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Gastrodia elata Blume Extract Modulates Antioxidant Activity and Ultraviolet A-Irradiated Skin Aging in Human Dermal Fibroblast Cells

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Abstract

Gastrodia elata Blume (GEB), a traditional herbal medicine, has been used to treat a wide range of neurological disorders (e.g., paralysis and stroke) and skin problems (e.g., atopic dermatitis and eczema) in oriental medicine. This study was designed to investigate the antioxidant ability of GEB and its antiaging effect on human dermal fibroblast cells (HDF). The total phenolic and flavonoid contents of GEB were 21.8 and 0.43 mg/g dry weight (DW), respectively. The ergothioneine content of GEB was 0.41 mg/mL DW. The DPPH and ABTS radical scavenging activities of GEB at 5 and 10 mg/mL approximately ranged between 31% and 44%. The superoxide dismutase activity of GEB at 10 and 25 mg/mL was 57% and 76%, respectively. GEB increased procollagen type 1 (PC1) production and inhibited matrix metalloproteinase-1 (MMP-1) production and elastase-1 activity in UVA-irradiated HDF. PC1 messenger RNA (mRNA) levels decreased upon UVA irradiation, but recovered in response to high doses of GEB in HDF. On the contrary, GEB significantly decreased MMP-1 and elastase-1 mRNA levels, which were markedly induced in UVA-irradiated HDF. Collectively, these results suggest that GEB has sufficient antioxidant ability to prevent the signs of skin aging in UVA-irradiated human skin cells, suggesting its potential as a natural antiaging product. © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition 2016.

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... Elastase inhibitory activity was determined after the use of the plant extracts prepared with Eugenia dysenterica [26], Gastrodia elata [27], Litchi sinensis [28], Magnolia officinalis [29], Malaxis acuminata [30], Manilkara zapota [14], Nephelium lappaceum [28], Phyllanthus emblica [14], Sclerocarya birrea [31], Sylibum marianum [14], Spatholobus suberectus [32], Tamarindus indica [28], and a polyherbal formulation containing Nyctanthes arbor-tristis leaf, unripe and ripe Aegle marmelos fruit pulp, and the terminal meristem of Musa paradisiaca extracts [33]; ii. ...
... The downregulation of MMP-1 expression was described after treatments with plant extracts of Alchemilla mollis [36], Allium sativum [49], Azadirachta indica [37], Camellia sinensis [38], Gastrodia elata [27], Kochia scoparia [41], Magnolia officinalis [29], Passiflora tarminiana [45], Penthorium chinense [47], Rosa multiflora ( [41], and Syzygium aromaticum [50]; vii. ...
... Alchemilla mollis DPPH and ABTS radical scavenging activity [36] Allium sativum DPPH radical scavenging activity Reduction in NO production Decrease in UVB-induced ROS generation [49] Camelia sinensis DPPH, ABTS, CUPRAC, FRAP, and ORAC radical scavenging activity Decrease in UVB-induced ROS generation in fibroblasts Upregulation of SOD, CAT, and GPX in fibroblasts Increase in Nrf2 transcriptional level and nuclear translocation in fibroblasts [38] Cassia fistula DPPH and ABTS radical scavenging activity [43] Curcuma heyneana DPPH radical scavenging activity [52] Gastrodia elata DPPH and ABTS radical scavenging activity Increase in SOD activity [27] Hibiscus sabdariffa DPPH and FRAP radical scavenging activity Decrease in UVB-induced ROS generation [53] Litchi chinensis DPPH, superoxide, and ABTS radical scavenging activity [28] Magnolia officinalis DPPH and FRAP radical scavenging activity [29] Malaxis acuminata DPPH and ABTS radical scavenging activity [30] Manikaria zapota DPPH and ABTS radical scavenging activity [14] Nephelium lappaceum DPPH, superoxide, and ABTS radical scavenging activity [28] Nictanthes arbor-tristis DPPH radical scavenging activity Reduction in UVB-induced ROS production in human fibroblasts [62] Passiflora tarminiana ORAC radical scavenging activity [45] Penthorum chinense DPPH radical scavenging activity [47] Phyllanthus emblica DPPH and ABTS radical scavenging activity [14] Piper cambodianum Reduction in UVB-induced ROS production in human fibroblasts [34] Pourthiaea villosa DPPH and ABTS + radical scavenging activity Inhibition of H 2 O 2 -induced intracellular ROS production Increase in SOD1 and SOD2 proteins levels Inhibition of H 2 O 2 -induced premature cellular senescence [51] Prosopis cineraria DPPH radical scavenging activity [63] Salvia officinalis DPPH radical scavenging activity [48] Spatholobus suberectus Reduction in UVB-induced ROS production in human fibroblasts [32] Silybum marianum DPPH and ABTS radical scavenging activity [14] Syzygium aromaticum Reduction in UVB-induced ROS production in human fibroblasts [50] ...
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Although aesthetic benefits are a desirable effect of the treatment of skin aging, it is also important in controlling several skin diseases, mainly in aged people. The development of new dermocosmetics has rapidly increased due to consumers’ demand for non-invasive products with lower adverse effects than those currently available on the market. Natural compounds of plant origin and herbal-derived formulations have been popularized due to their various safe active products, which act through different mechanisms of action on several signaling pathways for skin aging. Based on this, the aim of the review was to identify the recent advances in herbal-derived product research, including herbal formulations and isolated compounds with skin anti-aging properties. The studies evaluated the biological effects of herbal-derived products in in vitro, ex vivo, and in vivo studies, highlighting the effects that were reported in clinical trials with available pharmacodynamics data that support their protective effects to treat, prevent, or control human skin aging. Thus, it was possible to identify that gallic and ferulic acids and herbal formulations containing Thymus vulgaris, Panax ginseng, Triticum aestivum, or Andrographis paniculata are the most promising natural products for the development of new dermocosmetics with skin anti-aging properties.
... Many studies have been conducted on natural extracts in order to investigate the candidates for anti-aging products based on the anti-oxidative properties of chemicals including flavonoids, polyphenols, carotenoids, and vitamins C and E [13,14,16,17]. Plant extracts such as soy bean [18], sea buckthorn [19], turmeric, green tea, grape, soybean, milk thistle, pomegranate [20], Equisetum arvens [21], Gastrodia elata [22], Nymphaea tetragona [23], Euterpe oleracea, Matricaria chamomilla, and Camellia sinensi [24] have been widely studied. Although topical and oral applications of these plant extracts have been researched, there have been few studies dealing with skin aging and the anti-oxidative effects of marine bioactive compounds [25][26][27][28][29]. ...
... Numerous studies dealing with protection against photoaging have been carried out. The anti-inflammatory and anti-oxidative properties of various molecules, including flavonoids, polyphenols, carotenoids, and vitamins C and E, and natural extracts, have been investigated with regard to their ability to prevent or stimulate collagen degeneration or synthesis [13,14,[18][19][20][21][22][23][24]. However, no previous study exploring the therapeutic potential of marine bioactive material in skin photoaging has been carried out. ...
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Echinochrome A (Ech A, 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone) has been known to exhibit anti-oxidative and anti-inflammatory effects. However, no study has been carried out on the efficacy of Ech A against skin photoaging; this process is largely mediated by oxidative stress. Six-week-old male SKH-1 hairless mice (n = 36) were divided into five groups. Except for a group that were not treated (n = 4), all mice underwent ultraviolet-B (UVB) exposure for 8 weeks while applying phosphate-buffered saline or Ech A through intraperitoneal injection. UVB impaired skin barrier function, showing increased transepidermal water loss and decreased stratum corneum hydration. UVB induced dermal collagen degeneration and mast cell infiltration. Ech A injection was found to significantly lower transepidermal water loss while attenuating tissue inflammatory changes and collagen degeneration compared to the control. Furthermore, Ech A was found to decrease the relative expression of matrix metalloproteinase, tryptase, and chymase. Taken together, these results suggest that Ech A protects against UVB-induced photoaging in both functional and histologic aspects, causing a lowering of collagen degradation and inflammatory cell infiltration.
... Rhizome of Gastrodia elata Blume (RGE), "TianMa" in Chinese, is considered a valuable traditional Chinese medicine, and has been used for the treatment of convulsions, epilepsy, tetanus, vertigo and paralysis [1][2][3] for thousands of years. Modern pharmacological studies have shown that RGE extract has neuroprotective, antioxidant, anti-anxiety, anti-depressant, sedative, anti-inflammatory and anti-angiogenic effects [4][5][6][7][8][9][10]. Gastrodin (GAS) and p-hydroxybenzyl alcohol (HBA) have been considered to be the active ingredients for a long time, due to their significant pharmacological activities [11][12][13][14][15]. Therefore, they were listed as the quality evaluation indicators of RGE in the Chinese Pharmacopoeia all along. ...
... The transformation pathways of parishins are summarized in Figure 3. The compounds were all composed of citric acid and different amounts of GAS (6) or HBA. The protons on citric acid were replaced by R 1 , R 2 , R 3 , and the substituent groups included S 1 , S 2 and S 3 . ...
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To explore the transformation mechanisms of free gastrodin and combined gastrodin before and after steaming of Gastrodia elata (G. elata), a fresh G. elata sample was processed by the traditional steaming method prescribed by Chinese Pharmacopoeia (2015 version), and HPLC-ESI-TOF/MS method was used to identify the chemical composition in steamed and fresh G. elata. Finally, 25 components were identified in G. elata based on the characteristic fragments of the compounds and the changes of the 25 components of fresh and steamed G. elata were compared by the relative content. Hydrolysis experiments and enzymatic hydrolysis experiments of 10 monomer compounds simulating the G. elata steaming process were carried out for the first time. As a result, hydrolysis experiments proved that free gastrodin or p-hydroxybenzyl alcohol could be obtained by breaking ester bond or ether bond during the steaming process of G. elata. Enzymatic experiments showed that steaming played an important role in the protection of gastrodin, confirming the hypothesis that steaming can promote the conversion of chemical constituents of G. elata—inhibiting enzymatic degradation. This experiment clarified the scientific mechanism of the traditional steaming method of G. elata and provided reference for how to apply G. elata decoction to some extent.
... Three types of UV rays, UVA (315-400 nm), UVB (280-315 nm), and UVC (200-280 nm), compose solar radiation and only UVA and UVB inflict damage to ground surface because UVC is screened out by the ozone layer (Ko, 2015). The deepest penetration is from UVA; even relative intensity is not more energetic than UVB, which can reach deeper skin layers (Binic et al., 2013;Kim et al., 2016;Song et al., 2016). Increased substantial ROS by UV irradiation in the cells augment proteins that deplete ECM components (Binic et al., 2013;Song et al., 2016;Rittié & Fisher, 2002;Tsuji et al., 2001). ...
... The deepest penetration is from UVA; even relative intensity is not more energetic than UVB, which can reach deeper skin layers (Binic et al., 2013;Kim et al., 2016;Song et al., 2016). Increased substantial ROS by UV irradiation in the cells augment proteins that deplete ECM components (Binic et al., 2013;Song et al., 2016;Rittié & Fisher, 2002;Tsuji et al., 2001). ...
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Background Among various extra stimuli of humans, ultraviolet (UV) has been the most studied factor because it arouses not only internal but also external irritation in the body. UVA, one type of UV rays, has a wavelength between 320 and 400 nm and capacity to penetrate the skin dermal layer. Therefore, studies on how to reduce UVA-induced maleficence have been investigated vibrantly. Angelic acid has been demonstrated to aid in wound healing and exhibited sedative and psychotropic properties. But there have not been sufficient reports whether angelic acid has potential properties in the cosmeceutical aspect. Methods To investigate protective effects of angelic acid on UVA-induced oxidative stress and disruption of extracellular matrix, researchers analyzed cell proliferation rate, intracellular reactive oxygen species (ROS) scavenging capacity, cellular senescence, transcriptional activity of activating protein-1 (AP-1) transcription factor, and gene expression of antioxidant enzymes and connective tissue-related proteins. ResultsPretreatment of angelic acid in normal human dermal fibroblasts (NHDFs) showed protective effect on UVA-induced proliferative inhibition. Via estimating ROS scavenging activity, angelic acid represented a scavenging effect of excessive increased intracellular ROS which is induced by UVA irradiation. Through quantitative real-time polymerase reaction, antioxidant enzyme and extracellular matrix (ECM)-related protein coded gene expressions were analyzed. Analysis of senescent cell and AP-1 promoter activity by beta-galactosidase assay and luciferase reporter gene assay, respectively, indicated how angelic acid regulates cellular mechanisms associated with connective tissue density. Conclusions Through the present study, researchers verify that angelic acid has dermal protective effect against UVA and suggest angelic acid as an efficacious cosmetic material preventing dermal cellular damages.
... The Roman archives (dating from 410 to 476) were looted by the barbarian tribes of Alaric (in 410-476), while the few classic vestiges of Athens (year 529) were destroyed in the Justinian period [24]. However, much of what was left of this scientific knowledge was rescued by the Arabs [47]. Many branches of Islam established a series of basic rules relating to purity and cleanliness, not only in body but also in spirit. ...
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The treatment of skin ageing is vital in controlling numerous skin problems, especially in the elderly, which is a welcome side effect. Consumer demand for non-invasive products with fewer harmful effects than those currently on the market has led to a rapid surge in the development of new dermocosmetics. Herbal-derived formulations and natural compounds from plants have gained popularity because to the wide range of effective, non-toxic active ingredients they contain, many of which target different parts of the skin's ageing signalling pathways. The purpose of this review was, therefore, to identify the most current developments in the study of herbal-derived products, such as herbal formulations and isolated components with skin anti-aging effects. Clinical trials with available pharmacodynamics data support the protective effects of herbal-derived products used to treat, prevent, or control the ageing of human skin, and these investigations assessed the biological effects of these products in in vitro, ex vivo, and in vivo settings.
... GEE could inhibit NO production and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) upon lipopolysaccharide (LPS) stimulation in RAW264.7 macrophages [9]. The anti-inflammatory and antioxidative activities of GEB accounted for the cure effects of many disorders, such as neurological disorders [10][11][12] and aging-related disorders [13][14][15]. GEB could protect against glutamate-induced apoptosis in IMR-32 human neuroblastoma cells [16], cerebral ischemia [17], corticosterone-induced apoptosis in PC12 cells [18], and scopolamine-induced learning and memory deficits in rats [19]. The neuroprotective effects of GE might be also mediated through the A(2A)-R/cAMP/PKA/CREBdependent pathway [20,21], such as to attenuate mutant Huntingtin aggregation [22], reduce amyloid beta-peptideinduced neuronal cell death in vitro [23], ameliorate circadian rhythm disorder-induced mice memory impairment [24], and improve epilepsy [25]. ...
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The traditional Chinese medicine Gastrodia elata (commonly called “Tianma” in Chinese) has been widely used in the treatment of rheumatism, epilepsy, paralysis, headache, and dizziness. Phenolic compounds, such as gastrodin, para-hydroxybenzyl alcohol (HBA), p-hydroxybenzaldehyde, and vanillin are the main bioactive components isolated from Gastrodia elata. These compounds not only are structurally related but also share similar pharmacological activities, such as antioxidative and anti-inflammatory activities, and effects on the treatment of aging-related diseases. Here, we investigated the effect of para-hydroxybenzyl alcohol (HBA) on neurodegenerative diseases and aging in models of Caenorhabditis elegans (C. elegans). Our results showed that HBA effectively delayed the progression of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease in models of C. elegans. In addition, HBA could increase the average lifespan of N2 worms by more than 25% and significantly improve the age-related physiological functions of worms. Moreover, HBA improved the survival rate of worms under stresses of oxidation, heat, and pathogenic bacteria. Further mechanistic investigation revealed that HBA could activate FOXO/DAF-16 and SKN-1 to regulate antioxidative and xenobiotic metabolism pathway. HBA could also activate HSF-1 to regulate proteostasis maintenance pathway, mitochondrial unfolded stress response, endoplasmic stress response and autophagy pathways. The above results suggest that HBA activated multiple cellular protective pathways to increase stress resistance and protect against aging and aging-related diseases. Overall, our study indicates that HBA is a potential candidate for future development of antiaging pharmaceutical application.
... GE contains bioactive compounds, such as 4-hydroxybenzyl alcohol, p-hydroxybenzaldehyde (HBAD), vanillyl alcohol, phydroxybenzyl alcohol (HBA), gastrodine, p-dihydroxybenzyl sulfoxide, and vanillin [7,8]. To date, GE has been reported to have antidepressant [9], anti-inflammatory [10], anticonvulsant [11], antioxidant [12], neuroprotective [13], and anti-platelet effects [14]. ZS contains bioactive compounds, such as limonene, citronellal, flavonoid compounds, and fatty acids, which are the main aromatic components [15]. ...
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Background and objectives: Blood vessel thrombosis causes blood circulation disorders, leading to various diseases. Currently, various antiplatelet and anticoagulant drugs, such as aspirin, warfarin, heparin, and non-vitamin K antagonist oral anticoagulants (NOACs), are used as the major drugs for the treatment of a wide range of thrombosis. However, these drugs have a side effect of possibly causing internal bleeding due to poor hemostasis when taken for a long period of time. Materials and Methods: Gastrodia elata Blume (GE) and Zanthoxylum schinifolium Siebold & Zucc (ZS) are known to exhibit hemostatic and antiplatelet effects as traditional medicines that have been used for a long time. In this study, we investigated the effect of a mixed extract of GE and ZS (MJGE09) on platelet aggregation and plasma coagulation. Results: We found that MJGE09 inhibited collagen-and ADP-induced platelet aggregation in vitro. In addition, collagen- and ADP-induced platelet aggregation were also inhibited in a dose-dependent manner on the platelets of mice that were orally administered MJGE09 ex vivo. However, compared with aspirin, MJGE09 did not prolong the rat tail vein bleeding time in vivo and did not show a significant effect on the increase in the prothrombin time (PT) and activated partial thromboplastin time (aPTT). Conclusions: These results suggest that MJGE09 can be used as a potential anticoagulant with improved antithrombotic efficacy.
... G. elata has also been found to treat anxiety, regulate the circulatory system, and improve memory (Niu et al., 2004). Additionally, G. elata could achieve its anti-aging effect by regulating certain signaling pathways (Song et al., 2016). Except for these, some chemical constituents such as antifungal protein GAFP-1 in G. elata also play an important role. ...
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Gastrodia elata Blume (G. elata) is a valuable traditional Chinese medicine with neuroprotection, anti-inflammatory, and immune regulatory functions. MicroRNAs (miRNA) is a kind of endogenous noncoding small RNAs that plays distinctly important roles for gene regulation of organisms. So far, the research on G. elata is mainly focused on the pharmacological functions of the natural chemical ingredients, and the function of G. elata miRNA remains unknown. In this study, 5,718 known miRNAs and 38 novel miRNAs were identified by high-throughput sequencing from G. elata. Based on GO and KEGG analysis, we found that the human genes possibly regulated by G. elata miRNAs were related to the cell cycle, immune regulation, intercellular communication, etc. Furthermore, two novel miRNAs as Gas-miR01 and Gas-miR02 have stable and high expression in the medicinal tissues of G. elata. Further bioinformatics prediction showed that both Gas-miR01 and Gas-miR02 could target Homo sapiensA20 gene, furthermore, the dual-luciferase reporter gene assay and Western Blotting verified the interaction of Gas-miR01 or Gas-miR02 with A20. These evidences suggested that G. elata-unique miRNAs might be involved in certain physiological processes. The animal experiment showed that Gas-miR01 and Gas-miR02 could be detected in some tissues of mice by intragastric administration; meanwhile, the A20 expression in some tissues of mice was downregulated. These results supported for the functional study of G. elata miRNAs.
... According to Huh and Han [70], Equisetum arvens extracts collected from the rhizome, stem and root exhibited 94% DPPH scavenging activity and 27% inhibition of hyaluronidase enzyme activity at 4.0 mg/mL. Extracts from Gastrodia elata (2 mg/mL) which have 34% and 44% free scavenging activities of DPPH and ABTS also inhibit elastase activity in human dermal fibroblast cells after exposure with UVA at 5.42 units/mg [71]. Nymphaea tetragona extracts, which have shown to possess inhibitory effects against Caspase-3 activity and mitochondrial dysfunction in human epidermal keratinocytes cell, also exhibit 49.73% and 50.26% ...
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Background: Skin is the largest and most visible organ of the body. Many of its functions include temperature regulation, immunity from microorganisms, maintaining electrolyte balance, and protection from physical injuries, chemical agents and ultraviolet (UV) radiation. Aging occurs in every layer of the skin, primarily due to the degradation of its components. Induction of degradative enzymes and the abundant production of reactive oxygen species lead to skin aging. Understanding the complexity of skin structure and factors contributing to the skin aging will help us impede the aging process. Applications of anti-aging products are a common method to prevent or repair damages that lead to aging. Conclusion: This review will provide information on the causes and indicators of skin aging as well as examine studies that have used plants to produce anti-aging products.
... In our previous study, we demonstrated that GEB extract ameliorated skin-photoaging signs by promoting antioxidant activity with sufficient amounts of polyphenols, flavonoid, and ergo and by altering expression/activity of procollagen type I, matrix metalloproteinase-1, and elastase-1 in UVA-irradiated human dermal fibroblasts [36]. In this study, GEB inhibited melanin synthesis through the suppression of tyrosinase activity and mRNA levels and protein expression of MITF, tyrosinase, Trp1, and Trp2 in a dose-dependent manner in murine B16F10 melanoma. ...
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Background/objectives: Gastrodia elata Blume (GEB), a traditional herbal medicine, has been used to treat a wide range of neurological disorders (e.g., paralysis and stroke) and skin problems (e.g., atopic dermatitis and eczema) in oriental medicine. This study was designed to investigate whether GEB extract inhibits melanogenesis activity in murine B16F10 melanoma. Materials/method: Murine B16F10 cells were treated with 0-5 mg/mL of GEB extract or 400 µg/mL arbutin (a positive control) for 72 h after treatment with/without 200 nM alpha-melanocyte stimulating hormone (α-MSH) for 24 h. Melanin concentration, tyrosinase activity, mRNA levels, and protein expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (Trp)1, and Trp2 were analyzed in α-MSH-untreated and α-MSH-treated B16F10 cells. Results: Treatment with 200 nM α-MSH induced almost 2-fold melanin synthesis and tyrosinase activity along with increased mRNA levels and protein expression of MITF, tyrosinase, Trp1 and Trp2. Irrespective of α-MSH stimulation, GEB extract at doses of 0.5-5 mg/mL inhibited all these markers for skin whitening in a dose-dependent manner. While lower doses (0.5-1 mg/mL) of GEB extract generally had a tendency to decrease melanogenesis, tyrosinase activity, and mRNA levels and protein expression of MITF, tyrosinase, Trp1, and Trp2, higher doses (2-5 mg/mL) significantly inhibited all these markers in α-MSH-treated B16F10 cells in a dose-dependent manner. These inhibitory effects of the GEB extract at higher concentrations were similar to those of 400 µg/mL arbutin, a well-known depigmenting agent. Conclusions: These results suggest that GEB displays dose-dependent inhibition of melanin synthesis through the suppression of tyrosinase activity as well as molecular levels of MITF, tyrosinase, Trp1, and Trp2 in murine B16F10 melanoma. Therefore, GEB may be an effective and natural skin-whitening agent for application in the cosmetic industry.
Article
As both a traditional medicine and food material, fresh Gastrodia elata requires a curing process for quality improvement. The effects of steaming and various drying methods (sun-, hot-air-, microwave-vacuum-, freeze- and vacuum-drying) on the total phenolic, total flavonoid, ascorbic acid, adenosine, and phenolic compound contents, antioxidant activities (scavenging DPPH•, ABTS⁺•, OH• and reducing power) and microstructures were investigated in this study. The contents of adenosine and individual phenolic compounds were analyzed using high-performance liquid chromatography. The results showed that steaming had adverse effects on the total phenolic, total flavonoid, adenosine, parishin C, vanillyl alcohol, quercetin and cinnamic acid contents, while subsequent hot-air- and freeze-drying showed compensatory effects. Steaming significantly increased the levels of gastrodin, p-hydroxybenzylalcohol, p-hydroxybenzaldehyde, parishins (A, B and E) and catechin (by 3.4-, 1.1-, 1.1-, 3.8-, 6-, 1.4- and 1.5-fold, respectively, p<0.05) compared to the fresh samples, which were further increased by hot-air- and freeze-drying. Hot-air- and freeze-drying significantly increased the levels of adenosine, gastrodin, p-hydroxybenzylalcohol, p-hydroxybenzaldehyde, parishins (A, B and C), vanillyl alcohol, catechin, caffeic acid, quercetin and cinnamic acid by 1.1-11.6-fold (p<0.05) compared to steaming treatment. Steaming reduced all the antioxidant activities, which were restored partially by hot-air- and freeze-drying. Principal component and clustering analyses revealed the relationship among the samples, phenolics, and antioxidant activities, which suggested a steaming-then-drying action mechanism in which steaming changes enzymes and starch hydrolysis and drying promote condensation reactions. Collectively, steaming-then-hot-air- or freeze-drying is a promising method for enhancing the quality of Gastrodia elata for food applications.
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Gastrodia elata tuber (GET) is a popular traditional Chinese medicines (TCMs). In this study, response surface methodology (RSM) with a Box–Behnken design (BBD) was performed to optimize the extraction parameters of gastrodin-type components (gastrodin, gastrodigenin, parishin A, parishin B, parishin C and parishin E). Different from the conventional studies that merely focused on the contents of phytochemical, we gave consideration to both quantitative analysis of the above six components by HPLC and representative bioactivities of GET, including antioxidation and protection of human umbilical vein endothelial cells (HUVEC). Four independent variables (ethanol concentration, liquid-material ratio, soaking time and extraction time) were investigated with the integrated evaluation index of phytochemical contents. With the validation experiments, the optimal extraction parameters were as follows: ethanol concentration of 41%, liquid–solid ratio of 28.58 mL/g, soaking time of 23.91 h and extraction time of 46.60 min. Under the optimum conditions, the actual standardized comprehensive score was 1.8134 ± 0.0110, which was in accordance with the predicted score of 1.8100. This firstly established method was proved to be feasible and reliable to optimize the extraction parameters of the bioactive components from GET. Furthermore, it provides some reference for the quality control and extraction optimization of TCMs.
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Research has been conducted in various fields in an attempt to develop new therapeutic agents for incurable neurodegenerative diseases. Gastrodia elata Blume (GE), a traditional herbal medicine, has been used in neurological disorders as an anticonvulsant, analgesic, and sedative medication. Several neurodegenerative models are characterized by oxidative stress and inflammation in the brain, which lead to cell death via multiple extracellular and intracellular signaling pathways. The blockade of certain signaling cascades may represent a compensatory therapy for injured brain tissue. Antioxidative and anti-inflammatory compounds isolated from natural resources have been investigated, as have various synthetic chemicals. Specifically, GE rhizome extract and its components have been shown to protect neuronal cells and recover brain function in various preclinical brain injury models by inhibiting oxidative stress and inflammatory responses. The present review discusses the neuroprotective potential of GE and its components and the related mechanisms; we also provide possible preventive and therapeutic strategies for neurodegenerative disorders using herbal resources.
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In previous studies, the Artocarpus incisus extract containing 45% w/w artocarpin showed activities of antioxidation, antimelanogenesis and restoration of wrinkled-skin fibroblasts. Here, extract containing 90% w/w artocarpin was tested for its antioxidant activity and in ultraviolet (UV) A-irradiated fibroblasts, its ability to restore type I collagen and inhibit matrix metalloproteinase-1 (MMP-1) elevation. This extract was a less effective antioxidant of EC50 of 116.0 +/- 5.1 mu g/mL than L-ascorbic acid (9.7 +/- 0.01 mu g/mL). The extract (0.625-50 mu g/mL) showed no cytotoxicity toward primary human skin fibroblasts. MMP-1 was markedly elevated at 72 h after UVA irradiation compared to non-irradiation cells (p < 0.01). This UVA-induced elevation was inhibited by 50 mu g/mL extract or 50 ng/mL all-trans retinoic acid. In an aged and sun-exposed skin tissue culture model, the increase of epidermal thickness in the 250 mu g/mL artocarpin-enriched extract or 75 mu g/mL all-trans retinoic acid-treated group when compared to the non-treated group was markedly observed since day 1 of treatment. Moreover, the extract or all-trans retinoic acid-treated groups exhibited higher density of immunofluorescence staining of type I collagen than non-treated group. This coincides with significantly higher (p < 0.05) collagen content, as indicated by measuring hydroxyproline. Our results firstly revealed that the artocarpin-enriched extract reversed the activities of UVA-irradiated fibroblasts and improved the type I collagen deposition in aged/photoaged skin.
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Background Cocoa pod is an outer part of cocoa fruits being discarded during cocoa bean processing. Authors found out that data on its usage in literature as cosmetic materials was not recorded in vast. In this study, cocoa pod extract was investigated for its potential as a cosmetic ingredient. Methods Cocoa pod extract (CPE) composition was accomplished using UHPLC. The antioxidant capacity were measured using scavenging assay of 1,2-diphenyl-2-picrylhydrazyl (DPPH), β-carotene bleaching assay (BCB) and ferric reducing antioxidant power (FRAP). Inhibiting effect on skin degradation enzymes was carried out using elastase and collagenase assays. The skin whitening effect of CPE was determined based on mushroom tyrosinase assay and sun screening effect (UV-absorbance at 200-400 nm wavelength). Results LC-MS/MS data showed the presence of carboxylic acid, phenolic acid, fatty acid, flavonoids (flavonol and flavones), stilbenoids and terpenoids in CPE. Results for antioxidant activity exhibited that CPE possessed good antioxidant activity, based on the mechanism of the assays compared with ascorbic acid (AA) and standardized pine bark extract (PBE); DPPH: AA > CPE > PBE; FRAP: PBE > CPE > AA; and BCB: BHT > CPE > PBE. Cocoa pod extract showed better action against elastase and collagenase enzymes in comparison with PBE and AA. Higher inhibition towards tyrosinase enzyme was exhibited by CPE than kojic acid and AA, although lower than PBE. CPE induced proliferation when tested on human fibroblast cell at low concentration. CPE also exhibited a potential as UVB sunscreen despite its low performance as a UVA sunscreen agent. Conclusions Therefore, the CPE has high potential as a cosmetic ingredient due to its anti-wrinkle, skin whitening, and sunscreen effects.
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Abstract Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging.
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The fact that the skin is the most visible organ makes us aware of the ageing process every minute. The use of plant extracts and herbs has its origins in ancient times. Chronological and photo-ageing can be easily distinguished clinically, but they share important molecular features. We tried to gather the most interesting evidence based on facts about plants and plant extracts used in antiaging products. Our main idea was to emphasize action mechanisms of these plant/herbal products, that is, their "strategies" in fighting skin ageing. Some of the plant extracts have the ability to scavenge free radicals, to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin. There are some plants that can affect skin elasticity and tightness. Certainly, there is a place for herbal principles in antiaging cosmetics. On the other hand, there is a constant need for more evaluation and more clinical studies in vivo with emphasis on the ingredient concentration of the plant/herbal products, its formulation, safety, and duration of the antiaging effect.
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The effects of human recombinant interleukin (IL)-1 beta on elastin gene expression were studied in human skin fibroblast cultures by Northern hybridization and transient transfection experiments. Incubation of the cells with IL-1 beta elevated the elastin mRNA steady-state levels by approximately 3- to 4-fold. A similar increase was noted at the protein level, when estimated by indirect immunofluorescence of cultured cells. This effect was independent of the on-going protein synthesis, as tested by incubation with cycloheximide. Transient transfections of the dermal fibroblasts with a human elastin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct suggested transcriptional regulation, since the CAT activity in cells incubated with IL-1 beta was similarly increased approximately 3-fold. Enhancement of the human elastin promoter activity by IL-1 beta was also noted in fibroblast cultures established from the skin and lungs of transgenic mice which have integrated the human promoter/CAT construct into their genome and express it in a tissue-specific manner. Furthermore, subcutaneous injection of IL-1 beta to the mice resulted in a approximately 4-fold elevation of the CAT activity in the skin after a 30-h incubation, as compared to the CAT activity in the skin of control animals. Collectively, these data indicate that IL-1 beta up-regulates elastin gene expression in fibroblast cultures as well as in the skin in vivo, and the activation occurs at the transcriptional level.
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Matrix metalloproteinases (MMPs) are thought to be responsible for dermal photoaging in human skin. In the present study, we evaluated the involvement of macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation in cultured human dermal fibroblasts. UVA (20 J/cm(2)) up-regulates MIF production, and UVA-induced MMP-1 mRNA production is inhibited by an anti-MIF antibody. MIF (100 ng/ml) was shown to induce MMP-1 in cultured human dermal fibroblasts. We found that MIF (100 ng/ml) enhanced MMP-1 activity in cultured fibroblasts assessed by zymography. Moreover, we observed that fibroblasts obtained from MIF-deficient mice were much less sensitive to UVA regarding MMP-13 expression than those from wild-type BALB/c mice. Furthermore, after UVA irradiation (10 J/cm(2)), dermal fibroblasts of MIF-deficient mice produced significantly decreased levels of MMP-13 compared with fibroblasts of wild-type mice. Next we investigated the signal transduction pathway of MIF. The up-regulation of MMP-1 mRNA by MIF stimulation was found to be inhibited by a PKC inhibitor (GF109203X), a Src-family tyrosine kinase inhibitor (herbimycin A), a tyrosine kinase inhibitor (genistein), a PKA inhibitor (H89), a MEK inhibitor (PD98089), and a JNK inhibitor (SP600125). In contrast, the p38 inhibitor (SB203580) was found to have little effect on expression of MMP-1 mRNA. We found that PKC-pan, PKC alpha/beta II, PKC delta (Thr505), PKC delta (Ser(643)), Raf, and MAPK were phosphorylated by MIF. Moreover, we demonstrated that phosphorylation of PKC alpha/beta II and MAPK in response to MIF was suppressed by genistein, and herbimycin A as well as by transfection of the plasmid of C-terminal Src kinase. The DNA binding activity of AP-1 was significantly up-regulated 2 h after MIF stimulation. Taken together, these results suggest that MIF is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts through PKC-, PKA-, Src family tyrosine kinase-, MAPK-, c-Jun-, and AP-1-dependent pathways.
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Ischaemic stroke is a leading cause of death and long-lasting disability. Gastrodia elata blume (GEB) is a Chinese herb that is widely used to treat convulsive disorders, such as epilepsy, and p-hydroxybenzyl alcohol (HBA) is the active ingredient in GEB. The present study was conducted to evaluate the effects of GEB and HBA on the brain damage and transcriptional levels of Protein disulfide isomerase (PDI) and 1-Cys peroxiredoxin (1-Cys Prx) genes known to play a role in antioxidant systems after transient focal ischemia in the rat brain. Focal ischemia was induced in rats by middle cerebral artery occlusion (MCAO). All animals underwent ischemia for 1 h, followed by 24 h of reperfusion. Coronal brain slices were stained with 2,3,5-triphenyltetrazolium chloride or total RNA was extracted for the analysis of gene expression. Histopathologic analysis revealed a significant (p<0.05) decrease in infarct size in the ipsilateral brain with GEB extracts or HBA. Moreover, the levels of PDI and 1-Cys Prx transcription were significantly increased in the GEB extract- or HBA-treated group compared with the untreated group (p<0.05). This study therefore indicated that GEB and HBA provide neuroprotection by preventing brain damage through the increased expression of genes encoding antioxidant proteins after transient focal cerebral ischemia and may be effective as neuroprotective agents at the cellular and molecular levels in the brain.
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Ethnopharmacological relevance: Traumatic brain injury (TBI) has an incident rate of 200-300 people per 100,000 annually in the developed countries. TBI has relatively high incidence at an early age and may cause long-term physical disability. Patients suffered from severe TBI would have motor and neuropsychological malfunctions, affecting their daily activities. Traditionally, Gastrodia elata Blume is a Chinese Medicines which was used for the head diseases, while their efficiency on reducing brain damage was still largely unknown. In the present study, we aimed to examine the effect of water extract of Gastrodia elata Blume (GE) against TBI and elucidate its underlying mechanism. Materials and methods: Sprague-Dawley rats were treated with GE for 7 days, immediately after controlled cortical impact-induced TBI. Impaired neurobehavioral functioning was measured on day 3 and 6 after TBI. Histology of TBI was examined to assess the extent of inflammation, and the expressions of pro-inflammatory cytokines were examined by immunofluorescence study on day 7. Results: GE treatment significantly improved the impaired locomotor functions induced by TBI. GE treatment reduced inflammation and gliosis in the penumbral area. The increase in brain levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha observed in non-GE treated TBI rats were also reversed. Conclusions: GE treatment attenuated the locomotor deficit caused by TBI. The anti-inflammatory activity might be mediated by inhibition of pro-inflammatory cytokines responses in the TBI-brain.
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This study was carried out to investigate the antioxidant activity and changes in major functional components of fermented Gastrodia elata Blume. Fermented G. elata Blume powder by Phellinus linteus repeated thrice (3^{rd} FGP) showed more DPPH radical scavenging activity than a non-fermented G. elata Blume powder (NFGP), and once fermented G. elata Blume powder (1^{st} FGP) at a concentration of 500 and 1,000 ppm. Free radical scavenging activity of 3^{rd} FGP was similar to that of BHA at a dose of 1,000 ppm. Moreover, the ABTS radical scavenging activity of the 3^{rd} FGP increased compared to NFGP and 1^{st} FGP at a concentration of 31.25 ppm. Total polyphenols and flavonoid contents were increased as fermentation progressed. Ergothioneine content was increased more than 8 times in the 1^{st} FGP, 3 times in the 3^{rd} FGP, respectively than NFGP. In conclusion, this study indicated that the antioxidant activity and functional component contents of G. elata Blume were increased depending on the fermentation number.
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L-ergothioneine is a naturally occurring antioxidant that is available from dietary sources. There is a lack of an adequate assay applicable to identify and quantify this antioxidant in plant material. Thus, the objective was to identify and quantify the ergothioneine content of mushrooms including Agaricus bisporus (white and brown strains), Lentinus edodes, Pleurotus ostreatus, P. eryngii, and Grifola frondosa by an analytical method utilizing a high-performance liquid chromatography and liquid chromatography-mass spectroscopy. Freeze dried mushroom powder was analyzed with two C18 columns in tandem utilizing an isocratic mobile phase consisting of an aqueous sodium phosphate buffer with 3% acetonitrile and 0.1% triethylamine. Ergothioneine was identified by matching the retention time and mass spectra of the authentic compound with the mushroom samples, while quantification was completed via absorbance at 254 nm. The ergothioneine content of the mushrooms ranged from 0.4-2.0 mg/g (dry wt). The white Agaricus bisporus contained the least ergothioneine and portabellas (brown) contained the highest within the varieties of A. bisporus. The specialty mushrooms tested (Lentinus edodes, Pleurotus ostreatus, P. eryngii, Grifola frondosa) all contained a statistically significant greater amount of ergothioneine compared to the A. bisporus; however, no significant difference was found between these specialty mushrooms.
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Gastrodia elata Bl. (GE) is a traditional Chinese herb that is commonly used in Chinese communities to treat convulsive disorders such as epilepsy. The purpose of the present study was to determine the anticonvulsive and free radical activities of GE in rats. In vitro studies were conducted by using brain tissue from 6 male Sprague-Dawley (SD) rats treated with 120 μg/ml of kainic acid (KA), with or without the addition of various concentrations of GE. In vivo studies were conducted in a total of 30 male SD rats divided into 5 groups of 6 rats which were treated as follows: 1) the normal group received an intraperitoneal injection (i.p.) of PBS (Phosphate buffer saline, 1 ml/kg); 2) the control group received KA (12 mg/kg) i.p.; 3) the GE 1.0 group received oral administration of GE 1.0 g/kg 30 min prior to KA administration; 4) the GE 0.5 group reveived oral administration of GE 0.5 g/kg 30 min prior to KA administration; 5) the PH group reveived oral administration of phenytoin 20 mg/kg 30 min prior to KA administration. Seizures were verified by behavioral observations, electroencephalograph (EEG) and electromyography (EMG). Lipid peroxide levels in the rat brain, luminol chemiluminescence (CL) and lucigenin-CL in the peripheral blood were measured simultaneously after behavioral observations. The results indicate that GE administration significantly reduced KA-induced lipid peroxide levels in vitro. Oral administration of GE 1.0 g/kg and phenytoin 20 mg/kg significantly reduced counts of wet dog shakes (WSS), paw tremor (PT) and facial myoclonia (FM) in KA-treated rats. In addition, oral administration of GE 1.0 g/kg significantly delayed the onset of WDS, from 30 min in the control group to 46 min in the 0.5 g/kg group, and 63 min in the GE 1.0 g/kg group. A significantly reduced level of lipid peroxides in the rat brain was found in the GE 1.0 g/kg, 0.5 g/kg, and phenytoin 20 mg/kg groups. The GE 1.0 g/kg group showed significant reduction of luminol-CL and lucigenin-CL counts in the peripheral blood compared to the control group. The results of the present study demonstrate that GE has anticonvulsive and free radical scavenging activities. Further studies are needed to determine the clinical effectiveness of GE as an anticonvulsant in humans.
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Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to display antioxidant activity. The present study aimed to investigate the protective effects of gastrodin on 1-methyl-4-phenylpyridinium (MPP⁺)-induced oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying mechanism for this neuroprotection. Results indicate that pre-treatment with gastrodin for 1 h significantly reduced the MPP⁺-induced viability loss, apoptotic rate and attenuated MPP⁺-mediated ROS production. In addition, gastrodin inhibited MPP⁺-induced lowered membrane potential, decreased Bcl-2/Bax ratio. Moreover, we have revealed the gastrodin increased Nrf2 nuclear translocation, which is upstream of heme oxygenase-1 (HO-1) expression and for the first time revealed gastrodin could increased antioxidant enzyme HO-1 expression in concentration-dependent and time-dependent manners. HO-1 siRNA transfection was employed, and confirmed gastrodin could active the expression of HO-1. And the increase in HO-1 expression was correlated with the protective effect of gastrodin against MPP⁺-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of gastrodin against MPP⁺-induced cell death. We also demonstrated that the specific p38 MAPK inhibitor, SB203580, concentration-dependently blocked on gastrodin-induced HO-1 expression, and meanwhile SB203580 reversed the protective effect of gastrodin against MPP⁺-induced cell death.
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Abstract— Previous work has shown that fibroblast-derived collagenase/matrix-metalloproteinase-1(MMP–1), responsible for the breakdown of dermal interstitial collagen, was dose-dependently induced in vitro and in vivo by UVA irradiation and this induction was at least partly mediated byinterleukin–6(IL–6). We here provide evidence that UVA-inducedIL–1α andIL–1β play a central role in the induction of the synthesis both ofIL–6 and collagenase/MMP–1. In contrast to the late increase ofIL–1α andIL–1β mRNA levels at 6 h postirradiation, bioactivity ofIL–1 is already detectable at 1 h postirradiation. This early peak ofIL–1 bioactivity appears to be responsible for the induction ofIL–6 synthesis and together withIL–6 lead to an increase of the steady-state mRNA level of collagenase/MMP–1 as deduced from studies usingIL–1α andIL–1β antisense oligonucleotides or neutralizing antibodies againstIL–1α andIL–1β Besides the early posttranslationally controlled release of intracellularIL–1, a latter pretranslationally controlled synthesis and release ofIL–1 perpetuates the UV response. From these data we suggest a UV-induced cytokine network consisting ofIL–1α,IL–1β andIL–6, which via interrelated autocrine loops induce collagenase/MMP–1 and thus may contribute to the loss of interstitial collagen in cutaneous photoaging.
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New developments in the realm of skin rejuvenation such as phytotherapy are at an astounding increasing pace in the cosmeceutical market. Yet, many of these products that are classified as cosmeceuticals are tested less vigorously and do not have to be approved by the Food and Drug Administration to establish efficacy and safety. Thus, as clinicians, we must ask the question, “Is there science-based evidence to validate the mechanism of these new treatments?” We assessed the top anti-aging creams currently on the market specifically evaluating their botanical ingredients. Some of the most common botanicals that are hot off the market are: Rosmarinus officinalis, Vitis vinifera (grape seed extract), Citronellol, Limonene, Oenothera biennis (evening primrose), Glycyrrhiza glabra (licorice extract), Aframomum angustifolium seed extract, Diosgenin (wild yam), N6 furfuryladenine (kinetin), and Ergothioneine. Through researching each of these botanical ingredients, we have concluded that randomized controlled trials are still needed in this area, but there is promise in some of these ingredients and science to validate them.
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The autoxidation of pyrogallol was investigated in the presence of EDTA in the pH range 7.9–10.6. The rate of autoxidation increases with increasing pH. At pH 7.9 the reaction is inhibited to 99% by superoxide dismutase, indicating an almost total dependence on the participation of the superoxide anion radical, O2·−, in the reaction. Up to pH 9.1 the reaction is still inhibited to over 90% by superoxide dismutase, but at higher alkalinity, O2·− -independent mechanisms rapidly become dominant. Catalase has no effect on the autoxidation but decreases the oxygen consumption by half, showing that H2O2 is the stable product of oxygen and that H2O2 is not involved in the autoxidation mechanism. A simple and rapid method for the assay of superoxide dismutase is described, based on the ability of the enzyme to inhibit the autoxidation of pyrogallol. A plausible explanation is given for the non-competitive part of the inhibition of catechol O-methyltransferase brought about by pyrogallol.
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Propolis is extensively used in Argentine folk medicine. Alcoholic extracts of propolis from different regions of Argentina were prepared. The extracts were analysed for the determination of total flavonoid content (from 13.3 to 42.6 mg/g of propolis) by using the aluminum nitrate method, UV spectrophotometry and thin layer chromatography. All of them contained high total flavonoid content. It was also observed that all samples of ethanolic extracts of propolis showed free radical-scavenging activity in terms of scavenging of the radical DPPH but the highest activities were found for samples from Tucumán and Santiago del Estero. In all cases with 20 μg/ml of soluble principles, the percentage of DPPH degradation was different (Banda Oeste: 67.5%; Verónica: 45%; Forres: 35%; Saenz Peña: 20% and Juan José Castelli: 55%). These results may justify their use as a source of natural antioxidants.
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The breakdown of collagenous networks with aging results in hypoactive changes in the skin. Accordingly, reviving stagnant collagen synthesis can help protect dermal homeostasis against aging. We searched for type I collagen biosynthesis-inducing substances in various foods using human dermal fibroblasts and found that cinnamon extract facilitates collagen biosynthesis. Cinnamon extract potently up-regulated both mRNA and protein expression levels of type I collagen without cytotoxicity. We identified cinnamaldehyde as a major active component promoting the expression of collagen by HPLC and NMR analysis. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, we examined the effect of cinnamaldehyde on IGF-I signaling. Treatment with cinnamaldehyde significantly increased the phosphorylation levels of the IGF-I receptor and its downstream signaling molecules such as insulin receptor substrate-1 and Erk1/2 in an IGF-I-independent manner. These results suggested that cinnamon extract is useful in antiaging treatment of skin.
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Gastrodia elata Blume (Orchidaceae, GE) a traditional plant in Oriental countries is known for its enormous benefits to treat headaches, dizziness, vertigo and convulsive illnesses. In the present study, the ethnopharmacological role of GE in neuroinflammation mediated by activated microglia and the mechanisms underlying were reported. BV-2 microglia activated by lipopolysaccharide (LPS) was employed and the effects of GE on corresponding neuroinflammatory parameters were assessed. GE extract inhibited LPS-stimulated production of inflammatory cytokines and down regulated the c-Jun NH(2)-Terminal Kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways, which are known to be involved in neuroinflammation. Further, inhibition of NO and iNOS by 4-hydroxybenzyl alcohol (4-HBA), one of the active constituent of GE in LPS-stimulated BV-2 cells suggest that 4-HBA might be the bioactive candidate. GE extract and its active constituent 4-HBA could be further exploited to mitigate microglial activation and may be developed as a new therapeutic remedy in treating various neuroinflammatory diseases.
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Since its discovery, the unique properties of the naturally occurring amino acid, L-ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine), have intrigued researchers for more than a century. This widely distributed thione is only known to be synthesized by non-yeast fungi, mycobacteria and cyanobacteria but accumulates in higher organisms at up to millimolar levels via an organic cation transporter (OCTN1). The physiological role of EGT has yet to be established. Numerous in vitro assays have demonstrated the antioxidant and cytoprotective capabilities of EGT against a wide range of cellular stressors, but an antioxidant role has yet to be fully verified in vivo. Nevertheless the accumulation, tissue distribution and scavenging properties, all highlight the potential for EGT to function as a physiological antioxidant. This article reviews our current state of knowledge. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.
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The large production of reactive oxygen species (ROS) leads to the oxidative stress and the subsequent functional decline of organ systems. p-Hydroxybenzyl alcohol (HBA) is known to play a pivotal protective role against oxidative stress-related diseases. We have developed biodegradable antioxidant copolyoxalate, in which HBA is chemically incorporated into its backbone for the treatment of oxidative stress-related diseases. HBA-incorporated copolyoxalate (HPOX) was designed to possess aromatic peroxalate ester linkages in its backbone and release HBA during its hydrolytic degradation. Peroxalate ester linkages in the backbone reacted with and scavenged hydrogen peroxide, leading the release of HBA in vitro. HBA released from HPOX exerted excellent antioxidant activity, such as inhibition of nitric oxide (NO) production by suppressing iNOS (inducible nitric oxide synthases) expression in lipopolysaccharide (LPS)-activated RAW 264.7 cells. HPOX nanoparticles delivered intranasally significantly reduced pulmonary inflammation and suppressed the iNOS expression. Given their excellent antioxidant and anti-inflammatory activities, we anticipate that HPOX nanoparticles are highly potent for the treatment of oxidative damage-related diseases, such as asthma.
Article
Gastrodia elata (GE) Blume (Orchidaceae) has been traditionally used as a folk medicine in Oriental countries since centuries for their variety of therapeutic benefits. This study is an attempt to investigate the protective effects of GE extract against MPP(+)-induced cytotoxicity in human dopaminergic SH-SY5Y cells and explore the neuroprotective mechanisms involved. Human dopaminergic SH-SY5Y cells were used to demonstrate the protective effects of GE against multiple parameters such as MPP(+)-induced cell viability, oxidative damage, expression of Bcl-2 and Bax, caspase-3 and poly(ADP-ribose) polymerase proteolysis. GE effectively attenuated the cytotoxicity and improved cell viability in a dose-dependent manner. GE was effective in inhibiting both, the increased production of reactive oxygen species (ROS) and increase in Bax/Bcl-2 ratio, cleaved caspase-3 and PARP proteolysis. Data from this study suggests the protective effects of GE on MPP(+)-induced cytotoxicity in dopaminergic cells, which may be ascribed to its significant anti-oxidative and anti-apoptotic properties, thus, GE might prove to be a valuable therapeutic agent for the treatment of various neurodegenerative diseases including progressive Parkinson's disease (PD).
Article
Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.
Article
The antioxidant activity (AA) of substances present in several plant species has been widely studied which reflects their fundamental role in the protection of skin tissue against the harmful action of reactive oxygen species. Given the importance of effective and long-lasting protection against ultraviolet radiation, we studied the AA of several plant derivatives and extracts over time. Several chemical in vitro methods may be used to evaluate antioxidant capability, among which the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method stands out, despite its unspecificity, as the most cited and described method in the literature. In this work the AA was evaluated by measuring their capacity to reduce DPPH in 30 min, which is suggested in the literature, and additionally at different times up to 8 h from the baseline reading. The methodology used to evaluate the AA over time was validated. It is important to emphasize that this study proposes to modify the conventional DPPH method, although considered to be non-specific, to be used to test new antioxidant agents. This represents a considerable advantage because some substances show no significant activity during the first 30 min of reaction. Among other plant products, we tested a proantocyanidin-rich grapeseed extract, a hesperidin derivative, a rutin-containing ginkgo extract, a polyphenol-containing yerba maté extract and tocopheryl acetate, all of which were properly standardized. As they have different antioxidant profiles, each ingredient showed a specific behaviour over time, which may promote the selection of anti-radical compounds capable of offering protection against external agents. Combining extracts and plant derivatives that present fast, medium and slow antioxidant kinetic it is possible to create complexes capable of offering an effective protection from the moment of application up to several hours later. It is a perfectly feasible method, and such combinations prove to be more effective and have more durable effect. L’activité antioxydante de substances présentes dans différentes espèces de plantes a été largement étudiée. Elle reflète leur rôle fondamental dans la protection des tissus cutané contre l’action altérante des espèces réactives de l’oxygène (ROS). Etant donné l’importance d’une protection efficace et durable contre les effets des radiations UV, nous avons mené une étude portant sur l’activité antioxydante de plusieurs dérivés de plantes et d’extraits en fonction du temps. Plusieurs méthodes chimiques in vitro ont été utilisées pour évaluer la capacité antioxydante, parmi lesquelles la méthode bien connue au 1,1-diphenyl-2-picrylhydrazyl (DPPH) qui est malgré sa non spécificité, la plus citée et la plus décrite dans la littérature. Dans ce travail, l’activité antioxydante a étéévaluée en mesurant la capacitéà réduire le DPPH en 30 min, ce qui est évoqué dans la littérature, et de façon complémentaire, en la mesurant, à différents temps allant jusqu’à 8 heures après la première lecture. La méthodologie utilisée pour évaluer l’activité antioxydante en fonction du temps a été validée. Il est important de signaler que cette étude propose de modifier la méthode conventionnelle DPPH qui, bien que considérée comme non spécifique, peut être utilisée pour tester de nouveaux agents antioxydants. Ceci représente un avantage considérable car certaines substances ne montrent aucune activité spécifique pendant les 30 premières minutes de réaction. Parmi les différents dérivés de plantes, nous avons testé un Extrait de Pépins de Raisins riches en Proantocyanidine, un Dérivé d’Hespéridine, un Extrait de Ginkgo contenant de la rutine, un Extrait de Mate Yerba contenant un Polyphénol et l’Acétate de Tocophéryle, tous étant correctement standardisés. Puisque tous ces produits possèdent un profil antioxydant différent, chacun d’entre eux présente un comportement spécifique en fonction du temps qui peut promouvoir la sélection de mélanges d’anti-radicalaires capables d’offrir une protection contre les agents extérieurs. La combinaison d’extraits et de dérivés de plantes qui présentent des cinétiques antioxydantes rapide, moyenne et lente rend possible la création de complexes capables d’offrir une protection efficace depuis le moment de l’application jusqu’à plusieurs heures après. C’est une méthode parfaitement réalisable et de telles combinaisons s’avèrent plus efficaces et ont des effets plus durables.
Article
The cellular defense system against harmful levels of reactive oxygen species consists of antioxidant enzymatic activities and small nonenzymatic molecules. L-ergothioneine has long been recognized as a potent and stable low-molecular-weight antioxidant that humans consume with diet and that accumulates in cells normally subjected to high levels of oxidative stress. As L-ergothioneine is plasma membrane-impermeative, its protective function is restricted to cells that express the L-ergothioneine-specific receptor/transporter OCTN1. Here we report for the first time that both as resident skin cells and in culture, epidermal keratinocytes synthesize OCTN1, which enables them to internalize and accumulate L-ergothioneine. This accumulation confers upon the cells an increased antioxidant potential. Consequently, it reduces the levels of reactive oxygen species and DNA, protein, and lipid damage in keratinocytes subjected to solar-simulating UV oxidative stress. Our results suggest that L-ergothioneine not only prevents oxidative damage but also may enable DNA repair in the UV-irradiated cells. The diminished oxidative damage to cellular constituents limits the apoptotic response and results in increased cell viability. The cells' ability to take up, accumulate, and utilize the potent antioxidant L-ergothioneine positions this naturally occurring amino acid and its receptor/transporter as an integral part of the antioxidative defense system of the skin.
Article
The interactions of three BPTI homologues with human leukocyte elastase and porcine pancreatic elastase have been investigated. The principal mutation in determining the specificity of inhibition was the Lys15-Val mutation at the P1 position. An additional mutation at P3, i.e., BPTI (Lys15-Val, Pro13-Ile), increased the inhibition of HLE to a Ki = 2.5 x 10(-10) M, but decreased the inhibition of PPE, showing this to be a useful site for improving selectivity. Kinetic evidence suggests that the inhibition of HLE by BPTI homologues probably takes place by a two-step mechanism in which an isomerization step occurs after initial binding. 1H NMR spectroscopy of the BPTI (Lys15-Val) and BPTI (Lys15-Val, Pro13-Ile) mutants indicates that small conformational changes are associated with the mutations, but these are localized in the immediate vicinity of the mutation in the outer binding loop and in the inner loop connected to it through the Cys14-Cys38 disulfide bridge.
Article
A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.
Article
UV irradiation acts as a broad activator of cell surface growth factor and cytokine receptors. This ligand-independent receptor activation induces multiple downstream signaling pathways that regulate expression of multiple genes. These signaling pathways converge to stimulate transcription factor AP-1. Among genes whose expression is regulated by AP-1 are several matrix-metalloproteinase (MMP) family members and type I procollagen. UV-enhanced matrix degradation is accompanied with decreased collagen production mediated not only by activation of AP-1, but also by inhibition of transforming growth factor (TGF)-beta signaling. Several alterations to skin connective tissue that occur during aging are mediated by mechanisms that are similar to those that occur in response to UV irradiation. Thus, skin aging is associated with increased AP-1 activity, increased MMP expression, impaired TGF-beta signaling, enhanced collagen degradation, and decreased collagen synthesis. Knowledge gained from examining molecular responses of human skin to UV irradiation provides not only a framework for understanding mechanisms involved in skin aging, but also may help in development of new clinical strategies to impede chronological and UV-induced skin aging.
Article
The phenolic glucoside gastrodin (Gas) is a main component extracted from the rhizome of Gastrodia elata, a Chinese herbal medicine, which has long been used for treating dizziness, epilepsy, stroke and dementia. In this study, we investigated the neuroprotective effects of Gas on cerebral ischemic injury in rats caused by transient middle cerebral arterial occlusion (MCAO), oxygen/glucose deprivation (OGD) and glutamate-induced injury in cultured rat hippocampal neurons. Additionally, the effects of Gas on the extracellular glutamate level and changes in intracellular Ca (2+) and the generation of nitric oxide (NO) were examined in cultured hippocampal neurons subjected to OGD in vitro. The results showed that the high dose of Gas (100 mg/kg) markedly decreased the infarct volume and edema volume, and improved the neurological functions after MCAO. Gas treatment (15 microg/mL, 30 microg/mL) also significantly inhibited OGD- and glutamate-induced neuronal cell death and reduced the extracellular glutamate level following OGD. Moreover, Gas treatment significantly inhibited the OGD-induced Ca (2+) and NO increases. In conclusion, the present study indicates that Gas has a neuroprotective action.
Article
Exposure to solar UV radiation is the main environmental factor that causes premature aging of the skin. Matrix metalloproteinases (MMP)-1 is a member of the MMP family and degrades types I and III collagens, which are the major structural components of the dermis. We evaluated the involvement IL-1beta and macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation. IL-1beta and MIF in MMP-1 expression in cultured human dermal fibroblasts and the UVA effects on MMPs production using IL-1alpha/beta-deficient mice were analyzed. Furthermore, fibroblasts derived from MIF-deficient mice were used to analyze the effect of IL-1beta-induced MMPs production. IL-1beta-enhanced MIF expression and induced MMP-1 in cultured human dermal fibroblasts. IL-1beta-induced MMP-1 expression is inhibited by neutralizing anti-MIF antibody. Dermal fibroblasts of IL-1alpha/beta-deficient mice produced significantly decreased levels of MMPs compared to wild-type mice after UVA irradiation. Furthermore, fibroblasts of MIF-deficient mice were much less sensitive to IL-1beta-induced MMPs production. On the contrary, IL-1beta produced significantly decreased levels of MMPs in MIF-deficient mice fibroblasts. The up-regulation of MMP-1 mRNA by IL-1beta stimulation was found to be inhibited by a p38 inhibitor and a JNK inhibitor. In contrast, the MEK inhibitor and inhibitor were found to have little effect on expression of MMP-1 mRNA. IL-1beta is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts, and IL-1beta and MIF cytokine network induce MMP-1 and contribute to the loss of interstitial collagen in skin photoaging.
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