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.
... 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.
... 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.
... 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.
... Achillea millefolium L Flavonoids, monoterpenes, and sesquiterpenes Skin inflammatory and wound healing [375][376][377][378][379] Aloe vera Acemannan (Fig. 11) Wound healing [380,381] Bletilla striata Triterpenoids and polysaccharides Drug delivery, wound dressing, and wound healing [382,383] Blumea balsamifera L-Borneol (Fig. 11) Dermatitis, eczema, skin bruises, and skin injury [384,385] Boswellia sacra Boswellic acids (Fig. 11) Improvement of blood circulation, pain treatment, and rheumatoid arthritis [386][387][388][389] Caesalpinia sappan Brazilin and Sappanchalcone (Fig. 11) Improvement of blood circulation, pain treatment, and oedema [390,391] Calendula officinalis Esculetin, and Quercetin-3-O-glucoside (Fig. 11) Burns, dermatitis, and wound healing [392][393][394] Celosia argentea Celosin I and Celosin II (Fig. 11) Skin sores and ulcers [395,396] Centella asiatica Asiaticoside and Madecassoside (Fig. 11) Wounds healing [397][398][399] Cinnamomum cassia Cinnamaldehyde (Fig. 5) Analgesia and improvement of blood circulation [399,400] Commiphora myrrha Furanoeudesma-1,3-diene and Terpene (Fig. 12) Gastrointestinal diseases, wounds, and pain [401][402][403][404] Curcuma longa Curcuminoids (Fig. 12) Digestive diseases, liver disorders, menstrual difficulties, pain disorders, sprains, and wounds [405,406] Entada phaseoloides Tannin (Fig. 12) Aging, atherosclerosis, cancer, diabetes, and neurodegenerative disorders [407,408] Ganoderma lucidum Ganoderma lucidum polysaccharide Cancer, diabetes, hepatitis, leukaemia, and ulcer [409][410][411][412][413] Ligusticum striatum Phthalide lactones, and alkaloids Antiatherosclerotic, antioxidant, neuroprotective, and vasorelaxant [414][415][416][417][418] Panax ginseng Ginsenosides (Fig. 12) Laser burn, excision wounds models in mice, cell migration, and wound healing assays [419][420][421][422][423][424] Polygonum cuspidatum Emodin, polydatin, and resveratrol ( Fig. 12) Hepatitis, hyperlipidemia. Jaundice, scald, skin burns, and suppurative dermatitis [425][426][427][428] Rheum officinale Emodin (Fig. 12) Chronic kidney disease, hepatitis, and wounds healing [429][430][431] Sanguisorba officinalis Polysaccharides, tannins, triterpenoid glycosides, and triterpenoids Burns, chronic intestinal infections, haemorrhoids, menorrhagia, and scalds [432][433][434] Sophora flavescens Kushenol, and sophoraflavanone B (Fig. 12) Asthma, burns, dysentery, eczema, fever, hematochezia, inflammatory Jaundice, oliguria, and vulvar swelling [435] Wedelia trilobata Kaurenoic acid (Fig. 12) and Luteolin (Fig. 5) Arthritic painful joints, rheumatism, and stubborn wounds [436,437] Zanthoxylum bungeanum Afzelin, hyperoside quercitrin, and rutin ( Fig. 12) Skin wrinkles [438,439] Page 27 of 45 Breijyeh and Karaman Future Journal of Pharmaceutical Sciences (2024) 10:68 grapefruit, grape, lemon, and EVs were also discovered in the xylem and phloem of woody plants, according to recent investigations [484,485]. ...
Article
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Background The study of plant-based medications, or phytomedicine, involves a wide spectrum of biological activi- ties. Due to the existence of secondary metabolites, herbal medicine has been used and practiced throughout history for the treatment of both acute and chronic conditions. Over the past century or so, numerous novel compounds with medicinal potential have been derived from plants. In the age of growing super infections and the emergence of resistant strains, natural medicines are inspiring optimism. Main body of the abstract The review discusses the role of herbal medicine as antibacterial agents and their use in wound care and management of wounds and the critical role of secondary metabolites of herbal plants in fight- ing bacterial infections. Some medicinal plants such as St. John’s wort (SJW) (Hypericum perforatum), Rosemary (Rosmarinus officinalis), Ginger (Zingiber officinale), and nopal cactus (Opuntia ficusindica (L.)) also possess wide range of biological activities and can give a synergistic effect if combined with antibiotics. In addition, natural biopolymers play an important role in the management of wounds as well as the physiological processes of the skin (hemostasis, inflammation, proliferation, and remodelling). Method A narrative review of papers relevant to the use of phytomedicine in treating infections was conducted by using electronic databases PubMed, CrossREF, and Google Scholar. Short conclusion Phytomedicine is one of the top options for the treatment of chronic illnesses for millions of peo- ple around the world. To learn about the bioactive components of medicinal plants, their medical benefits, and their synergistic or additive effects to enhance the action of medications, substantial new studies are still needed.
... Furthermore, the mechanisms we've delineated not only echo known signaling pathways but also emphasize the corroborated therapeutic potential. Notably, P. ginseng is recognized for enhancing Type I collagen synthesis via Smad signaling pathway activation, reflecting its contribution to tissue repair and anti-aging [45]. Similarly, the ginsenoside Rh1 has been observed to enhance the anti-inflammatory effects of dexamethasone, likely through the modulation of the NF-κB signaling pathway [46]. ...
Article
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Background Network pharmacology has emerged as a powerful tool to understand the therapeutic effects and mechanisms of natural products. However, there is a lack of comprehensive evaluations of network-based approaches for natural products on identifying therapeutic effects and key mechanisms. Purpose We systematically explore the capabilities of network-based approaches on natural products, using Panax ginseng as a case study. P. ginseng is a widely used herb with a variety of therapeutic benefits, but its active ingredients and mechanisms of action on chronic diseases are not yet fully understood. Methods Our study compiled and constructed a network focusing on P. ginseng by collecting and integrating data on ingredients, protein targets, and known indications. We then evaluated the performance of different network-based methods for summarizing known and unknown disease associations. The predicted results were validated in the hepatic stellate cell model. Results We find that our multiscale interaction-based approach achieved an AUROC of 0.697 and an AUPR of 0.026, which outperforms other network-based approaches. As a case study, we further tested the ability of multiscale interactome-based approaches to identify active ingredients and their plausible mechanisms for breast cancer and liver cirrhosis. We also validated the beneficial effects of unreported and top-predicted ingredients, in cases of liver cirrhosis and gastrointestinal neoplasms. Conclusion our study provides a promising framework to systematically explore the therapeutic effects and key mechanisms of natural products, and highlights the potential of network-based approaches in natural product research.
... The PPD-type ginsenosides include Rb1, Rb2, Rb3, Rc, Rd, F2, and Rg3, while the PPT-type ginsenosides include Re, Rg1, Rg2, Rg4, Rh1, and Rh4 [20]. Furthermore, single ginsenosides possess diverse beneficial biological activities that find use in cosmetology including increased collagen synthesis [21], antioxidant effects [22], anti-wrinkle effects [23], and the induction of hair growth [24]. As the major low-polarity PPT-type ginsenoside, Rg4 is one of the most effective steroidal saponins among these ginsenosides. ...
Article
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In cancer treatment, multi-target approach has paid attention to a reasonable strategy for the potential agents. We investigated whether (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) could exert an anticancer effect by dual-regulating VEGFR2 and PPARγ. MMPP showed modulating effects in TNBC type (MDA-MB-231 and MDA-MB-468) and luminal A type (MCF7) breast cancer cell lines. MMPP enhanced PPARγ transcriptional activity and inhibited VEGFR2 phosphorylation. MMPP-induced signaling by VEGFR2 and PPARγ ultimately triggered the downregulation of AKT activity. MMPP exhibited anticancer effects, as evidenced by growth inhibition, inducement of apoptosis, and suppression of migration and invasion. At the molecular level, MMPP activated pro-apoptotic proteins (caspase3, caspase8, caspase9, and bax), while inhibiting the anti-apoptotic proteins (bcl2). Additionally, MMPP inhibited the mRNA expressions of EMT-promoting transcription factors. Therefore, our findings showed molecular mechanisms of MMPP by regulating VEGFR2 and PPARγ, and suggested that MMPP has potential to treat breast cancer.
... It was also found that saponins increased collagen synthesis through phosphorylation of Smad 2 protein. Hence, saponins promote the regeneration of matrix at the wound site [37]. ...
Chapter
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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.
... 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.
... 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
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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.
... 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
Full-text available
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.
... 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.
... 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.
... 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. ...
Article
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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.
... [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. ...
Article
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.
... 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.
... 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. ...
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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.
... 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). ...
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Background: Mountain ginseng (Panax ginseng Meyer), which belongs to Araliaceae family, grows naturally in the mountains of Korea. It is highly valued owing to its enhanced pharmacology effects such as immunostimulating, antioxidant, anti-cancer and antiaging activity. An alternative to accessing the sparse mountain ginseng therapy benefits is by tissue-cultured roots of mountain ginseng. The aim of this study is to evaluate the effect of water extract of cultured roots of mountain ginseng (CRMG) and specifically its major compound ginsenoside Re (Re) on melanin synthesis in α- MSH-stimulated mouse melanoma B16BL6 cells (B16). Materials and Methods: Cell cytotoxicity was evaluated trough a comparative study using normal human dermal fibroblast (HDF) and B16. Then, α-MSH-stimulated B16 cells were analyzed, using melanin and tyrosinase activity assay. Tyrosinase gene expression was evaluated trough reverse transcription polymerase chain reaction analysis and quantitative PCR analysis. Finally, an in silico docking study was performed. Results: The study demonstrated that CRMG and Re were non-toxic compounds and significantly reduced tyrosinase activity and melanin content in B16 cells. Re decreased the mRNA expression of tyrosinase and other melanin synthesisrelated genes in B16 cells. In addition, in silico docking studies showed that Re had stronger interaction with tyrosinase compared to control drug arbutin due to its higher binding affinity. Conclusion: Taken together, our results suggest that CRMG and Re possess potential anti-melanogenic activities and may be used as antimelanogenic cosmeceutical agents.
... 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]. ...
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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.
... 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. ...
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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.
... 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. ...
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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 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.
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Intestinal inflammatory imbalance and immune dysfunction may lead to a spectrum of intestinal diseases, such as inflammatory bowel disease (IBD) and gastrointestinal tumors. As the king of herbs, ginseng has exerted a wide range of pharmacological effects in various diseases. Especially, it has been shown that ginseng and ginsenosides have strong immunomodulatory and anti-inflammatory abilities in intestinal system. In this review, we summarized how ginseng and various extracts influence intestinal inflammation and immune function, including regulating the immune balance, modulating the expression of inflammatory mediators and cytokines, promoting intestinal mucosal wound healing, preventing colitis-associated colorectal cancer, recovering gut microbiota and metabolism imbalance, alleviating antibiotic-induced diarrhea, and relieving the symptoms of irritable bowel syndrome. In addition, the specific experimental methods and key control mechanisms are also briefly described.
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The global aging population is expanding at an increasingly rapid pace, with approximately one-fourth of the world’s population expected to be composed of elderly individuals by 2050. Aging skin is one of the major characteristics expressed in the elderly. The study comprehensively utilizes both cell and animal experiments to confirm the skin anti-aging effects of Poria cocos (P. cocos), which is one of the most important traditional Chinese medicines classified as tonic Chinese medicine, commonly used to treat physical weakness and aging-associated diseases. We demonstrate in this study that P. cocos lanostane triterpenoids extract (Lipucan®) ameliorates aging skin and promotes collagen accumulation and hyaluronic acid production in galactose-induced aging rats. Purified lanostane triterpenoids were initially identified as active components in P. cocos, which significantly increased collagen and hyaluronic acid levels in cultured human skin cells.
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Skin ageing is a natural human "ageing mosaic" that manifests over time and takes different trajectories. The biological process of skin ageing is intricate and is impacted by both endogenous (intrinsic) and exogenous (extrinsic) elements. Several anti-aging formulas have been created in recent years due to the fact that skin health and attractiveness are thought to be among the primary aspects indicating general "well-being" and the sense of "health" in humans. The intention of this work is to formulate and evaluate antiaging cream using grape powder. Loaded with antioxidants for healthy, glowing skin, grapes have also found their way into the cosmetic industry. Grape extract inhibits the action of enzymes such as hyaluronidase, collagenase and elastase which are responsible for premature aging of the skin and also provides UV protection. The cream was formulated with aloe vera gel, neem oil, grape powder, olive oil of different concentrations. The evaluation of the formulations was done on different parameters like pH, spreadability, stability, irritancy, viscosity, total antioxidants capacity, etc. According to this research, the extracts and cream base's composition is stable and safe, and it could even have a synergistic effect. It can be concluded that herbal creams with antioxidant properties can be used as a barrier to preserve the skin and delay the ageing process. These creams have no adverse effects.
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In this study, we isolated Weizmannia ginsengihumi LGHNH (KCTC 14462BP) from 30-year-old wild Panax ginseng C.A. Meyer and elucidated the characteristics of the isolated bacterium and its industrial potential as an anti-aging material. W. ginsengihumi LGHNH was investigated to produce indole-3-acetic acid (IAA), a plant growth-promoting hormone (1.38 μg/ml to 2.22 μg/ml). We also confirmed the existence of bioconversion activity via the comparison of the ginsenoside content before and after fermentation. As for the converted minor ginsenoside, Rg2(R), Rg4, Rg6, Rg3(S), Rg3(R), Rk1, Rg5, Rh1(R), Rk3 and Rh4 are known to have high bioavailability and various skin effects. We measured mitochondrial membrane potential and ATP biosynthesis to elucidate W. ginsengihumi LGHNH cultured product (WCP) as an anti-aging material. As a result, the mitochondrial membrane potential in HaCaT cells with UVB decreased to 39.3% compared to the unirradiated group, but was recovered to 57.3% and 58.1% by 0.001% (v/v) and 0.01% (v/v) WCP, respectively. In addition, we measured mitochondrial ATP biosynthesis. It decreased to 94.3% compared to the unirradiated group with UVB, but was recovered to 105.3% and 105.7% by 0.001% (v/v) and 0.01% (v/v) WCP.
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Collagen loss in the skin dermis is a major cause of age-related changes to the skin. Natural phytochemical substances are desirable for the prevention of skin aging and the formation of wrinkles. Ipomoea pes-caprae (IPC) has been utilized for nutritional and therapeutic purposes, and its extract contains collagenase inhibitory activity while causing no cytotoxicity. The purpose of this study was to examine the impact of IPC extracts on cell proliferation and collagen production in human fibroblasts (CCD-986sk cells). IPC leaves were macerated in 70% and 95% ethanol and the chemical composition of the resulting extracts (IPC70 and IPC95) were determined using high performance liquid chromatography (HPLC). The bioactivity of IPC extracts was examined in CCD-986sk cells, including antioxidant capacity, inhibition of collagenase, effects on cell proliferation and collagen production, as well as wound healing using an in vitro scratch test. Changes in expression of collagen type I (COL1A1), tumor growth factor beta 1 (TGFB1), and beta-fibroblast growth factor (FGF2) genes were also evaluated. The antioxidant and collagenase inhibitory properties of IPC extracts were associated with 3,5-di-caffeoylquinic acid, chlorogenic acid, and ferulic acid. IPC extracts at noncytotoxic concentrations significantly increased cell proliferation, collagen production, and wound healing. These effects appear linked to the upregulation of COL1A1, TGFB1, and FGF2 genes. The bioactivity of the IPC70 extract was greater than that for IPC95. This is useful in cosmeceutical applications for human skin aging. Our findings indicate that IPC extracts have the potential for use in skin anti-aging cosmeceutical preparations.
Chapter
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.
Book
Ginseng is the most well-known Chinese medicine, as well as one of the most commonly used herbal medicines having a wide range of medical and pharmacological uses. The botanical description and complexity of "Ginseng" species, phytochemistry, traditional and biotechnological production systems, traditional usage, current applications, and future directions for the development of ginseng compounds as effective medicinal agents are covered in this book.
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Management of chronic wound has an immense impact on social and economic conditions in the world. Healthcare costs, aging population, physical trauma, and comorbidities of diabetes and obesity seem to be the major factors of this increasing incidence of chronic wounds. Conditions of chronic wound could not restore functional epidermis; thus, delaying the closure of the wound opening in an expected manner. Failures in restoration of skin integrity delay healing due to changes in skin pathology, such as chronic ulceration or nonhealing. The role of different traditional medicines has been explored for use in the healing of cutaneous wounds, where several phytochemicals, such as flavonoids, alkaloids, phenolic acids, tannins are known to provide potential wound healing properties. However, the delivery of plant-based therapeutics could be improved by the novel platform of nanotechnology. Thus, the objectives of novel delivery strategies of principal bioactive from plant sources are to accelerate the wound healing process, avoid wound complications and enhance patient compliance. Therefore, the opportunities of nanotechnology-based drug delivery of natural wound healing therapeutics have been included in the present discussion with special emphasis on nanofibers, vesicular structures, nanoparticles, nanoemulsion, and nanogels.
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Background. Wound healing is a complex process of replacing devitalized cellular structures and tissues with healthy cells and tissue. Nanotechnology has been increasingly proposed as a novel platform to treat wounds and skin regeneration. The aim of this study was to evaluate the antibacterial, antioxidant, cytotoxic, and cutaneous wound healing activities of phytosynthesized Au NPs using Abelmoschus esculentus (okra) and synthesized Au NPs by using the citrate synthesis method. The Ok Au NPs were characterized using various techniques like UV-Vis absorption spectroscopy, FTIR, X-ray diffraction (XRD), and transmission electron microscopy (TEM). Cutaneous wounds were created on 30 rats and randomized into three groups: untreated and two groups treated with Ch Au NPs and Ok Au NPs. The treatment was carried out daily for 12 days. A peak characterized the Ok Au NPs at 538 nm in the UV-Vis spectrum. Based on the results of FTIR spectroscopy, various functional oxygenated groups such as hydroxyl, carboxyl, and nitrogenous groups were observed. XRD confirmed the crystalline nature of the nanoparticles. TEM images of Ok Au NPs showed a spherical shape and size range of 75 nm. DPPH test showed similar antioxidant potentials for Au NPs. The Au NPs showed cell viability in a dose-dependent manner, and this technique was found to be nontoxic. Agar well diffusion, which is the method to determine antibacterial characteristics of Au NPs, showed a significant beneficial effect against a variety of bacterial species. In addition, histopathological results showed that Au NPs could accelerate wound closure. Therefore, Au NPs could be suitable for wound healing applications.
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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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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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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.
Chapter
The concept of beauty and cosmetics is as ancient as mankind and civilization where everyone is obsessed with looking charming and young. A cosmetic is defined by the US Food and Drug Administration as the preparation used for cleaning, perfuming, and improving the appearance of the human body. Plants have emerged as the best source of cosmetic ingredients that meet the characteristics of efficiency and safety, thus increasingly replacing synthetic ingredients. Accordingly, there is a growing demand for naturally based cosmetics worldwide and an ever-growing interest in understanding their molecular and mechanistic aspects. In this chapter, we discussed the role of plants in cosmetology and skin care and how the various chemical structures exert biological activities on the skin of human.
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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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Objective Fusarium oxysporum is a common pathogenic fungus in ginseng cultivation. Both pathogens and antagonistic fungi have been reported to induce plant resistance responses, thereby promoting the accumulation of secondary metabolites. The purpose of this experiment is to compare the advantages of one of the two fungi, in order to screen out more effective elicitors. The mechanism of fungal elicitor-induced plant resistance response is supplemented. Methods A gradient dilution and the dural culture were carried out to screen strains. The test strain was identified by morphology and 18s rDNA. The effect of different concentrations (0, 50, 100, 200, 400 mg/L) of Penicillium sp. YJM-2013 and F. oxysporum on fresh weight and ginsenosides accumulation were tested. Signal molecules transduction, expression of transcription factors and functional genes were investigated to study the induction mechanism of fungal elicitors. Results Antagonistic fungi of F. oxysporum was identified as Penicillium sp. YJM-2013, which reduced root biomass. The total ginsenosides content of Panax ginseng adventitious roots reached the maximum (48.95 ± 0.97 mg/g) treated with Penicillium sp. YJM-2013 at 200 mg/L, higher than control by 2.59-fold, in which protopanoxadiol-type ginsenosides (PPD) were increased by 4.57 times. Moreover, Penicillium sp. YJM-2013 activated defense signaling molecules, up-regulated the expression of PgWRKY 1, 2, 3, 5, 7, 9 and functional genes in ginsenosides synthesis. Conclusion Compared with the pathogenic fungi F. oxysporum, antagonistic fungi Penicillium sp. YJM-2013 was more conducive to the accumulation of ginsenosides in P. ginseng adventitious roots. Penicillium sp. YJM-2013 promoted the accumulation of ginsenosides by intensifying the generation of signal molecules, activating the expression of transcription factors and functional genes.
Article
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.
Article
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.
Chapter
Cosmeceuticals, defined for the purpose of this chapter as highly efficacious functional ingredients or final products, are becoming more commonplace in the skincare market globally, in particular within the anti-aging category. Many of these ingredients or products aim to improve the clinical features of photoaged skin such as wrinkles and pigmentation through targeting the underlying causes of these clinical features, with increasingly comprehensive efficacy and mechanistic data to support these claims. In this chapter, we review the main classes of cosmeceuticals, the biological endpoints they target together with the evidence that supports their clinical efficacy.
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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 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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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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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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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, 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 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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The mitogen-activated protein kinase (MAPK) pathway is a conserved eukaryotic signaling module that converts receptor signals into various outputs. MAPK is activated through phosphorylation by MAPK kinase (MAPKK), which is first activated by MAPKK kinase (MAPKKK). A genetic selection based on a MAPK pathway in yeast was used to identify a mouse protein kinase (TAK1) distinct from other members of the MAPKKK family. TAK1 was shown to participate in regulation of transcription by transforming growth factor-β (TGF-β). Furthermore, kinase activity of TAK1 was stimulated in response to TGF-β and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-β superfamily members.
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Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes. It has recently been reported that ceramide activates stress-activated protein kinase (SAPK, also known as c-Jun NH2-terminal kinase JNK), a subfamily member of mitogen-activated protein kinase superfamily molecules and that the ceramide/SAPK/JNK signaling pathway is required for stress-induced apoptosis. However, the molecular mechanism by which ceramide induces SAPK/JNK activation is unknown. Here we show that TAK1, a member of the mitogen-activated protein kinase kinase kinase family, is activated by treatment of cells with agents and stresses that induce an increase in ceramide. Ceramide itself stimulated the kinase activity of TAK1. Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. Furthermore, expression of a kinase-negative form of TAK1 interfered with the activation of SAPK/JNK induced by ceramide. These results indicate that TAK1 may function as a mediator of ceramide signaling to SAPK/JNK activation.
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Smad proteins are essential components of the intracellular signaling pathways utilized by members of the transforming growth factor-beta (TGF-beta) superfamily of growth factors. Certain Smad proteins (e.g. Smad1, -2, and -3) can act as regulated transcriptional activators, a process that involves phosphorylation of these proteins by activated TGF-beta superfamily receptors. We demonstrate that the intracellular kinase mitogen-activated protein kinase kinase kinase-1 (MEKK-1), an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase pathway, can participate in Smad2-dependent transcriptional events in cultured endothelial cells. A constitutively active form of MEKK-1 but not mitogen-activated protein kinase kinase-1 (MEK-1) or TGF-beta-activated kinase-1, two distinct intracellular kinases, can specifically activate a Gal4-Smad2 fusion protein, and this effect correlates with an increase in the phosphorylation state of the Smad2 protein. These effects do not require the presence of the C-terminal SSXS motif of Smad2 that is the site of TGF-beta type 1 receptor-mediated phosphorylation. Activation of Smad2 by active MEKK-1 results in enhanced Smad2-Smad4 interactions, nuclear localization of Smad2 and Smad4, and the stimulation of Smad protein-transcriptional coactivator interactions in endothelial cells. Overexpression of Smad7 can inhibit the MEKK-1-mediated stimulation of Smad2 transcriptional activity. A physiological level of fluid shear stress, a known activator of endogenous MEKK-1 activity in endothelial cells, can stimulate Smad2-mediated transcriptional activity. These data demonstrate a novel mechanism for activation of Smad protein-mediated signaling in endothelial cells and suggest that Smad2 may act as an integrator of diverse stimuli in these cells.
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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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Oxidative stress has been implicated in the pathophysiology of myocardial failure. We tested the hypothesis that oxidative stress can regulate extracellular matrix in cardiac fibroblasts. Neonatal and adult rat cardiac fibroblasts in vitro were exposed to H(2)O(2) (0.05-5 microM) or the superoxide-generating system xanthine (500 microM) plus xanthine oxidase (0.001-0.1 mU/ml) (XXO) for 24 h. In-gel zymography demonstrated that H(2)O(2) and XXO each increased gelatinase activity corresponding to matrix metalloproteinases (MMP) MMP-13, MMP-2, and MMP-9. H(2)O(2) and XXO decreased collagen synthesis (collagenase-sensitive [(3)H]proline incorporation) without affecting total protein synthesis ([(3)H]leucine incorporation). H(2)O(2) and XXO decreased the expression of procollagen alpha(1)(I), alpha(2)(I), and alpha(1)(III) mRNA but increased the expression of fibronectin mRNA, suggesting a selective transcriptional effect on collagen synthesis. H(2)O(2), but not XXO, also decreased the expression of nonfibrillar procollagen alpha(1)(IV) and alpha(2)(IV) mRNA. To determine the role of endogenous antioxidant systems, cells were treated with the superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DDC, 100 microM) to increase intracellular superoxide or with the glucose-6-phosphate dehydrogenase inhibitor dehydroisoandrosterone 3-acetate (DHEA; 10 microM) to increase intracellular H(2)O(2). DDC and DHEA decreased collagen synthesis and increased MMP activity, and both effects were inhibited by an SOD/catalase mimetic. Thus increased oxidative stress activates MMPs and decreases fibrillar collagen synthesis in cardiac fibroblasts. Oxidative stress may play a role in the pathogenesis of myocardial remodeling by regulating the quantity and quality of extracellular matrix.
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Exposure of renal mesangial cells to sphingosine 1-phosphate (S1P) leads to a rapid and transient activation of the mitogen- and stress-activated protein kinases but also the protein kinase B. Here, we show that S1P also induces phosphorylation of Smad proteins, which are members of the transforming growth factor-beta (TGF-beta) signaling device. However, Smad phosphorylation occurred more slowly with a maximal effect after 20-30 min of S1P stimulation when compared with the rapid activation of the MAPKs. Interestingly, Smad phosphorylation is increased by pertussis toxin, which is in contrast to the complete inhibition of S1P-induced MAPK phosphorylation by pertussis toxin. TGF-beta is a potent anti-inflammatory cytokine, which in mesangial cells attenuates the expression of (i) inducible nitricoxide synthase (iNOS) caused by interleukin (IL)-1beta, (ii) secreted phospholipase A(2) (sPLA(2)), and (iii) matrix metalloproteinase-9 (MMP-9). These gene products are also down-regulated by S1P in a concentration-dependent manner. Furthermore, the expression of connective tissue growth factor is enhanced by both TGF-beta(2) and S1P. These effects of S1P are not mediated by the MAPK cascade as neither pertussis toxin nor the MAPK cascade inhibitor U0126 are able to reverse this inhibition. Overexpression of the inhibitory Smad-7 or down-regulation of co-Smad-4 lead to a reversal of the blocking effect of S1P on IL-1beta-induced NO release. Moreover, down-regulating the TGF-beta receptor type II by the siRNA technique or antagonizing the S1P(3) receptor subtype with suramin abrogates S1P-stimulated Smad phosphorylation. In summary, our data show that S1P trans-activates the TGF-beta receptor and triggers activation of Smads followed by activation of connective tissue growth factor gene transcription and inhibition of IL-1beta-induced expression of iNOS, sPLA(2), and MMP-9.
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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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Peroxisome proliferator-activated receptor γ (PPARγ), 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 PPARγ and adipogenes in 3T3-L1. Using a GAL-4/PPARγ transactivation assay, 20(S)-protopanaxatriol (PPT), one of the ginsenoside metabolites, was found to increase PPARγ-transactivation activity dose-dependently with similar activity as troglitazone, a well-known PPARγ agonist. PPT enhanced adipogenesis by increasing the expression of PPARγ 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 PPARγ agonist for the improvement of insulin resistance associated with diabetes.
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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 tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
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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.
Article
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.
Article
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.
Article
A number of pathogenic and proinflammatory stimuli, and the transforming growth factor-beta (TGF-beta) exert opposing activities in cellular and immune responses. Here we show that the RelA subunit of nuclear factor kappaB (NF-kappaB/RelA) is necessary for the inhibition of TGF-beta-induced phosphorylation, nuclear translocation, and DNA binding of SMAD signaling complexes by tumor necrosis factor-alpha (TNF-alpha). The antagonism is mediated through up-regulation of Smad7 synthesis and induction of stable associations between ligand-activated TGF-beta receptors and inhibitory Smad7. Down-regulation of endogenous Smad7 by expression of antisense mRNA releases TGF-beta/SMAD-induced transcriptional responses from suppression by cytokine-activated NF-kappaB/RelA. Following stimulation with bacterial lipopolysaccharide (LPS), or the proinflammatory cytokines TNF-alpha and interleukin-1beta (IL-1beta, NF-kappaB/RelA induces Smad7 synthesis through activation of Smad7 gene transcription. These results suggest a mechanism of suppression of TGF-beta/SMAD signaling by opposing stimuli mediated through the activation of inhibitory Smad7 by NF-kappaB/RelA.
Article
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.
Article
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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