Article

Panax ginseng induces human Type I collagen synthesis through activation of Smad signaling

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Abstract

Skin aging appears to be principally related to a decrease in levels of Type I collagen, the primary component of the dermal layer of skin. It is important to introduce an efficient agent for effective management of skin aging; this agent should have the fewest possible side effects and the greatest wrinkle-reducing effect. In the course of screening collagen production-promoting agents, we obtained Panax ginseng C.A. Meyer. This study was designed to investigate the possible collagen production-promoting activities of Panax ginseng C.A. Meyer root extract (PGRE) in human dermal fibroblast cells. As a first step to this end, human COL1A2 promoter luciferase assay was performed in human dermal fibroblast cells. In this assay, PGRE activated human COL1A2 promoter activity in a concentration-dependent manner. Human Type I procollagen synthesis was also induced by PGRE. These results suggest that PGRE promotes collagen production in human dermal fibroblast cells. Additionally, we have attempted to characterize the mechanism of action of PGRE in Type I procollagen synthesis. PGRE was found to induce the phosphorylation of Smad2, an important transcription factor in the production of Type I procollagen. When applied topically in a human skin primary irritation test, PGRE did not induce any adverse reactions. Therefore, based on these results, we suggest the possibility that PGRE may be considered as an attractive, wrinkle-reducing candidate for topical application.

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... Choi [10] demonstrated the facilitating effects of WG on epidermal cell proliferation by upregulating the expression of proliferation-related factors. Many previous studies have reported that ginseng has antiwrinkle effects [11], protects against ultraviolet radiation-induced skin aging [12], and exhibits antimelanogenesis properties [13]. Some studies have also described its benefits in skin care. ...
... Fibronectin is also characteristically present in loose connective tissue, where it plays the role of a linker for binding to collagens, proteoglycans, and many ECM molecules, with important roles in wound healing, tissue regeneration, and anti-aging of skin [28]. Type I collagen in the dermis is one of the fundamental building blocks of the skin, which is composed of more than 90% organic matter [29], whereas WG extracts promoted the synthesis of type I collagen in the dermis [11]. In the present study, collagen expression was not altered by LTAPP, despite the increase in fibronectin. ...
... Treatment with LTAPP for 5 min opened up the barrier system of skin through the inhibition of Ecadherin, which was almost restored with 3 hours [22]. As the components from WG such as ginsenosid and saponin are well known to induce the activity in skin [8,[10][11][12], the WG extracts treated with plasma could promote healthy skin. Therefore, the WG extracts treated with plasma could promote healthy skin. ...
Article
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Wild ginseng (WG) is a well-known traditional medicinal plant that grows in natural environments in deep mountains. WG has been thought to exert potent physiological and medicinal effects, and, recently, its use in skin care has attracted much interest. This study investigated the efficient penetration of WG extracts into the skin by means of low-temperature atmospheric pressure plasma (LTAPP), and its effects on the skin at the cellular and tissue levels. NIH3T3 mouse embryonic fibroblasts and HRM-2 hairless mice were used to confirm the improved absorption of WG extracts into the skin using LTAPP. The gene expression levels in NIH3T3 cells and morphological changes in skin tissues after WG treatment were monitored using both in vitro and in vivo experiments. Although WG extracts did not show any significant effects on proliferative activity and cytotoxicity, at a concentration of 1:800, it significantly increased the expression of fibronectin and vascular endothelial growth factor. In the in vivo study, the combinational treatment of LTAPP and WG markedly induced the expression of fibronectin and integrin α6, and it thickened. Our results showed that LTAPP treatment safely and effectively accelerated the penetration of the WG extracts into the skin, thereby increasing the effects of WG on the skin.
... Panax ginseng (PG) has a wide range of pharmacological effects including anti-inflammatory (14,15), antioxidant (16), anticancer (17) and anti-aging (18)(19)(20)(21)(22) effects as well as the promotion of hair growth (23,24). PG contains many other ingredients such as sugars, proteins and lipids besides ginsenosides. ...
... The major finding of the current study is that PG extract antagonizes DKK-1-induced HF changes, resulting in hair loss. Previous studies (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)27) revealed that PG regulates a variety of biological effects such as anti-inflammatory, antioxidant, anticancer, and anti-aging effects, and of course, the promotion of hair growth. Recently, the authors prepared a highly concentrated ginseng extract with the repeated fractionalizing method and found that the PG extract contained 194.8 mg/g (19.48% w/w) of ginsenosides (27). ...
Article
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It is well known that Panax ginseng (PG) has various pharmacological effects such as anti-aging and anti-inflammation. In a previous study, the authors identified that PG extract induced hair growth by means of a mechanism similar to that of minoxidil. In the present study, the inhibitory effect of PG extract on Dickkopf-1 (DKK-1)-induced catagen-like changes in hair follicles (HFs) was investigated in addition to the underlying mechanism of action. The effects of PG extract on cell proliferation, anti-apoptotic effect, and hair growth were observed using cultured outer root sheath (ORS) keratinocytes and human HFs with or without DKK-1 treatment. The PG extract significantly stimulated proliferation and inhibited apoptosis, respectively, in ORS keratinocytes. PG extract treatment affected the expression of apoptosis-related genes Bcl-2 and Bax. DKK-1 inhibited hair growth, and PG extract dramatically reversed the effect of DKK-1 on ex vivo human hair organ culture. PG extract antagonizes DKK-1-induced catagen-like changes, in part, through the regulation of apoptosis-related gene expression in HFs. These findings suggested that PG extract may reduce hair loss despite the presence of DKK-1, a strong catagen inducer via apoptosis.
... Asian ginseng (Panax ginseng root) has numerous applications for central nervous systems, cardiovascular and human skin applications (Lee et al. 2007). Panax ginseng extracts can also promote collagen in human dermal fibroblast cells (Lee et al. 2007;Pajoumshariati et al. 2015) and positive effect on osteogenesis and cell proliferation. ...
... Asian ginseng (Panax ginseng root) has numerous applications for central nervous systems, cardiovascular and human skin applications (Lee et al. 2007). Panax ginseng extracts can also promote collagen in human dermal fibroblast cells (Lee et al. 2007;Pajoumshariati et al. 2015) and positive effect on osteogenesis and cell proliferation. On nanofiber scaffolds, (Pajoumshariati et al. 2015) results indicate that ginseng extracts show an improvement in cell attachment and proliferation, and it also enhanced the MSCs osteogenic differentiation with high level of calcium content deposited on the surface of fibers which shows a potential candidate for bone tissue engineering. ...
Chapter
The field of biomedical applications for hydrogels requires the development of nanostructures with specific controlled diameter and mechanical properties. Nanofibers are ideal candidates for these advanced requirements, and one of the easiest techniques that can produce one-dimensional nanostructured materials in fibrous form is the electrospinning process. This technique provides extremely thin fibers with controlled diameter and highly porous microstructure with interconnected pores. Electrospinning demonstrates extreme versatility allowing the use of different polymers for tailoring properties and applications. It is a simple cost-effective method for the preparation of scaffolds. In this section, we will discuss recent and specific applications with a focus on their mechanisms. As such, we conclude this section with a discussion on perspectives and future possibilities on this field.
... They found that ginseng recovered the UVB-induced decrease in antiapoptotic gene expression in the human keratinocytes and dermal fibroblast, indicating that ginseng can protect cells from apoptosis caused by strong UVB radiation [9]. Another study showed that ginseng extract induced type I collagen production in human dermal fibroblast cells by activation of Smad signaling, suggesting ginseng as a potential candidate as a wrinklereducing agent by topical application [10]. ...
... Those regulations finally increased collagen type I (or procollagen type I) expression [15,16,21]. Also, other studies observed that Panax ginseng induces collagen type I synthesis through activation of Smad or peroxisome proliferator-activated receptordelta signaling [10,22]. In addition, enzyme-treated extract of red ginseng reversed the inhibitory effects of UV irradiation on filaggrin and profilaggrin production in both the epidermis and dermis in mice [15]. ...
Article
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Background: During the aging process, skin shows visible changes, characterized by a loss of elasticity and the appearance of wrinkles due to reduced collagen production and decreased elasticity of elastin fibers. Panax ginseng Meyer has been used as a traditional medicine for various diseases due to its wide range of biological activities including skin protective effects. Ginsenosides are the main components responsible for the biological activities of ginseng. However, the protective activities of an enzymatic preparation of red ginseng against human skin aging have not been investigated. Methods: The efficacy of an enzyme-treated powder complex of red ginseng (BG11001) in preventing human skin aging was evaluated by oral administration to 78 randomized individuals. All patients were requested to take three daily capsules containing either 750 mg of BG11001 or a placebo vehicle for 24 wk; at the end of the testing period, skin roughness, elasticity, and skin water content were measured. Results: BG11001 significantly reduced the average roughness of eye wrinkles and the Global Photo Damage Score compared with the placebo, although there were no significant differences in arithmetic roughness average between the groups. In addition, gross elasticity and net elasticity values increased, and transepidermal water loss level decreased, indicating improved skin elasticity and moisture content. Conclusion: In conclusion, enzyme-treated red ginseng extract significantly improved eye wrinkle roughness, skin elasticity, and moisture content. Moreover, enzyme-treated red ginseng extract would be useful substance as a bio-health skin care product.
... e root extracts of Panax ginseng have been shown to protect skin in C57BL mice from acute UVB irradiation [233] and significantly improve healing after laser burn injury and excisional wounding [221,234,235]. Studies demonstrate Panax ginseng extracts enhance keratinocyte migration [221,236], as well as stimulate proliferation [237] and increase collagen synthesis in human dermal fibroblasts [238] in vitro. In addition, Choi demonstrated that the ginsenoside Rb2, isolated from Panax ginseng, induces the formation of the epidermis in raft culture via increased expression of epidermal growth factor and its receptor, fibronectin and its receptor, and keratin 5/14 and collagenase I [239], all of which have critical roles in wound healing. ...
... Water, ethanolwater In vitro cell viability and proliferation assays [220] Antidiabetic [218] Anti-inflammatory [217] Antioxidant [214] Antitumour [216] Neuroprotective [215] Genital diseases [360] Improvement of blood circulation [361] Ointment Winvivo (Puji) ointment Evidence-Based Complementary and Alternative Medicine 13 Laser burn and excision wounds models in mice [236] Cell migration and wound healing assays [221,[237][238][239] Antiaging [230] Antiallergic [229] Anticancer [227] Anti-inflammatory [225] Antimicrobial [228] Antioxidant [226] Immunomodulating [231] Wound healing [221] Not available [260] Polydatin [258] Resveratrol [256] Roots Ethanol Full-thickness excision wounds in rats [259] Antiaging [256,257] Antibacterial [260] Anticancer [256,257] Anti-inflammatory [256,257] Antioxidant [256,257] Antiviral [260] Cardioprotective [256,257] Hepatitis [255] Hyperlipemia [255] Jaundice [255] Scald [255] Skin burns [255] Suppurative dermatitis [255] Capsules Resveratrol supplement ...
Article
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Cutaneous wound healing is the process by which skin repairs itself. It is generally accepted that cutaneous wound healing can be divided into 4 phases: haemostasis, inflammation, proliferation, and remodelling. In humans, keratinocytes re-form a functional epidermis (reepithelialization) as rapidly as possible, closing the wound and reestablishing tissue homeostasis. Dermal fibroblasts migrate into the wound bed and proliferate, creating “granulation tissue” rich in extracellular matrix proteins and supporting the growth of new blood vessels. Ultimately, this is remodelled over an extended period, returning the injured tissue to a state similar to that before injury. Dysregulation in any phase of the wound healing cascade delays healing and may result in various skin pathologies, including nonhealing, or chronic ulceration. Indigenous and traditional medicines make extensive use of natural products and derivatives of natural products and provide more than half of all medicines consumed today throughout the world. Recognising the important role traditional medicine continues to play, we have undertaken an extensive survey of literature reporting the use of medical plants and plant-based products for cutaneous wounds. We describe the active ingredients, bioactivities, clinical uses, formulations, methods of preparation, and clinical value of 36 medical plant species. Several species stand out, including Centella asiatica , Curcuma longa, and Paeonia suffruticosa , which are popular wound healing products used by several cultures and ethnic groups. The popularity and evidence of continued use clearly indicates that there are still lessons to be learned from traditional practices. Hidden in the myriad of natural products and derivatives from natural products are undescribed reagents, unexplored combinations, and adjunct compounds that could have a place in the contemporary therapeutic inventory.
... According to recent studies, the extracts from various types of ginseng modified by different processes increased type I procollagen production through Smad signaling activation [21] or MMP activation [18] in human dermal fibroblasts. In our study, SG effectively increased endogenous collagen synthesis in dermal fibroblasts with lower doses as compared to those used in other studies [18,21]. As the newly synthesized collagen plays a role in stimulating the fibroblast proliferation, the increased number of fibroblasts may produce more collagen molecules. ...
... In aged human skin, the type I collagen content decreased in vivo and in vitro as compared to young fibroblasts [20]. According to recent studies, the extracts from various types of ginseng modified by different processes increased type I procollagen production through Smad signaling activation [21] or MMP activation [18] in human dermal fibroblasts. In our study, SG effectively increased endogenous collagen synthesis in dermal fibroblasts with lower doses as compared to those used in other studies [18,21]. ...
Article
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In the present study, effects of sun ginseng (SG) on the collagen synthesis and the proliferation of dermal fibroblast were investigated. Collagen synthesis was measured by assaying procollagen type I C-peptide production. In addition, the level of matrix metalloproteinase (MMP)-1 was assessed by western blot analysis. SG suppressed the MMP-1 protein level in a dose-dependent manner. In contrast, SG dose-dependently increased tissue inhibitors of MMP (TIMP)-1 production in fibroblasts. SG increased type I collagen production directly and/or indirectly by reducing MMP-1 and stimulating TIMP-1 production in human dermal fibroblasts. SG dose-dependently induced fibroblast proliferation and this, in turn, can trigger more collagen production. These results suggest that SG may be a potential pharmacological agent with anti-aging properties in cultured human skin fibroblast.
... 35 Saponins also contribute to induce collagen production in skin fibroblasts via phosphorylation of Smad2 protein. 36 Furthermore, antioxidant and antibacterial properties of saponins could assist faster wound healing. 37 Other than saponins, flavonoids have been reported to increase collagen secretion and consequently induce tissue granulation. ...
Article
Background : Phytomedicines are gaining a spotlight in wound management, where much research has suggested the wound healing potential of Barringtonia racemosa . The objective of this study was to investigate the effectiveness of B. racemosa kernel extract in accelerating wound healing process in animal models. Methods: B. racemosa kernel was extracted using ethanol:water (7:3) solvent and was then used as a bioactive ingredient in a Carbopol 940-based gel formulation in four different concentrations (1, 3, 5 and 7 ppm). A 3 cm diameter wound was made in the dorsal area of Rattus norvegicus rat and wound healing process was assessed up to 12 days using DESIGN (Depth, Exudate, Size of Inflammation/Infection, Granulation tissue, and Necrotic tissue) scoring system. Results: Our data suggested that the DESIGN scores were significantly different among concentration groups after the 3 rd day onward suggesting B. racemosa extract accelerated the wound healing process. Rats treated with gel formulation containing 7 ppm of B. racemosa kernel extract had faster wound healing than that treated with topical Metcovazin. Conclusion: B. racemosa kernel extract was effective in accelerating wound healing on rats. Further study is warranted to purify the bioactive component and the action mechanism in wound healing process.
... Ginsenoside Rb1 (Rb1) (Fig. 1a), an aglycone with a dammarane skeleton steroidal saponin, is isolated from the roots of ginseng (Panax ginseng C. A. Meyer). Recently, ginsenoside Rb1 has been reported to show various biological functions, which include protecting cellular apoptosis from ultraviolet (UV) radiation by inducing DNA repair (4), inhibiting collagen degradation after UV irradiation on mice skin (5), inducing human type I collagen synthesis through activation of SMAD signaling (6), promoting both COL1A2 messenger RNA (mRNA) and protein expression mainly mediated through PPARδ, and reducing microRNA-25 expression to promote COL1A2 mRNA translation (7). The first objective of the study is to show that Rb1 may also inhibit melanin production in mouse B16 melanoma cells by measuring the melanin contents and tyrosinase activities in these cells. ...
Article
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Ginsenoside Rb1 (Rb1) is the most predominant ginsenoside isolated from the roots of ginseng (Panax ginseng C. A. Meyer). This compound is active in various human biological pathways that are involved in human collagen synthesis and inhibition of cell apoptosis. In this study, the skin-whitening effects of Rb1 were investigated in B16 melanoma cells. Our results showed that Rb1 inhibited melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 cells in a dose-dependent manner, which collectively indicated that Rb1 may have skin-whitening effects and may be formulated into skin-whitening products for skin care. Accordingly, a ginsenoside collagen transdermal patch was developed as a vehicle to topically deliver Rb1 into pig skin. The percutaneous permeation, retention within skin, and release in vitro of Rb1 from seven transdermal patch formulas were studied. It was determined that the best formula for ginsenoside collagen transdermal patch is made of protein collagen hydrolysate powder (PCHP) 2.0% (w/w), methyl cellulose (MC) 0.5% (w/w), polyethyleneglycol 6000 (PEG6000) 0.5% (w/w), ginsenoside 0.036% (w/w), azone 0.4% (v/w), menthol 0.20% (w/w), and water.
... Panax quinquefolium L., commonly known as American ginseng, belongs to the Araliaceae family and has gained tremendous global trade and recognition as a health food supplement. The dried root powder of this plant has been used extensively for its antitumor, anti-stress, anti-ageing, anti-fatigue, cardioprotective and hepatoprotective properties 1,2 . Ginsenoside are secondary metabolites of the P. quinquefolium and its major pharmacologically active components. ...
Article
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Here, we combine elicitors and transcriptomics to investigate the inducible biosynthesis of the ginsenoside from the Panax quinquefolium. Treatment of P. quinquefolium adventitious root with methyl jasmonate (MJ) results in an increase in ginsenoside content (43.66 mg/g compared to 8.32 mg/g in control group). Therefore, we sequenced the transcriptome of native and MJ treated adventitious root in order to elucidate the key differentially expressed genes (DEGs) in the ginsenoside biosynthetic pathway. Through DEG analysis, we found that 5,759 unigenes were up-regulated and 6,389 unigenes down-regulated in response to MJ treatment. Several defense-related genes (48) were identified, participating in salicylic acid (SA), jasmonic acid (JA), nitric oxide (NO) and abscisic acid (ABA) signal pathway. Additionally, we mapped 72 unigenes to the ginsenoside biosynthetic pathway. Four cytochrome P450s (CYP450) were likely to catalyze hydroxylation at C-16 (c15743_g1, c39772_g1, c55422_g1) and C-30 (c52011_g1) of the triterpene backbone. UDP-xylose synthases (c52571_g3) was selected as the candidate, which was likely to involve in ginsenoside Rb3 biosynthesis.
... In particular, current studies demonstrate that P. ginseng has anti-inflammatory, antioxidant, antimicrobial and immunomodulating effects (10)(11)(12)(13)(14)(15)(16)(17)(18). In addition, P. ginseng improves protein synthesis, neovascularization and angiogenesis (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Considered together, these features suggest that P. ginseng may play an important role in the wound-healing process. ...
Article
Current studies of Panax ginseng (or Korean ginseng) have demonstrated that it has various biological effects, including angiogenesis, immunostimulation, antimicrobial and anti-inflammatory effects. Therefore, we hypothesised that P. ginseng may also play an important role in wound healing. However, few studies have been conducted on the wound-healing effects of P. ginseng. Thus, the purpose of this in vitro pilot study was to determine the effects of P. ginseng on the activities of fibroblasts, which are key wound-healing cells. Cultured human dermal fibroblasts were treated with one of six concentrations of P. ginseng: 0, 1, 10 and 100 ng/ml and 1 and 10 µg/ml. Cell proliferation was determined 3 days post-treatment using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, and collagen synthesis was evaluated by the collagen type I carboxy-terminal propeptide method. Cell proliferation levels and collagen synthesis were compared among the groups. The 10 ng/ml to 1 µg/ml P. ginseng treatments significantly increased cell proliferation, and the 1 ng/ml to 1 µg/ml concentrations significantly increased collagen synthesis. The maximum effects for both parameters were observed at 10 ng/ml. P. ginseng stimulated human dermal fibroblast proliferation and collagen synthesis at an optimal concentration of 10 ng/ml.
... HDF and B16 cell lines were obtained from the Korean Cell Line Bank (Seoul, Korea). Cell lines were cultured in DMEM supplemented with 10% FBS and 1% penicillinstreptomycin at 37°C in a humidified 95% air/5% CO 2 atmosphere as described earlier.19,20 The cytotoxic effect of nanoparticles on cell viability was measured by MTT assay method. ...
Article
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There has been a growing interest in the design of environmentally affable and biocompatible nanoparticles among scientists to find novel and safe biomaterials. Panax ginseng Meyer berries have unique phytochemical profile and exhibit beneficial pharmacological activities such as antihyperglycemic, antiobesity, antiaging, and antioxidant properties. A comprehensive study of the biologically active compounds in ginseng berry extract (GBE) and the ability of ginseng berry (GB) as novel material for the biosynthesis of gold nanoparticles (GBAuNPs) and silver nanoparticles (GBAgNPs) was conducted. In addition, the effects of GBAuNPs and GBAgNPs on skin cell lines for further potential biological applications are highlighted. GBAuNPs and GBAgNPs were synthesized using aqueous GBE as a reducing and capping agent. The synthesized nanoparticles were characterized for their size, morphology, and crystallinity. The nanoparticles were evaluated for antioxidant, anti-tyrosinase, antibacterial, and cytotoxicity activities and for morphological changes in human dermal fibroblast and murine melanoma skin cell lines. The phytochemicals contained in GBE effectively reduced and capped gold and silver ions to form GBAuNPs and GBAgNPs. The optimal synthesis conditions (ie, temperature and v/v % of GBE) and kinetics were investigated. Polysaccharides and phenolic compounds present in GBE were suggested to be responsible for stabilization and functionalization of nanoparticles. GBAuNPs and GBAgNPs showed increased scavenging activity against 2,2-diphenyl-1-picrylhydrazyl free radicals compared to GBE. GBAuNPs and GBAgNPs effectively inhibited mushroom tyrosinase, while GBAgNPs showed antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, GBAuNPs were nontoxic to human dermal fibroblast and murine melanoma cell lines, and GBAgNPs showed cytotoxic effect on murine melanoma cell lines. The current results evidently suggest that GBAgNPs can act as potential agents for antioxidant, anti-tyrosinase, and antibacterial activities. In addition, GBAuNPs can be further developed into mediators in drug delivery and as antioxidant, anti-tyrosinase, and protective skin agents in cosmetic products. Consequently, the study showed the advantages of using nanotechnology and green chemistry to enhance the natural properties of GBs.
... Cell lines were cultured in DMEM and supplemented with 10% of FBS and 1% penicillin-streptomycin at 37 C in a humidified 95% air and 5% CO 2 atmosphere as described previously [22,23]. ...
Article
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Panax ginseng berry extract possess remarkable pharmacological effects on skin treatment such as anti-aging, antioxidant, promotor of collagen synthesis and alleviation against atopic dermatitis. In recent years, gold nanoparticles have gained much attention due to their extensive range of applications in particular in the field of drug delivery as a result of their biological compatibility and low toxicity. In a previous study, we designed and developed biocompatible gold and silver nanoparticles based on phytochemical profile and pharmacological efficacy of P. ginseng berry extract, we were able to reduce gold ions to nanoparticles through the process of green synthesis. However, its potential as a cosmetic ingredient is still unexplored. The aim of the present study is to investigate the moisture retention, in-vitro scavenging and whitening properties of gold nanoparticles synthesized from P. ginseng berry in cosmetic applications. Our findings confirm that P. ginseng berry mediated gold nanoparticles exhibited moisture retention capacity. In addition, MTT assay results confirmed that P. ginseng berry mediated gold nanoparticles are non-toxic to human dermal fibroblast and murine melanoma skin cells, possess scavenging activity, protect and provide alleviation against injured caused by H2O2-induced damage. In addition, P. ginseng berry mediated gold nanoparticles, significantly reduced melanin content and suppress tyrosinase activity in α-MSH-stimulated B16BL6 cells. We conclude that P. ginseng berry mediated gold nanoparticles are biocompatible and environmental affable materials and can be a potential novel cosmetic ingredient.
... A recent study revealed that when saponin was used to treat skin tissue exposed to ultraviolet rays, collagen synthesis of fibroblasts was increased and expression of matrix metalloproteinases was inhibited [32]. Furthermore, it was also revealed that saponin increased collagen synthesis in skin fibroblasts through phosphorylation of Smad 2 protein [33]. Thus, it is assumed that saponin will promote the re-synthesis of matrix at the site of a skin wound. ...
Article
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In this study, we investigated the effects of total ginseng saponin (TGS) on the cutaneous wound healing process using histological analysis. A total of 24 ICR mice, 5-weeks-old, were used for all in vivo experiments. Mice were divided into control and TGS-treated groups and four equidistant 1-cm full-thickness dorsal incisional wounds were created. The wounds were extracted at days 1, 3, 5, and 7 post-injury for histomorphometrical analysis including wound area and contracture measurements, keratinocyte migration rate, and calculation of infiltrating inflammatory cells. The results showed that the wound area was smaller and keratinocyte migration rate was higher in the TGS-treated group than that of the control group from days 3 to 7. Inflammatory cells in the TGS-treated group at days 1 and 3 were reduced compared to the control group. Wound contraction in the TGS-treated group was greater than in the control group on days 3 to 5, and collagen deposition in the TGS-treated group was higher than in the control group during wound healing. The results indicate a beneficial effect of TGS when used to treat skin wounds.
... Furthermore, there were studies that have been reported that saponin extracts increase collagen production [14] . The saponin extract was said to increase collagen production in skin fibroblast cells by means of phosphorylation of Smad 2 protein which results in the assumption that at the site of a skin wound, this phytochemical extract will promote the resynthesis of the matrix [15] . However, there are still no studies reported regarding the inhibitory properties of triterpenoid saponins from H. scabra against MMP-1. ...
Article
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Matrix metalloproteinase-1 (MMP-1) is a collagenase that cleaves the collagen present in the extracellular matrix (ECM), which results in skin wrinkling. In this in silico study, the triterpenoid saponins present from Holothuria scabra (desholothurin A, holothurinoside C, pervicoside C), were studied to determine its inhibitory properties against MMP-1. The approach was done via determining its dermatologic activity, its binding affinity against MMP-1 via molecular docking, followed by its pharmacokinetic properties. Dermatologic activity assessment of each triterpenoid saponins gave a Pa value of 0.408 for desholothurin A, 0.481 for holothurinoside C, and 0.297 for pervicoside C. In molecular docking, all triterpenoid saponins exhibited strong (such as conventional hydrogen bonding) and weak molecular interactions (such as van der Waals forces and carbon-carbon interactions). These molecular interactions was described by binding affinity giving desholothurin A a binding energy of-6.03 kcal/mol (37.79 uM), following holothurinoside C with-5.46 kcal/mol (99.14 uM), and pervicoside C with-3.05 kcal/mol (5480 uM). Lastly, in silico pharmacokinetic studies were done, which demonstrated poor drug-like properties of the compounds.
... Human dermal fibroblast (HDF) and B16 cell lines were purchased from Korean Cell Line Bank (SEL, KO). Cells were cultivated in DMEM media and complemented with 10 % FBS and 1 % PS at 37 °C, 95 % humidified air and 5 % CO 2 conditions as previous described (Lee et al., 2007;Yoo et al., 2011). ...
... 35 Saponins also contribute to induce collagen production in skin fibroblasts via phosphorylation of Smad2 protein. 36 Furthermore, antioxidant and antibacterial properties of saponins could assist faster wound healing. 37 Other than saponins, flavonoids have been reported to increase collagen secretion and consequently induce tissue granulation. ...
Article
Background : Phytomedicines are gaining a spotlight in wound management, where much research has suggested the wound healing potential of Barringtonia racemosa . The objective of this study was to investigate the effectiveness of B. racemosa kernel extract in accelerating wound healing process in animal models. Methods: B. racemosa kernel was extracted using ethanol:water (7:3) solvent and was then used as a bioactive ingredient in a Carbopol 940-based gel formulation in four different concentrations (1, 3, 5 and 7 ppm). A 3 cm diameter wound was made in the dorsal area of Rattus norvegicus rat and wound healing process was assessed up to 12 days using DESIGN (Depth, Exudate, Size of Inflammation/Infection, Granulation tissue, and Necrotic tissue) scoring system. Results: Our data suggested that the DESIGN scores were significantly different among concentration groups after the 3 rd day onward suggesting B. racemosa extract accelerated the wound healing process. Rats treated with gel formulation containing 7 ppm of B. racemosa kernel extract had faster wound healing than that treated with topical Metcovazin. On day 6, macroscopic observation on 7 ppm group revealed that the wound had persistent redness, lesion area of < 3 cm ² , and 80% healthy granulation, where presence of exudate and redness were not observable. Conclusion: B. racemosa kernel extract was effective in accelerating wound healing on rats. Further study is warranted to purify the bioactive component and the action mechanism in wound healing process.
... The antiaging effects of P. ginseng root extract were attributed to the induction of type-1 pro-collagen via phosphorylation of Smad2 and activation of human collagen-A2 promoter in human dermal fibroblast. According to this study, P. ginseng root extract did not exhibit any sensitivity reaction to human skin [25]. Another marker of the aging process is wrinkle formation, which is often associated with a reduced level of hyaluronan in the dermis. ...
Article
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The functional aspect of scalp hair is not only to protect from solar radiation and heat/cold exposure but also to contribute to one’s appearance and personality. Progressive hair loss has a cosmetic and social impact. Hair undergoes three stages of hair cycle: the anagen, catagen, and telogen phases. Through cyclical loss and new-hair growth, the number of hairs remains relatively constant. A variety of factors, such as hormones, nutritional status, and exposure to radiations, environmental toxicants, and medications, may affect hair growth. Androgens are the most important of these factors that cause androgenic alopecia. Other forms of hair loss include immunogenic hair loss, that is, alopecia areata. Although a number of therapies, such as finasteride and minoxidil, are approved medications, and a few others (e.g., tofacitinib) are in progress, a wide variety of structurally diverse classes of phytochemicals, including those present in ginseng, have demonstrated hair growth-promoting effects in a large number of preclinical studies. The purpose of this review is to focus on the potential of ginseng and its metabolites on the prevention of hair loss and its underlying mechanisms.
... The obtained information can be used to rationally clarify some experimental facts regarding the mechanism of induction of collagen synthesis by phytochemicals. For example, the possible activity of Panax ginseng C.A. Meyer root extract for promotion of type 1 procollagen production in human dermal fibroblast cells by induction of the phosphorylation of Smad2 (which is still unclarified) [26] might occur through the inhibition of PP1. These results may be valuable for further discovering and developing noncovalent type PP1 inhibitors with potent activity and high specificity used for enhancing collagen production. ...
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The most prominent feature of UV-induced photoaged skin is decreased type 1 procollagen. Increase of the TGF-β/Smad signaling through inhibition of the TβRI dephosphorylation by the GADD34–PP1c phosphatase complex represents a promising strategy for the increase in type 1 collagen production and prevention of UV-induced skin photoaging. In this study, the molecular docking and dynamics simulations, and pharmacophore modeling method were run to investigate a possible binding site as well as binding modes between apigenin, daidzein, asiaticoside, obovatol, and astragaloside IV and PP1c. Through docking study, the possible binding site for these phytochemicals was predicted as the hydrophobic (PP1–substrate binding) groove. The result indicates that PP1 is the significant target of these compounds. Moreover, the 20,000-ps MD simulations present that the binding locations and modes predicted by the docking have been slightly changed considering that the MD simulations proffer more reliable details upon the protein–ligand recognition. The MM-GBSA binding free energy calculations and pharmacophore modeling rationally identify that the highly hydrophobic surfaces/pockets at close proximity of the catalytic core are the most favorable binding locations of the herbal compounds, and that some experimental facts upon a possible mechanism of increase in collagen biosynthesis can be explained. The present study theoretically offers the reliable binding target of the herbal compounds, and therefore helps to understanding the action mechanism for natural small molecules that enhance collagen production.
... In another study, P. ginseng root extract induced type1 pro-collagen synthesis in human dermal fi- broblast cells and did not elicit any sensitivity reaction in human skin test. Phosphorylation of Smad 2 and activation of human COL1A2 promoter are proposed mediators for the anti-aging prop- erties of this extract [32]. ...
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Ginseng has gained fame as one of the most popular herbs originating from Eastern countries. Among different species which are known as ginseng, Panax ginseng C. A. Mey. (Korean or Asian ginseng) is the most frequently used one. Ginsenosides have been proposed to account for most of the biological activities of ginseng. The widely appreciated health-promoting effect of ginseng pertains to the beneficial effects of this plant against immune, cardiovascular and sexual diseases and cancer. In addition, there are some new aspects of the pharmacological activity of this plant which justify its use in dermatologic diseases. In dermatology, ginseng has been investigated mechanistically for its therapeutic effects in photoaging, wound and injury, skin cancer, dermatitis, hair loss, alopecia and cold hypersensitivity. Here, we reviewed experimental and clinical studies exploring the therapeutic efficacy of ginseng and ginsenosides in the field of dermatology.
... [10][11][12][13][14][15][16][17][18] In addition, P. ginseng improves protein synthesis, neovascularisation, and angiogenesis. 16,[19][20][21][22][23][24][25][26][27][28][29] Considered together, these features suggest that P. ginseng may play an important role in the healing process of chronic wounds with attenuated fibroblast activity and a prolonged inflammatory phase. Despite the theoretical potential of P. ginseng in treating chronic wounds, there have been few studies addressing the effect of P. ginseng on chronic wound healing. ...
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Numerous studies have demonstrated the various medicinal properties of Panax ginseng, including angiogenic, immuno‐stimulating, antimicrobial, and anti‐inflammatory activities, which can be helpful in chronic wound healing. However, a direct role for P. ginseng in chronic wound healing has not been demonstrated. The present study was designed to evaluate the effects of P. ginseng extract on diabetic fibroblasts in vitro. Human diabetic fibroblasts were cultured in the presence of Ginsenoside Rb1 (G‐Rb1), the active component in P. ginseng (10 ng/mL), and untreated diabetic fibroblasts were used as controls. Cell proliferation, collagen synthesis, the production of various growth factors (basic fibroblast growth factor [bFGF]; vascular endothelial growth factor [VEGF]; and transforming growth factor‐β1 [TGF‐β1]), and the synthesis of matrix metalloproteinase 1 (MMP‐1) and tissue inhibitor of metalloproteinases 1 (TIMP‐1) were compared using enzyme‐linked immunosorbent assay and immunofluorescence staining. Compared with the control group, G‐Rb1‐treated fibroblasts showed significantly (P < 0.05) higher levels of cell proliferation, collagen synthesis, VEGF, TGF‐β1, and TIMP‐1. However, no significant differences in bFGF and MMP‐1 levels were observed between the two groups. These results suggest that P. ginseng treatment may stimulate the wound‐healing activity of diabetic fibroblasts in vitro.
... In previous studies, ursane-type triterpene 28-O-oligoglycosyl esters, asiaticoside and madecassoside, were isolated from Centella asiatica, a herb used in Sri Lankan and Indian Ayurvedic traditional medicine (Matsuda et al., 2001a,b). These triterpene saponins were reported to be promoters of human type-I collagen synthesis (Bonte et al., 1994;Lee et al., 2007;Liu et al., 2008). The structures of asiaticoside and madecassoside resembled saponin constituents from B. perennis flowers; thus, similar activities were expected. ...
Article
The methanol extract from Bellis perennis (Asteraceae) flowers was found to promote collagen synthesis in normal human dermal fibroblasts (NHDFs). Seven oleanane-type triterpene saponins, perennisosides XIII-XIX, and two known saponins, bellissaponins BS5 and BS9, were isolated from the methanol extract. The structures were determined based on chemical and physicochemical data, and confirmed using previously isolated related compounds as references. Among the isolates, including 19 previously reported saponins, perennisosides XVIII, I, II, VII, IX, and XI, asterbatanoside D, bernardioside B2, and bellissaponins BS5 and BS9 significantly promoted collagen synthesis at 3-30μM without cytotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.
... Plant C. Cinereum contains secondary metabolites which can accelerate the healing process of the wound, one of which is saponin. Previous reserarch, saponin compounds can increase collagen synthesis in skin fibrolast in wound healing process [16] . Apart from saponins, plants C. cinereum also has a secondary metabolite tannin type. ...
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Sirangak (Cyanthillium cinereum; Asteraceae) is a medicinal plant traditionally used by Minangkabaunese, West Sumatra to heal the wounds. However, the underlying mechanism of this plant in healing the wounds is scientifically unelucidated. This current research aimed to clarify that Sirangak could potently accelerate the wound healing by enhanching the hematological performances. We conducted an experiment by using adult male mice consisted of control group and Sirangak oil-topical treated group after being wounded by superficial slice cuting. Subsequently, the wound healing rate was determined and the hematological profiles were monitored periodically for a week. The results demonstrated that Sirangak oil could significantly accelerate the wound healing by 85.6% as compared to control with a 71.6% of wound recovery. The hematological analysis indicated that Sirangak oil could significantly increase the erythrocyte count, hemoglobin concentration, hematocrite, mean cell volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) particularly during the early day of treatment. However, Sirangak oil did not significantly affect the leucocyte profiles except for the granulocyte. Therefore, the Sirangak oil could potently accelerate wound healing by enhanching the physiological endurance particularly the erythrocyte and hemoglobin level. This finding underpins a scientific evidence for further use of Sirangak in medicine.
... Some known efficacies were confirmed. For example, Ginseng Radix 15 and Lycii Fructus were reported to exert anti-aging effects 15,16 . Most reports studied skin cells in vitro or in vivo, and evidence of dermal efficacy was also evaluated. ...
Article
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Background Korean cosmetics are widely exported throughout Asia. Cosmetics exploiting traditional Korean medicine lead this trend; thus, the traditional medicinal literature has been invaluable in terms of cosmetic development. We sought candidate medicinal herbs for skincare. Methods We used data mining to investigate associations between medicinal herbs and skin-related keywords (SRKs) in a classical text. We selected 26 SRKs used in the Donguibogam text; these referred to 626 medicinal herbs. Using a term frequency-inverse document frequency approach, we extracted data on herbal characteristics by assessing the co-occurrence frequencies of 52 medicinal herbs and the 26 SRKs. Results We extracted the characteristics of the 52 herbs, each of which exhibited a distinct skin-related action profile. For example Ginseng Radix was associated at a high-level with tonification and anti-aging, but Rehmanniae Radix exhibited a stronger association with anti-aging. Of the 52 herbs, 46 had been subjected to at least one modern study on skincare-related efficacy. Conclusions We made a comprehensive list of candidate medicinal herbs for skincare via data mining a classical medical text. This enhances our understanding of such herbs and will help with discovering new candidate herbs.
... Therefore, objective evidence of a reduction in facial wrinkles by long-term ingestion of red ginseng was provided for the first time; the clinical improvement was substantiated by biochemical and histological evidence of increased collagen and elastic fiber synthesis in the dermis [35]. The clinical improvement may be due to the activation of COL1A2 promoter and Smad signaling [36], through ginseng's estrogen-like activity [37], and/or additionally through increased hyaluronan levels by a metabolite of ginsenosides [38]. ...
Article
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Oral supplementation of micronutrients, or functional foods, to prevent aging has gained much attention and popularity as society ages and becomes more affluent, and as science reveals the pathological mechanisms of aging. Aging of the skin combines biologic aging and extrinsic aging caused predominantly by sunlight and other environmental toxins. Anti-aging functional foods exert their influence mostly through their anti-oxidant and anti-inflammatory effects, thereby abrogating collagen degradation and/or increasing procollagen synthesis. Clinical evidence supporting a role in preventing cutaneous aging is available for oral supplements such as carotenoids, polyphenols, chlorophyll, aloe vera, vitamins C and E, red ginseng, squalene, and omega-3 fatty acids. Collagen peptides and proteoglycans are claimed to provide building blocks of the dermal matrix. This review summarizes the current study findings of these functional foods.
... Panax ginseng is known for its anti-aging, antiinflammatory, and antioxidant activities, and its ability to inhibit col-lagen degradation after UV irradiation and to induce human type I collagen synthesis [52][53][54][55]. Its major components namely ginsenosides have been shown anti-inflammatory, antitumor, and neuroprotective properties. ...
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Skin aging is an inevitable biological phenomenon of human life. Advancing age brings changes to all components of the integumentary system with consequent signs on the skin. Skin aging is mainly due to intrinsic (chronologic) and extrinsic aging (photo-aging). Photo-aging is a consequence the exposure to ultraviolet radiations. Despite variable economic conditions, the skin care market based on natural products continues to see strong growth. In this context, the research of naturally occurring anti-aging agents is greatly expanding and in recent years numerous plant-derived products have been investigated. This review article focuses on highlighting recent advances in current knowledge on anti-aging natural products grouped and presented according to their family origin. Plants from 35 families were reviewed. A variety of phytomolecules, derived in particular from polyphenols, triterpenes and sterols classes, demonstrated a promising activity. Among them carnosic acid, curculigoside, curcumin, glycyrrhizic acid, mangiferin, mirkoin, asiaticoside, rosmarinic acid, tectorigenin, tyrosol etc., able to inhibit tyrosinase, hyaluronidase, elastase, and collagenase, to scavenge free radicals from skin cells, to prevent trans-epidermal water loss, and to contribute to protect skin from wrinkles, were largely investigated and herein discussed. Extracts and pure compounds from Fabaceae, Asperaceae and Zingiberaceae families have shown particular interest and appear the most promising in the development of anti-aging products.
... However the in vivo efficacy and composition of many of these formulations have yet to be scientifically validated. Certain extracts are suggested to exert a preventative effect through antioxidant activity [82] whilst others have been implicated in dermal matrix repair through MMP inhibition or deposition of ECM components [83][84][85][86][87][88][89][90][91][92][93] (Table 2). For many of these botanical extracts, few studies have been published, little is known of their potential mechanisms of action and problems with batch to batch consistency plague attempts to define their molecular compositions. ...
... However, most natural compounds found in cosmetic products were attributed to their anti-oxidative properties, only few of them were able to directly increase collagen synthesis. Ginsenoside Rb 1 (molecular weight: 1109), the major ginsenoside in Panax ginseng, was shown to induce type-I collagen expression in dermal fibroblasts [25,26]. Another study found that a laminin tyrosineisoleucine-glycine-serine-arginine (YIGSR) peptide could enhanced collagen synthesis of human dermal fibroblasts [23]. ...
... Human dermal fibroblast have different functions and are classified as key wound-healing cells because their function includes the production of collagen, growth factors, antioxidants and a balance of matrixproducing proteins and protease enzymes. In the Human fibroblast P. ginseng root extract activates human collagen A2 promotes and induces type-1 pro-collagen via phosphorylation of Smad2 [28]. ...
Chapter
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The hair follicle is the unique organ that has the capacity of undergoing cyclic transformations following periods of growth (anagen), regression (catagen), and rest (telogen) regenerating itself to restart the cycle. The dynamic capacity of hair to growth and rest enables mammals to control hair growth and length in different body side and to change their coats. Unlike what is observed in many animals in which the pelage synchronously passes from one phase of the cycle to other all stages of growth cycle are simultaneously found in the human pelage, the growth pattern is a mosaic where the hair cycling staging of one hair root is completely independent of it nearest hair follicle, meaning that each follicular unit (FU) can contain follicles in different stages at any given time. A variety of factors, such as nutritional status, hormones, exposure to radiations, chemotherapy or radiotherapy, environmental pollution or drugs may affect hair growth, and affects the number of hairs, this progressive hair loss has a cosmetic and social impact that often significantly affects social and psychological well-being of the patient that suffers from this hair loss. Although a number of therapies, such as finasteride and minoxidil, are approved medications, a wide variety of classes of phytochemicals and natural products, including those present in ginseng are being testing. The purpose of this chapter is to focus on study the potential of ginseng and its metabolites in hair loss.
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Herbs and spices have been used in retaining and boosting human beauty since time immemorial. Herbal cosmetic has growing demand in the worldwide market and is an invaluable gift of Mother Nature. In the present review, the focus is on the cosmetic herbs of Southeast Asian countries namely Malaysia, Cambodia, Laos, Myanmar [Burma], Thailand, Vietnam, Brunei, East Timor, Indonesia, Philippines and Singapore in highlighting both traditional and scientific knowledge or background of the selected potential herbs. The available literature was searched in the following scientific database such as PubMed, Google Scholar, Science Direct and Springer for publications and patents. In view of traditional uses, herbs like Allium sativum, Aloe vera, Centella asiatica, Curcuma longa, Hibiscus rosa-sinensis, Lawsonia inermis and Tamarindus indica L. were classified as need of special mention. Many herbs have been scientifically evaluated for their cosmetic potentials such as anti-aging, antiacne, melanogenic and anti-tyrosinase activities. The great void remains for a systematic study, thorough review of scientific report that provides a basis for the use of specific herbs due to their efficacy as cosmetics. In addition, two of the Malay herbs; Labisia pumila (Kacip Fatimah) and Ficus deltoidea (Mas cotek), are proposed to be clinically studied for their safety in cosmetic application aspects wherein the need for safety evaluation and fruitful application of herbal cosmetics were emphasized.
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Gradual scale-up culture of adventitious roots of Panax quinquefolium L. has been successfully achieved.Production of ginsenosides and polysaccharides was enhanced in a bioreactor compared with flask-type culture. The conditions for culture of adventitious roots were optimized.Partial least-squares discriminant analysis of the results showed growth rate and amounts of some compounds correlated positively with use of a 5-L balloon-type bubble bioreactor at an angle of 90° and with an aeration volume of 0.5 v/v/min.
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The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 13 Panax spp root-derived ingredients as used in cosmetics. Panax "spp" indicates that multiple species within the genus are used in cosmetics, but not all species within that genus. Four species are being considered in this safety assessment. These ingredients function mostly as skin-conditioning agents-miscellaneous, fragrance ingredients, skin-conditioning agents-humectant, skin-conditioning agents-emollient, and cosmetic astringents. The Panel reviewed available data related to these ingredients and addressed the issue of pulegone, a constituent of these ingredients and other ingredients, such as peppermint oil. The Panel concluded that these Panax spp root-derived ingredients are safe in the practices of use and concentration as given in this safety assessment.
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Medicinal plants as a therapeutic agent with osteogenic properties can enhance fracture-healing process. In this study, the osteo-inductive potential of Asian Panax Ginseng root extract within electrospun polycaprolactone (PCL) based nanofibers has been investigated. Scanning electron microscopy images revealed that all nanofibers were highly porous and beadles with average diameter ranging from 250 to 650 nm. The incorporation of ginseng extract improved the physical characteristics (i.e., hydrophilicity) of PCL nanofibers, as well as the mechanical properties. Although ginseng extract increased the degradation rate of pure PCL nanofibers, the porous structure and morphology of fibers did not change significantly after 42 days. It was found that nanofibrous scaffolds containing ginseng extract had higher proliferation (up to ~1.5 fold) compared to the pristine PCL. The qRT-PCR analysis demonstrated the addition of ginseng extract into PCL nanofibers induced significant expression of osteogenic genes (Osteocalcin, Runx-2 and Col-1) in MSCs in a concentration dependent manner. Moreover, higher calcium content, alkaline phosphatase activity and higher mineralization of MSCs were observed compared to the pristine PCL fibers. Our results indicated the promising potential of ginseng extract as an additive to enhance osteo-inductivity, mechanical and physical properties of PCL nanofibers for bone tissue engineering application.
Chapter
The recovery of skin wounds is a complex biological process involving three basic mechanisms: inflammatory phase, re-epithelialization followed by granulation and tissue remodeling. The interactions between inflammatory cells, fibroblasts, and keratinocytes induce microenvironmental changes at the wound site. Tissue remodeling is initiated by matrix-producing proteins and protease enzymes and collagen fibers in the dermis. A saponin extracted from ginseng, known as ginsenoside, has been shown to accelerate neovascularization in burn wounds in mice. It also increases levels of vascular endothelial growth factor and interleukin (IL-β). IL-β accelerate wound healing by promoting accumulation of macrophages at skin wound sites. Saponins are major active constituents of ginseng. They contain many ginsenosides. The purified ginsenosides or the extracts of ginseng root have been reported to have beneficial effects on damaged skin. For instance, red ginseng root extract protected skin from acute UVB-irradiation. Ginsenoside F1, an enzymatically modified derivative of the ginsenoside Rg1, protected HaCaT against UVB-induced apoptosis. Panax ginseng root extract promotes type I collagen synthesis in human dermal fibroblasts (HDF) via the Smad activation pathway and exhibits antioxidant activity against free radicles including diphenyl-p-picrylhydrazyl treatment. In addition, ginsenoside Rb1 promotes healing process of burn wound by enhancing angiogenesis. Among the various ginsenosides, ginsenoside Rb1 has been found to most potent agent for wound healing.
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In this study, Candida tropicalis, Aspergillus niger, and a mixture of their cultures were previously used as fungal elicitors in Panax quinquefolium adventitious root culture to enhance ginsenoside production. The result showed that ginsenoside content (11.47 ± 0.54 mg g−1) was significantly enhanced to 3.25-fold of the control group after treatment with 400 mg L−1C. tropicalis. The polysaccharide content (213.01 ± 18.63 mg g−1) reached the highest when A. niger was at the concentration of 200 mg L−1. HPLC–ESI-MSn analysis was performed, showing that ginsenosides Rh1 and Ro were identified after treatment with fungal elicitors. Furthermore, we found that C. tropicalis, A. niger, and mix elicitor significantly up-regulated the expression of the squalene synthase, squalene epoxidase, dammarenediol synthase, β-amyrin synthase, protopanaxadiol synthase, protopanaxatriol synthase, and UDP-glycosyltransferase. SDS-polyacrylamide gel electrophoresis was used to analysis the changes of protein. A new band was discovered at the size of 75 kDa. In addition, it found that fungal elicitors significantly increased the activities of catalases and peroxidase.
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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.
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In this study, we investigated the effect of fish scale collage (FSC) on type I procollagen expression in cultured human dermal fibroblasts using real-time polymerase chain reaction and ELISA, under normal and UV exposure condition. Also, FSC encapsulated negatively surface modified nanoliposome (NLsurf mod) was fabricated, and the physicochemical characteristics of the liposomes and skin permeation properties were evaluated. FSC increased type I procollagen mRNA and protein expression in human dermal fibroblasts. The mean particle size, zeta potential value and encapsulation efficiency of the NLsurf mod were about 175 nm, −44 mV and 11%, respectively. The skin localization effect was enhanced by NLsurf mod. Conclusively, FSC is able to elevate the type I procollagen expression in human dermal fibroblasts and FSC-loaded NLsurf mod would be a good candidate for the topical delivery of FSC.
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Background Bioactive compounds in plant extracts are able to reduce metal ions to nanoparticles through the process of green synthesis. Panax ginseng is an oriental medicinal herb and an adaptogen which has been historically used to cure various diseases. In addition, the P. ginseng leaves-mediated gold nanoparticles are the value-added novel materials. Its potential as a cosmetic ingredient is still unexplored. The aim of this study was to evaluate the antioxidant, moisture retention and whitening properties of gold nanoparticles (PgAuNPs) in cosmetic applications. Methods Cell-free experiments were performed to evaluate PgAuNP's antioxidant and moisture retention properties and inhibition activity on mushroom tyrosinase. Furthermore, in vitro cell cytotoxicity was evaluated using normal human dermal fibroblast and murine B16BL6 melanoma cells (B16) after treatment with increasing concentrations of PgAuNPs for 24 h, 48 h, and 72 h. Finally, in vitro cell assays on B16 cells were performed to evaluate the whitening effect of PgAuNPs through reduction of cellular melanin content and tyrosinase activity. Results In vitro DPPH radical scavenging assay results revealed that PgAuNPs exhibited antioxidant activity in a dose-dependent manner. PgAuNPs exhibited moisture retention capacity and effectively inhibited mushroom tyrosinase. In addition, 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide results revealed that PgAuNPs were not toxic to human dermal fibroblast and B16 cells; in addition, they significantly reduced melanin content, tyrosinase activity, and mRNA expression of melanogenesis-associated transcription factor and tyrosinase in B16 cells. Conclusion Our study is the first report to provide evidence supporting that P. ginseng leaves-capped gold nanoparticles could be used as multifunctional ingredients in cosmetics.
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The seed oil of andiroba (Carapa guianensis, Meliaceae) was found to promote collagen synthesis in normal human dermal fibroblasts. To characterize the active constituents of this oil, the collagen synthesis-promoting activities of 10 principal limonoid constituents, gedunin (1), 6α-acetoxygedunin (2), 7-deacetoxy-7-oxogedunin (3), 7-deacetoxy-7α-hydroxygedunin (4), andirolide H (5), 6α-hydroxygedunin (6), methyl angolensate (7), 17β-hydroxyazadiradione (8), and carapanosides C (9) and R (10), were examined. Among them, 1–4, 6, 7, and 9 were found to significantly promote collagen synthesis without cytotoxicity at the effective concentrations.
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Ginseng leaves contain high saponin composition and content, but are used less often than the root part. To develop a use for the leaves that exploits their properties, we studied ginseng leaves as the raw material of anti-aging cosmetics. This study highlights an assessment of the cellular factivity and clinical efficacy of ginseng leaf extract, providing necessary information relevant to the development of new cosmetic products. Panax ginseng leaf purified extracts (PGLE) were shown to have high contents of Rb3 and Rb2. Rb3, the major chemical components of PGLE, promoted collagen synthesis though the activation of transforming growth factor-β (TGF-β) in human skin fibroblast cells. In addition, the possibility of PGLE as an anti-skin-aging agent has also been clinically validated. Our analysis of the crow's feet wrinkle showed that there was a decrease in the depth of deep furrows in the region of interest (RI) treated with PGLE lotion over an eight-week period. Based on these results, we suggest the possibility that PGLE, having high levels of Rb3, be considered as an attractive, wrinkle-reducing candidate for topical application.
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The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks FBG cream significantly reduced appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.
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The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks, FBG cream significantly reduced the appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with a control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced from 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.
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As the largest organ in our body, the skin acts as a barrier against external stress and damages. There are various cell types of skin, such as keratinocytes, melanocytes, fibroblasts, and skin stem cells. Korean ginseng, which is one of the biggest distributions of ginseng worldwide, is processed into different products, such as functional food, cosmetics, and medical supplies. This review aims to introduce the functional role of Korean ginseng on different dermal cell types, including the impact of Korean ginseng in anti-photodamaging, anti-inflammatory, anti-oxidative, anti-melanogenic, and wound healing activities, etc. We propose that this information could form the basis of future research of ginseng-derived components in skin health.
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Wounds are among the most common skin conditions, displaying a large etiological diversity and being characterized by different degrees of severity. Wound healing is a complex process that involves multiple steps such as inflammation, proliferation and maturation and ends with scar formation. Since ancient times, a widely used option for treating skin wounds are plant- based treatments which currently have become the subject of modern pharmaceutical formulations. Triterpenes with tetracyclic and pentacyclic structure are extensively studied for their implication in wound healing as well as to determine their molecular mechanisms of action. The current review aims to summarize the main results of in vitro, in vivo and clinical studies conducted on lupane, ursane, oleanane, dammarane, lanostane and cycloartane type triterpenes as potential wound healing treatments.
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Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities, including antioxidant and anti-inflammatory properties, in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture, and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 µg/mL) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth, including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4, but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway, including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.
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Emerging traditional drug-multiresistant bacteria has become a critical health problem worldwide, which has motivated the development of alternative therapies and technologies to combat infections associated with such bacteria. The application of antibacterial and non-cytotoxic natural extracts combined with the therapeutic use of cold plasma offers alternatives to antibiotics and conventional therapies. Thus, the present review aims to show that research of the synergistic effect of plasma treatment on the antibacterial and therapeutic properties of natural extracts (e.g., Rosmarinus officinalis, Citrus sinensis, Azadirachta indica, Rhizome Atractylodes macrocephala) is a relatively new field with few reports, but with promising published results. The cited publications were recovered from scientific databases such as Google Scholar, SpringerLink, Wiley, and Elsevier – ScienceDirect through an extensive search. In this concern, it is reported that a more significant reduction of the bacterial population in wet samples (e.g., food material, cell cultures, broths, tissues) and polymer fabrics (e.g., polyethene terephthalate, cellulose) could be achieved by using cold plasma treatments combined with natural extracts rather than use them separately. Simultaneously, it is reported that the use of cold plasma and natural extracts enhances cell growth and attachment under in vitro and in vivo conditions. It was found that atmospheric-pressure plasma jet devices, instead of the dielectric barrier discharge ones, have primarily been used to improve the antibacterial activity of polymer fabrics and in wound healing therapies. Thus, some promising results on the antibacterial and non-cytotoxic properties of plasma-enhanced natural extracts have been reported, but more research (especially comparative studies) is needed to determine their therapeutically safe use.
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The wound healing process is a dynamic process such as hemostasis, inflammation, proliferation, and remodeling phases overlapping each other. Many studies have reported that complementary therapy, such as honey, sea cucumber and other therapy, can affect wound healing. Honey has effect on wound healing caused by its constituents. So far, many studies have reported honey having effect on wound such as burn, acute, and chronic. Another complementary therapy is achieved using sea cucumber. Sea cucumber also affects wound healing and biofilm. However, there are a few studies to know its effects on wound healing. In clinical setting, sometime practitioners combine both oral and topical therapy for wound care. Mix herbs (radix rhamanniae, panax ginseng, and gypsum florosum) by oral and topical (natural honey, black seed, and sea cucumber) could heal diabetic foot ulcers. Future studies need to conduct research on large sample.
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Transforming growth factor-beta (TGF-beta) superfamily members are multifunctional cell-cell signaling proteins that play pivotal roles in tissue homeostasis and development of multicellular animals. They mediate their pleiotropic effects from membrane to nucleus through distinct combinations of type I and type II serine/threonine kinase receptors and their downstream effectors, known as Smad proteins. Certain Smads, termed receptor-regulated Smads, become phosphorylated by activated type I receptors and form heteromeric complexes with a common-partner Smad4, which translocates into the nucleus to control gene transcription. In addition to these signal transducing Smads, inhibitory Smads have been identified that inhibit the activation of receptor-regulated Smads. In contrast to the still growing TGF-beta superfamily (with approximately 30 members in mammals), relatively few type I and type II receptors as well as Smads have been identified. We will focus on recent insights into the molecular mechanisms by which signaling specificity between different TGF-beta superfamily members is achieved and regulated, and how a single family member can elicit a broad scala of biological responses.-Piek, E., Heldin, C.-H., ten Dijke, P. Specificity, diversity, and regulation in TGF-beta superfamily signaling.
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The six major ginsenosides, Rg1, Re, Rb1, Rc, Rb2, and Rd, in roots and leaves of American ginseng have been isolated and quantified by high-performance liquid chromatography. In 4-year-old roots, the main ginsenosides were Re and Rb1, and together they accounted for >75% of the total ginsenosides. In leaves, the concentration and composition of ginsenosides varied with the maturity of the leaf tissue. One-month-old leaves contained 1.33−2.64 g ginsenoside/100 g dry weight, and the ginsenoside Re accounted for >50% of the total concentration. In mature, 4-month-old leaves, the total ginsenoside content ranged from 4.14 to 5.58 g/100 g dry weight, and the ginsenosides Re and Rd each accounted for 40% of the total ginsenosides. The production site of ginseng influenced the ginsenoside contents of roots and leaves. However, few significant correlations were found between root and leaf ginsenosides and between ginsenoside levels and mineral composition of the leaves and soil. Keywords: Panax quinquefolium; saponins; ginsenosides; HPLC analysis; soil fertility; leaf tissue nutrient status
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A crude extract from ginseng root inhibits high-threshold, voltage-dependent Ca2+ channels through an unknown receptor linked to a pertussis toxin-sensitive G protein. We now have found the particular compound that seems responsible for the effect: it is a saponin, called ginsenoside Rf (Rf), that is present in only trace amounts within ginseng. At saturating concentrations, Rf rapidly and reversibly inhibits N-type, and other high-threshold, Ca2+ channels in rat sensory neurons to the same degree as a maximal dose of opioids. The effect is dose-dependent (half-maximal inhibition: 40 microM) and it is virtually eliminated by pretreatment of the neurons with pertussis toxin, an inhibitor of G(o) and Gi GTP-binding proteins. Other ginseng saponins--ginsenosides Rb1, Rc, Re, and Rg1--caused relatively little inhibition of Ca2+ channels, and lipophilic components of ginseng root had no effect. Antagonists of a variety of neurotransmitter receptors that inhibit Ca2+ channels fail to alter the effect of Rf, raising the possibility that Rf acts through another G protein-linked receptor. Rf also inhibits Ca2+ channels in the hybrid F-11 cell line, which might, therefore, be useful for molecular characterization of the putative receptor for Rf. Because it is not a peptide and it shares important cellular and molecular targets with opioids, Rf might be useful in itself or as a template for designing additional modulators of neuronal Ca2+ channels.
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Transforming growth factor-β (TGF-β) regulates many aspects of cellular function. A member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family, TAK1, was previously identified as a mediator in the signaling pathway of TGF-β superfamily members. The yeast two-hybrid system has now revealed two human proteins, termed TAB1 and TAB2 (for TAK1 binding protein), that interact with TAK1. TAB1 and TAK1 were co-immunoprecipitated from mammalian cells. Overproduction of TAB1 enhanced activity of the plasminogen activator inhibitor 1 gene promoter, which is regulated by TGF-β, and increased the kinase activity of TAK1. TAB1 may function as an activator of the TAK1 MAPKKK in TGF-β signal transduction.
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To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients. In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. Ginseng may be a useful therapeutic adjunct in the management of NIDDM.
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In an attempt to define the role of increased oxidative stress in the transition from compensatory hypertrophy to heart failure, this study examined the effects of long-term vitamin E therapy on the occurrence of heart failure subsequent to chronic pressure overload in guinea pigs. Hyperfunctional heart hypertrophy has been shown to be accompanied by an increase in the endogenous antioxidant reserve, whereas congestive heart failure is accompanied by a decrease in this reserve. The effects of vitamin E, a naturally occurring antioxidant, on the development of heart failure from a hypertrophic stage were examined. The ascending aorta in guinea pigs was coarcted. For vitamin treatment, slow-release pellets were implanted at the time of the operation. The animals were assessed at 10 and 20 weeks for hemodynamic function, myocardial structure, antioxidant agents and oxidative stress. Banding of the ascending aorta in guinea pigs resulted in hyperfunctional hypertrophy at 10 weeks, which was followed by congestive heart failure at 20 weeks. Hypertrophied hearts showed decreased oxidative stress, as evidenced by a higher oxidation-reduction (redox) state and less lipid peroxidation, whereas the failure stage was characterized by increased oxidative stress. Supplementation of animals with timed-release vitamin E tablets resulted in an increased myocardial content of the vitamin, and the banded animals did not develop any signs of heart failure at 20 weeks. Hemodynamic function at 20 weeks in these vitamin E-treated animals was also better maintained. The myocardial reduced glutathione/oxidized glutathione ratio of vitamin E-treated animals at 20 weeks was higher and lipid peroxidation was less compared with the untreated animals. Ultrastructural abnormalities were significantly less in the vitamin E-treated hearts compared with the untreated failing hearts at 20 weeks. An improved myocardial redox state with vitamin E therapy, coupled with the modulation of the development of heart failure, may indicate a pathophysiologic role for increased oxidative stress in the pathogenesis of heart failure. This study suggests the potential therapeutic value of long-term antioxidant treatment in modulating or preventing the pathogenesis of heart failure.
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Ginseng is a highly valued herb in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the beneficial effects of ginseng and its constituents. The major active components of ginseng are ginsenosides, a diverse group of steroidal saponins, which demonstrate the ability to target a myriad of tissues, producing an array of pharmacological responses. However, many mechanisms of ginsenoside activity still remain unknown. Since ginsenosides and other constituents of ginseng produce effects that are different from one another, and a single ginsenoside initiates multiple actions in the same tissue, the overall pharmacology of ginseng is complex. The ability of ginsenosides to independently target multireceptor systems at the plasma membrane, as well as to activate intracellular steroid receptors, may explain some pharmacological effects. This commentary aims to review selected effects of ginseng and ginsenosides and describe their possible modes of action. Structural variability of ginsenosides, structural and functional relationship to steroids, and potential targets of action are discussed.
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The Smad signalling pathway is critical for transmitting transforming growth factor-beta (TGF-beta) superfamily signals from the cell surface to the nucleus. In the nucleus, Smads regulate transcriptional responses by recruiting co-activators and co-repressors to a wide array of DNA-binding partners. Thus, Smads function as transcriptional co-modulators to regulate TGFbeta-dependent gene expression.
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FAST as a Smad partner in Nodal pathwaysAn interaction of Smad proteins with a DNA-binding factor, resulting in tight binding of this complex to DNA, was first described for the Xenopus FAST-1 protein (Chen et al., 1996). FAST-1 is a member of the winged-helix family of DNA-binding proteins. It was identified by its ability to bind to the ARE, an enhancer responsive to an Activin-like factor—most likely, Nodal—in the Xenopus Mix.2 homeobox gene. FAST-1 is now known to mediate activation of an entire panel of homeobox genes in the specification of mesoderm (Watanabe and Whitman, 1999). A mammalian homolog (alternatively named FAST-1 or FAST-2) may mediate activation of the homeobox gene goosecoid following gastrulation (Labbé et al., 1998; Zhou et al., 1998) and the TGF-β family members lefty-2 and nodal during establishment of the left-side lateral plate mesoderm in response to an initial pulse of Nodal (Saijoh et al., 2000). Other Smad-dependent TGF-β or Activin responses do not involve FAST, suggesting that different DNA-binding partners may mediate these responses.Studies on Smads and FAST have revealed basic principles governing Smad interactions with DNA-binding cofactors (Chen et al., 1997; Liu et al., 1997; Yeo et al., 1999). FAST interacts with Smad2–Smad4 or Smad3–Smad4 complexes, but not with BMP-activated Smad complexes. A few subtype-specific residues in the α-helix 2 region of the Smad2/3 MH2 domain determine the specificity of this interaction (Figure (Figure3)3) (Chen et al., 1998). Both FAST and the associated Smads are required for efficient binding to target enhancers. The Smad4 MH1 domain is not required for high-affinity binding of Smad3–Smad4–FAST complexes to DNA, but is required when the complex contains Smad2, which lacks intrinsic DNA-binding activity. The FAST-binding sequence in the Mix.2, goosecoid, nodal and lefty2 enhancers is similar, but the proposed Smad-binding sequences may differ. Smads appear to contact an inverted SBE (GTCT) downstream of the FAST site in Mix.2, long GC-rich sequences (that may represent degenerate SBEs) upstream of the FAST site in goosecoid, and SBEs in various orientations in nodal and lefty2 (Labbé et al., 1998; Yeo et al., 1999; Saijoh et al., 2000). Both Smad4 and Smad2 (or Smad3) are required for efficient transactivation from the ARE, suggesting that both types of Smads jointly recruit coactivators regardless of their individual contributions to DNA binding. Via a motif homologous to the Smad interacting domain of FAST, the homeodomain proteins Mixer and Milk recruit Smad2–Smad4 to the activin-responsive enhancer of goosecoid during Xenopus development (Germain et al., 2000).
Article
The mechanisms responsible for the antidiabetic activity of both the white ginseng radix (Ginseng Radix Alba, GRA) and the rootlet (Ginseng Radix Palva, GRP) were investigated. After a four week oral administration, the fasting blood glucose levels in the GRA- and GRP-treated groups were lower when compared to the control group. To elucidate the hypoglycemic mechanism(s) of the ginseng radices, glucose absorption from the small intestine, hepatic hexokinase and glucose-6-phosphatase activities, in addition to PPAR-gamma expression in adipose tissue were examined. The results strongly suggest that GRA can improve hyperglycemia in KKAy mice, possibly by blocking intestinal glucose absorption and inhibiting hepatic glucose-6-phosphatase, and GRP through the upregulation of adipocytic PPAR-y protein expression as well as inhibiting intestinal glucose absorption.
Article
Honokiol and magnolol, two major phenolic constituents of Magnolia sp., have been known to exhibit antibacterial activities. However, until now, their antibacterial activity against Propionibacterium sp. has not been reported. To this end, the antibacterial activities of honokiol and magnolol were detected using the disk diffusion method and a two-fold serial dilution assay. Honokiol and magnolol showed strong antibacterial activities against both Propionibacterium acnes and Propionibacterium granulosum, which are acne-causing bacteria. The minimum inhibitory concentrations (MIC) of honokiol and magnolol was 3-4 microg/ml (11.3-15 microM) and 9 microg/ml (33.8 microM), respectively. In addition, the killing curve analysis showed that magnolol and honokiol killed P. acnes rapidly, with 10(5) organisms/ml eliminated within 10 min of treatment with either 45 microg (169.2 microM) of magnolol or 20 microg (75.2 microM) of honokiol per ml. The cytotoxic effect of honokiol and magnolol was determined by a colorimetric (3-(4,5-dimetyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay using two animal cell lines, human normal fibroblasts and HaCaT. In this experiment, magnolol exhibited lower cytotoxic effects than honokiol at the same concentration, but they showed similar cytotoxicity when triclosan was employed as an acne-mitigating agent. In addition, they reduced secretion of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) induced by P. acnes in THP-1 cells indicating the anti-inflammatory effects of them. When applied topically, neither phenolic compound induced any adverse reactions in a human skin primary irritation test. Therefore, based on these results, we suggest the possibility that magnolol and honokiol may be considered as attractive acne-mitigating candidates for topical application.
Article
Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation and extracellular matrix (ECM) synthesis in wound healing. The precise mechanism, however, in molecular and gene expression levels is still unclear. Using cDNA microarray technology, the alteration of gene expression profiles was determined for human dermal fibroblasts in vitro in the presence of asiaticoside (30 microg mL(-1)). Fifty-four genes, with known functions for cell proliferation, cell cycle progression and synthesis of ECM, were significantly upregulated in our 'genome-nest' expression profile at various time points. Furthermore, the mRNA levels and protein production of certain genes responsible for ECM synthesis (e.g. encoding type I and type III collagen proteins) were evaluated by Northern blot and radioimmunoassay, respectively. We found that there is a close correlation between the gene profile, mRNA and protein production in the response of the cells to asiaticoside stimulation. This information could be used for exploring the response of the target genes to asiaticoside in fibroblasts.
Article
Propionibacterium acnes, an anaerobic pathogen, plays an important role in the pathogenesis of acne and seems to initiate the inflammatory process by producing proinflammatory cytokines. In order to demonstrate the anti-inflammatory effects and action mechanisms of magnolol and honokiol, several methods were employed. Through DPPH and SOD activity assays, we found that although both magnolol and honokiol have antioxidant activities, honokiol has relatively stronger antioxidant activities than magnolol {[for DPPH assay, % of DPPH bleaching of magnolol and honokiol (500 μM magnolol: 19.8 %; 500 μM honokiol: 67.3 %)]; [for SOD assay, SOD activity (200 μM magnolol: 53.4 %; 200 μM honokiol: 64.3 %)]}. Moreover, the production of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) induced by P. acnes in THP-1 cells, a human monocytic cell line, was reduced by magnolol and honokiol {[for IL-8 (10 μM magnolol: 42.7 % inhibition; 10 μM honokiol: 51.4 % inhibition)]; [for TNF-α (10 μM magnolol: 20.3 % inhibition; 10 μM honokiol: 39.0 % inhibition)]}. Cyclooxygenase-2 (Cox-2) activity was also suppressed by them [(15 μM magnolol: 45.8 % inhibition), (15 μM honokiol: 66.3 % inhibition)]. Using a nuclear factor-κB (NF-κB) luciferase reporter assay system and Western analysis, we identified that magnolol and honokiol exert their anti-inflammatory effects by inhibiting the NF-κB element, which exists in Cox-2, IL-8, and TNF-α promoters [(15 μM magnolol: 44.8 % inhibition), (15 μM honokiol: 42.3 % inhibition)]. Of particular note is that magnolol and honokiol operate downstream of the MEKK-1 molecule. Together with their previously known antibacterial activity against P. acnes and based on these results, we suggest that magnolol and honokiol may be introduced as possible acne-mitigating agents. Abbreviations IL:interleukin LPS:lipopolysaccharide TNF-α:tumor necrosis factor-α NF-κB:nuclear factor-κB
Article
Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor of ligand-activated transcription factors, regulates the expression of key genes involved in lipid and glucose metabolism or adipocyte differentiation. Ligands for this receptor have emerged as potent insulin sensitizers used in the treatment of Type2 diabetes. Ginseng saponins or ginsenosides are reported to provide anti-diabetic activity as well as to modulate glucose metabolism, although the mechanism remains unclear. In this study, we examined the effect of ginsenosides on activation of PPARgamma and adipogenes in 3T3-L1. Using a GAL-4/PPARgamma transactivation assay, 20(S)-protopanaxatriol (PPT), one of the ginsenoside metabolites, was found to increase PPARgamma-transactivation activity dose-dependently with similar activity as troglitazone, a well-known PPARgamma agonist. PPT enhanced adipogenesis by increasing the expression of PPARgamma target genes such as aP2, LPL and PEPCK. Furthermore, PPT significantly increased expression of glucose transporter 4 (GLUT4). These results indicate that PPT can be developed as a PPARgamma agonist for the improvement of insulin resistance associated with diabetes.
Article
Skin aging appears to be principally related to a decrease in the levels of type I collagen, the primary component of the skin dermis. Asiaticoside, a saponin component isolated from Centella asiatica, has been shown to induce type I collagen synthesis in human dermal fibroblast cells. However, the mechanism underlying asiaticoside-induced type I collagen synthesis, especially at a molecular level, remains only partially understood. In this study, we have attempted to characterize the action mechanism of asiaticoside in type I collagen synthesis. Asiaticoside was determined to induce the phosphorylation of both Smad 2 and Smad 3. In addition, we detected the asiaticoside-induced binding of Smad 3 and Smad 4. In a consistent result, the nuclear translocation of the Smad 3 and Smad 4 complex was induced via treatment with asiaticoside, pointing to the involvement of asiaticoside in Smad signaling. In addition, SB431542, an inhibitor of the TGFβ receptor I (TβRI) kinase, which is known to be an activator of the Smad pathway, was not found to inhibit both Smad 2 phosphorylation and Type 1 collagen synthesis induced by asiaticoside. Therefore, our results show that asiaticoside can induce type I collagen synthesis via the activation of the TβRI kinase-independent Smad pathway. Abbreviations TGF:transforming growth factor Smad:sma- and Mad-related protein TβRI kinase:TGFβ receptor I kinase
Ginseng therapy in non-insulin-dependent diabetic patients Identification of a member of the MAPKKK family as a potential mediator of TGF-? signal transduc-tion
  • E A Sotaniemi
  • E Haapakoski
  • A Rautio
  • K Yamaguchi
  • K Shirakabe
  • H Shibuya
  • K Irie
  • I Oishi
  • N Ueno
  • T Taniguchi
  • E Nishida
  • K Matsumoto
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