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Abstract

Subclinical, chronic tissue inflammation involving the generation of cytokines (e.g., interleukin-6 and tumor necrosis factor-alpha) might contribute to the cutaneous aging process. This study aims to screen for an active ingredient with anti-inflammatory (i.e., reduction of interleukin-6 and tumor necrosis factor-alpha) and matrix-stimulating efficacy which improves the clinical signs of skin aging in vivo. In vitro studies with pure Arctiin were performed investigating the inhibition of cytokine induction and stimulation of collagen neo-synthesis. In vivo home-in-use studies using an Arctium lappa fruit extract-containing formulation were carried out to determine procollagen and hyaluronan synthesis, hyaluronan synthase-2 gene expression, and reduction of wrinkle volume after treatment. In vitro studies on human dermal fibroblasts and monocyte-derived dendritic cells supplemented with pure Arctiin showed relative to untreated control cells a stimulation of collagen synthesis and a decrease in interleukin-6 and tumor necrosis factor-alpha concentration, respectively. In addition, topical in vivo application of an A. lappa fruit extract-containing formulation for 12 weeks significantly stimulated procollagen synthesis and increased hyaluronan synthase-2 expression as well as hyaluronan levels compared to vehicle-treated control areas. Similarly, after a 4-week treatment with an A. lappa fruit extract-containing formulation, wrinkle volume in the crow's feet area was significantly reduced as compared to treatment with the vehicle. Our data show that topical treatment with a natural A. lappa fruit extract significantly improves the metabolism of the dermal extracellular matrix and leads to a visible wrinkle reduction in vivo. In conclusion, A. lappa fruit extract represents a targeted means to regenerate dermal structures and, thus, offers an effective treatment option for mature skin.

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... Jednocześnie ekstrakt z korzenia łopianu wpływa na adhezję komórek oraz pośrednio wpływa na biosyntezę siarczanu chondrotoiny co w efekcie może wspomóc proces gojenia się ran i poprawiać ogólny stan skóry [21]. Dzięki zawartości arktyiny o udo­ wodnionym działaniu przeciwzapalnym (obniżenie IL­6 i TNF­α) oraz zdolności do stymulacji neosyntezy kolagenu [22] a także arktygeniny, która powoduje inhibicję proliferacji limfocytów T i obniża ekspresję genów dla IL­2, interferonu gamma (IFN­γ) i czynnika jądrowego aktywowanych komórek T (NFAT) [23] surowce z korzenia mogą być cennym składnikiem produktów do pielęgnacji skóry suchej, skłonnej do podrażnień oraz produktów redukujących zmarszczki. Oprócz polifenoli w korzeniu obecne są fruk­ tany, które nie tylko są materiałem energetycznym ale również chronią roślinę przed deficytem wody (suszą), zbyt niską temperaturą oraz mogą pełnić funkcję osmoregulatorów. ...
... Przeciwzapalne działanie ekstraktów z owoców łopianu wynika z obec­ ności lignanów [27]. Głównym składnikiem owoców jest arktyina, o wspomnianym już działaniu prze­ ciwzapalnym i stymulującym syntezę neokolagenu [22,28]. Skuteczność przeciwstarzeniowa ekstraktu z owoców została potwierdzona w badaniach in vivo, które pokazały, że stosowanie balsamu z 1,2% ekstrak­ tu przez 12 tygodni spowodowało wzrost syntezy ko­ lagenu (1,3 raza) względem obszaru nietraktowanego kosmetykiem. ...
... Nastąpiła również widoczna redukcja widoczności zmarszczek. [22] Kolejnym lignanem obecnym w owocach jest trachelogenina, która jest antagonistą Ca 2+ i wykazuje potwierdzone badaniami działanie przeciw HIV. Wśród terpenoidów na uwagę zasługuje b­eudesmol o działaniu przeciwbakteryjnym i antyangiogennym. ...
Article
Łopian (Arctium lappa L.) to popularna roślina uważana za chwast w naszej strefie klimatycznej, podczas gdy w krajach Azji Wschodniej, łopian jest uprawiany jako warzywo (korzeń) i roślina lecznicza. W ostatnich latach, łopian był szeroko badany pod kątem składników aktywnych zawartych w korzeniu, liściach i nasionach, oraz ich właściwości fizykochemicznych i biochemicznych. Badania te potwierdzają przeciwrodnikowe, przeciwutleniające i antybakteryjne działanie surowców z łopianu. Z praktycznego punktu widzenia, nieobrany korzeń łopianu, który nie został poddany obróbce cieplnej najlepiej nadaje się do wytwarzania surowców kosmetycznych. Ekstrakty z łopianu charakteryzują się zdolnością hamowania wzrostu niektórych drobnoustrojów (m. in. endodontycznych) więc mogą one być stosowane w mydłach antybakteryjnych i pastach do zębów. Chociaż surowce kosmetyczne z korzeni, nasion, owoców lub liści łopianu wykazują właściwości istotne przy projektowaniu kosmetyków oraz są dostępne na rynku, nadal są rzadko stosowane w kosmetykach.
... 8 Plants like Arctium lappa increased dermal ECM metabolism, which in turn reduced the appearance of wrinkles in human skin in vivo while the healing properties of Calendula officinalis have led to its inclusion in a wide variety of polyherbal preparations. 11,12 There have been a lot of researches that have proposed different targets for these active chemicals that ultimately improve the healing process. These are mediated by numerous cascades, which include mitogenic pathways, 13 extracellular matrix synthesis routes, 14 free radical scavenging pathways, 6 atherosclerosis pathways, 15 and anti-inflammatory mechanisms. ...
... 45 Several different polyherbal formulations have been discovered to possess extremely excellent antioxidant, antibacterial and anti-inflammatory effects. 6,[9][10][11][12]16 These findings were published in a number of different academic journals. In separate investigations, numerous plant extracts have been revealed to independently possess beneficial antioxidant and anti-inflammatory properties. ...
... It also significantly increased serum total antioxidants capacity (P < 0.001) and activities of superoxide dismutase (P = 0.009) thus improving the inflammatory status and oxidative stress in patients with knee osteoarthritis [30]. Knott et al. (2008) published results of an In-vitro and In-vivo study on anti-wrinkle properties of Articum Lappa extract. In-vitro study with pure Arctiin was conducted on human dermal fibroblasts and monocyte-derived dendritic cells in laboratory setting. ...
... In the In-vivo study, topical application of an Articum Lappa fruit extract-containing formulation was used in home setting for 12 weeks. The results of this study revealed that Articum Lappa fruit extracts stimulated procollagen and hyaluronan synthesis, increased hyaluronan synthase-2 gene expression, and resulted in reduction of wrinkle volume after treatment compared to vehicle-treated control areas [31]. ...
Article
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Arctium lappa commonly called Burdock has been used in Western folk medicine and traditional Chinese medicine for thousands of years with excellent results in skin diseases like eczema, psoriasis, and acne. It a biannual plant that belongs to Asteraceae family and is native to temperate and tropical regions of Asia including Iraq, Iran, India, and Nepal. This review was conducted to summarize the available scientific information obtained from literature, medical databases, laboratory studies and human clinical studies on Arctium Lappa. Its hypoglycemic property is attributed to total lignans. Two lignans extracted from this plant namely-Arctigenin and Lappaol F have anti-cancer properties. Arctigenin also has anti-hypertensive and anti-ulcer properties. The anti-oxidant property is attributed chlorogenic acid and caffeic acid. The root extracts of this plant are hepato-protective and help in collagen neo-synthesis leading to reduction in wrinkle formation in mature skin. The homoeopathic preparations of Articum Lappa have been pharmacologically proven beneficial for acne.
... Scientific analyses demonstrate Arctium lappa has antioxidant [44], anti-inflammatory [45], antidiabetic [46], antimicrobial [47], antiviral [48], anticancer [49], and hepatoprotective [50] properties. e root extract of Arctium lappa has been shown to significantly improve dermal ECM metabolism, affecting glycosaminoglycan turnover and reducing visible wrinkles in human skin in vivo [51]. Arctium lappa is also reported to regulate cell adhesion and gene expression in canine dermal fibroblasts, affecting the Wnt/ β-catenin signalling pathway, known to be a key regulator of wound healing [52]. ...
... Asteraceae Arctigenin [324] Arctiin [42] Caffeic acid [42] Chlorogenic acid [42] Diarctigenin [42] Inulin [42] Lappaol F [49] Tannin [42] Trachelogenin 4 [42] Leaves Whole root No extraction, whole leaves Aqueous Human burn wounds [53] Canine dermal fibroblast adhesion assay [52] Anticancer [49] Antidiabetic [46] Anti-inflammatory [45] Antimicrobial [47] Antiviral [48] Hepatoprotective [50] Radical scavenging [44] Acne vulgaris [43] Boils [42] Burns [53] Rashes [42] Sore throat [42] Wrinkles [51] Ointment [53] Not available ...
Article
Full-text available
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.
... Medicinal herbs, as lavander (Lavandula officinalis) essential oil (EO) (Alnamer et al., 2012;Koca Kutlu et al., 2013;Mori et al., 2016) or burdock (Arctium lappa) extracts (Knott et al., 2008;Sohn et al., 2011;Gilca et al., 2018) are considered alternative treatments in wound healing and skin affections because of their anti-inflammatory and cicatrising properties. The wound healing potential of lavender oil was demonstrated by acceleration of granulation and wound contraction through induction of transforming growth factor (TGF)-β in a rat model (Mori et al., 2016). ...
... Another research showed that wound closure progressed more rapidly with topical application of lavender oil associated with increased expression of platelet-derived growth factor (PDGF)-A and EGF (Koca Kutlu et al., 2013). Moreover, natural A. lappa fruit extract significantly improved the metabolism of dermal ECM and led to visible wrinkle reduction in vivo (Knott et al., 2008). The anti-allergic and anti-inflammatory effects of butanol extract from A. lappa were demonstrated by checking the release of b-hexosaminidase in activated RBL-2H3 MCs and the levels of IL-4 and IL-5 in primary splenocytes after treatment with concanavalin A Yang et al., 2016). ...
Article
Burns present major impacts worldwide which stimulate the search for therapeutic alternatives, and the herbal medicines with anti-inflammatory and healing properties are potential targets. In the present study, we evaluated topical treatments with Lavandula officinalis essential oil (EO) and Arctium lappa extract in a second degree burn model. Wistar rats were anesthetized and submitted to thermal burns. The lesions were treated 2x/day with a cream containing 0.5% of L. officinalis EO plus 10% of A. lappa extract. Healing process evolution was evaluated on days 3, 7, 14, 21 and 30 after burns. Macroscopical and histopathological analyses showed more discreet edema and better reepithelialization in herbal treated animals. Higher expression of epidermal growth factor receptor in all phases of wound healing and lower expression of matrix metalloproteinases 2 and 9 especially at remodeling stages were observed in treated animals. Phytotherapic treatment reduced levels of interleukin-1β and tumor necrosis factor-α in scar tissues after 30 days. Aspartate aminotransferase levels were also decreased in herbal-treated animals. Our data showed better healing in animals treated with L. officinalis EO in association with A. lappa extract, pointing these phytotherapics as strategies for skin burns treatment.
... The collagen synthesis in the human dermal fibroblast cells is upregulated with the use of Labisia pumila. The presence of phenolic acids and bioflavonoids in the herbal extract of Labisia pumila has shown the ability to safeguard the human skin from the ROS attack which is generated by the critical UVB exposure [30]. ...
Article
Full-text available
Herbal preparations have been used in medicines and cosmetics over the past few decades. As ultraviolet (UV) radiation can cause sunburns, wrinkles, dark spot, premature aging, and cancer so, it is essential to protect the skin from UV radiation and prevent from their side effects. Moreover, as skin is the most visible organ so it makes us more cautious to maintain a flawless, glowing, smooth healthy skin. Herbal products are already gaining attention in order to protect the skin from aging and sunburns with no serious side effects. Previous studies have stated that many herbal ingredients impart their photo-protective effects through the regulation of UV-induced skin inflammation, antioxidant effects and aging. Additionally, natural components can inhibit free radical formation and neutralize reactive oxygen species and enhance skin protection from UV rays. Therefore, traditional use of herbs in medication or beautification is the basis for researches and making new trends in cosmetics by providing effective and cost-efficient skin care products which would be of great benefit to the society. This review focuses on several active constituents responsible for photo protection, types of UV radiations, damaging effects of UV radiation, and study of different active constituents present in various herbal plants responsible for UV protecting effect.
... Geraniol is a natural acyclic monoterpene alcohol found in the essential oils of lemon grass, palmarosa, citronella, and other plants [28] . It is used in cosmetics, shampoos, and other non-cosmetic products [29] . ...
Article
Full-text available
The aim of the study was to evaluate the effects of essential oil from Cymbopogon martinii (CMEO) on lipopolysaccharide (LPS)-stimulated human fibroblast cells. The fibroblasts were cultured using Iscove's medium and stimulated by LPS (1μg/mL). The cytotoxicity of CMEO was evaluated by MTT and collagen concentration by Sirius red. Collagenase activity, hyaluronic acid, and the concentrations of IL-1β; IL-6; MCP-1, and MIP-1-α were evaluated by ELISA. The effect of CMEO on the mRNA levels and the secretion of MMP-1; MMP-2; and MMP-9 enzymes in fibroblasts were evaluated by RT-qPCR and ELISA, respectively. CMEO was cytotoxic against fibroblasts, in which 10μg/mL inhibited 50% of cell viability. When treated with CMEO, the fibroblasts produced more collagen and hyaluronic acid compared to control cells. When stimulated by LPS, fibroblasts exhibited higher production of IL-6, IL-1β, MCP-1, and MIP-1α compared to control cells. However, the treatment of fibroblasts with CMEO reduces cytokines secretion and enzyme expression. In summary, CMEO reduced the secretion of cytokines and metalloproteinases, in addition to increasing the synthesis of extracellular matrix elements. The study demonstrated the effects of CMEO on the modulation of inflammatory mediators and decreasing the mRNA and secretion levels of metalloproteinases.
... Herbal product penetration is good via skin and provides pharmacological effect in topical delivery and that is why the pharmaceutical sectors will invest more in controlled clinical trials and use the HPLC, gas chromatography techniques to develop overall growth as the interest will increase in the future to develop these herbal products. Hence, Strict guidelines will develop to produce these herbal products as required for the overall development as is desirable [83]. ...
Article
Full-text available
Aim: In the recent advanced study, the popularity of herbal nano-formulation has gained around the whole world. As we know the reason behind it is that herbal products have comparatively lesser side effects than other synthetic products. Significance: These natural plant extracts have wide medicinal importance as they increase the overall bioavailability of products toward tissues. Key findings: This review provides the use of different herbal nano-formulations, their safety considerations, and the challenges being faced. It also highlights the various Clinical Trials and Patents that are published for skin disorders. Conclusion: The present review describes how the rise of herbal products has made wider interest in transdermal formulations and improve the overall productivity by preventing various skin disorders.
... Plants like Aloe vera contain many natural bioactive compounds like anthraquinones, saponins, and pyrocatechol making it a potent antimicrobial agent [64]. Arctium lappa was found to have elevated dermal ECM metabolism reducing wrinkles in human skin in vivo [65]. Formulations of Astragalus propinquus and Rehmannia glutinosa roots are widely used in diabetic wound healing [66]. ...
Article
Full-text available
Background: The disruptions in skin integrity contribute to its disorientation, and tissue annihilations result in acute or chronic wound formation. Polyherbal formulations are widely used in traditional systems of mecdicine like ayurveda for wound healing. The combination of these traditional therapies with clinical therapies has helped in the development of various wound-healing products. Method: In this systematic review, the therapeutic potency of several polyherbal formulations from different medicinal floras is summed together in response to their impact on wound healing. The literature search was performed on Pubmed, Scopus, and ScienceDirect databases between 2010-2020. PRISMA methodology was applied to extract relevant information about polyherbal formulations. Result: A total of 54 articles were selected under all themes for the data extraction as per the PRISMA guidelines. These 54 articles have high-quality scores ≥3. Forty-three records were used for the narrative analysis, while nine records were used for the critical analysis in the narrative review. Further, theme-wise key data sets were screened from the selected literature and summarized in a tabular form. Bibliometric analysis of the Scopus database has also drawn attention to limited academic literature showcasing randomized clinical trials in the current subject. Most of these polyherbal formulations are tested in laboratory-scale studies, thus portraying further research options. Conclusion: Polyherbal formulations are effective in promoting the wound-healing process. They can stimulate a variety of physiological functions that accelerates the process of healing. These formulations merit further investigation in clinical trials, and production up scaling will aid in the creation of a new horizon of polyherbal wound healing products.
... Scientific analyses demonstrate Arctium lappa has antioxidant 90 , antiinflammatory 91 , antidiabetic 92 , antimicrobial 93 , antiviral 94 , anticancer 95 , and hepatoprotective 96 properties. The root extract of Arctium lappa has been shown to significantly improve dermal ECM metabolism, affecting glycosaminoglycan turnover and reducing visible wrinkles in human skin in vivo 97 . Arctium lappa is also reported to regulate cell adhesion and gene expression in canine dermal fibroblasts, affecting the Wnt/β-catenin signalling pathway, known to be a key regulator of wound healing 98 . ...
Article
Wound healing is the process by which skin repairs itself. Wound healing can be divided into 4 phases: haemostasis, inflammation, proliferation, and remodelling. In humans, keratinocytes re-form a functional epidermis (re-epithelialization) 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 non-healing, hypertrophic scarring and chronic ulceration. Various plant products have been used in the treatment of wounds over the years. Recognizing the important role of traditional plants, we have undertaken an extensivesurvey of literature reporting the use of medicinal plants for wounds. We describe the activeingredients, bioactivities, clinical uses of 8 medicinal plant species. Several species including curcuma longa, honey, Terminalia chebula, Aloe vera, Centella asiatica, Arctium lappa, Commiphora myrrha, showing wound healing activities by their antiinflammatory and antioxidant mechanisms.
... [90] Furthermore, polysaccharides obtained from extracts of A. lappa regulated lipid metabolism in animal models for type 1 and 2 diabetes. [79,80] Different other properties have also been reported as effective in the treatment of several conditions including, acne, [130] anti-aging, [44,131] antiobesity, [89] skin whitening agent, [19] anti-constipation and intestinal flora regulation, [83] neuroprotective effect, [13,82] hepatoprotective, [7,78,86] anti-tuberculosis, [61] anti-ulcer, [24,56] and cachexia induced by cancer. [132] ...
Article
Arctium lappa L., also known as burdock, is an edible wild plant which has the ability to grow in distinct environments and is considered a weed in several parts of the world. This species has great value in the biological and medical fields with its major secondary components being phenolic compounds and terpenes, substances rich in desired biological activities as antioxidant, antimicrobial, antitumor and anti‐inflammatory. In addition, burdock leaves extracts have shown a modulatory effect on the complement system, which plays an important role in the development of inflammatory diseases, with an inhibitory effect on all complement pathways. Thus, natural products with those relevant activities are promising agents for healthcare applications. Therefore, the species A. lappa may represent an interesting asset for researching and developing new therapies for inflammatory afflictions.
... Traditionally it is used therapeutically throughout Europe, North America, and Asia to treat tonsillitis, throat discomfort, arthritis, rashes and other skin disorders, diuretic, diaphoretic, and blood purifier. In vivo, Arctium lappa root extract has been demonstrated to enhance dermal extracellular matrix metabolism, affect glycosaminoglycan turnover, and reduce apparent wrinkles in the human skin (Knott et al. 2008). In canine dermal fibroblasts, Arctium lappa has been shown to influence cell adhesion and gene expression by affecting the Wnt/β-catenin signaling pathway, which is known to be a major regulator of wound healing (Pomari et al. 2013). ...
... HA is mainly produced by hyaluronan synthases (HAS), for which roles have been reported in several biological functions including skin hydration and wound healing [8]. HAS are implicated in improving overall skin health by reducing signs of skin aging [9,10]. Aquaporin 3 (AQP3) which permeates both water and glycerol in epidermis is directly associated with the hydration of skin, with a relevant role in wound healing [11] and is often used as a marker of hydration in dermatological studies [12,13]. ...
Article
Full-text available
Skin aging is a biological process leading to visible skin alterations. The mechanism of action, clinical efficacy and tolerance of a novel anti-wrinkle technology were evaluated in two skin care products formulated for different skin types. Two single-arm monocentric, open-label observational clinical studies, which were 56 days long, evaluated a cream-gel (n = 30) and a cream (n = 33) on the face and neck. Morphometric analyses of five types of wrinkles were performed at 0, 7, 28 and 56 days. Structural changes in extracellular matrix (ECM) including collagen, elastin and hyaluronic acid (HA) were visualized and quantified by histochemical imaging after daily treatment of skin explants for 6 days. Protein and gene expression related to barrier and hydration were analyzed using ELISA and qRT-PCR, respectively, in a reconstituted human skin model treated daily for 48 h. A decrease in wrinkle dimensions was found in the majority of parameters after 28 days of treatment. Collagen, elastin, HA, procollagen type I, hyaluronan synthases, HAS2 and HAS3 were all stimulated. Based on significant and consistent changes in our investigations, we conclude that the underlying mechanism of action of the novel anti-wrinkle technology could be the remodeling of dermal ECM, and both the test formulations were efficacious and well tolerated.
... Plant species with higher UV demonstrated that their informants have more common knowledge of plant uses and frequently reported for the 2004; Zhang et al., 2020). Arctium lappa is an important plant for skin diseases management; its seeds are proceeds to deep-fry, ground, and take with water for the treatment of sore throat (Knott et al., 2008). Infectious and functional diseases have a relatively large impact and require timely medical treatment. ...
Article
Full-text available
Medicinal plants are the primary sources of healthcare among the people of developing countries in villages and local towns. Documenting and reporting the traditional knowledge of medicinal plants may contribute to pharmaceutical research development. For this reason, we present our findings on ethnomedicinal plants from Lingchuan County, Shanxi, China, an unexplored area rich in medicinal plant resources. Information of ethnomedicinal plants were collected through questionnaire/semi-structured interviews from 180 informants, including traditional healers. Field surveys were conducted in 53 villages of Lingchuan County from 2017 to 2018. Informed consent was obtained from each participant before conducting the interview process. Quantitative analysis was performed for each recorded species, such as Relative Frequency Citation (RFC), Use Value (UV), and Factor of Informant Consensus (FIC). Diseases were categorized into twelve groups. A total 138 species of medicinal plants were recorded, belonging to 123 genera of 58 families. Asteraceae was the dominant plant family with 19 species, followed by Rosaceae and Fabaceae. Herbs were dominant among plant life-forms with 96 species, followed by shrubs and trees (15 species each). Roots were the most commonly used plant parts with 58 species, followed by whole plants and fruits (28 species each). Most plant species were reported non-toxic (84, 60%), followed by unknown toxicity (35, 25%), poisonous, and less toxic (19, 14%). Quantitative analysis revealed that Forsythia suspensa was with higher (0.33) RFC value, and Scutellaria baicalensis was recorded with a higher (0.91) UV. Treated diseases were categorized in 12 groups and evaluated by their FIC value, in which gynecological diseases have higher (0.93) FIC value followed by urinary system diseases. Most medicinal plants are used to clear away heat and relieve the surface. The present study revealed that local people of Lingchuan County confidently use ethnomedicinal plants for their healthcare needs. The higher indices value of a plant species resulted from quantitative analysis warrants further investigation, which may possess valuable phytochemical compounds that may result in new drugs for treating various human disorders.
... [44][45][46][47][48][49][50][51] Randomized, placebo, as well as controlled clinical studies, have shown that burdock fructus mucus has a therapeutic effect on dryness, itching, and skin burns. 52,53 The data presented in the topic-related literature proves the prospects of the Arctium lappa L. fructus and leaves use for medical purposes. Therefore, it is necessary to establish microscopic, macroscopic and analytical standards in order to avoid falsification. ...
Article
Full-text available
Introduction: The state quality assurance system ensures the confidence of consumers that the product meets its quality requirements. In this study, pharmacognostic standards of the leaves and fructus of burdock are specified for the first time. Methods: Microscopic analysis was carried out by using the microscope Carl Zeiss. The UV spectrum were measured on an SF-2000 spectrophotometer. Results: Macroscopically, the leaves are heart-shaped, broad-heart-ovate-shaped with a spaced emarginatedserrate or whole edge, with a wide, wedge-shaped, rounded, uneven base, acute apex, green on the outer surface, grayish slightly pubescent on the inner surface. The fructus are obovate or wedge-compressed, slightly curved, the color is brown/black with spots, or variegated with black spots on a gray background. The microscopic examination of the leaves revealed the presence of epidermis, large submerged and non-submerged stomata of the anomocytic type, 2 types of simple unbranched multi-cellular and glandular capitate trichomes; essential oil glands. Microscopic examination of the leaf petiole revealed the presence of 2 types of simple multi-cellular trichomes, epidermis, angular collenchyma, bicollateral bundles, parenchyma. The stomatal index value is 8.28±0.81 per 1cm2. The microscopy of the fructus revealed the presence of elongated cells of the pericarp epidermis; mesocarp; endocarp; endosperm with aleurone grains and drops of fatty oil. The qualitative phytochemical analysis of revealed the presence of polysaccharides, tannins, flavonoids, terpenoids, saponins, phenolic acids. Conclusion: Physical and chemical parameters (moisture, extractive value, ash content) were also specified. These specific data are important for establishing diagnostic indicators for standardization, identification, preparation of new quality standards.
... Geraniol is a natural acyclic monoterpene alcohol found in the essential oils of lemon grass, palmarosa, citronella, and other plants [28] . It is used in cosmetics, shampoos, and other non-cosmetic products [29] . ...
Article
Full-text available
The study evaluated the effects of essential oil from Cymbopogon martini (CMEO) on lipopolysaccharide (LPS)-stimulated human fibroblasts. Samples were collected in Monte Verde, Minas Gerais, Brazil and analyzed by gas chromatography with mass spectrometry. The fibroblasts were cultured in a monolayer using Iscove's medium and stimulated by LPS (1 μg/mL) and incubated for 24 h at 37°C. The cytotoxicity was evaluated by MTT assay and collagen concentration by Sirius red. Collagenase activity, hyaluronic acid, and the concentrations of IL-1β; IL-6; MCP-1 (CCL2), and MIP-1-α (CCL3) were evaluated. The effect of CMEO on the expression of mRNA and the secretion of enzymes in fibroblasts were evaluated by RT-qPCR and ELISA, respectively. CMEO was cytotoxic against fibroblasts, in which 10 μg/mL inhibited 50% of cell viability. When treated with CMEO, the fibroblasts produced more collagen and hyaluronic acid than control cells. When stimulated by LPS, fibroblasts exhibited higher production of IL-6, IL-1β, MCP-1, and MIP-1α than control cells. The study demonstrated the effects of CMEO on the modulation of mediators related to inflammation and decreasing the mRNA and secretion levels of metalloproteinases, revealing to be a promising candidate for anti-aging effects and wound healing treatments.
... For the treatment of skin diseases (F IC =0.81), the most important plant is Arctium lappa, which has active ingredients are inulin and polyphenols. Arctium lappa seeds are proceeds to deep-fry, grinded and take with water for the treatment of sore throat [32]. For the treatment of infectious and functional diseases (F IC =0.65), the plants used by people are relatively inconsistent. ...
Preprint
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Background Lingchuan County is the main producing area of Chinese medicinal materials in Shanxi Province, rich in medicinal plant resources. The aboriginal residents of Lingchuan County have certain traditional knowledge and experience in the use of medicinal plants and can effectively use medicinal plants to treat common diseases. MethodologyA field survey in 53 villages was carried out over one year, i.e., November 2017—August 2018. Ethnomedicinal data was collected through designed questionaries/interviews by involving 180 informants familiar with medicinal plants utilization. Documented data were evaluated using the quantitative indices. ResultsA total of 138 traditional medicinal plants were investigated, belonging to 123 genera of 60 families. Among them, Asteraceae was the dominant plant family with 19 species. Roots were the most commonly used plant parts, and the dominant life form was herbs. Quantitative analysis revealed that Forsythia suspensa was with higher (0.33) RFC value, and Scutellaria baicalensis was recorded with higher (0.91) UV. Treated diseases were categorized in 12 groups and evaluated by their F IC value, in which gynecological diseases having higher (0.93) F IC value followed by urinary system diseases. The most medicinal plants are used to clear away heat and relieve the surface. At the same time, people use boiled water to use medicinal plants. Most of the plants investigated are non-toxic. Conclusion This study reported traditional herbal medicines for the first time to be used against various disorders in Lingchuan County, China and are still practiced by the local communities. Some of the new ethnobotanical claims documented in this investigation should need to be further explored clinically. The medicinal plants with the highest use values recorded in this study may signpost the probable existence of valuable phytochemical compounds that requires a search for prospective new drugs to cure many human disorders.
... Arctiin Antihyalorunidase activity [171] Wild yam Dioscorea villosa Diosgenin Anticollagenase activity [172] Temulawak ...
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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.
... The roots of burdock (Arctium lappa L.) are commonly used as herbal medicine based on its valuable phytochemical content. Pereira et al. [29], Gentil et al. [30] and Pirvu et al. [31] showed antibacterial activity against Gram-positive and Gram-negative bacteria of crude extracts from burdock, and Knott et al. and Jingvi et al. [32,33] proved skin improvement when using burdock extracts. One of the molecules in burdock roots responsible for antibacterial properties can be peptides because every organism (from microorganisms to Mammalia) has an innate defense system, which is determined by the presence of, among others, antimicrobial peptides (AMPs) [34]. ...
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This work aimed to study the anti-bacterial, anti-biofilm and anti-oxidant potential effects of low molecular weight (LMW) peptides (Br-p) isolated from burdock (Arctium lappa L.) roots. We conducted a preliminary study to exclude or confirm the antibiotic activity of the LMW peptides fraction of this plant. Br-p were isolated using gel filtration and a 10 kDa cut-off membrane. The obtained peptides were identified by MALDI TOF/TOF. Antibacterial activity was tested against acne strains using diffusion tests, MIC and MBC. The fibroblast cytotoxicity of Br-p was tested, and the selectivity index (SI) value was determined. The fraction of 46 Br-p peptides isolated from burdock root with a molecular weight below 5000 Da and theoretic pI (isoelectric point) of 3.67–11.83 showed a narrow spectrum of activity against Gram-positive acne bacterial strains. One of the Br-p peptides assessed on MALDI RapidDeNovo was LRCDYGRFFASKSLYDPLKKRR cationic peptide. It was analogous to that contained in A. lappa protein, and theoretically it was matched as a peptide with antibiotic nature. Br-p did not show toxicity to fibroblasts in the tested concentration up to 10 mg/mL, obtaining CC50 10 mg/mL. The SI value for the tested Propionibacterium strains ranged from 160 to 320. Finally, an active dressing based on chitosan/alginate/genipin was prepared using freeze-drying. The formed dressing was evaluated for its anti-acne activity. To sum up: preliminary biological studies confirmed the anti-acne properties of the isolated peptide fraction from burdock root and pointed to the possibility of using it to create an active dressing on the skin.
... To date, biologically active ingredients of natural products, exclusively plant extracts, have led to the finding of novel drugs used for treatment of skin aging [14]. For instance, plant extracts such as Labisia pumila [15], Ficus deltoidea [16], Arctium lappa [17], Panax ginseng [18], Coffea Arabica [19] and Cucumaria frondosa [20] have been established for their inhibitory potential against UV-A induced photoaging. Moreover, the bioactive compounds such as Ellagic acid [21], 10-Hydroxy-2decanoic acid [22], Epigallocatechin-3-gallate [23], Vitamin-E (Tocopherols) [24,25], Vitamin-A [26], Vitamin-C [27], etc. have also shown their activity against UV-induced photoaging. ...
... To date, biologically active ingredients of natural products, exclusively plant extracts, have led to the finding of novel drugs used for treatment of skin aging [14]. For instance, plant extracts such as Labisia pumila [15], Ficus deltoidea [16], Arctium lappa [17], Panax ginseng [18], Coffea Arabica [19] and Cucumaria frondosa [20] have been established for their inhibitory potential against UV-A induced photoaging. Moreover, the bioactive compounds such as Ellagic acid [21], 10-Hydroxy-2decanoic acid [22], Epigallocatechin-3-gallate [23], Vitamin-E (Tocopherols) [24,25], Vitamin-A [26], Vitamin-C [27], etc. have also shown their activity against UV-induced photoaging. ...
... Based on this valuable phytochemical content, Bardanae radix represents an important ingredient for traditional medicine practitioners, and has also achieved international recognition for its numerous healthy effects [1]; Romanian folk medicine also considers a bardanae radix hot water extract (decoction type) as an effective expectorant, anti-tussive, emollient, diuretic and anti-inflammatory remedy thus being recommended for different lung, digestive, renal and skin ailments [6]. Proving these, studies have reported burdock products and corresponding separate extracts or specific compounds (especially lignans such as arctiin and arctigenin, and polyphenols compounds) having antioxidant, anti-inflammatory, antitumor, antibacterial and antiviral activities [1], as well as hepatoprotective [7], antiurolithiasic [8] and skin improving [1,9] effects, with some clinical studies also proving their effectiveness in knee osteoarthritis [10] and for dental infectious conditions [11,12]; burdock root and fruits are also reported to have antidiabetic activity [1,4], with their beneficial effects being attributed to the copresence of sitosterol, inulin and lignans [2]. Furthermore, the combination arctigenin -polyphenols have shown the capacity to block tumor cell growth and metastasis [13]. ...
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Confounding by indication is a critical challenge in evaluating the effectiveness of surgical interventions using observational data. The threat from confounding is compounded when using medical claims data due to the inability to measure risk severity. If there are unobserved differences in risk severity across patients, treatment effect estimates based on methods such a multivariate regression may be biased in an unknown direction. A research design based on instrumental variables offers one possibility for reducing bias from unobserved confounding compared to risk adjustment with observed confounders. This study investigates whether a physician’s preference for operative care is a valid instrumental variable for studying the effect of emergency surgery. We review the plausibility of the necessary causal assumptions in an investigation of the effect of emergency general surgery (EGS) on inpatient mortality among adults using medical claims data from Florida, Pennsylvania, and New York in 2012–2013. In a departure from the extant literature, we use the framework of stochastic monotonicity which is more plausible in the context of a preference-based instrument. We compare estimates from an instrumental variables design to estimates from a design based on matching that assumes all confounders are observed. Estimates from matching show lower mortality rates for patients that undergo EGS compared to estimates based in the instrumental variables framework. Results vary substantially by condition type. We also present sensitivity analyses as well as bounds for the population level average treatment effect. We conclude with a discussion of the interpretation of estimates from both approaches.
... It is often used in India and Russia for the treatment of cancer. Burdock can be used safely, except for those who are on potassium lowering diuretic therapy, as it contains fairly high quantities of potassium[8][9][10][11][12][13][14][15] . ...
Article
"Cancer" is the term we give to a large group of diseases that vary in type and location but have one thing in common: abnormal cells growing out of control. It continues multiplying uncontrollably and the result of this accumulation of abnormal cells is a mass of cells called a "cancer". The Plant Kingdom produces naturally occurring secondary metabolites which are being investigated for their anticancer activities leading to the development of new clinical drugs. With the success of these compounds that have been developed into staple drugs for cancer treatment new technologies are emerging to develop the area further. New technologies include nanoparticles for Nano-medicines which aim to enhance anticancer activities of plant-derived drugs by controlling the release of the compound and investigating new methods for administration. This review discusses the demand for naturally-derived compounds from medicinal plants and their properties which make them targets for potential anticancer treatments. The purpose of this brief review is to assemble current literature on some herbal drugs and to focus on their beneficial roles and drug targets in cancer therapy and chemoprevention. Keywords: 20 Herbal drugs, Cancer, Cell cycle
... Arctium species were also some of the most commonly used ingredients in the preparation of traditional mehlems (Bosnian balms prepared from freshly chopped or freshly pressed parts of various herbs). 26 Many studies, some of them in humans also, confirmed several burdock EPAs, supporting the traditional claims: anti-allergic, antiinflammatory (in vitro, animal model), [39][40][41][42] wound healing (in vitro, human clinical studies), [43][44][45] skin antiaging (human clinical study), 46 antiacne (human clinical study), 47 and antimicrobial (in vitro) 48 activities. Chamomile's use in ethnodermatology benefits also from increasing scientific evidence. ...
Article
The geographic and ecologic specificity of Romania and other East European countries has resulted in the development of an exceptional diversity of medicinal plants. The purpose of this study was to provide an overview of the ethnobotanical dermatology practices based on the use of medicinal plants in this region. The indications, ethnopharmacologic activities, parts used, and administration for 106 medicinal plants are provided. We also discuss the relative importance of these species, using two modified indeces of quantitative ethnobotany: Use Value Index and Relative Dermatologic Importance, which were calculated on the basis of etic constructions (indications and ethnopharmacologic activities). The species identified to have the highest dermatologic importance (on a scale of 100) were: Brassica oleracea L. (100) Matricaria chamomilla L. (79.17), Arctium lappa L. (74.82), Daucus carota L. (72.28), Equisetum arvense L. (70.47), Juglans regia L. (69.93), Populous nigra L. (65.94), Symphytum officinale L. (63.59), Chelidonium majus L. (57.78), Calendula officinalis L. (57.78), Achillea millefolium L. (57.43), Melilotus officinalis L. (55.25), Allium cepa L. (51.45), Quercus robur L. (51.08) and Betula spp. (50.91). This preliminary study on ethnobotanic dermatology practices indicates that Eastern European traditional medical knowledge represents an important heritage that is currently underexploited.
... Arctiin, a lignin compound isolated from Arctium lappa, also known as greater burdock, possesses a variety of anti-viral, anti-inflammatory and anti-proliferative effects in mammalian cells (13)(14)(15). Arctiin has recently been demonstrated to improve procollagen type I synthesis and exhibits a protective effect against ultraviolet B (UVB) radiation (16,17). An extract of A. lappa or isolated arctiin induces collagen synthesis in the dermis (18). ...
Article
Arctiin, a lignin isolated from Arctium lappa, exhibits a variety of biological effects, including anti‑viral, anti‑inflammatory, and anti‑proliferative actions, in mammalian cells. In a previous study, arctiin was demonstrated to induce procollagen type I synthesis and exhibited protective effects against ultraviolet B (UVB) radiation in normal human dermal fibroblasts (nHDFs). However, the underlying molecular mechanism of arctiin‑mediated collagen synthesis remains unknown. In the present study, the mechanism for increased expression of collagen type 1α 1 chain (COL1A1) mRNA in arctiin‑induced nHDFs was identified. The expression of microRNA‑378b (miR‑378b), downregulated by arctiin, was correlated with the expression of sirtuin‑6 (SIRT6) mRNA, a regulator of COL1A1 mRNA. Furthermore, it was revealed that arctiin protected the UVB radiation‑mediated decrease in COL1A1 mRNA expression, through the miR‑378b/SIRT6 signaling pathway. In conclusion, these results suggest that arctiin regulates COL1A1 through the miR‑378b‑SIRT6 axis.
... Based on this valuable phytochemical content, Bardanae radix represents an important ingredient for traditional medicine practitioners, and has also achieved international recognition for its numerous healthy effects [1]; Romanian folk medicine also considers a bardanae radix hot water extract (decoction type) as an effective expectorant, anti-tussive, emollient, diuretic and anti-inflammatory remedy thus being recommended for different lung, digestive, renal and skin ailments [6]. Proving these, studies have reported burdock products and corresponding separate extracts or specific compounds (especially lignans such as arctiin and arctigenin, and polyphenols compounds) having antioxidant, anti-inflammatory, antitumor, antibacterial and antiviral activities [1], as well as hepatoprotective [7], antiurolithiasic [8] and skin improving [1,9] effects, with some clinical studies also proving their effectiveness in knee osteoarthritis [10] and for dental infectious conditions [11,12]; burdock root and fruits are also reported to have antidiabetic activity [1,4], with their beneficial effects being attributed to the copresence of sitosterol, inulin and lignans [2]. Furthermore, the combination arctigenin -polyphenols have shown the capacity to block tumor cell growth and metastasis [13]. ...
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This work aimed to study the potential effects of four Arctii folium extracts, 5 mg gallic [GAE] acid equivalents per 1 mL sample, on six antibiotics (Ampicillin/AM, Tetracycline/TE, Ciprofloxacin/CIP, Sulfamethoxazole-Trimethoprim/SXT, Chloramphenicol/C and Gentamicin/CN) tested on four Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, and Staphylococcus epidermidis ATCC 12228) and five Gram-negative (Proteus mirabilis ATCC 29245, Escherichia coli ATCC 35218, E. coli ATCC 11229, E. coli ATCC 8739, and Bacillus cereus ATCC 11778) bacteria. Arctii folium extracts were the whole ethanol extract/W and subsequent ethyl acetate/EA, aqueous/AQ, and chloroform/CHL fractions. Chemical qualitative analysis (HPTLC method) emphasized five main polyphenol compounds in Arctii folium polar extracts: chlorogenic acid (Rf≈0.52/0.55) and its isomer, 1,5-di-O-caffeoylquinic acid (Rf≈0.90/0.92), plus cynarin (Rf≈0.77), hyperoside (Rf≈0.68/0.64) and isoquercitrin (Rf≈0.69/0.71). Microbiological screening indicated Arctii folium polar extracts (AQ and W) efficacy on S. epidermidis ATCC 12228; the MIC values were in the range of common antibiotics, being 32 and 128 μg GAE per mL sample respectively. The unpredictable effects (stimulatory or inhibitory) of Arctii folium extracts in combination with typical antibiotics as well as a potential use of the whole ethanol extract/W for restoring the antimicrobial potency of susceptible antibiotics have also been evidenced.
... Arctium lappa fruit extract was found to inhibit IL-6 and TNF-␣ concentration generated by DCs [39]. A recent study documented the effect of Saucerneol D, a lignan constituent of Saururus chinensis plant, on BMDCs, which decreased expression of maturation proteins (MHC I/II, CD40, CD80, and CD86), inflammatory mediators (NO, IL-12, IL-1␤, and TNF-␣), and inhibition of allogenic T-cell activation [40]. ...
... Arctium lappa fruit extract was found to inhibit IL-6 and TNF-␣ concentration generated by DCs [39]. A recent study documented the effect of Saucerneol D, a lignan constituent of Saururus chinensis plant, on BMDCs, which decreased expression of maturation proteins (MHC I/II, CD40, CD80, and CD86), inflammatory mediators (NO, IL-12, IL-1␤, and TNF-␣), and inhibition of allogenic T-cell activation [40]. ...
... 2.3.2. Modulation of cytokine secretion Arctium lappa fruit extract was found to inhibit IL-6 and TNF-concentration generated by DCs [39]. A recent study documented the effect of Saucerneol D, a lignan constituent of Saururus chinensis plant, on BMDCs, which decreased expression of maturation proteins (MHC I/II, CD40, CD80, and CD86), inflammatory mediators (NO, IL-12, IL-1, and TNF-), and inhibition of allogenic T-cell activation [40]. ...
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Since ancient times people around the world used medicinal plants for their therapeutic potential. Some studies of the antioxidant, antimicrobial, anti-inflammatory, and hepatoprotective effects of the extracts from plants of the genus Arctium have been conducted. The extracts obtained from these plants are considered safe with low toxicities; however, little is known about the toxicity of the Arctium tomentosum Mill. extract. Therefore, our work aimed to study the toxic effect of a carbon dioxide extract from the A. tomentosum Mill. root through MTT assay, acute, and sub-chronic toxicity studies. In the MTT assay, a low cytotoxic effect was observed at concentrations between 0.078 mg/mL and 0.001 mg/mL. The IC50 value – 0.091 mg/mL was determined through non-linear regression analysis. The acute toxicity test demonstrated that the LD50 is >5000 mg/kg and in the sub-chronic toxicity test, a dose of 200 mg/kg did not induce the toxic effect. In this way, the present study can serve as a base for the further investigation of the antimicrobial, antioxidant, and hepatoprotective effects of the A. tomentosum Mill—root extract.
Article
Ethnopharmacological relevance: Arctium lappa L., is a biennial plant that grows around the Eurasia. Many parts of Arctium lappa L. (roots, leaves and fruits, etc.) are medically used in different countries. Arctium lappa L. fruit, also called Arctii Fructus, is traditionally applied to dispel wind-heat, ventilate lung to promote eruption, remove toxicity substance and relieve sore throat. The aim of the review: The review aims to integrate the botany, ethnopharmacology, quality control, phytochemistry, pharmacology, derivatives and toxicity information of Arctii Fructus, so as to facilitate future research and explore the potential of Arctii Fructus as an agent for treating diseases. Materials and methods: Related knowledge about Arctii Fructus were acquired from Science Direct, GeenMedical, PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, Pharmacopoeia of the People's Republic of China, Doctoral and Master's thesis, ancient books, etc. RESULTS: Arctii Fructus as an herb used for medicine and food was pervasively distributed and applicated around the world. It was traditionally used to treat anemopyretic cold, dyspnea and cough, sore throat, etc. To date, more than 200 compounds have been isolated and identified from Arctii Fructus. It contained lignans, phenolic acids and fatty acids, terpenoids, volatile oils and others. Lignans, especially arctigenin and arctiin, had the extensive pharmacological effects such as anti-cancer, antiviral, anti-inflammatory activities. The ester derivatives of arctigenin had the anti-cancer, anti-Alzheimer's disease and immunity enhancing effects. Although Arctii Fructus extract had no toxicity, arctigenin was toxic at a certain dose. The alleviating effects of Arctii Fructus on chronic inflammation and ageing have been demonstrated by clinical studies. Conclusion: Arctii Fructus is regarded as a worthy herb with many chemical components and various pharmacological effects. Several traditional applications have been supported by modern pharmacological research. However, their action mechanisms need to be further studied. Although many chemical components were isolated from Arctii Fructus, the current research mainly focused on lignans, especially arctiin and arctigenin. Therefore, it is very important to deeply clarify the pharmacological activities and action mechanism of the compounds and make full medicinal use of the resources of Arctii Fructus.
Article
Background The medicinal properties of plants can be predicted by virtue of phylogenetic methods, which nevertheless has not been utilized to explore the regularity of skin related bioactivities of ethnomedicinal plants. We aim to investigate the distribution of skin efficacy of Asteraceae and Ranunculales plants on the species-level Tree of Life. Methods The clinical efficacy data of 551 ethnomedicinal species belonging to Ranunculales, as well as 579 ethnomedicinal species of Asteraceae, were systematically collected and collated; these therapeutic data fell into 15 categories, including skin disease/cosmeceutical. The large phylogenetic tree of all China angiosperm species was used to detect the phylogenetic signals of ethnomedicinal plants by calculating the D statistic, phylogenetic diversity (PD), net relatedness index (NRI) and nearest taxon index (NTI). Of all Chinese ethnomedicinal plants of Ranunculales and Asteraceae, 339 (61.5% of all ethnomedicinal species) and 382 (66.0% of all) are used for skin problems. In Ranunculales, a clustered structure was suggested by NRI value for skin uses. In Asteraceae, the skin utility was not clustered; Artemisia, Aster, Cremanthodium, Ligularia and Saussurea are the most used Asteraceae genera for skin issues. Results The clustering structure was identified in Artemisia, and the skin efficacy in other genera was of overdispersion (NRI < 0). NTI values and D statistic largely agree with NRI. When compared with PD values of other therapeutic categories, the PD value of skin category was relatively high in Cremanthodium, Ranunculales, Asteraceae and Artemisia, suggesting the enormous efficacy space in the unexplored taxa of these taxonomic groups. Conclusion By resolving the distribution of therapeutic effects of Ranunculales/Asteraceae taxa, the importance of phylogenetic methods in mining botanical resources with skin utilities is validated.
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Wounds are common external or internal damages to the body, usually caused by a physical, chemical, or biological agents. There exists natural repair wound healing repair in that includes immunological responses i.e., inflammation and necrosis. Naturally, body repairs wounds itself, but the period of healing is relatively slow. This healing process may further be delayed by the pathogens attack or weaker immune response. Wounds heal biochemically, but the time of the healing can be reduced by applying different herbs like the plant-based treatments. Sub-continent is rich in having an immense variety of medicinal plants as well. This literature review is about the role of different plants in wound healing, the efficacy of herbs on wound healing.
Chapter
Burdock (Arctium lappa) is a plant root native to Asia and Europe. It has a long history of use in China, both as a food and a medicine. Although scientific research on the medicinal benefits of this root is sparse, it appears to be safe, as evidenced by its long history of culinary and medicinal use. Burdock has cholagogic, choleretic, immunostimulant, and anti-inflammatory effects. It may be beneficial for diverticulitis prophylaxis, diabetic nephropathy, photoaging, acne, and inflammation. This chapter examines some of the scientific research conducted on burdock, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of the burdock’s use in treating bowel, renal, musculoskeletal, dermatologic, and oncologic disorders. Finally, the chapter presents a list of burdock’s active constituents, different Commonly Used Preparations and Dosage, and a Section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
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The review summarizes information from the literature on the distribution, study of the composition and biological activity of metabolites, total extracts of plants of the genus Arctium L. of the world flora. In Russia, the roots of three species are allowed to be harvested and used: A. lappa, A. tomentosum, A. minus. To date, the most studied composition of metabolites and pharmacological properties of great burdock. The chemical composition of A. atlanticum, A. debrayi, A. leiobardanum, A. neumani, A. platylepis, A. pseudarctium, A. sardaimionense, A. scanicum, A. nemorosum and A. palladini has not been studied. About 360 substances related to polysaccharides, sesquiterpenes, triterpenes, fatty acids, phenolcarbonic acids, tannins, vitamins, lignans, sterols, polyacetylenes, amino acids, alkaloids, flavonoids, macro-and microelements and other were isolated and identified from the studied species. There are only a few publications about pharmacological activity of Arctium nemorosum, A. palladini, A. tomentosum and A. minus, and there is no information for other types. Total extracts and individual compounds of the studied burdock species in the experiment have a wide range of pharmacological activity. The information provided in the review shows that plants of the genus Arctium L., are promising for creating effective medicines. In addition, the fragmentation and lack of information on the composition of metabolites, pharmacological activity of most species of the genus burdock opens up great opportunities for researchers.
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Arctium lappa is a weed used in traditional medicine in the treatment of skin inflammation and digestive tract diseases. Arctium tomentosum is used in folk medicine interchangeably with Arctium lappa and, according to European Medicines Agency (EMA) monography, provides an equal source of Arctii radix (Bardanae radix), despite the small amount of research confirming its activity and chemical composition. The aim of the study was the comparison of the anti-lipoxygenase and the antioxidant activity, scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion (O2•−), and hydrogen peroxide (H2O2), of 70 % (v/v) ethanolic extracts from the aerial parts and the roots of Arctium lappa and Arctium tomentosum. In the tested extracts, the total polyphenols content and the chemical composition, analyzed with the HPLC–DAD–MSn method, were also compared. The extracts were characterized by strong antioxidant properties, but their ability to inhibit lipoxygenase activity was rather weak. A correlation between the content of polyphenolic compounds and antioxidant activity was observed. The extracts from A. lappa plant materials scavenged reactive oxygen species more strongly than the extracts from A. tomentosum plant materials. Moreover, the extracts from A. lappa plant materials were characterized by the statistically significantly higher content of polyphenolic compounds.
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Autophagy is a catabolic process that degrades dysfunctional proteins and organelles and plays critical roles in cancer development. Our preliminary screening identified that extracts of the fruits of Arctium lappa and the fruits of Forsythia suspensa notably suppressed the proliferation of hepatocellular carcinoma HepG2 cells and downregulated the autophagy. In this study, we explored the effect of arctigenin (ARG), a bioactive lignan in both extracts, on cell proliferation and autophagy-related proteins in HepG2 cells. ARG inhibited the proliferation of HepG2 cells. Analysis of autophagy-related proteins demonstrated that ARG might block the autophagy that leads to sequestosome 1/p62 (p62) accumulation. The stage of inhibition in autophagy by ARG differed from those by the autophagy inhibitors 3-methyladenine (3-MA) or chloroquine (CQ). ARG could also inhibit starvation-induced autophagy. Further analysis of apoptosis-related proteins indicated that ARG did not affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative effect of ARG can occur independently of apoptosis. In summary, our study showed that ARG suppresses cell proliferation and inhibits autophagy, and might lead to the development of agents for autophagy research and cancer chemoprevention.
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Cancer commands the second highest global mortality rate and causes severe public health problems. Recent advances have been made in cancer therapy but incidence of the disease remains high. Research on more efficient treatment methods with reduced side effects is necessary. Historically, edible plants have been used as traditional medicines for various diseases. These demonstrate the potential of natural products as sources of bioactive compounds for anticancer treatment. Anticancer properties of phytochemicals are attributed to bioactive compounds in plant extracts which suppress cancerous cell proliferation and growth by inducing both cell cycle arrest and apoptosis. This review presents a summary of the molecular identification of phytochemicals with anticancer properties and details their action mechanisms and molecular targets. Moreover, the effects of natural product on both immunomodulatory and anticancer properties are provided.
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The proper functioning of human immune system is essential for organism survival against infectious, toxic and oncogenic agents. The present study aimed to describe the scientific evidence regarding the immunomodulatory properties of the main micronutrients and specific phytochemicals. Plants of food interest have the ability to dynamically affect the immune system through particular molecules. Plant species, type of compounds and biological effects were herein reviewed mainly focusing on plants which are not commonly used in food supplements. Several efficient phytoproducts showed significant advantages compared to synthetic immunomodulators, being good candidates for the development of immunotherapeutic drugs.
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Background The anti-inflammatory actions of Polygonum cuspidatum, Angelica gigas, Sophora flavescens and Arctium fruit are well known. Nonetheless, effects of herbal combination (PASA) or its fermentation by microorganisms (F-PASA) on the allergic response remain unknown. Purpose We investigated whether PASA or F-PASA could inhibit IgE/antigen complex (IgE/Ag)-mediated allergic responses. Methods To evaluate and compare anti-allergic actions of PASA and F-PASA, we performed cell viability, β-hexosaminidase activity, ELISA assays for cytokines and eicosanoids, immunoblot analysis, HPLC analysis and passive cutaneous anaphylaxis (PCA) models. Results F-PASA had stronger anti-degranulation actions (IC50, 510.9 µg/ml) than PASA (IC50, 1,261 µg/ml) without cytotoxicity until 2000 µg/ml in IgE/Ag-activated RBL-2H3 cells. Additionally, F-PASA inhibited formation of tumor necrosis factor-α (IC50, 147.4 µg/ml), interleukin-4 (IC50, 213.4 µg/ml), prostaglandin D2 (IC50, 42.40 µg/ml) and leukotriene C4 (IC50, 157.9 µg/ml). Moreover, F-PASA dose-dependently inhibited the phosphorylation and expression of proteins that are related to the FcεRI and arachidonate cascades. Consistent with in vitro studies, F-PASA from 25 to 100 mg/kg also suppressed IgE/Ag-induced PCA reaction more than PASA did in mice. In phytochemical analysis, using PASA and F-PASA, F-PASA showed a higher level of emodin-8-O-β-d-glucoside, whereas the level of arctiin, an artigenin glycoside, was reduced compared with that using PASA. Conclusion These findings indicate that F-PASA, including both artigenin and emodin-8-O-β-d-glucoside, possesses stronger anti-allergic properties. Therefore, F-PASA may be useful as a functional food or as a phytomedicine for allergic diseases.
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Pre-clinical cell and animal nutrigenomic studies have long suggested the modulation of the transcription of multiple gene targets in cells and tissues as a potential molecular mechanism of action underlying the beneficial effects attributed to plant-derived bioactive compounds. To try to demonstrate these molecular effects in humans, a considerable number of clinical trials have now explored the changes in the expression levels of selected genes in various human cell and tissue samples following intervention with different dietary sources of bioactive compounds. In this review, we have compiled a total of 75 human studies exploring gene expression changes using quantitative reverse transcription PCR (RT-qPCR). We have critically appraised the study design and methodology used as well as the gene expression results reported. We herein pinpoint some of the main drawbacks and gaps in the experimental strategies applied, as well as the high interindividual variability of the results and the limited evidence supporting some of the investigated genes as potential responsive targets. We reinforce the need to apply normalized procedures and follow well-established methodological guidelines in future studies in order to achieve improved and reliable results that would allow for more relevant and biologically meaningful results.
Thesis
C'est au coeur du pays des trois frontières (Allemagne, Luxembourg, France) que se trouve Montenach, un petit village doté d'une réserve naturelle. On y reconnaît un milieu particulier, les pelouses calcaires, qui sont riches en diversité floristique et faunistique.Dans un premier temps, cette réserve va être présentée, ses particularités vont être énoncées. Et plus particulièrement on s'intéressera aux caractéristiques de ces pelouses calcaires.Puis dans un second temps, nous allons découvrir les plantes médicinales qui s'y trouvent, à travers leur description botanique, leur composition chimique, leur usages traditionnels. De là en découle les propriétés pharmacologiques attribués aux principes actifs découverts jusqu'à aujourd'hui.
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Age-dependent modification of the facial subcutaneous white adipose tissue (sWAT) connected with reduction of its volume, modification of collagen content and adhesion between dermal and adipose layers can significantly influence mechanical stability of the skin and cause the development of aging symptoms such as wrinkles. Typical aging appearance in facial skin is at least partly connected with special phenotypical features of facial preadipocytes and mature adipocytes. In this paper, we have discussed the possible roles of local inflammation, compartmental structure of facial sWAT and trans-differentiation processes such as beiging of white adipocytes and adipocyte-myofibroblast transition in facial skin aging.
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The Arctium lappa (Arctii Fructus) seed and its major active compound, arctigenin (ARC), are known to have anti-cancer, anti-obesity, anti-osteoporosis, and anti-inflammatory activities. However, the effect of Arctii Fructus and ARC on mast cell-mediated allergic inflammation and the associated mechanism have not been elucidated. Therefore, we attempted to investigate the anti-allergic activity of Arctii Fructus and ARC on mast cells and experimental mouse models. Arctii Fructus water (AFW) or ethanol extract (AFE) and ARC reduced the production of histamine and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and TNF-α in mast cells. AFW, AFE, and ARC inhibited phosphorylation of MAPKs and NF-κB in activated mast cells. Moreover, IgE-mediated passive cutaneous anaphylaxis and compound 48/80-induced anaphylactic shock were suppressed by AFW, AFE, and ARC administration. These results suggest that Arctii Fructus and ARC are potential therapeutic agents against allergic inflammatory diseases.
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Objectives : Hwangheuk-san is a complex prescription composed of oriental traditional medicine and has been reported for antioxidant, antimicrobial and anticancer effects in the recent study. Methicillin-resistant Staphylococcus aureus (MRSA) is one of important causes of fatal infectious diseases such as septicemia, endocarditis, toxic shock syndrome, pneumonia, skin and soft tissue infections (SSTIs). S. aureus is reported as being for a variety of human diseases and its epidemiological relevance is mainly due to their ability of becoming highly resistant to common antimicrobials such as tetracycline, penicillin, cphalosporin and aminoglycoside. The objective of this study is to determine the antimicrobial effect of Hwangheuk-san ethanol extracts (HHS) and synergistic effects with antibiotics oxacillin against MRSA.Methods : The antimicrobial activity of HHS was measured by the disc diffusion method, broth microdilution method and the checkerboard dilution test, time-kill curve assay was performed to investigate synergistic effects with antibiotics oxacillin against MRSA.Results : HHS showed antimicrobial activity against MRSA with a MIC value of 125 ?/?. In the checkerboard test, the interaction of HHS with antibiotics oxacillin produced almost synergy or partial synergy against MRSA. This study showed that HHS reduced the MICs of oxacillin tested, and a remarkable antibacterial effect of HHS, with membrane permeability enhancers.Conclusions : These results suggest that HHS has the antimicrobial effect and synergistic effects with antibiotics oxacillin against MRSA. This study thus can be a valuable source for the development of a new drug with low MRSA resistance.
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We investigated the burdock extract on the inhibitions of NO generation, COX-2 expression, and the generations of IL-6 and TNF-α, to find out its anti-inflammatory effect in this study. After the treatment of the burdock extract in the cells, we measured the amount of NO generated in the inflammatory cells developed by LPS and UVB, and confirmed the developments of inflammatory mediators by RT-PCR. Upon the results on the NO generation after the development of inflammation by LPS in Raw 264.7 cell, we found approximately 50% of inhibitory effect at 200 μg/ml concentrations of the burdock extract. It was confirmed that the expression levels of TNF-α, COX-2, and IL-6 were declined to the levels of control by LPS and UVB stimulated inflammation in HaCat cell. This means the anti-inflammatory effect of the burdock extract.
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Type VII collagen is the major component of anchoring fibrils in the cutaneous basement membrane zone. In this study, we have examined the effects of various cytokines on the expression of types I and VII collagen genes in dermal fibroblasts in culture. The pro-inflammatory cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and leukoregulin (LR) strongly elevated (approximately 5-9-fold) type VII collagen mRNA levels, as measured by Northern blot hybridizations. These effects were also observed at the protein level by indirect immunofluorescence using a monoclonal antibody specific for type VII collagen. By contrast, IL-1 beta had only a slight stimulatory effect (approximately 2-fold) on type I collagen gene expression, while TNF-alpha and LR markedly reduced type I collagen mRNA steady-state levels. Interestingly, IL-1, TNF-alpha and LR had additive effects with transforming growth factor-beta (TGF-beta) on type VII collagen gene expression, whereas they counteracted the up-regulatory effect of TGF-beta on type I collagen gene expression. Thus, our data indicate that the modulation of type I and type VII collagen gene expression by cytokines involves different regulatory pathways.
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Ultraviolet (UV) irradiation exerts multiple effects on skin cells, including the induction of several cytokines involved in immunomodulation. Specifically, UV irradiation has been shown to upregulate the level of tumor necrosis factor-alpha (TNF-alpha) mRNA in keratinocytes. To determine whether the induction of TNF-alpha mRNA is regulated by transcriptional or post-transcriptional mechanisms, we examined cells of keratinocytic lineage (SCC12F) for steady state level, transcription rate, and stability of TNF-alpha mRNA after UV irradiation. Within 4 h there was a 20-40-fold induction of TNF-alpha mRNA that persisted at lower levels through 48 h. Consistently, TNF-alpha protein secretion increased at 24 and 48 h after UV irradiation. UV irradiation increased the half-life of TNF-alpha mRNA from approximately 35 min to approximately 10 h. Conversely, the transcription rate of the TNF-alpha gene increased < 2-fold at the time of peak mRNA steady state levels. Thus, post-transcriptional mechanisms play a major role in UV induced TNF-alpha transcript level.
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In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.
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Ageing has been defined as the accumulation of molecular modifications which manifest as macroscopic clinical changes. Human skin, unique among mammalians insofar as it is deprived of fur, is particularly sensitive to environmental stress. Major environmental factors have been recognized to induce modifications of the morphological and biophysical properties of the skin. Metabolites from ingested or inhaled substances do affect skin, which is also sensitive to endogenous hormone levels. Factors as diverse as ultraviolet radiation, atmospheric pollution, wounds, infections, traumatisms, anoxya, cigarette smoke, and hormonal status have a role in increasing the rate of accumulation of molecular modifications and have thus been termed 'factors of ageing'. All these factors share as a common feature, the capability to directly or indirectly induce one of the steps of the micro-inflammatory cycle, which includes the expression of ICAM-1 in endothelial cells. This triggers a process leading to the accumulation of damages in the skin resulting in skin ageing since ICAM-1 expression provokes recruitment and diapedesis of circulating immune cells, which digest the extracellular matrix (ECM) by secreting collagenases, myeloperoxidases and reactive oxygen species. The activation of these lytic processes provokes random damage to resident cells, which in turn secrete prostaglandines and leukotrienes. These signaling molecules induce the degranulation of resident mast cells which release the autacoid histamine and the cytokine TNF-alpha thus activating endothelial cells lining adjacent capillaries which release P-selectin and synthesize ICAM-1. This closes a self-maintained micro-inflammatory cycle, which results in the accumulation of ECM damage, i.e. skin aging. In this paper we review the evidence that two factors able to induce macroscopical and molecular modifications in the skin, protein glycation and stretch, activate the micro-inflammatory cycle. We further present evidence that three additional factors, two external factors (electromagnetic fields and psychological stressors) and one internal factor (neuropeptides) also activate the micro-inflammatory cycles and may therefore be considered as factors of skin ageing.
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Licochalcone A (LicA), a major phenolic constituent of the licorice species Glycyrrhiza inflata, has recently been reported to have anti-inflammatory as well as anti-microbial effects. These anti-inflammatory properties might be exploited for topical applications of LicA. We conducted prospective randomized vehicle-controlled clinical trials to assess the anti-irritative efficacy of cosmetic formulations containing LicA in a post-shaving skin irritation model and on UV-induced erythema formation. The clinical trials were accompanied by a series of in vitro experiments to characterize anti-inflammatory properties of LicA on several dermatologically relevant cell types. Topical LicA causes a highly significant reduction in erythema relative to the vehicle control in both the shave- and UV-induced erythema tests, demonstrating the anti-irritative properties of LicA. Furthermore, LicA is a potent inhibitor of pro-inflammatory in vitro responses, including N-formyl-MET-LEU-PHE (fMLP)- or zymosan-induced oxidative burst of granulocytes, UVB-induced PGE(2) release by keratinocytes, lipopolysaccharide (LPS)-induced PGE(2) release by adult dermal fibroblasts, fMLP-induced LTB(4) release by granulocytes, and LPS-induced IL-6/TNF-alpha secretion by monocyte-derived dendritic cells. The reported data suggest therapeutic skin care benefits from LicA when applied to sensitive or irritated skin.
Chapter
The quantitative determination of the skin’s surface topology, both skin roughness and macrostructures such as wrinkles or cellulite, is one of the most important and probably most frequently performed investigations in the field of cosmetics, and increasingly in dermatological research as well. A still very common method of evaluating skin roughness involves the use of silicon replica as used in dentistry. But especially when we focus on macrostructures, making these imprints is either quite challenging and sometimes error-prone (for example, when investigating wrinkles), or actually nearly impracticable (for example, when investigating cellulite or face and body contours).
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Tumor necrosis factor-α(TNF-α) is a potent inhibitor of connective tissue formation. The cellular effects of TNF-α are mediated by two distinct cell-surface receptors, TNF-R55 and TNF-R75, both present on various types of cells, including fibroblasts. In this study we wanted to elucidate the role of TNF-R55 as a mediator of the connective tissue effects of TNF-α by using a mutant, TNF-R55-specific form of human TNF-α. This mutant TNF-α markedly induced collagenase and stromelysin-1 gene expression in dermal fibroblasts, the maximal activation (up to 42-fold) being 65%-89% of that noted with wild-type human TNF-α. In addition, TNF-R55-specific TNF-α suppressed type I collagen mRNA levels as potently as wild-type TNF-α (by 60%). The enhancement of collagenase gene expression by TNF-R55-specific TNF-α was augmented by simultaneous treatment of normal and scleroderma skin fibroblasts with interferon-γ, indicating specific enhancement of TNF- R55 signaling pathway by interferon-α. These results show that stimulation of the TNF-R55 signaling pathway is sufficient for the inhibitory effects of TNF-α on extracellular matrix formation by dermal fibroblasts. It is conceivable that due to reduced systemic toxicity, TNF-R55-specific forms of human TNF-α may prove to be feasible in the therapy of fibrotic disorders.
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Abstract— Previous work has shown that fibroblast-derived collagenase/matrix-metalloproteinase-1(MMP–1), responsible for the breakdown of dermal interstitial collagen, was dose-dependently induced in vitro and in vivo by UVA irradiation and this induction was at least partly mediated byinterleukin–6(IL–6). We here provide evidence that UVA-inducedIL–1α andIL–1β play a central role in the induction of the synthesis both ofIL–6 and collagenase/MMP–1. In contrast to the late increase ofIL–1α andIL–1β mRNA levels at 6 h postirradiation, bioactivity ofIL–1 is already detectable at 1 h postirradiation. This early peak ofIL–1 bioactivity appears to be responsible for the induction ofIL–6 synthesis and together withIL–6 lead to an increase of the steady-state mRNA level of collagenase/MMP–1 as deduced from studies usingIL–1α andIL–1β antisense oligonucleotides or neutralizing antibodies againstIL–1α andIL–1β Besides the early posttranslationally controlled release of intracellularIL–1, a latter pretranslationally controlled synthesis and release ofIL–1 perpetuates the UV response. From these data we suggest a UV-induced cytokine network consisting ofIL–1α,IL–1β andIL–6, which via interrelated autocrine loops induce collagenase/MMP–1 and thus may contribute to the loss of interstitial collagen in cutaneous photoaging.
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We have recently established a novel fibroblast culture system supplemented with L-ascorbic acid 2-phosphate. The addition of L-ascorbic acid 2-phosphate enables human dermal fibroblasts to organize a three-dimensional dermis-like structure by accumulating collagens and extracellular matrices. The purpose of this study was to examine the effects of tumour necrosis factor-alpha (TNF-alpha) on collagen gene expression by human dermal fibroblasts in this culture system in comparison with monolayer culture. TNF-alpha suppressed the expression of pro alpha 1 (I) and pro alpha 1 (III) collagen mRNA in monolayer culture. In contrast, their expression was elevated in the three-dimensional culture system. TNF-alpha increased the mRNA expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 both in monolayer and three-dimensional culture. These data suggest that responses of human dermal fibroblasts to TNF-alpha are distinct under the different culture conditions. Extracellular matrices may modulate the responsiveness of fibroblasts to TNF-alpha.
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Human skin fibroblasts of phase II ("young" cells derived from populations with a low population doubling level) and of phase III ("old" cells from populations, which were approx. 2 population doublings before the last possible subculture) were kept under subconfluent conditions in a defined serum-free medium. Thereby the cells are in a non-proliferative "quiescent" state. Glycosaminoglycan (GAG)- and especially hyaluronan (HA)-synthesis and release into the medium were investigated by the incorporation rate of 14C-glucosamine. About 95% of the synthesized (48 h) GAGs and HA were medium-released and 5% cell-bound. HA synthesis rate of phase III-cultures was significantly reduced, as compared with phase II-cultures. Stimulation of HA-synthesis of phase III-cells--in comparison with phase II-cells--by serum, PDGF or IGF-I was strongly reduced. While HA-synthesis of phase II-cells was maximally stimulated by 5% FCS or 20 ng/ml PDGF, phase III-cells dit not exhibit a saturation kinetics up to 20% FCS or 60 ng/ml PDGF. The strongly reduced HA-synthesis rate of phase III-cells--compared with phase II-cells--in the non-stimulated quiescent state as well as after stimulation by PDGF, IGF-I or serum might be considered as a biomarker of in vitro (and in vivo?) ageing.
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In elderly individuals all components of the skin and subcutaneous tissue undergo histologic and ultrastructural changes. The turgidity of the dermis appears decreased, presumably due to altered patterns and levels of glycosaminoglycans (GAGS), especially hyaluronic acid and dermatan sulfate that are the most common. A linear, age-related decrease in the content of GAGS (mainly hyaluronic acid) has been hypothesized in human aged skin. We used the cationic dye Alcain Blue to selectively stain hyaluronic acid within the dermis in old and young subjects to compare ultrastructurally its topography and variations with age. We demonstrated a progressive reduction in the number of electron-dense granules of hyaluronic acid and of their filaments until they were completely absent in subjects aged 60. We propose that the variations of the levels of hyaluronic acid in the dermis in aging could account for some of the most striking alterations of the aged skin, including decreased turgidity, less support for microvessels, wrinkling, and altered elasticity.
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The mechanisms responsible for impaired wound healing in patients with cachexia-associated infection, inflammation, and cancer are unknown. As tumor necrosis factor (TNF)-alpha is elevated in these diseases, and TNF-alpha inhibits collagen alpha1(I) gene expression in cultured fibroblasts, we analyzed whether chronically elevated serum TNF-alpha affects collagen metabolism in vivo by inoculating nude mice with Chinese hamster ovary cells secreting TNF-alpha (TNF-alpha mice) or control Chinese hamster ovary cells (control mice). Before the onset of weight loss, TNF-alpha mice had a selective decrease in collagen synthesis and collagen alpha1(I) mRNA in the skin. In addition, TNF-alpha mice displayed impaired healing of incisional and excisional skin wounds, compared with control animals, before the onset of cachexia. The expression of transforming growth factor-beta1, a potent fibrogenic factor, was inhibited by TNF-alpha in the skin. In studies with transgenic mice expressing the human growth hormone under the direction of 5' regulatory regions of the human collagen alpha1(I) gene, TNF-alpha treatment inhibited the expression of the collagen alpha1(I) human growth hormone transgene containing -2.3 kb of the 5' region, whereas transgene expression directed by -0.44 kb of the 5' region was not affected. These experiments suggest that TNF-alpha may play an important role in the impaired wound healing of chronic diseases that are characterized by a high production of this cytokine and provide insights for potential therapeutic approaches.
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Recent studies have demonstrated that tumour necrosis factor-alpha (TNF-alpha) decreases alpha 1(I) procollagen gene (COL1A1) expression in cultured human dermal fibroblasts. The purpose of this study was to analyse the transcriptional control of COL1A1 by TNF-alpha. Cultured human dermal fibroblasts were transiently transfected with plasmids containing 5' flanking sequences of COL1A1 fused to the chloramphenicol acetyltransferase (CAT) gene, and were incubated for 48 h in medium with or without TNF-alpha. TNF-alpha inhibited the CAT activity of fibroblasts transfected with plasmids containing 2.3 kb of 5' flanking sequences of COL1A1, whereas the activity of control plasmids containing the herpes simplex thymidine kinase promoter gene (pBLCAT) was unaltered. A series of deletion constructs of various small substitution mutations of the COL1A1 5' flanking region fused to the CAT gene were also transfected, and CAT activity was measured after incubation with TNF-alpha. TNF-alpha suppressed COL1A1 promoter activity through proximal short promoter elements containing only 107 bp. Short substitution mutations between -101 and -97 bp or between -46 and -38 bp abolished TNF-alpha suppression of COL1A1 promoter activity. DNA-protein complex formation was observed involving both sites in gel retardation assays. These results suggest that TNF-alpha suppressed COL1A1 promoter activity through elements located between -101 and -97 bp and between -46 and -38 bp of the COL1A1 promoter, and that the suppression involved DNA-protein interactions.
Article
The in vivo response to ultraviolet B (UVB) radiation in skin is characterized by the accumulation of both mononuclear and polymorphonuclear cells within the dermis and an induction of vascular endothelial adhesion molecules. Epidermal production of cytokines (IL-8 and TNF-alpha) has been strongly implicated in the development of UVB-induced inflammation. In the current study, we examined the time course of IL-8 and TNF-alpha mRNA and protein expression in the epidermis over a 24-h period after in vivo UVB irradiation. Also, the induction of adhesion molecule expression and the accumulation of neutrophils within the dermis were followed. We found constitutive expression of both cytokines (mRNA and protein) in the epidermis of unirradiated skin. IL-8 was rapidly upregulated after irradiation and mRNA and protein increased at 4 h, reaching a maximum between 8 and 24 h. TNF-alpha mRNA and protein was minimally increased by 8 h after UVB irradiation and reached a maximum by 24 h. No significant alteration in ICAM-1 or VCAM-1 expression was observed. E-selectin expression, which was absent from control samples, was increased from 4 h onward and also reached a maximum at 24 h, coinciding with peak neutrophil accumulation. A strong correlation (r = 0.96) was found between number of E-selectin-positive vessels and numbers of infiltrating neutrophils at this time. Moreover, because E-selectin expression was increased before any apparent increase in TNF-alpha protein (4 h), TNF-alpha does not appear to be involved in the early induction of the adhesion molecule, but cytokines such as TNF-alpha and IL-8 may act subsequently to augment the inflammatory response.
Article
Cytokines induced in skin by ultraviolet radiation cause local and systemic immunosuppression. Tumor necrosis factor alpha, interleukin-1, and interleukin-10 are key mediators in the mouse, but less is known about cytokine synthesis and function in ultraviolet-irradiated human skin. We exposed human skin to 3 minimal erythema doses of solar-simulated radiation and raised suction blisters at intervals to 72 h. Alloantigen presentation was suppressed in a mixed epidermal cell-lymphocyte reaction by 69% from 4 to 15 h post-solar-simulated radiation, but recovered to control values by 24 h. Tumor necrosis factor alpha was raised at 4 h after solar-simulated radiation, reached a maximum 8-fold increase at 15 h, then rapidly declined to control values. Interleukin-1alpha and interleukin-1beta were first increased at 15 h, and remained raised to 72 h, although interleukin-1beta declined from its 15 h maximum. Interleukin-10 increased a maximum 2-fold between 15 and 24 h, coincident with recovery of mixed epidermal cell-lymphocyte reaction responses and downregulation of tumor necrosis factor alpha and interleukin-1beta. Solar-simulated radiation differentially affected soluble tumor necrosis factor alpha receptors; soluble tumor necrosis factor-RI was suppressed 33% at 8-15 h whereas soluble tumor necrosis factor-RII increased 2-fold from 15 to 48 h. Interleukin-1 receptor antagonist was raised at all times post-irradiation. Interleukin-12 was not detectable in control or irradiated skin. These kinetics suggest the tumor necrosis factor alpha network has primary importance in ultraviolet-damaged human skin. The small increase in interleukin-10 implies that 3 minimal erythema doses of solar-simulated radiation is the threshold dose for its induction and local, rather than systemic, functions for interleukin-10 in immunosuppression and regulation of other cytokines.
Article
Reactive oxygen species (ROS) and free radicals can be generated in skin by ultraviolet (UV) irradiation, ultrasonication, toxic or allergic chemical noxes, or even during normal metabolic processes of cells. More than 1010 ROS are generated per day and per cell under normal physiological conditions, which have to be dealt with by the endogenous antioxidant system. Oxidative stress arises when the balance between antioxidant and prooxidant processes drifts in favor of a prooxidant status. Some of the general events in the early phase of oxidative stress response in skin are depletion of endogenous intra- and intercellular antioxidants, the enhancement of the intracellular hydroperoxide level, and the induction of specific signal transduction pathways. This chapter presents an example of a screening strategy for the successful selection of in vivo functional topical antioxidants using special in vitro, ex vivo, and in vivo methods. The screening protocol used is subdivided into three steps. In the primary step, the efficacy of antioxidants is evaluated in vitro in cultures of primary skin cells, and the biocompatibility of the selected efficient antioxidants is proved in vitro and in vivo. In the second step, the antioxidant efficacy is tested ex vivo in a clinical pilot study using biopsies from in vivo-pretreated skin sites. In the third step, the in vivo efficacy of preselected antioxidants has been confirmed in clinical studies on panels of human volunteers.
Article
High-dose ultraviolet B (UVB) irradiation is known to induce apoptosis of keratinocytes, but low-dose UVB dose not. In this paper we present evidence that low-dose UVB can induce TNF-alpha-dependent apoptosis of keratinocytes. In our study, 5 mJ/cm(2) doses of UVB were not sufficient by themselves to induce apoptosis of cultured human keratinocytes, but 20 mJ/cm(2) doses of UVB were. The combination of 5 mJ/cm(2) doses of UVB and exogenous TNF-alpha (15 ng/ml) induced significant apoptosis of keratinocytes, although exogenous TNF-alpha without UVB did not. This phenomenon was accompanied by enhanced clustering of tumor necrosis factor receptor 1 (TNFR1). TNF-alpha's promotion of the induction of apoptosis by low-dose UVB was seen until 30 min after irradiation but not at 1 h. We confirmed this finding using a skin organ culture system. UVB (20 mJ/cm(2)), which did not induce transformation of epidermal keratinocytes into sunburn cells, induced apoptosis when TNF-alpha was added to the culture medium. These results suggest that one of the possible mechanisms of inducing keratinocyte apoptosis by low-dose UVB and TNF-alpha is that low-dose UVB augments ligand-binding-induced TNFR1 clustering, resulting in increased apoptotic cell death.
Article
Extracellular matrix metalloproteinases (MMPs) are crucial factors involved in connective tissue remodeling that accompanies ultraviolet radiation-induced actinic damage. This study investigated whether the cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-10 modulate the expression of MMPs in cultured human newborn skin fibroblasts. Different concentrations of TNF-alpha, IL-1 beta, and IL-10 were added to human dermal fibroblasts grown in monolayers or embedded in three-dimensional (3D) collagen gels, a model closer to skin. Supernatant from the fibroblast cell culture was collected 24 hours later. The concentrations of MMP-1 and MMP-3 were assaysed by enzyme-linked immunosorbent assay (ELISA) while the concentrations of MMP-2 and MMP-9 were analysed by zymography. Basal production of MMPs was significantly greater in fibroblasts grown in 3D gels than in cells grown as monolayers. TNF-alpha and IL-1 beta induced increases in the concentrations of MMP-1, MMP-3, and MMP-9, but not in MMP-2 or tissue inhibitor of matrix metalloproteinase (TIMP)-1 or -2. The inducibility of MMP secretion is more significant in 3D gels. IL-10 did not significantly modulate MMPs. This study demonstrated that basal concentrations of MMPs are higher in fibroblasts cultured in 3D gels and their response to cytokines is different to that of cells grown as monolayers. Cytokines can increase the collagenolytic and gelatinolytic activity involved in extracellular matrix remodeling and hence contribute to photoaging.
Article
Addition of human recombinant interleukin 6 (IL-6) to culture medium (supplemented MEM without or with 10% fetal calf serum (FCS)) of human skin fibroblasts exerted a stimulating effect in a dose-dependent manner on glycosaminoglycan (GAG) synthesis, including hyaluronic acid (hyaluronan) synthesis, of young (phase-II) skin fibroblasts in concentrations of 1 ng/ml and 10 ng/ml. Stimulation was mainly due to an increase in extracellular GAGs (secreted into culture medium), and to a lesser extent to an increase in peri- and intracellular GAGs. Stimulation with 1 ng/ml and 10 ng/ml IL-6 led to an increase in hyaluronic acid from 48% to 61% (-FCS) and from 77% to 90% (+10% FCS), respectively. Maximum stimulation, with and without FCS, was achieved by 10 ng/ml IL-6. Compared to young (phase-II) cells, senescent (phase-III) cells, showed no significant stimulation of total GAG (including hyaluronic acid) synthesis by IL-6. The diminished response of GAG- and hyaluronic acid synthesis during aging of these in vitro cultured fibroblasts should motivate further research if similar processes occur during aging in an organism.
Article
Chronic ultraviolet irradiation leads to photoaging in human skin, which is associated with degradation of connective tissue. This is partly due to the fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]). Using complementary DNA array technique we demonstrate that after UV irradiation, MMP-1, MMP-3 and the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) are time-dependently induced on the messenger RNA level in dermal fibroblasts in vitro and in vivo in human buttock skin. This increase in gene expression is paralleled by an increase of latent and active MMP-1 protein after low-dose UV-A exposure in vitro. In vivo the concentration of latent MMP-1 in suction blister fluids peaks 24 h after irradiation with 2 minimal erythema doses of solar simulated radiation. However, only a small proportion of MMP-1 in vitro (5.5 +/- 1.5%) and in vivo is active, whereas the majority of MMP-1 remains in its inactive proform. Interestingly, in suction blister fluid the concentration and duration of TIMP-1 expression exceeds that of MMP-1. Taken together, these data indicate that MMP-1 activity is tightly regulated transcriptionally and posttranscriptionally. Furthermore, the pronounced individual differences in all targets investigated provide a possible explanation for the different susceptibility of individuals to UV exposure and, thus, to the clinical features of photodamage.
Article
To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO(2)) laser resurfacing of photodamaged human skin. Serial in vivo biochemical analyses after laser therapy. Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. Subjects Volunteer sample of 28 adults, 48 to 76 years old, with clinically evident photodamage of the forearms. Intervention Focal CO(2) laser resurfacing of photodamaged forearms and serial biopsies at baseline and various times after treatment. Reverse transcriptase real-time polymerase chain reaction technology and immunohistochemistry were used to assess levels of type I and type III procollagens; matrix metalloproteinases (MMPs) 1, 3, 9, and 13; tropoelastin; fibrillin; primary cytokines interleukin 1beta and tumor necrosis factor alpha; and profibrotic cytokine transforming growth factor beta1. Production of type I procollagen and type III procollagen messenger RNA peaked at 7.5 and 8.9 times baseline levels, respectively, 21 days after treatment and remained elevated for at least 6 months. Increases in messenger RNA levels of several cytokines (interleukin 1beta, tumor necrosis factor alpha, and transforming growth factor beta1) preceded and/or accompanied changes in collagen levels. Marked increases in messenger RNA levels of MMP-1 (39 130-fold), MMP-3 (1041-fold), MMP-9 (75-fold), and MMP-13 (767-fold) were noted. Levels of fibrillin and tropoelastin rose in a delayed fashion several weeks after treatment. The biochemical changes seen after CO(2) laser resurfacing proceed through a well-organized and highly reproducible wound healing response that results in marked alterations in dermal structure. These quantitative changes may serve as a means for comparison as other therapeutic modalities meant to improve the appearance of photodamaged skin are evaluated.
Article
Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of infrared radiation on skin aging. In addition to photons, heat is likely to be generated as a consequence of infrared irradiation, and heat shock is widely considered to be an environmental stress. Here we investigated the effect of heat shock on the expressions of matrix metalloproteinase (MMP)-1, MMP-2, and MMP-3 in cultured human skin fibroblasts. Heat shock induced the expression of MMP-1 and MMP-3, but not MMP-2, at the mRNA and protein levels in a temperature-dependent manner, and caused the rapid activation of three distinct mitogen-activated protein kinases (MAPK), extracelluar signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. The heat shock-induced MMP-1 and MMP-3 expression was suppressed by the inhibition of ERK and JNK but not by p38 MAPK inhibition. Furthermore, heat shock increased the synthesis and release of interleukin-6 (IL-6) into culture media. The specific inhibition of IL-6 using a monoclonal antibody against IL-6 greatly reduced the expression of MMP-1 and MMP-3 induced by heat shock. Taken together, our results suggest that ERK and JNK play an important role in the induction of MMP-1 and MMP-3 by heat shock and that the heat shock-induced expression of MMP-1 and MMP-3 is mediated via an IL-6-dependent autocrine mechanism.
Article
It is known that solar ultraviolet (UV) irradiation exerts multiple effects on mammalian skin tissues, one of which is the induction of local and systemic immunosuppression as well as inflammation. Tumor necrosis factor-alpha (TNF-alpha) and other cytokines are suggested to play a role in these responses. Quantitative real-time polymerase chain reaction (TaqMan RTPCR) was used to elucidate the effect of UVA and UVB irradiation on the expression of genes coding for TNF-alpha, IL-1beta, IL-10, FasL, matrilysin, TACE and furin in HaCaT cells over a 48 h period (IL-1beta, interleukin-1beta; FasL, Fas ligand). Cultured HaCaT cells were either sham irradiated (control) or exposed to UVA (2000 and 8000 J/m2) or UVB (200 and 2000 J/m2) radiation. RNA was extracted from cells at 0, 4, 8, 12, 16, 24, 48 h post-irradiation and reverse transcribed to generate cDNA for subsequent real-time PCR amplification. Significant increases in the mRNA levels for all genes tested were detected in both UVA- and UVB-irradiated HaCaT cells compared with control (sham-irradiated) cells. TNF-alpha mRNA levels were immediately up-regulated (0 h) after irradiation, with maximal induction at 8 h post 2000 J/m2 UVA and 200 J/m2 UVB irradiation, at 4 h post 8000 J UVA irradiation and at 48 h post 2000 J/m2 UVB irradiation. No correlation was observed between TNF-alpha, TACE and furin mRNA induction in the different irradiated cohorts. Results suggest that time-distinct gene induction of TNF-alpha, furin, IL-1beta and matrilysin may be involved in UV-induced cellular responses, but not for TACE. In general, mRNA induction was dose dependent at some time points post-irradiation, but not throughout the whole time course tested. Our results show that quantitative real-time PCR is a useful tool in the analysis of quantitative changes of mRNA levels in cultured HaCaT cells after UV exposure.
Article
A large part of the aging phenotype, including immunosenescence, is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status we proposed to call inflammaging. Within this perspective, healthy aging and longevity are likely the result not only of a lower propensity to mount inflammatory responses but also of efficient anti-inflammatory networks, which in normal aging fail to fully neutralize the inflammatory processes consequent to the lifelong antigenic burden and exposure to damaging agents. Such a global imbalance can be a major driving force for frailty and common age-related pathologies, and should be addressed and studied within an evolutionary-based systems biology perspective. Evidence in favor of this conceptualization largely derives from studies in humans. We thus propose that inflammaging can be flanked by anti-inflammaging as major determinants not only of immunosenescence but eventually of global aging and longevity.
[Decreased stimulation of glycosaminoglycan synthesis by human skin fibroblasts by interleukin 6 within the scope of in vitro aging.]
  • Bieker E