogen receptor subtypes. 3-BC and 4-MBC stimulated MCF-7 cell proliferation (EC(50): 0.68 and 3.9 microM). The uterotrophic assay of 3-BC (oral gavage) in immature rats showed unexpected potency with ED50 45.3mg/kg per day; lowest effective dose 2mg/kg per day, and maximum effect with 70% of ethinylestradiol. After comparing with literature data, we found that the oral 3-BC was considerably more potent than oral bisphenol A and almost as active as subcutaneous genistein. 3-BC and 4-MBC displaced 16alpha 125I-estradiol from porcine uterine cytosolic receptors (IC(50): 14.5 and 112 microM), and from recombinant human estrogen receptor beta (hERbeta) (IC(50): 3-BC, 11.8 microM; 4-MBC, 35.3 microM), whereas no displacement was detected at human estrogen receptor alpha (hERalpha) up to 3mM. This subtype selectivity makes the two camphor derivatives interesting model compounds. Their activity on immature rat uterus is not easily explained by ERbeta activation. It cannot be excluded that active metabolites with possibly different receptor binding characteristics are formed in vivo.
Article
While defining the no effect level for the 5 alpha-reductase inhibitor finasteride in the Hershberger assay, we encountered an inverted-U low-dose trophic effect on the prostate gland of the rat. Two attempts to confirm this observation were unsuccessful, and we concluded that the positive effect initially observed was associated with normal biologic variability. During the same period we attempted, unsuccessfully, to repeat our own observation of weak uterotrophic activity in the rat for the sunscreen 3-(4-methylbenzylidene)camphor (4MBC). Further evaluation led us to conclude that 4MBC is uterotrophic only when the control uterine weights are at the low end of their normally encountered range. This led us to reevaluate our earlier mouse uterotrophic assay data for bisphenol A (BPA). Originally we had concluded that BPA gave irreproducible evidence of weak uterotrophic activity, but upon ordering the eight experiments we had conducted, according to decreasing control uterine weight, we confirmed reproducible weak uterotrophic activity for BPA when the control uteri were at the low end of their normal range. In this article, we describe these observations, together with a reanalysis of the data associated with several reported instances of weak or low-dose endocrine effects that have proven difficult to confirm in independent laboratories. These include the activity of BPA on the CF1 mouse prostate; the activities of BPA, octylphenol, and nonylphenol on the rat testis; and the effect of polycarbonate caging on control mouse uterine weight. In all of these cases, variability among controls provides a major obstacle to data interpretation and confirmation. Our recommendations on experimental design are also presented, with a view to ending the current impasse on the reality, or otherwise, of low-dose or weak endocrine toxicities.
Article
The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in the last decade clearly demonstrates that TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many are phosphorylated indirectly. In this review, we summarize some recent developments in this fast-evolving field. We describe both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis. We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity.
Article
It has been called into question whether the commonly used beta-galactosidase staining is a reliable biomarker of cellular senescence because induction of beta-galactosidase activity also occurs independently of senescence. Here, we tested whether cytochemically detectable beta-galactosidase activity is reproducible and reflects the rate of cellular aging in vitro. Therefore, we serially cultured fibroblasts from 12 different donors and stained the cells for beta-galactosidase at pH 6 until the onset of the permanent growth arrest of the individual cultures. All fibroblast strains displayed a high replicative capacity with a similar growth pattern during the exponential growth phase and a very high interbiopsy variability in the onset of decreased mitotic activity and in the onset of growth arrest. Correspondingly, beta-galactosidase activity was low during the exponential growth phase, with an individually defined significant increase in activity when the growth speed of the culture decreased. The increase in beta-galactosidase activity was a better predictor for the onset of the decreased growth speed than the chronological life span of the culture expressed in population doublings. Within the phase of decreased mitotic activity, we observed a high fluctuation in the percentage of positively stained fibroblasts. Thus, our results support beta-galactosidase activity as a reliable biomarker for the course of replicative senescence, if used under defined standardized conditions.
Article
The skin, the largest organ of the body, is the organ in which changes associated with aging are most visible. With increasing frequency, patients are requesting information and treatments that improve the appearance of their skin. Corresponding to this trend, there is an increasing number of products and methods available that claim to aid this pursuit. First, a change of the patient's lifestyle (eg, sun behavior, nicotine abuse, and nutrition) must take place. Only then may other methods be used. This article reflects on the following topics: topical retinoids, peels, botulinum neurotoxin, soft tissue fillers, lasers, topical and systemic endocrinological therapies, and phytohormones. A thorough knowledge of the properties (benefits, limitations, and complications) of the expanding array of possibilities for rejuvenation of the skin is essential for any physician treating patients with cosmetic complaints.
UV-light-induced signal cascades and skin aging
  • Rittie
Rittie L, Fisher GJ. 2002. UV-light-induced signal cascades and skin aging. Ageing Res Rev 1(4): 705-720.
  • Benefit Of
  • Camphor On
  • Fibroblast
  • Uv-Exposed
  • Mouse
  • Copyright
BENEFIT OF CAMPHOR ON DERMAL FIBROBLAST AND UV-EXPOSED MOUSE SKIN Copyright © 2015 John Wiley & Sons, Ltd. Phytother. Res. 29: 1917–1925 (2015)
Bornan-2-one (camphor, synthetic) The Hague: Health Council of the Netherlands
Health Council of the Netherlands. 2000. Bornan-2-one (camphor, synthetic). The Hague: Health Council of the Netherlands, 2000; publication no.2000/15osh018.