Article

Cinnamon Extract Promotes Type I Collagen Biosynthesis via Activation of IGF-I Signaling in Human Dermal Fibroblasts

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  • DHC Corporation, Japan, Tokyo
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Abstract

The breakdown of collagenous networks with aging results in hypoactive changes in the skin. Accordingly, reviving stagnant collagen synthesis can help protect dermal homeostasis against aging. We searched for type I collagen biosynthesis-inducing substances in various foods using human dermal fibroblasts and found that cinnamon extract facilitates collagen biosynthesis. Cinnamon extract potently up-regulated both mRNA and protein expression levels of type I collagen without cytotoxicity. We identified cinnamaldehyde as a major active component promoting the expression of collagen by HPLC and NMR analysis. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, we examined the effect of cinnamaldehyde on IGF-I signaling. Treatment with cinnamaldehyde significantly increased the phosphorylation levels of the IGF-I receptor and its downstream signaling molecules such as insulin receptor substrate-1 and Erk1/2 in an IGF-I-independent manner. These results suggested that cinnamon extract is useful in antiaging treatment of skin.

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... The same result of increased hardness level was reported by Laheng et al. (2016) in striped catfish, after feeding a diet supplemented with 1% cinnamon leaf powder and 0.1% cinnamon leaf extract. This finding indicates that cinnamon powder and extract can improve meat hardness levels by increasing protein deposition in the form of collagen in the fibroblasts (Takasao et al. 2012). The improved striped catfish meat texture level was associated with color quality showing a decreased yellowness level and an increased lightness level. ...
... High xanthophyll production in meat is caused by the meat lipid degradation due to environmental stress (temperature storage and microorganism effect), resulting in slow xanthophyll metabolism. Decreased meat lipids, which also caused increased meat protein content indicate that cinnamon powder, cinnamon extract, and cinnamaldehyde, can increase protein deposition through the transcription of the IGF-1 (insulin-like growth factor I) hormone and collagen protein synthesis enhancement, which increases the protein deposition in meat fibroblasts (Takasao et al. 2012). Anderson et al. (2016) added that cinnamon supplementation can inhibit triacylglycerol synthesis by inhibiting 3T3-L1 cell activation in muscle adipose tissue. ...
Article
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This study aimed to evaluate the effect of dietary supplementation with cinnamon products on the growth, meat quality, liver structure, and blood composition of striped catfish. All diets were developed using intact protein and formulated to have similar protein (25.5–25.7%) and lipid (7.3–7.9%) contents. The control diet was formulated without cinnamon products (C), while dietary treatments were formulated by adding 1% cinnamon powder (CM), 0.1% cinnamon extract (CE), and 0.1% cinnamaldehyde (CN). Each treatment contained four replications. Striped catfish (n=25, average size of 11.97±0.55 g) were stocked in 2 × 1 × 1.5 m³ cages on 20 × 10 m² pond and fed until apparent satiation twice a day for 72 days. The results demonstrated the differences among CM, CE, and CN diets compared to C diet based on protein retention (27.77% vs 32.62, 34.39, 34.96%, respectively), lipid retention (71.10% vs 60.96, 52.83, 52.93%, respectively), meat hardness (197.07 gf vs 278.37, 283.87, 248.27 gf), lightness (48.37 vs 52.73, 49.93, 48.62, respectively), muscle lipid (7.74% vs 2.61, 2.72, 3.80%, respectively), muscle protein (13.17% vs 18.75, 18.66, 16.35%, respectively), malondialdehyde (0.13 μmol/L vs 0.07, 0.06, 0.06 μmol/L, respectively), and superoxide dismutase enzyme (3.52 U/g protein vs 7.70, 8.71, 7.92 U/g protein, respectively). The CM, CE, and CN diets also improved the fish liver tissue followed by decreased low-density lipoprotein level in blood plasma (1226.27 mg/dL vs 839.77, 811.52, 849.40 mg/dL, respectively). Therefore, cinnamon products can improve the growth, meat quality, liver structure, and blood composition of striped catfish.
... Collagen synthesis was stimulated in human dermal fibroblasts by C. verum extracts (Takasao et al., 2012). C. verum extract enhanced both mRNA and protein expression levels of type I collagen without cytotoxicity, and cinnamaldehyde was the most active component stimulating the expression of collagen, suggesting that C. verum extracts might be useful in skin anti-aging treatments (Takasao et al., 2012). ...
... Collagen synthesis was stimulated in human dermal fibroblasts by C. verum extracts (Takasao et al., 2012). C. verum extract enhanced both mRNA and protein expression levels of type I collagen without cytotoxicity, and cinnamaldehyde was the most active component stimulating the expression of collagen, suggesting that C. verum extracts might be useful in skin anti-aging treatments (Takasao et al., 2012). Moreover, C. verum extracts inhibited osteoclastogenesis (Tsuji-Naito, 2008). ...
Article
The genus Cinnamomum includes a number of plant species largely used as food, food additives and spices for a long time. Different traditional healing systems have used these plants as herbal remedies to cure diverse ailments. The aim of this comprehensive and updated review is to summarize the biodiversity of the genus Cinnamomum, its bioactive compounds, the mechanisms that underlie the pharmacological activities and toxicological safety. All the data in this review have been collected from databases and recent scientific literature including Web of Science, PubMed, ScienceDirect etc. The results showed that the bioactive compounds of Cinnamomum species possess antimicrobial, antidiabetic, antioxidant, anti-inflammatory, anticancer and neuroprotective effects. The preclinical (in vitro/in vivo) studies provided the possible molecular mechanisms of these action. As a novelty, recent clinical studies described in this paper support and confirm the pharmacological importance of the genus Cinnamomum. In conclusion, the obtained results from preclinical studies and clinical trials, as well as reduced side effects provide insights into future research of new drugs based on extracts and bioactive compounds from Cinnamomum plants.
... The increase in protein retention as a result of adding cinnamon may be due to contribution of effective polyphenol compounds in improving metabolism of sugar and fatty acids in the blood, as well as improving health of fish, enhanced protein availability, which reflected in protein retention, which contributed on live biomass of fish (Setiawati et al., 2016a). Cinnamon containing cinnamaldehyde compounds helped stimulate insulin-like growth factor (IGF-1) (Takasao et al., 2012). Which has a positive role in promoting production of protein and colagen deposition, which plays a major role in increasing biomass of fish , NRC, 2011. ...
... The use of cinnamon and coriander powder resulted in a significant increase (P≤ 0.05) in protein levels in edible portion compared to control diet ( Table 6). The results included an increase in content of raw protein consumed portion of fish fed on diets containing cinnamon powder, which may be due to cinnamon content of cinnamaldehyde compound, which has ability to activate insulin-like growth factor (IGF-1), which dynamically enhances protein and collagen production in body tissues caused increases deposition of proteins to build muscle in body (Abdel-Tawwab et al., 2018 andTakasao et al., 2012). As well as contribution of polyphenol compounds that have efficacy in improving blood sugar metabolism, fatty acids as well as their role in improving fish health, thus making the protein prepared to supporting fish growth (Setiawati et al., 2016a). ...
... Sinamaldehid merupakan senyawa utama yang terdapat di dalam minyak atsiri daun kayu manis (Khazanah et al. 2017). Sinamaldehid mampu mengaktifkan insulinlike growth factor yang dapat meningkatkan biosintesis protein dan kolagen sehingga meningkatkan deposisi protein dalam tubuh untuk membentuk daging (Takasao et al. 2012). Jusadi et al. (2016) melaporkan bahwa pemberian tepung daun kayu manis 1% pada ikan mas selama 37 hari mampu memberikan kualitas daging yang kompak dan rasa yang lebih manis. ...
... Penambahan tepung daun kayu manis menunjukkan nilai jumlah konsumsi pakan yang tidak berbeda nyata (p>0,05), namun dapat meningkatkan bobot akhir, laju pertumbuhan harian, dan Pertumbuhan ikan nila ditandai dengan meningkatnya bobot akhir sejalan dengan meningkatnya laju pertumbuhan dan retensi protein ikan nila. Sinamaldehid daun kayu manis juga memiliki kemampuan untuk mengaktifkan insulin-like growth factor (IGF-1) yang mampu meningkatkan biosintesis protein dan kolagen dalam jaringan tubuh (Takasao et al. 2012). ...
Article
Tekstur dan aroma menjadi salah satu indikator kualitas filet ikan nila untuk diekspor. Salah satu upaya untuk meningkatkan kualitas filet ikan dapat dilakukan dengan pemberian tepung daun kayu manis pada pakan. Penelitian ini bertujuan untuk menentukan periode waktu pemberian tepung daun kayu manis (DKM) yang dapat meningkatkan kualitas daging dan pertumbuhan ikan nila. Dosis tepung daun kayu manis yang diberikan pada adalah 1%. Pakan diberikan selama 15 hari (15D), 30 hari (30D), 45 hari (45D) dan 60 hari (60D) sebelum panen. Pemeliharaan ikan dilakukan menggunakan 20 hapa berukuran 2x1x1,5 m3 dengan padat tebar 20 ekor ikan/hapa, bobot ikan 30,23±0,15 g/ekor dan panjang 11-13 cm/ekor. Hasil penelitian menunjukkan bahwa pemberian tepung DKM mampu meningkatkan kualitas tekstur daging ikan nila dengan perlakuan terbaik pada 30D dengan nilai 547,5±9,1 gf. Uji kinerja pertumbuhan bobot dan retensi protein perlakuan 60D memberikan nilai yang berbeda nyata dibanding kontrol dengan nilai 3.854,3±219,0 g dan 44,0±6,3%. Nilai glikogen hati menunjukkan semua perlakuan memberikan nilai yang berbeda nyata dibanding kontrol dengan nilai berturut-turut 0,33±0,01, 0,35±0,01, 0,35±0,00,dan 0,35±0,00 (mg g-1). Nutrien berupa protein, lemak dan kadar air paling baik ditunjukkan pada perlakuan 60D dengan nilai masing-masing 18,8±0,7%, 1,85±0,14%, dan 76,6±0,9%. Berdasarkan hasil penelitian, dapat disimpulkan bahwa pemberian pakan mengandung daun kayu manis selama periode waktu 30 hari memberikan kualitas kekerasan daging ikan paling tinggi.
... stem barks, is well known for its ability to increase skin blood flow and for its antimicrobial properties against different bacteria including P. aeruginosa. These properties have been shown in different studies [9][10][11][12][13][14][15][16]; however, there are few reports of its healing effects [17,18]. ...
... A study by Takasao et al. [17] showed that the in vitro incubation of cinnamaldehyde with human skin fibroblasts induces collagen synthesis. More recently, this compound was found to stimulate human endothelial cell proliferation in vitro [18]. ...
Article
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Wound healing can be delayed following colonization and infection with the common bacterium Pseudomonas aeruginosa. While multiple therapies are used for their treatment, these are ineffective, expensive, and labour-intensive. Thus, there is an enormous unmet need for the treatment of infected wounds. Cinnamaldehyde, the major component of cinnamon oil, is well known for its antimicrobial properties. Herein, we investigated the effects of sub-inhibitory concentrations of cinnamaldehyde in the virulence of P. aeruginosa. We also assessed its healing potential in P. aeruginosa-infected mouse skin wounds and the mechanisms involved in this response. Sub-inhibitory concentrations of cinnamaldehyde reduced P. aeruginosa metabolic rate and its ability to form biofilm and to cause haemolysis. Daily topical application of cinnamaldehyde on P. aeruginosa-infected skin wounds reduced tissue bacterial load and promoted faster healing. Lower interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and nitric oxide levels were detected in cinnamaldehyde-treated wound samples. Blockage of transient receptor potential ankyrin 1, the pharmacological target of cinnamaldehyde, abrogated its healing activity and partially reversed the inhibitory actions of this compound on VEGF and IL-17 generation. We suggest that topical application of sub-inhibitory concentrations of cinnamaldehyde may represent an interesting approach to improve the healing of P. aeruginosa-infected skin wounds.
... Similarly, preincubation of human dermal fibroblasts with thioredoxin-1 (antioxidant) shown to inhibit UVA-induced MMP-1 upregulation, and blocked UVBinduced procollagen 1 degradation [6]. Another study showed that cinnamon extracts potently increased the type I collagen biosynthesis in dermal fibroblast without cytotoxicity [27]. The key finding of our study is that, t-CA pretreatment dosedependently inhibited UVA-induced MMP-1 and MMP-3 upregulation, and restored type I procollagen in skin fibroblasts. ...
... Nevertheless, based on the convincing evidence from our in vitro studies, we postulate that antioxidant or anti-inflammatory properties of t-CA at least in part may contribute to prevent UVAinduced dermal damage in mice. Evidence from previous in vitro and in vivo studies demonstrated the potent antioxidant and antiinflammatory properties of cinnamon extracts, and treatment with cinnamon extract promoted type I collagen in dermal fibroblasts [18,27]. Incorporating of antioxidants in preparation of sunscreens and skincare products is a growing trend to replenish the natural reservoirs and texture of the skin. ...
Article
Background: UVA irradiation-induced skin damage/photoaging is associated with redox imbalance and collagen degradation. Objective: Dermato-protective efficacies of trans-cinnamic acid (t-CA), a naturally occurring aromatic compound have been investigated against UVA irradiation, and elucidated underlying molecular mechanism. Methods: Human foreskin fibroblast-derived (Hs68) cells and nude mice were treated with t-CA prior to UVA exposure, and assayed the anti-photoaging effects of t-CA. Results: We found t-CA (20-100 μM) pretreatment substantially ameliorated UVA (3 J/cm2)-induced cytotoxicity, and inhibited intracellular ROS production in Hs68 cells. UVA-induced profound upregulation of metalloproteinase (MMP)-1/-3 and degradation of type I procollagen in dermal fibroblasts were remarkably reversed by t-CA, possibly through inhibition of AP-1 (c-Fos, but not c-Jun) translocation. The t-CA-mediated anti-photoaging properties are associated with increased nuclear translocation of Nrf2. Activation of Nrf2 signaling is accompanied with induction of HO-1 and γ-GCLC expressions in t-CA-treated fibroblasts. Furthermore t-CA-induced Nrf2 translocation is mediated through PKC, AMPK, CKII or ROS signaling cascades. This phenomenon was confirmed with respective pharmacological inhibitors, GF109203X, Compound C, CKII inhibitor or NAC, which blockade t-CA-induced Nrf2 activation. Silencing of Nrf2 signaling with siRNA showed no anti-photoaging effects of t-CA against UVA-induced ROS production, loss of HO-1 and type I collagen degradation in fibroblasts. In vivo evidence on nude mice revealed that t-CA pretreatment (20 or 100 mM/day) significantly suppressed MMP-1/-3 activation and maintained sufficient type I procollagen levels in biopsied skin tissue against UVA irradiation (3 J/cm2/day for 10-day). Conclusion: t-CA treatment diminished UVA-induced photoaging/collagen degradation, and protected structural integrity of the skin.
... An Alinked proanthocyanidin trimer molecule isolated from the CZ extract has shown to contain a significant proportion of this inhibitory activity [21]. CZ extracts facilitate collagen biosynthesis in human dermal fibroblasts [22]. CZ extract up-regulated both mRNA and protein expression levels of type I collagen without cytotoxicity, cinnamaldehyde was the major active component promoting the expression of collagen by HPLC and NMR analysis. ...
... CZ extract up-regulated both mRNA and protein expression levels of type I collagen without cytotoxicity, cinnamaldehyde was the major active component promoting the expression of collagen by HPLC and NMR analysis. This suggests that CZ extracts might be useful in anti-aging treatment of skin [22]. CZ extracts have also exhibited strong inhibitory effects on osteoclastogenesis [23]. ...
... It also has remarkable pharmacological effects in the treatment of type II diabetes and insulin resistance (Sathishkumar et al., 2009). Up-regulation of both mRNA and protein expression levels of type I collagen using cinnamon extract containing cinnamaldehyde was reported (Takasao, Tsuji-Naito, Ishikura, Tamura, & Akagawa, 2012). Cinnamaldehyde is a naturally occurring aromatic ␣,␤-unsaturated aldehyde derived from cinnamon. ...
... Cinnamon bark powder (2 g) was extracted with 100 ml of chloroform at 30 • C for 2 h. The extract was filtered through filter paper and concentrated to 50 ml at 50 • C (Takasao et al., 2012). The concentration of cinnamaldehyde was determined using UV-visible spectral analysis as described below. ...
Article
Biomaterials based entirely on biological resources are ideal for tissue engineering applications. Here we report the preparation of hybrid collagen scaffolds comprising gulmohar seed polysaccharide (GSP) and cinnamon bark extract as cross-linking agent. 1H NMR spectrum of GSP confirms the presence of galactose and mannose in the ratio of 1:1.54, which was further corroborated using FT-IR. The hybrid scaffolds show better enzyme and thermal stability in contrast to pure collagen scaffold probably due to weak interactions from GSP and covalent interaction through cinnamaldehyde. Gas permeability and scanning electron microscopic analysis show that the porosity of the hybrid scaffolds is slightly reduced with the increase in the concentration of GSP. The infrared and circular dichroic spectral studies show that the secondary structure of the collagen did not change after the interaction with GSP and cinnamaldehyde. The hybrid scaffolds stabilized with cinnamaldehyde show good antimicrobial activity against the common multi-drug resistant wound pathogens. These results suggest that the prepared hybrid scaffolds have great potential for antimicrobial wound dressing applications.
... Menurut Vasanthi dan Parameswari (2010), senyawa bioaktif kayu manis mampu meningkatkan penyerapan glukosa, pemanfaatan asam lemak dalam tubuh. Takasao et al. (2012), menambahkan kandungan sinamaldehid kayu manis mampu mengaktifasi Insulin-like growth factor (IGF-1) yang meningkatkan biosintesis protein dan kolagen dalam jaringan tubuh sehingga meningkatkan deposisi protein dalam tubuh untuk membentuk otot (daging), tulang, organ tendon, dan ligament (NRC 2011). ...
Article
p>This study aimed to evaluate the effect of extract and cinnamon (Cinnamomum burmannii) leaf flour in the diet in increasing quality of meat of catfish (Pangsianodon hypopthalmus). Catfish with a weight of 319.64 ± 35.99 g/nets reared in 9 nets with dimension 2x1x1,5 m3 at a density of 15 fish/nets for 60 days of maintenance. The fish were fed with leaves of cinnamon at a dose that was: 0% cinnamon leaf, 0.1% cinnamon leaf extract, and 1% cinnamon leaf flour. The fish were fed 2 times a day with the feeding rate of 3% of the average weight of the body. The results showed the treatment of leaf extract and flour, cinnamon capable of decreasing levels of body fat, fat meat by 10,31-12,27%, 37,26-50,23%, respectively, compared to controls (p<0,05), however, cinnamon leaf extract treatment is more effective in improving the quality of meat catfish that looks meat texture compact, white flesh color and a slightly sweet taste. Keywords: cinnamon leaf, meat quality, Pangsianodon hypopthalmus</p
... Similarly, cinnamon is known for its antidiabetic and anticancer activity (Rao and Gan 2014) and is also known to have anti-ageing skin benefits. The active ingredient, cinnamaldehyde is known to promote the biosynthesis of type I collagen, thus reducing the hypoactive changes in the ageing skin (Takasao et al. 2012). Dermatology is a branch of western medicine that deals with the study of skin, its anatomy, disorders and their respective symptomatic treatments via ingestion and topical uses of synthetic medicines. ...
Chapter
Skin conditions causing discomfort are of common occurrence. Dermatology is a branch of western medicine dedicated to the study of skin complications which is complimented with medicine to provide symptomatic treatment. These skin disorders have also been mentioned in Ayurveda as the disease of 'Kustha' which is caused by the imbalances in tridoshas and dhatus (bodily elements). Ayurvedic texts describe the use of plant derived polyherbal medicines and other products of common use in an Indian kitchen with potential to provide relief and treat a variety of skin conditions. Despite their diverse uses, they are known to impart adverse effects and interfere with the metabolome of the cells. This chapter outlines different skin conditions and an integrated approach of western and Ayurvedic medicines to treat them, some plant derived products of common usage and their associated side effects.
... aeruginosa) and its reduction of the inflammatory reaction by inhibiting high-influx of inflammatory infiltrates. Moreover, numerous reports have demonstrated that CME is capable of accelerating collagen production and the induction of mammalian endothelial cell growth, which is crucial for wound healing [226,235,236]. This was demonstrated in a study by Ferro et al. ...
Article
Full-text available
The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections affecting patients’ quality of life. Unfortunately, antibiotics are not always helpful due to their poor penetration of bacterial biofilms and the emergence of antimicrobial resistance. Hence, there is an urgent need to explore antibiotics-free compounds/formulations with proven or potential antimicrobial, anti-inflammatory, antioxidant, and wound healing efficacy. The mechanism of antibiotics-free compounds is thought to include the disruption of the bacteria cell structure, preventing cell division, membrane porins, motility, and the formation of a biofilm. Furthermore, some of these compounds foster tissue regeneration by modulating growth factor expression. In this review article, the focus is placed on a number of non-antibiotic compounds possessing some of the aforementioned pharmacological and physiological activities. Specific interest is given to Aloe vera, curcumin, cinnamaldehyde, polyhexanide, retinoids, ascorbate, tocochromanols, and chitosan. These compounds (when alone or in formulation with other biologically active molecules) could be a dependable alternative in the management or prevention of chronic wounds.
... In this context, also reported high levels of growth hormone in the blood of European sea bass treated with dietary cinnamon. The activation of insulin-like growth factor (IGF-1) by medicinal herbs is thought to enhance growth hormone production from the pituitary gland (Takasao et al., 2012), leading to the improved synthesis of proteins needed to build the entire body tissues (Hlebowicz et al., 2009). The enhanced secretion of growth hormone could also explain the increased growth performance of European sea bass in this study. ...
Article
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Coriander seeds are among the functional herbal supplements, but their effects on aquatic animals are still lacking. Herein we evaluated the effects of coriander seeds on the growth performance, growth hormone, antibacterial capacity, and immune response of European sea bass (Dicentrarchus labrax). Fish with initial mean weights of 5.08 ± 0.12 g/fish were allocated in four groups (in triplicate) and fed dietary coriander at 0, 5, 10, and 20 g/kg for 150 days. The growth performance, feed utilization, and survival rate of fish-fed dietary coriander meaningfully increased (P<0.05). The protein efficiency ratio gradually increased (P<0.05) in fish-fed coriander seeds compared with the control. On the other hand, the feed conversion ratio was gradually decreased (P<0.05) in fish-fed coriander seeds comparing with the control. The survival rate was markedly increased (P<0.05) in European sea bass-fed dietary coriander regardless of the inclusion level. Further, no differences were seen among fish fed varying levels of coriander (P<0.05). The level of blood growth hormone was markedly higher (P<0.05) in European sea bass-fed dietary coriander at 20 g/kg than fish-fed 0 and 5 g/kg. The abundance of intestinal Vibrio spp. and Faecal Coliform were obviously lower (P<0.05) in fish fed 10 and 20 g/kg than fish fed the coriander-free diet. Further, fish fed 20 g/kg had lower (P<0.05) Vibrio spp. and Faecal Coliform counts than fish fed 10 g/kg. Fish fed dietary coriander had significantly higher (P<0.05) hematocrit, hemoglobulin, red blood cells (RBCs), and white blood cells (WBCs) than fish fed the control. The lysozyme and phagocytic activities were meaningfully increased (P<0.05) in fish fed 10 and 20 g/kg compared with fish fed 0 and 5 g/kg of dietary coriander. In conclusion, dietary coriander could be included in the diets at 10–20 g/kg to improve the growth performance, growth hormone, feed utilization, and immune response of European sea bass.
... 2) Insulin secretion and obesity: Since impaired insulin secretion was one of the pathophysiological abnormalities in type 2 diabetes, IGF (insulin-like growth factors)-I, which was shown to inhibit insulin secretion, would play a key role in the process (Leahy and Vandekerkhove, 1990;Pørksen et al., 1997). CA could increase the phosphorylation levels of the IGF-I receptor and its downstream signaling molecules (Takasao et al., 2012). It was interesting that binding IGF-I to its receptor could cause the activation of the tyrosine kinase, leading to autophosphorylation of the intrinsic tyrosines, which transduced the IGF-I signal to a complex network that was ultimately responsible for cell proliferation, modulation of tissue differentiation, and protection from apoptosis (Laviola et al., 2007). ...
Article
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Peptide–protein complexes play important roles in multiple diseases such as cardiovascular diseases (CVDs) and metabolic syndrome (MetS). The peptides may be the key molecules in the designing of inhibitors or drug targets. Many Chinese traditional drugs are shown to play various roles in different diseases, and comprehensive analyses should be performed using networks which could offer more information than results generated from a single level. In this study, a network analysis pipeline was designed based on machine learning methods to quantify the effects of peptide–protein complexes as drug targets. Three steps, namely, pathway filter, combined network construction, and biomarker prediction and validation based on peptides, were performed using cinnamon (CA) in CVDs and MetS as a case. Results showed that 17 peptide–protein complexes including six peptides and four proteins were identified as CA targets. The expressions of AKT1, AKT2, and ENOS were tested using qRT-PCR in a mouse model that was constructed. AKT2 was shown to be a CA-indicating biomarker, while E2F1 and ENOS were CA treatment targets. AKT1 was considered a diabetic responsive biomarker because it was down-regulated in diabetic but not related to CA. Taken together, the pipeline could identify new drug targets based on biological function analyses. This may provide a deep understanding of the drugs’ roles in different diseases which may foster the development of peptide–protein complex–based therapeutic approaches.
... Kayu manis merupakan spesies dari genus Cinnamomum dengan famili Lauraceae yang memiliki senyawa polifenol, sinamaldehid, tanin dan flavonoid sebagai tanaman herbal (Jayaprakasha dan Rao 2011;Vangalapati et al., 2012;Azima et al. 2004;Prasad et al., 2009). Sinamaldehid merupakan senyawa terbesar penyusun daun kayu manis (Khazanah et al., 2017) dan dapat membentuk biomasa daging dengan cara peningkatan deposisi protein dalam pembentukan otot dari adanya peningkatan biosintesis protein dan kolagen (Takasao et al., 2012). Senyawa polifenol dan antioksidan mampu menghambat terbentuknya trigliserida yang merupakan deposit utama lemak dalam tubuh (Ciftci et al., 2010). ...
Article
This study aims to apply the appication of cinnamon leaf flour in feeding to the meat quality of vannamei shrimp (Litopenaeus vannamei). The concentrations of cinnamon leaf flour given were 0%, 0,5%, 1,0% and 1,5%. The vannamei shrimp used had an average weight of 10,06 ± 0,15 g/tail which was kept in an aquarium for 60 days. The quality test result showed that on 1,5% treatment, the shrimp meat had the lowest fat content on 1,46% and the highest HDL content on 96,75%. The results of organoleptic test on the quality of shrimp meat showed no difference in aroma, color, taste and texture that could be detected by the panelists (p>0,05). The average responses were: aroma 4,43, 4,31, 4,45; color 4,67, 4,67, 4,60; texture 4,52, 4,67, 4,52 and taste 4,48, 4,38, 4,52. From the results of the organoleptic test, all parameters showed a number above 4, where the value of 4 indicated that tested parameters were as good as the control (0%).
... The enhanced growth performance in this study can be attributed to increased growth hormone levels in the blood of European seabass treated with cinnamon. It has been hypothesized that cinnamon can increase the secretion of growth hormone from the pituitary gland by activating insulin-like growth factor (IGF-1) under the effect of cinnamaldehyde [49]. High expression of IGF-1 led to the synthesis of proteins required to fulfill the primary metabolic function and build entire body tissues [50]. ...
Article
Full-text available
Dietary cinnamon has several bioactive compounds with growth-promoting and immunomodulation potential and is suggested for finfish species. This study evaluated the inclusion of cinnamon at 0, 10, 15, and 20 g/kg in European sea bass (Dicentrarchus labrax) diets. After 90 days, the highest final weight, weight gain, specific growth rate, protein efficiency ratio, and the lowest feed conversion ratio were seen in fish treated with 10 g/kg (p < 0.05). Further, the measured growth hormone in the blood indicated that fish treated with 10 g/kg had a higher level than fish 0 and 20 g/kg. After the feeding trial, fish treated with cinnamon at varying levels had higher lipid content than fish before the feeding trial (p < 0.05). Lower Vibrio spp. and Faecal Coliform counts were observed in fish treated with cinnamon than fish fed a cinnamon-free diet (p < 0.05). The hematocrit level was markedly (p < 0.05) increased in fish fed cinnamon at 10 g/kg compared to the control without significant differences with fish fed 15 and 20 g/kg. Hemoglobin was significantly increased in fish treated with cinnamon at 10, 15, and 20 g/kg compared to fish fed a cinnamon-free diet (p < 0.05). Red and white blood cells (RBCs and WBCs) were meaningfully (p < 0.05) increased in fish treated with cinnamon compared with the control. Markedly, fish treated with cinnamon had higher serum total lipids than the control with the highest value in fish treated with 15 g/kg (p < 0.05). The lysozyme activity was markedly higher in fish treated with 15 g cinnamon/kg than fish fed 0, 10, and 20 g/kg (p < 0.05). Moreover, phagocytic activity was significantly higher in fish treated with cinnamon at 10, and 15 g/kg than fish fed 0 and 20 g/kg (p < 0.05). In conclusion, dietary cinnamon is suggested at 10–15 g/kg for achieving the high production and wellbeing of European sea bass.
... The enhanced growth performance in this study can be attributed to increased growth hormone levels in the blood of European seabass treated with cinnamon. It has been hypothesized that cinnamon can increase the secretion of growth hormone from the pituitary gland by activating insulin-like growth factor (IGF-1) under the effect of cinnamaldehyde [49]. High expression of IGF-1 led to the synthesis of proteins required to fulfill the primary metabolic function and build entire body tissues [50]. ...
Article
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Dietary cinnamon has several bioactive compounds with growth-promoting and immunomodu-lation potential and is suggested for finfish species. This study evaluated the inclusion of cinna-mon at 0, 10, 15, and 20 g/kg in European sea bass (Dicentrarchus labrax) diets. After 90 days, the highest final weight, weight gain, specific growth rate, protein efficiency ratio, and the lowest feed conversion ratio were seen in fish treated with 10 g/kg (P < 0.05). Further, the measured growth hormone in the blood indicated that fish treated with 10 g/kg had a higher level than fish 0 and 20 g/kg. After the feeding trial, fish treated with cinnamon at varying levels had higher lipid con-tent than fish before the feeding trial (P < 0.05). Lower Vibrio spp. and Faecal Coliform counts were observed in fish treated with cinnamon than fish fed cinnamon-free diet (P < 0.05). The hematocrit level was markedly (P < 0.05) increased in fish fed cinnamon at 10 g/kg compared to the control without significant differences with fish fed 15 and 20 g/kg. Hemoglobin was signifi-cantly increased in fish treated with cinnamon at 10, 15, and 20 g/kg compared to a fish-fed cin-namon-free diet (P < 0.05). Red and white blood cells (RBCs and WBCs) were meaningfully (P < 0.05) increased in fish treated with cinnamon compared with the control. Markedly, fish treated with cinnamon had higher serum total lipids than the control with the highest value in fish treat-ed with 15 g/kg (P < 0.05). The lysozyme activity was markedly higher in fish treated with 15 g cinnamon/kg than fish fed 0, 10, and 20 g/kg (P < 0.05). Moreover, phagocytic activity was signif-icantly higher in fish treated with cinnamon at 10 and 15 g/kg than fish fed 0 and 20 g/kg (P < 0.05). In conclusion, dietary cinnamon is suggested at 10-15 g/kg for achieving the high produc-tion and wellbeing of European sea bass.
... Importantly, cinnamon nanoparticles may enhance the development of beneficial microorganisms and microbial enzyme activities and/or inhibit pathogens in the digestive tract that consequently improve the feed digestibility and growth rate of fish [14]. Additionally, cinnamaldehyde was able to stimulate the insulin-like growth factor and trigger protein and collagen biosynthesis in the tissues thus increasing the deposition of proteins to build the body muscle [39]. Cinnamaldehyde supplementation for grass carp boosted the capacity of digestion and absorption through improving the activities of hepatopancreatic and intestinal digestive enzymes (trypsin chymotrypsin, amylase and lipase) thus improving the growth performance [40]. ...
Article
The present study was conducted to investigate the effects of dietary cinnamaldehyde nanoemulsion (CNE) on growth, digestive activity, antioxidant and immune responses and resistance against Streptococcus agalactiae (S. agalactiae) in Nile tilapia. Four experimental diets were formulated containing CNE at levels of 0, 100, 200 and 300 mg/kg diet for 12 weeks. At the end of the experiment, all fish were challenged by S. agalactiae. The results showed that the final body weight was increased in fish groups fed 200 and 300 mg CNE/kg diet by 18.4 and 17.2 % with respect to the control group. Moreover, feed conversion ratio and digestive enzymes` activities were improved in groups fed 200 and 300 then 100 mg of dietary CNE/kg diet. Groups fed CNE exhibited a significant increase in serum immune-related parameters when compared with control group. Additionally, the hypocholesterolemic effects was achieved after CNE feeding unlike the control group in a dose dependent manner. With increasing dietary CNE levels, genes expression of cytokines and antioxidant enzymes were upregulated. Less severe adverse clinical symptoms and respectable cumulative mortalities associated with S. agalactiae infection were observed in fish fed CNE. To our knowledge, this study was the first offering a protective effect of CNE against S. agalactiae infection in Nile tilapia with a maximum down-regulation of cylE and hylB virulence genes expression noticed in group fed 300 mg of CNE/kg diet (up to 0.10 and 0.19- fold, respectively). Therefore, the present study recommended that an incorporation of CNE at level of 300 mg/kg diet for Nile tilapia could promote their growth, enhance their immunity and antioxidant status and provide protection against virulent S. agalactiae.
... Cinnamaldehyde It promotes type I collagen biosynthesis within dermal fibroblasts [183] Carrot ...
Chapter
The concept of beauty and cosmetics is as ancient as mankind and civilization where everyone is obsessed with looking charming and young. A cosmetic is defined by the US Food and Drug Administration as the preparation used for cleaning, perfuming, and improving the appearance of the human body. Plants have emerged as the best source of cosmetic ingredients that meet the characteristics of efficiency and safety, thus increasingly replacing synthetic ingredients. Accordingly, there is a growing demand for naturally based cosmetics worldwide and an ever-growing interest in understanding their molecular and mechanistic aspects. In this chapter, we discussed the role of plants in cosmetology and skin care and how the various chemical structures exert biological activities on the skin of human.
... Pemberian tepung daun kayu manis yang berlebih dihindari karena daun kayu manis memiliki zat antinutrisi berupa tanin dan saponin (Azima et al, 2004) Namun demikian, terdapat kandungan lain pada daun kayu manis yakni kandungan sinamaldehid, flavonoid, eugenol dan lainnya yang diduga berperan sebagai antioksidan, sehingga penambahan daun kayu manis dapat meningkatkan imunitas (Safratilofa et al. 2014) Kandungan sinamaldehid pada daun kayu manis juga dapat meningkatkan metabolisme lemak, selain berfungsi sebagai antioksidan (Jayaprakasha dan Rao, 2011). Menurut Takasao et al.(2012), menambahkan kandungan sinamaldehid kayu manis mampu mengaktifasi insulin-like growth factor (IGF-1) yang meningkatkan biosintesis protein dan kolagen dalam jaringan tubuh sehingga meningkatkan deposisi protein dalam tubuh untuk membentuk otot (daging). Senyawa bioaktif dalam daun kayu manis tersebut diduga berperan dalam meningkatkan pertumbuhan ikan. ...
Article
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Cork fish is one of the commodities from the freshwater fisheries sector which is commonly found in rivers, swamps and swamps that have high economic value and high market demand. The availability of cork fish is still limited to the results of their catch in the wild. And efforts to develop cork fish culture are still small due to slow growth in cork fish and the low response of cork fish to commercially-made feed compared to natural feed. This research is intended to improve the growth of cork fish fed with cinnamon leaf flour (Cinnamomumm burnamani) at different doses.The design used in this study was a completely randomized design (CRD) consisting of 4 treatments with 3 replications. The treatments performed were control (P1), addition of 0.5% cinnamon leaf flour (P2), addition of cinnamon leaf flour 1% (P3), and addition of cinnamon leaf flour 1.5% (P4). The research parameters observed were absolute weight, absolute length, daily growth rate, EP, fat in SR fish body, and cork fish water quality. The results showed that the addition of cinnamon leaf flour at a dose of 1% influenced the growth of absolute weight, absolute length, LPH, and EP. The addition of anis wood leaf flour with a dose of 1.5% can reduce fat content in the body of cork fish.Keywords: Canna striata, Cinnamomum burnamni
... Lastly, it can activate insulin-like growth factor-1 (IGF1) signaling in fibroblasts, which reduces insulin resistance and improves blood glucose control. Moreover, cinnamon can down-regulate insulin signaling in adipocytes (Takasao et al., 2012). Beyond effects on glucose homeostasis, cinnamon has positive effects on other aspects of PCOS patient health. ...
Article
Ethnopharmacological relevance Cinnamon as a traditional medicine has been widely used in various disorders such as headache, toothache, common cold, diarrhea, flatulence, fever, amenorrhea frigidity. However, the effect of cinnamon supplementation on metabolic parameters of polycystic ovary syndrome (PCOS) patients has not been fully assessed. Aim of the study Clinical trials have shown contradictory effects of cinnamon supplementation on metabolic parameters of polycystic PCOS patients. Therefore, we evaluated the effect of cinnamon supplementation on metabolic parameters of PCOS patients through a systematic review and meta-analysis of clinical trials. Materials and methods PubMed, Embase, the Cochrane library, Scopus and Web of Science databases (until August 2019) were searched to identify potential clinical trials with information on cinnamon supplementation on metabolic parameters among PCOS patients. Weighted Mean Differences was pooled using a random-effects model. Standard methods were used for assessment of heterogeneity, publication bias and sensitivity analysis. Results Pooling five clinical trials (five treatment arms) together did not show any significant effect on body weight (WMD: -0.74 kg, 95% CI: -3.17 to 1.69) and body mass index (BMI) (WMD: -1.47, 95% CI: -4.07 to 1.12). Our results illustrated that a significant decrease of fasting blood sugar (WMD: -5.32, mg/dL95% CI: -10.46 to -0.17), fasting insulin (WMD: -4.10, μIU/dL95% CI: -6.76 to -0.144) and HOMA-IR (WMD: -0.69 95% CI: -1.37 to -0.004) were observed after cinnamon treatment. Moreover, our findings demonstrated that oral cinnamon supplementation in PCOS patients led to significant reduction of serum level of LDL-C, total cholesterol, and triacylglycerol. Besides, an improvement of serum concentration of HDL-C was shown by cinnamon supplementation. Conclusion Generally, present study indicated that cinnamon supplementation may help PCOS patients to manage their metabolic parameters. Future prospective randomized clinical trials with longer intervention duration are warranted to obtain a precise conclusion.
... signaling is in the Smad-independent pathway, but there have been few reports on the stimulation of collagen synthesis via these pathways. 30,31) Given this, we believe that the PPE is an incredibly useful substance. ...
Article
The ability of dermal fibroblasts to synthesize collagen decreases with ages. The integrity of collagen fibers severely decreases in aged skin, causing its characteristic morphological changes such as wrinkles and sagging. To prevent and improve skin aging, the stimulation of collagen synthesis in dermal fibroblasts is important. Potato peels contain many biofunctional compounds, but not much is known about their effects on human skin physiology. To characterize the potential effects of a potato peel extract (PPE) against skin aging, we examined its effects on the synthesis of type I collagen by normal human dermal fibroblasts (NHDFs). Treatment with the PPE significantly increased the expression of type I collagen mRNA in NHDFs and their secretion of type I collagen. To elucidate the mechanism involved, we examined the signaling pathway controlled by transforming growth factor-β (TGF-β), which regulates the synthesis of type I collagen. Treatment of NHDFs with the PPE significantly increased the expression of TGF-β receptor mRNA. TGF-β signaling involves Smad-dependent and Smad-independent pathways, like phosphatidylinositol-3 kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). The PPE did not activate Smad, but significantly activated Akt and ERK. These results demonstrate that the PPE activates PI3K/Akt and MAPK/ERK signals via TGF-β receptors, which stimulate the synthesis of type I collagen in NHDFs. These results suggest that the PPE could be a novel and effective antiaging material. Graphical Abstract Fullsize Image
... In addition, the ethanolic extract of cinnamon shown to inhibit the synthesis of TNF-α, a pro-inflammatory signaling protein, which in turn fastens the angiogenesis and matrix degradation that promotes healing (Joshi et al., 2010). Furthermore, cinnamon extract promotes type I collagen, a crucial component for skin regeneration, via activation of IGF-I signaling pathway in human dermal fibroblasts (Takasao et al., 2012). ...
Article
Wound healing is a natural intricate cascade process involving cellular, biochemical and molecular mechanism to restore the injured or wounded tissue. Malaysia's multi-ethnic social fabric is reflected in its different traditional folk cuisines with different nutritional important ingredients. Despite these differences, there are some commonly used pantry ingredients among Malaysians and these ingredients may possess some healing power for acute and chronic wounds. These essential nutritional ingredients are included Amla (Ribes uva-crispa), Cinnamon (Cinnamomun venum), Curry Leaves (Murraya koenigii), Coriander (Coriandrum sativum), Fenugreek (Trigonella foenum-graecum), Garlic (Allium indica), Onion (Allium cepa) and Tamarind (Tamarindus indica). This article provides a review of the remedies with confirmed wound healing activities from previous experiments conducted by various researchers. Most of the researchers have focused only on the preliminary studies through appropriate model; hence detailed investigations which including pharmacological and pre-clinical studies are needed to discover its molecular mechanisms. In this review article, we have discussed about the wound healing potential of few commonly used edible plants and their known mechanism.
... In addition, the ethanolic extract of cinnamon shown to inhibit the synthesis of TNF-α, a pro-inflammatory signaling protein, which in turn fastens the angiogenesis and matrix degradation that promotes healing (Joshi et al., 2010). Furthermore, cinnamon extract promotes type I collagen, a crucial component for skin regeneration, via activation of IGF-I signaling pathway in human dermal fibroblasts (Takasao et al., 2012). ...
Article
Wound healing is a natural intricate cascade process involving cellular, biochemical and molecular mechanism to restore the injured or wounded tissue. Malaysia's multi-ethnic social fabric is reflected in its different traditional folk cuisines with different nutritional important ingredients. Despite these differences, there are some commonly used pantry ingredients among Malaysians and these ingredients may possess some healing power for acute and chronic wounds. These essential nutritional ingredients are included Amla (Ribes uva-crispa), Cinnamon (Cinnamomun venum), Curry Leaves (Murraya koenigii), Coriander (Coriandrum sativum), Fenugreek (Trigonella foenum-graecum), Garlic (Allium indica), Onion (Allium cepa) and Tamarind (Tamarindus indica). This article provides a review of the remedies with confirmed wound healing activities from previous experiments conducted by various researchers. Most of the researchers have focused only on the preliminary studies through appropriate model; hence detailed investigations which including pharmacological and pre-clinical studies are needed to discover its molecular mechanisms. In this review article, we have discussed about the wound healing potential of few commonly used edible plants and their known mechanism. © 2019 Pakistan Journal of Pharmaceutical Sciences. All Rights Reserved.
... Ainsi, l'extrait de camomille (Chamomilla recutita) est utilisé pour traiter des maladies cutanées ou pour soigner la peau lors d'une brûlure depuis l'époque égyptienne. Aujourd'hui de nombreux extraits végétaux sont utilisés pour leurs effets antioxydants (Chompoo et al., 2012;Park et al., 2012), anti-vieillissement (Kim et al., 2012;Takasao et al., 2012), anti-inflammatoire Güvenç et al., 2012) ou encore leurs effets protecteurs vis-à-vis des UV (Korać et Khambholja, 2012;Giampieri et al., 2012;Shan et al., 2012). Certains composés favorisent la cicatrisation en induisant la prolifération des kératinocytes et des fibroblastes (Araújo et al., 2012;Warashina et al., 2012) ou inhibent des infections fongiques au sein de la peau (Ozaslan, 2011;Sule et al., 2012). ...
Thesis
The skin is the largest organ of the body. It is a natural barrier between the environment and the organism that plays a key role in the protection of the body against abiotic or biotic stress. The skin is made up of three different cell layers, namely the hypodermis, the dermis and the epidermis. The epidermis is, in turn, composed of four different layers, the basal, the spinous, the granular and the horny layer. In the epidermis, keratinocytes is the major cell type known to originate from basal cells. In the present work, we have studied the expression of a number of genes (antimicrobial peptide genes and pro-inflammatory cytokine genes) in different layers of healthy human epidermis using quantitative real-time PCR coupled to Laser Capture Microdissection (LCM). Using the same approach, we have also investigated the effect of bacteria belonging the human epidermal microbiota on the expression of the same genes within the epidermal layers. In addition, the spatial distribution of gene products has also been examined using immunocytochemsitry. The major findings are: 1) We have developed an optimized LCM protocol for the isolation of human epidermal layers. We have been able to isolate two fractions highly enriched in keratinocytes from the basal and the granular layers (Percoco et al. 2012. Experimental Dermatology. 21, 531-534). Such a method can now be easily applied in dermatological research. 2) We have found that, in healthy human epidermis, innate immunity-related genes including human beta-defensin genes are differentially expressed within different layers. 3) We have found that the three bacteria Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas fluorescens induce a significant increase in the expression of beta-defensin (hBD2 and hBD3) and pro-inflammatory cytokines (IL-1 alpha, IL-1 beta and IL-6) genes. 4) We have localized the gene products within different cell layers using specific antibodies in conjunction with immunofluorescence and immunogold-electron microscopy (Percoco et al., Submitted).
... There are many medicinal plants with antimicrobial effects like thyme, clove, garlic and cinnamon [19][20][21][22] . Cinnamon plays a significant role in treatment of wide spectrum of inflammatory disease such as regeneration of collagen and recover skin damage 23 , treating cancer because of its antioxidant activity and reducing gastrointestinal disorders 24 . ...
Article
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Antibiotic resistance is widespread rapidly between pathogenic bacteria which causes main problems in clinical treatments. Since antimicrobial activities of plants have been proven, they could be suitable choice for antimicrobial agents. Also, recently it has been determined that one of the attractive targets for inhibiting the pathogenicity of bacteria is Quorum sensing (QS) system. In this study, we investigated the ability of alcoholic and aqueous cinnamon bark extract on the expression of lasI/lasR QS system, elastase and exotoxin A genes in Pseudomonas aeruginosa strain PAO1 by Real-Time qPCR method. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were measured. Then, in order to investigate the gene expression of elastase and exotoxin A, quantitative Real-Time PCR was performed at sub-MBC concentrations. According to obtained results, aqueous extracts of cinnamon have strongest inhibition activity on the gene expression against P. aeruginosa PAO1 rather than the alcoholic extract. The results showed that aqueous extracts of cinnamon at the concentration of 0.125 mg/ml decreased the expression of lasB, toxA and lasI genes. The obtained results indicated that cinnamon extract can inhibit LasI/LasR QS system and also subsequent products such as elastase and exotoxin A.
... The administration of cinnamaldehyde markedly upregulated phosphorylated IRS-1 in human dermal fibroblasts as an anti-aging treatment for skin. 29 Li et al 30 found that cinnamaldehyde increased IRS-1 expression in the gastrocnemius of type 2 diabetic rats, which lead to an improvement of diabetes via insulin signaling. Cinnamaldehyde also increased the mRNA expression of the insulin receptor (IR) in the adipose tissue. ...
Article
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OBJECTIVE To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde (tCA) through the activation of endothelial nitric oxide synthase (eNOS). METHODS Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and stimulated with tCA to determine cell viability using the methyl thiazolyl tetrazolium assay. The effect of tCA on nitric oxide (NO) production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of eNOS, AMPK, PKA, and AKT. The effect of tCA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension (SHR. Cg-Leprcp/NDmcr) rats. The phosphorylation of eNOS and protein expression of the insulin-signaling pathway (InsR-IRS1-PI3K-AKT) were measured by western blot. RESULTS tCA at concentrations less than 100 did not affect cell viability in cultured HUVECs. Stimulation with tCA promoted NO release in a time-dependent manner compared with the control group. tCA-treated HUVECs also significantly increased AKT-Ser473 and eNOS- Ser1177 phosphorylation. In SHR-CP rats, treatment with tCA at a dose of 40 mg/kg/day for 6 weeks markedly reduced the systolic blood pressure and diastolic blood pressure, increased the phosphorylation of AKT and eNOS, and increased urinary nitric oxidation. CONCLUSION tCA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats. The underlying mechanisms may involve the increase in AKT and eNOS phosphorylation and the release of eNOS-derived NO.
... During the 60-day-feeding-trial, the feed intake (FI) of catfish for both treatments and Table 2. Initial weight (IW), final weight (FW), feed intake (FI), specific growth rate (SGR), feed efficiency (FE), protein retention (PR), fat retention (FR), and survival of catfish during the 60-day-feeding-trial. Takasao et al. (2012), cinnamaldehyde was able to activate the insulin-like growth factor (IGF-1), enhanced the biosynthesis of protein and collagen in the tissues of the body, thereby increasing the deposition of proteins in the body to build muscle. These results were in line with Setiawati et al. (2014) that the inclusion of 1% cinnamon leaves meal in the diet of catfish larvae increased 1.5% of the protein retention. ...
Article
p align="center"> ABSTRACT Catfish farming has confronted with the problem of slow growth to reach the fillet size and less tender of fish fillets. This study aimed to investigate the effect of cinnamon leaf flour and shrimp head flour in formulated diets on growth of catfish Pangasi anodon hypopthalamus . Catfish with an initial weight of 207.04 ± 2.70 g/fish reared in 12 cages with a dimension of 2×1×1.5 m<sup>3</sup> (L×W×H) and its fish density was 15 fishes for 60 days. Fish were fed with following experimental diets: (1) Control; (2) cinnamon leaf (1%) (CL); (3) 45% of protein source from shrimp head (SH); (4) CL+SH mix. The fishes fed twice a day with feeding rate 3.5% of fish biomass. The study found that the use of cinnamon leaf and shrimp head increased the specific growth rate 1.67-1.70%, the feed efficiency 57.55-57.67%, and protein retention 55.61% compared to its control (P<0.05). Triglyceride level, cholesterol, and blood HDL were 416.00-524.05 mg/dL, 139.65-156.68 mg/dL, 73.18-103.70 mg/dL (P>0.05), respectively. HSI value ranged between 0.3-1.9% compared to its control (P<0.05). Keywords: Cinnamomum burmannii , feed, growth, Pangasianodon hypopthalmus , shrimp head. ABSTRAK Budidaya ikan patin dihadapkan pada permasalahan pertumbuhan dan kualitas daging yaitu pertumbuhan yang lambat untuk mencapai ukuran fillet serta tekstur daging kurang kompak. Tujuan penelitian ini adalah untuk menguji pengaruh penggunaan tepung daun kayu manis dan tepung kepala udang dalam pakan terhadap pertumbuhan ikan patin Pangasi anodon hypopthalmus . Ikan patin dengan bobot 207,04 ± 2,70 g/ekordipelihara selama 60 hari di hapa sebanyak 12 buah (berukuran 2×1×1,5 m<sup>3</sup>)dengan padat tebar 15 ekor/jaring. Ikan diberi pakan perlakuan yang terdiri dari: (1) Kontrol; (2) daun kayu manis 1% (DKM); (3) 45% sumber protein dari kepala udang (TKU); dan (4) campuran DKM+TKU. Pemberian pakan sebanyak 2 kali sehari dengan feeding rate 3,5% dari biomassa ikan. Hasil dari penelitian penggunaan daun kayu manis dan kepala udang meningkatkan nilai laju pertumbuhan harian 1,67-1,70%, efisiensi pakan 57,55-57,67% dan retensi protein 55,61% dibanding kontrol (P<0,05). Kadar trigliserida, kolesterol, dan HDL darah berturut-turut adalah 416,00-524,05 mg/dL, 139,65-156,68 mg/dL, 73,18-103,70 mg/dL (P>0,05). Nilai HSI ikan patin berkisar antara 0,3-1,9% dibanding kontrol (P<0,05). Kata kunci: Cinnamomum burmannii, kepala udang, pakan, Pangasianodon hypopthalmus , pertumbuhan. </p
... Furthermore, in olfactory systems, this causes a decline in the growth and/or differentiation of mature ORNs from olfactory progenitor cells, thereby resulting in a reduced number of mature ORNS, which is predicted to lead to a decline in olfactory function (Figure 5). Based on studies indicating that IGF-1 administration in the auditory system improves hearing in individuals with hearing impairment (Nakagawa et al., 2014), and that IGF-1 stimulates collagen biosynthesis and helps to prevent skin aging (Takasao et al., 2012;Blackstock et al., 2014), IGF-1 is expected to directly affect the olfactory system or . LP is the lamina propria, and OE is the olfactory epithelium. ...
Article
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Background: The incidence of olfactory impairment increases with age; however, the detailed molecular and cellular mechanisms underlying this increase are yet to be determined. Methods: We examined the influence of aging on olfactory receptor neurons (ORNs), which are maintained by a unique stem cell system, from olfactory progenitor cells to mature ORNs, by histological comparisons of the physiological status of the olfactory epithelium between young adult and aged mice. Furthermore, we clarified the expression of genes encoding inflammatory cytokines, neurotrophins, growth factors, and extracellular matrix proteins to reveal the molecular mechanisms underlying olfactory impairment caused by aging. Results: The numbers of mature and immature ORNs, but not olfactory progenitors, decreased in the aged olfactory epithelium, with a concurrent reduction in Ki-67-positive proliferating cells. Transcriptome analyses revealed an increase in Il6, encoding a component of senescence-associated secretary phenotypes (SASP), and a decrease in Igf1, encoding a growth factor for ORNs, in the aged nasal mucosa. Interestingly, expression levels of several extracellular matrix genes, including Col1a2, decreased in the aged nasal mucosa. Consistent with the transcriptional changes, the number of Col1a2-GFP-positive cells decreased in the aged lamina propria. Conclusions: Our data suggest that reduction in ORN number and cell proliferation, reduced extracellular matrix gene expression, and increased SASP contribute to olfactory impairment during aging.
... The present results indicate that the dietary CNP induced protein deposition alone in whole-fish body. This result may because cinnamaldehyde (the main constituent of cinnamon) is capable to activate the insulin-like growth factor, which enhanced the biosynthesis of protein and collagen in the body tissues [63], thereby increasing the protein deposition. These results are in concomitant with Rolin et al. [64] who found that administration of 1% cinnamon extract in Asian catfish diet increased protein retention by 24% compared to the control diet. ...
Article
An experiment was conducted to evaluate the effect of dietary cinnamon nanoparticles (CNP) on growth performance, antioxidant and digestive enzymes activities, and innate immunity of Nile tilapia, Oreochromis niloticus (L.). Fish (9.7 ± 0.3 g) were fed on diets enriched with 0.0, 0.25, 0.5, 1.0, 3.0, 5.0, and 10.0 g CNP/kg diet for 8 weeks. After the feeding trial, fish were challenged against hypoxia stress or pathogenic bacteria (Aeromonas hydrophila) infection. Fish performance was significantly improved with increasing CNP levels over the control diet. Furthermore, only crude protein contents in whole-fish body were significantly higher in CNP-fed fish than those fed the control diet. Antioxidant-stimulated activity was observed with dietary CNP where malondialdehyde (MDA) level and activities of superoxide dismutase (SOD) and catalase (CAT) increased significantly, whereas glutathione peroxidase (GPx) activity decreased significantly in CNP-fed fish. Likewise, CNP supplementation induced the secretion of protease, lipase, and amylase, which were maximized at 3.0 – 10.0 g CNP/kg diet. All innate immunity variables i.e. nitrous oxide (NO), nitro blue tetrazolium (NBT), and lysozyme activity were significantly higher in CNP-fed fish than the control one. No fish mortality was observed during hypoxia stress among all treatments, but CNP administration protectd fish against A. hydrophila infection. No mortality was observed in fish fed 3.0 - 10.0 g CNP/kg diet after bacterial challenge; meanwhile the mortality of fish fed the control diet was 66.7%. This study evoked that dietary CNP enhanced performance, antioxidant and digestive enzymes activity, and innate immunity of Nile tilapia and its optimum level is 3.0 g CNP/kg diet.
... In this experiment, it is assumed that RVE restores the suppressed synthesis of collagen, and maintains the stability of collagen. On the other hand, royal jelly and cinnamon extract, known as natural anti-aging substances, have been reported to have anti-aging effects by stimulating various signaling pathways that promote the synthesis of collagen, such as TGF-beta and insulin-like growth factor-1 in fibroblasts 24,37 . While RVE is thought to be involved in collagen synthesis in a similar manner, further research will be necessary to ascertain this. ...
Article
Full-text available
Background Rhus verniciflua Stokes (RV) has traditionally been used in Korea as an indigenous food (Rhus chicken soup) and as an herbal medicinal plant. While the anticancer, antimicrobial, and anti-inflammatory properties of RV have been actively studied in the medical field, its antioxidant effects in the skin that resist the reactive oxygen species in keratinocytes and fibroblasts is less understood. Objective We designed to evaluate the effects of R. verniciflua Stokes extract (RVE) on the photo-aged skin by an in vitro experiment using human fibroblasts and an in vivo experiment using a photo-aged murine model. Methods For the in vitro experiments, human fibroblasts irradiated with ultraviolet (UV) B were treated with RVE or vehicle, and the growth levels and the expression level of type 1 procollagen were compared. For the in vivo experiment, photo-aged mice irradiated with UVB and UVA were administered drinking water with or without RVE, and histological changes and the expression level of type 1 procollagen and matrix metalloprotease (MMP)-13 were compared. Results In vitro experiments using fibroblasts irradiated with UVB showed that RVE promoted growth and significantly increased the expression of type 1 procollagen as compared to the control group. In the photo-aged mice, RVE increased collagen content in the dermis and promoted the synthesis of type 1 procollagen without any visible decrease in MMP-13 as compared to control group. Conclusion In addition to the previously reported antioxidant effects of RVE, oral intake of RVE effectively inhibited photo-aging in hairless mice by enhancing collagen synthesis.
... The moderate activity in the collagenase assay demonstrated by CZ in the present study may be partly due to it reported capacity in promoting the biosynthesis of collagen type I, through the activation of insulin-like growth factor-1 signaling, as reported by Takasao et al. [41]. ...
Article
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Essential oils (EOs) extracted from six medicinal herbs and food plants [Cinnamomum zeylanicum, Psiadia arguta, Psiadia terebinthina (PT), Citrus grandis (CGp), Citrus hystrix (CH), and Citrus reticulata (CR)] were studied for any inhibitory potential against key physiological enzymes involved in diabetes (α-glucosidase), skin aging (collagenase and elastase), and neurodegenerative disorders (acetylcholinesterase). Kinetic studies of the active EOs on the aforementioned enzymes were determined using Lineweaver–Burk plots. The intracellular and extracellular antimelanogenic potential of the EOs were evaluated on B16F10 mouse melanocytes. CH and CR were found to significantly inhibit (2.476 ± 0.13 μg/mL and 3.636 ± 0.10 μg/mL, respectively) acetylcholinesterase, compared with galantamine (3.989 ± 0.16 μg/mL). CH inhibited collagenase (50% inhibitory concentration 28.71 ± 0.16 μg/mL) compared with the control (24.45 ± 0.19 μg/mL). The percentage inhibition in the elastase assay of CH was 63.21% compared to the positive control (75.09%). In addition, CH, CR, CGp, Cinnamomum zeylanicum, and PT were found to significantly inhibit α-glucosidase (276.70 ± 0.73 μg/mL, 169.90 ± 0.58 μg/mL, 240.60 ± 6.50 μg/mL, 64.52 ± 0.69 μg/mL, and 313.0 ± 5.0 μg/mL, respectively), compared to acarbose (448.80 ± 0.81 μg/mL). Active EOs showed both uncompetitive and competitive type of inhibition. The EOs also inhibited intracellular (50% inhibitory concentration 15.92 ± 1.06 μg/mL, 23.75 ± 4.47 μg/mL, and 28.99 ± 5.70 μg/mL for CH, CR, and CGp, respectively) and extracellular (< 15.625 μg/mL for CH, CR, CGp, and PT) melanin production when tested against B16F10 mouse melanocytes. Results from the present study tend to show that EOs extracted from these medicinal plants can inhibit key enzymes and may be potential candidates for the cosmetic and pharmaceutical industries.
... Cinnamaldehyde increases the expression levels of peroxisome proliferator-activated receptor γ (PPARγ) and activates AMP kinase that induces insulin sensitivity (40,41). Cinnamon can activate insulin-like growth factor 1 (IGF1) signaling in fibroblast, that tend to lowering insulin resistance and improvement in glycemic control but it can down-regulate insulin signaling in adipocytes (42). Modulating mitochondrial physiology and elevation of cellular metabolism are another anti-diabetic mechanism of cinnamon (43). ...
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Objective(s) Nowadays, cardiovascular diseases (CVDs) are the major risk factors of death globally. One of the most undeniable reasons of CVDs is metabolic syndrome (MetS). MetS is defined as a complex of diseases including insulin resistance, hyperglycemia, obesity, high blood pressure and dyslipidemia. The use of complementary medicine such as traditional herbal species can be effective in treatment of MetS’s complications. Cinnamomum verum (family Lauraceae) is a medicinal global plant which has been used daily by people all over the world. Positive effects of cinnamon in reducing blood pressure, plasma glucose, obesity and ameliorating dyslipidemia which represented in traditional medicine introduced it as probable decreasing MetS’s complications agent. The aim of this review was to investigate the mechanisms of C. verum in reducing the MetS’s complications and CVDs risk factors. Materials and Methods Various databases such as PubMed, Science Direct, Scopus, Web of Science, Google Scholar and Persian Websites such as www.sid.ir with keywords search of cinnamon, cinnamomum, cinnamaldehyde, atherogenic, hypertension, hyperglycemia, insulin resistance, obesity and dyslipidemia have been included in this search. Results Clinical data and mechanisms of action of C. verum and its active ingredients that have been shown in this review indicated that cinnamon has protective effects against MetS’s aspects in various ways. Conclusion The use of this plant can be effective in reducing MetS’s complications and its morbidity and mortality.
... Menurut Vasanthi dan Parameswari (2010), senyawa bioaktif kayu manis mampu meningkatkan penyerapan glukosa, pemanfaatan asam lemak dalam tubuh. Takasao et al. (2012), menambahkan kandungan sinamaldehid kayu manis mampu mengaktifasi Insulin-like growth factor (IGF-1) yang meningkatkan biosintesis protein dan kolagen dalam jaringan tubuh sehingga meningkatkan deposisi protein dalam tubuh untuk membentuk otot (daging), tulang, organ tendon, dan ligament (NRC 2011). ...
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This study aimed to evaluate the effect of extract and cinnamon (Cinnamomum burmannii) leaf flour in the diet in increasing quality of meat of catfish (Pangsianodon hypopthalmus). Catfish with a weight of 319.64 ± 35.99 g/nets reared in 9 nets with dimension 2x1x1,5 m3 at a density of 15 fish/nets for 60 days of maintenance. The fish were fed with leaves of cinnamon at a dose that was: 0% cinnamon leaf, 0.1% cinnamon leaf extract, and 1% cinnamon leaf flour. The fish were fed 2 times a day with the feeding rate of 3% of the average weight of the body. The results showed the treatment of leaf extract and flour, cinnamon capable of decreasing levels of body fat, fat meat by 10,31-12,27%, 37,26-50,23%, respectively, compared to controls (p
... The cinnamon extract upregulated the mRNA protein expression of the type 1 collagen in human fibroblasts. Cinnamaldehyde significantly increased the phosphorylation levels of the insulin-like growth factor-I receptor and its downstream signaling molecules [53]. ...
Article
We are an aging community where the number of aging individuals is markedly increasing. This is associated with enormous aging-related decline of the body functions and increase in the prevalence of diseases involving the skin among other organs. The aging skin does not only shows wrinkles, uneven tone, loss of elasticity, and thinning, but also exhibits delayed healing, recurrent infections, and an elevated incidence of both benign and malignant tumors. In the last decades, the need for antiaging skin treatment, which can combat both aging signs and dysfunction, has been markedly increasing. Understanding the mechanism behind skin aging will help us understand the mechanism of action, and hence the potential benefits of the claimed antiaging products. Topical substitution with sex hormones and vitamins, different antioxidants, botanical components, sunscreens, and different lipid substitutes are all included in numerous antiaging compounds. In this review, we are reporting on the mechanisms behind effectiveness of the topical noninvasive antiaging compounds in use and also on the mechanism of action of potential topical antiaging substances under research.
Article
The aim of this study was to investigate the effects of dietary supplementation of γ-irradiated cinnamon ethanolic extract on the growth performance, digestive enzymes, lysozyme activity level and hematological factors in the juvenile rainbow trout. The fish were divided into five groups, including control group and four experimental groups (received diets enriched with 10 g/kg of non-irradiated or irradiated CEE at the radiation doses of 10, 20 and 40 KGy. At the end of the feeding trial (60` days), 10 fish were sampled from each tank after 12 h of feed deprivation. The results showed that the fish dietary irradiated CEE at doses of 10 KGy and 20 KGy had significantly higher final weights, weight gain, specific growth rates and growth hormone levels, and lower feed conversion ratios compared to the other groups (P≤0.05). The blood glucose level significantly lowered in the fish group fed with dietary γ-irradiated CEE, and increased the activity of lysozyme activity level and digestive enzymes compared to the control group (P≤0.05). In conclusion, dietary supplementation of γ-irradiated CEE at a dose of 10 KGy can enhance the positive effects of cinnamon extract and improve the growth performance, digestion and lysozyme activity in juvenile rainbow trout.
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The quality of the flesh is evaluated by nutritional value and sensory quality. Cinnamaldehyde (CIN) improves mammalian meat quality, but researches on aquaculture are scarce. In this research, five levels of CIN (0, 36, 72, 108, 144 mg/kg diet) were fed to grass carp reared for 60 days. Results showed CIN supplementation increased nutritional value by increasing the content of crude protein. Meanwhile, CIN improved sensory quality by increasing shear force, pH, and content of collagen, decreasing lactate and cooking loss. These changes might be related to changes in muscle fiber growth by increasing myofiber diameter. The increasing myofiber diameter by CIN is associated with activating TOR signaling and inhibiting FOXO3a signaling, which might be associated with PTP1B/IGF-1/PI3K/AKT signaling. In conclusion, 72 mg/kg CIN diet improved grass carp's nutritional value and sensory quality.
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Cinnamon Botany, Agronomy, Chemistry and Industrial Applications
Chapter
Ceylon cinnamon, which is also known as true cinnamon, has been very popular as a spice and a traditional medicine for centuries. Cinnamon growing in Sri Lanka was sought after by many countries. Presently, Cinnamomum zeylanicum is considered a superior quality material and fetches a high price. Research undertaken on the health benefits of cinnamon are conducted using the bark, bark powder, extracts and bark and leaf essential oils. Many antioxidants, flavonoids and phenolic compounds have been isolated. Value addition of this material can be undertaken to convert it to additional products, such as health supplements and herbal healthcare products, which are gaining popularity at the present time. The applications using cinnamon are being subjected to scientific research in order to be used for medicinal purposes. Results so far obtained using in vitro and animal in vivo models indicate that cinnamon has antimicrobial, antioxidant, anti-inflammatory, cardiovascular, cholesterol-lowering, antidiabetic and immunomodulatory effects. Yet, only very few controlled clinical studies have been done to confirm these potential health benefits. The promising applications of cinnamon as a flavour in aromatherapy and in nutraceutical and cosmeceutical industries are outlined with future market prospects.
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Sri Lanka is the market leader of Ceylon cinnamon with a 90% global market share. Cinnamon is one of the leading foreign exchange earners from among agricultural exports of Sri Lanka. The cinnamon extent of cultivation, production, and yield has only marginally increased over the past few decades despite high potential in the global market. However, the major competitive product cassia produced and exported predominantly by Indonesia, China, and Vietnam has contributed to the erosion of Ceylon cinnamon market share, notwithstanding warning from leading health agencies about its negative impact on health due to high content of coumarin. Ceylon cinnamon has the potential to become Sri Lanka’s number one foreign exchange earner from the agriculture sector by building on its competitive edge as the main true cinnamon supplier. Product and process innovation with a focus on compliance with food safety and quality requirements remains the most feasible and practical option to exploit the competitive edge of Ceylon cinnamon in the global marketplace. Marketing strategies should focus on product diversification, value addition, and brand recognition.
Chapter
Cinnamomum zeylanicum Blume or Ceylon cinnamon is a native medicinal and aromatic plant in Sri Lanka, which has been used extensively in treatment of various diseases in traditional systems of medicine in Asia. It is also a household remedy for primary care in aches, pains and certain other diseases. The claimed health benefits have been extensively tested using modern scientific methods to validate the health properties. It has been used clinically for treatment and management of diseases and in health foods, nutraceutical and cosmeceutical industries. The pharmacological properties tested and reported from C. zeylanicum bark, leaf and essential oils are discussed with special reference to antioxidant, anti-diabetic, antilipidemic, anticancer, anti-inflammatory, antiarthritic, immunomodulatory, antibiotic, antinociceptive, analgesic, cardioprotective, antihypertensive, gastroprotective, skin protection, skin whitening and anti-ageing properties, including clinical studies and toxicology.
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Antioxidant activity, anti-aging effects and cytotoxicity activity of cinnamon essential oils from Cinnamomum zeylanicum were investigated in this study. The antioxidant activities of the cinnamon essential oil at the concentrations of 125, 250, 500, and 1000 µg/mL were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS). The inhibitory activities against collagenase, elastase and tyrosinase were evaluated for anti-aging effects. The antioxidant activity determined by DPPH and ABTS assays varied from 4.91 - 28.74% and 4.96 - 50.17%, respectively. In addition, cinnamon essential oil at all concentrations tested (100, 200, 500, and 1000 µg/mL) inhibited tyrosinase activity by 61.68 - 93.12 %, collagenase activity by 2.83 - 30.28 % and elastase activity by 4.37 - 33.92 %. The cytotoxicity activity determined by the diphenyltetrazolium (MTT) assay revealed that the cinnamon essential oil at the concentration less than 100 µg/mL did not exhibit cytotoxicity activity on human fibroblast cells while the percentage of cell viability decreased when exposed to this oil at the concentration higher than 150 µg/mL. These results demonstrated that the cinnamon essential oil has antioxidant, tyrosinase inhibitory, collagenase inhibitory, and elastase inhibitory activities. In addition, cinnamon essential oil at each effective concentration did not show any toxicity when tested on normal human fibroblast cell. Therefore, this essential oil could be a potential candidate for cosmetic and pharmaceutical products.
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The present study evaluated the effect of cinnamaldehyde (CIN) on the growth performance and digestion and absorption capacity of grass carp (Ctenopharyngodon idella). Fish were fed five diets including graded levels of CIN for 60 days. The results indicated that (1) appropriate CIN supplementation increased the growth performance and promoted the intestine growth of grass carp; (2) dietary appropriate CIN supplementation increased the digestion and absorption capacity by increasing the activities of intestinal and hepatopancreas digestive enzymes (lipase, chymotrypsin, trypsin, and amylase) and intestinal brush border enzymes (creatine kinase (CK), Na+/K+-ATPase, γ-glutamyl transpeptidase (γ-GT), and alkaline phosphatase (AKP)); (3) dietary CIN increased the absorption capacity which may be associated with the upregulated messenger RNA (mRNA) abundances of their amino acid transporters (AATs) in the intestine, which might be associated with activating the target of rapamycin (TOR) signaling pathway. The best CIN supplementation in the diets of grass carp was estimated to be 76.40 mg kg−1 diet based on the best percent weight gain (PWG). In general, CIN increased the digestion and absorption capacity of grass carp and raised the mRNA abundances of AATs which may be partly related to activation of the TOR signaling pathway.
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Galangin, a natural flavonol, has anti‐inflammatory and antioxidative potential. However, the cytoprotective effects of galangin against oxidative‐induced aging in human fibroblasts have not been well studied. IGF‐1 signaling pathway is associated with the control of aging and longevity in human. The goal of this study was to investigate the effects of galangin on human skin fibroblast HS68 cells under H2O2 exposure to induce aging. In this study, we demonstrate that galangin could decrease the levels of pro‐inflammatory proteins and enhanced collagen formation through promoting the IGF‐1R pathway. Furthermore, aging markers such as senescence‐associated β‐galactosidase p53, p21Cip1/WAF1, and p16INK4A were upregulated under H2O2 exposure and galangin could reverse its effects. Taken together, these data indicated that anti‐inflammatory and antiaging activities of galangin may be mediated through the IGF‐1R signaling pathway. These findings may provide the evidence for galangin to develop as an antiwrinkle product on human skin.
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The human hair follicle, a mini-organ formed with neuroectodermal-meso-dermal interaction, is a complex structure, in the active steady state (anagen) the dermal papilla can be considered as a ball of extracellular matrix, surrounding specialized fibroblasts. The cross-talk of dermal papilla with neighbouring matrix cells results in the maintenance of hair fibre production. This study aimed to investigate the proliferative potential of the compound TrichotechTM, a phytocomplex obtained from a mixture of essential oils, on cultured human fibroblasts and its ability to modulate the gene expression of FGF-7 and FGF-10. TrichotechTM was shown to enhance fibroblasts proliferation in concentrations of 0.5% to 2.0%, and also increase the percentage of cells in the S/G2/M phases of the cell cycle. TrichotechTM at both 1.0% and 2.0% induced a statistically significant effect on wound healing assay compared to the untreated control. We examined the interaction between cell survival (PI3K/Akt) and mitogenic (Ras/MAPK) signal transduction pathways after TrichotechTM treatment (1.0% and 2.0%) on the fibroblast cell line. TrichotechTM caused phosphorylation of ERK1/2, as well as greater phosphorylation of MEK in comparison with both the untreated control and ERK1/2. PI3K and AKT, however, were not shown to be significantly more phosphorylated following TrichotechTM exposure. To verify the relative expression of mRNA for FGF-7 and FGF-10 genes, a real-time polymerase chain reaction (qPCR) protocol was used. Results show the increase in mRNA expression by fibroblasts after treatment with TrichotechTM. In both concentrations tested, TrichotechTM was found to increase the expression of FGF-7 and FGF-10. Sirius red staining allows for rapid assessment of collagen content, it showed a significant increase in collagen content in treated fibroblasts. Further investigation concerning TrichotechTM could be helpful towards the development of new bioactive phytocomplexes for dermatological and trichological use.
Chapter
The occurrence of most non-infectious diseases increases as we get older. There is now a growing research effort to understand aging, and try to slow it in order to treat a broad range of diseases. The underlying molecular mechanisms of aging are not clear, and there are many theories, each with varying degrees of support. A hallmark of aging is a decreased resistance to environmental stresses such as heat, and the lifespan of many organisms is inversely related to body temperature. One strategy for slowing the aging process is to screen for drugs and botanical extracts that can extend lifespan in model organisms such as the fruit fly, Drosophila melanogaster. Several botanical extracts have been recently identified to increase lifespan in flies. Surprisingly, there is no overall correlation between increased lifespan and an increased tolerance to heat. In one case, an extract that increased fly lifespan had a marked decreased in heat tolerance and heat shock protein expression. These results parallel those of the direct study of HSP expression and lifespan in fruit flies. In summary, there is no clear relationship between the induction of HSPs and extension of lifespan in fruit flies through the use of botanical extracts.
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Gastrodia elata Blume (GEB), a traditional herbal medicine, has been used to treat a wide range of neurological disorders (e.g., paralysis and stroke) and skin problems (e.g., atopic dermatitis and eczema) in oriental medicine. This study was designed to investigate the antioxidant ability of GEB and its antiaging effect on human dermal fibroblast cells (HDF). The total phenolic and flavonoid contents of GEB were 21.8 and 0.43 mg/g dry weight (DW), respectively. The ergothioneine content of GEB was 0.41 mg/mL DW. The DPPH and ABTS radical scavenging activities of GEB at 5 and 10 mg/mL approximately ranged between 31% and 44%. The superoxide dismutase activity of GEB at 10 and 25 mg/mL was 57% and 76%, respectively. GEB increased procollagen type 1 (PC1) production and inhibited matrix metalloproteinase-1 (MMP-1) production and elastase-1 activity in UVA-irradiated HDF. PC1 messenger RNA (mRNA) levels decreased upon UVA irradiation, but recovered in response to high doses of GEB in HDF. On the contrary, GEB significantly decreased MMP-1 and elastase-1 mRNA levels, which were markedly induced in UVA-irradiated HDF. Collectively, these results suggest that GEB has sufficient antioxidant ability to prevent the signs of skin aging in UVA-irradiated human skin cells, suggesting its potential as a natural antiaging product. © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition 2016.
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Bacterial biofilms are widely associated with persistent infections. High resistance to conventional antibiotics and prevalent virulence makes eliminating these bacterial communities challenging therapeutic targets. We describe here the fabrication of a nanoparticle-stabilized capsule with a multicomponent core for the treatment of biofilms. The peppermint oil and cinnamaldehyde combination that comprises the core of the capsules act as potent antimicrobial agents. An in situ reaction at the oil/water interface between the nanoparticles and cinnamaldehyde structurally augments the capsules to efficiently deliver the essential oil payloads, effectively eradicating biofilms of clinically isolated pathogenic bacteria strains. In contrast to their antimicrobial action, the capsules selectively promoted fibroblast proliferation in a mixed bacteria/mammalian cell system making them promising for wound healing applications.
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Herbs and spices have been used in retaining and boosting human beauty since time immemorial. Herbal cosmetic has growing demand in the worldwide market and is an invaluable gift of Mother Nature. In the present review, the focus is on the cosmetic herbs of Southeast Asian countries namely Malaysia, Cambodia, Laos, Myanmar [Burma], Thailand, Vietnam, Brunei, East Timor, Indonesia, Philippines and Singapore in highlighting both traditional and scientific knowledge or background of the selected potential herbs. The available literature was searched in the following scientific database such as PubMed, Google Scholar, Science Direct and Springer for publications and patents. In view of traditional uses, herbs like Allium sativum, Aloe vera, Centella asiatica, Curcuma longa, Hibiscus rosa-sinensis, Lawsonia inermis and Tamarindus indica L. were classified as need of special mention. Many herbs have been scientifically evaluated for their cosmetic potentials such as anti-aging, antiacne, melanogenic and anti-tyrosinase activities. The great void remains for a systematic study, thorough review of scientific report that provides a basis for the use of specific herbs due to their efficacy as cosmetics. In addition, two of the Malay herbs; Labisia pumila (Kacip Fatimah) and Ficus deltoidea (Mas cotek), are proposed to be clinically studied for their safety in cosmetic application aspects wherein the need for safety evaluation and fruitful application of herbal cosmetics were emphasized.
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Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. It possesses anti-diabetic properties in vitro and in vivo and has anti-inflammatory and anti-cancer effects. To explore whether cinnamaldehyde was linked to altered advanced glycation end products (AGE)-mediated diabetic nephropathy, the molecular mechanisms of cinnamaldehyde responsible for inhibition of AGE-reduced nitric oxide (NO) bioactivity in human renal proximal tubular cells were examined. We found that raising the ambient AGE concentration causes a dose-dependent decrease in NO generation. Cinnamaldehyde significantly reverses AGE-inhibited NO generation and induces high levels of cGMP synthesis and PKG activation. Treatments with cinnamaldehyde, the NO donor S-nitroso-N-acetylpenicillamine, and the JAK2 inhibitor AG490 markedly attenuated AGE-inhibited NOS protein levels and NO generation. Moreover, AGE-induced the JAK2-STAT1/STAT3 activation, RAGE/p27Kip1/collagen IV protein levels, and cellular hypertrophy were reversed by cinnamaldehyde. The ability of cinnamaldehyde to suppress STAT activation was also verified by the observation that it significantly increased SCOS-3 protein level. These findings indicate for the first time that in the presence of cinnamaldehyde, the suppression of AGE-induced biological responses is probably mediated by inactivating the JAK2-STAT1/STAT3 cascade or activating the NO pathway. This article is protected by copyright. All rights reserved
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The fibrous collagens form the structural basis of all mammalian connective tissues, including the vasculature, dermis, bones, tendons, cartilage, and those tissues that support organs such as the heart, kidneys, liver, and lungs. The helical structure of collagen has been extensively studied but in addition to its helical character, its molecular packing arrangement (in its aggregated or fibrillar form) and the presence of specific amino acid sequences govern collagen's in vivo functions. Collagen's molecular packing arrangement helps control cellular communication, attachment and movement, and conveys its tissue-specific biomechanical properties. Recent progress in understanding collagen's molecular packing, fibrillar structure, domain organization, and extracellular matrix (ECM) interactions in light of X-ray fiber diffraction data provides significant new insights into how the ECM is organized and functions. In this review, the hierarchy of fibrillar collagen structure is discussed in the context of how this organization affects ECM-"ligand" interactions, with specific attention to collagenolysis, integrins, fibronection, glycoprotein VI receptor (GPVI), and proteoglycans (PG). Understanding the complex structure of collagen and its attached ligands should provide new insights into tissue growth, development, regeneration, and disease.
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Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic, to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before definitive recommendations can be made.
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Insulin/insulin-like growth factor (IGF) signaling plays a major role in the control of aging and life span in invertebrates. Major extension of life span in growth hormone receptor knock out (GHR-KO) mice that are GH resistant, and subsequently, IGF-I-deficient indicates that similar mechanisms may operate in mammals. This conclusion is supported by association of reduced IGF-I levels and delayed aging in three different GH-deficient mutant mice and in animals subjected to caloric restriction, but is difficult to reconcile with neuroprotective effects of IGF-I and with the suspected role of declining GH levels during aging. We suggest that the role of IGF in the regulation of growth and adult body size is important in mediating the effects of longevity genes on aging and life span. Suspected mechanisms of IGF-I action in aging also include reduced insulin signaling, enhanced sensitivity to insulin, and reduced thermogenesis with diminished oxidative damage of macromolecules being the likely final common pathway of these effects. We suspect that IGF-I is important in evolutionarily conserved mechanisms that link life history, including development, reproduction, and aging with availability of energy resources.
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GH and IGF-I and -II were first identified by their endocrine activity. Specifically, IGF-I was found to mediate the linear growth-promoting actions of GH. It is now evident that these two growth factor systems also exert widespread activity throughout the body and that their actions are not always interconnected. The literature highlights the importance of the GH and IGF systems in normal skin homeostasis, including dermal/epidermal cross-talk. GH activity, sometimes mediated via IGF-I, is primarily evident in the dermis, particularly affecting collagen synthesis. In contrast, IGF action is an important feature of the dermal and epidermal compartments, predominantly enhancing cell proliferation, survival, and migration. The locally expressed IGF binding proteins play significant and complex roles, primarily via modulation of IGF actions. Disturbances in GH and IGF signaling pathways are implicated in the pathophysiology of several skin perturbations, particularly those exhibiting epidermal hyperplasia (e.g., psoriasis, carcinomas). Additionally, many studies emphasize the potential use of both growth factors in the treatment of skin wounds; for example, burn patients. This overview concerns the role and mechanisms of action of the GH and IGF systems in skin and maintenance of epidermal integrity in both health and disease.
Article
The insulin-like growth factors I and II are single chain polypeptides homologous to proinsulin. IGF I and IGF II contribute to cell regulation and stimulate protein synthesis via signaling through type I receptors which are homologous to insulin receptors and activate phosphorylation cascades. IGFs enhance the proliferation of chondocytes and the proliferation of their collagen and proteoglycan matrix; IGFs stimulate longitudinal (endochondral) bone growth. Throughout life, IGFs are constitutvely expressed ubiquitous factors which help to maintain the survival of differentiated cells, Increased expression is found during growth and tissue repair, Six specific binding proteins, IGFBP 1-6, allow additional tissue compartment specific control of IGF activity; IGFBP production favours storage and IGFBP cleavage leads to activation.
Article
Insulin and insulin-like growth factor (IGF-1) are mitogenic for fibroblasts and smooth muscle cells. IGF-1 increases in inflamed and fibrotic tissues and induces proliferation of rat hepatic stellate cells (HSC). This study evaluates the potential roles of these hormones in the development of liver fibrosis. Insulin and IGF-1 receptor expression was evaluated by immunohistochemistry in both cultured human HSC and human liver tissue. Phosphorylation of both 70-kd S6 kinase and extracellular-regulated kinase (ERK), cell proliferation, type I collagen gene expression, and accumulation in HSC culture media were evaluated by Western blot, immunohistochemistry for bromodeoxyuridine (BrdU), Northern blot, and enzyme-linked immunosorbent assay, respectively. Insulin and IGF-1 receptors were detected in HSC in vitro and in liver sections from patients with chronic active hepatitis. Insulin and IGF-1 induced 70-kd S6 kinase phosphorylation in HSC, whereas IGF-1 only induced ERK phosphorylation. Insulin and IGF-1 stimulated HSC proliferation in a dose-dependent fashion, with IGF-1 being four to five times more potent than insulin. Cell exposure to specific inhibitors showed that both phosphatidylinositol 3-kinase (PI3-K) and ERK are involved in IGF-1–induced mitogenesis, whereas insulin stimulated mitogenesis through a PI3-K–dependent ERK-independent pathway. IGF-1 increased type I collagen gene expression and accumulation in HSC culture media through a PI3-K– and ERK-dependent mechanism. In conclusion, insulin and IGF-1, which stimulate HSC mitogenesis and collagen synthesis, may act in concert to promote liver fibrosis in vivo by a differential activation of PI3-K– and ERK1-dependent pathways.
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This article highlights the common disorders associated with inherited abnormalities of the collagen, elastin and keratin. The derrnal structural proteins (extracellular matrix proteins) comprise predominantly collagens, of which at least 19 types are known. Collagens constitute most of the dermis, and abnormalities lead to impaired wound healing illustrated by the Ehlers-Danlos syndromes. They also have a critical role at the basement membrane zone, and defects lead to loss of epidermal adhesion and blistering, resulting in certain types of epidermolysis bullosa. Pseudoxanthoma elasticum is a disorder characterized by cutaneous, ocular and cardiovascular complications and is associated with elastic fibre abnormalities. The exact function of the transmembrane transport gene (ABCC6) implicated has not yet been fully elucidated. Keratins have an integral role in the integrity of epidermal cells and their expression varies between body sites. Abnormalities lead to a wide variety of clinical phenotypes, most commonly keratoderma.
Article
Coumarin is a flavoring which can cause hepatotoxicity in experimental animals and in a proportion of the human population. The tolerable daily intake (TDI) may be exceeded in consumers with high intake of cinnamon containing high levels of coumarin. The objective of this study was to determine these levels in cinnamon samples and to identify possible factors influencing them. A HPLC method to quantify coumarin and related constituents (cinnamaldehyde, cinnamic acid, cinnamyl alcohol, eugenol) in a single run was used. Results found in 47 cinnamon powder samples obtained from the German retail market confirmed high levels of coumarin in cassia cinnamon. A huge variation was observed in stick samples from two packages (range from below the limit of detection to about 10000 mg/kg). Cassia bark samples of five trees received directly from Indonesia were analyzed additionally. Interestingly, a high variation was observed in one of the trees, whereas no coumarin was detected in the samples of two other trees. In conclusion, coumarin levels in cassia cinnamon can vary widely even within a single tree.
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The collapse of collagenous networks with aging results in comprehensive changes in the functional properties of skin. α-Lipoic acid (LA) is known to possess beneficial effects against skin aging, effects often presumed to be its antioxidant potential. However, the effects of LA on fibrillogenesis in dermal fibroblasts have not been adequately assessed. In this study, we demonstrated for the first time that LA enhances the biosynthesis of new collagen in normal human dermal fibroblasts (NHDFs). By using a quantitative dye-binding method and immunochemical approaches, we showed that LA effectively increased the expression and subsequently the deposition of type I collagen in NHDFs. LA also facilitated the expression of a collagen-processing enzyme, prolyl-4-hydroxylase, pointing to the existence of a posttranslational mechanism among the LA-mediated effects on collagen synthesis. In addition, we determined that both Smad 2/3 were rapidly phosphorylated by treatment with LA within 30 min, indicating that LA enhances type I collagen synthesis through the activation of Smad signaling. Pretreatment of SB431542, a specific transforming growth factor-β (TGF-β) receptor type I (TβRI) kinase inhibitor, blocked LA-mediated Smad 2/3 phosphorylations and both type I collagen and prolyl-4-hydroxylase expression, suggesting that LA-mediated cell responses are regulated by TβRI kinase-dependent pathway. Levels of TGF-β secretion after 4 hr of treatment with LA were not remarkably elevated, indicating that LA may be able to mimic TGF-β-mediated cell response. The study results produced new insights into the molecular pharmacology of LA in NHDFs, with potential applications in the treatment of aging skin.
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Type 2 diabetes patients show defects in insulin signal transduction that include lack of insulin receptor, decrease in insulin stimulated receptor tyrosine kinase activity and receptor-mediated phosphorylation of insulin receptor substrates (IRSs). A small molecule that could target insulin signaling would be of significant advantage in the treatment of diabetes. Berberine (BBR) has recently been shown to lower blood glucose levels and to improve insulin resistance in db/db mice partly through the activation of AMP-activated protein kinase (AMPK) signaling and induction of phosphorylation of insulin receptor (IR). However, the underlying mechanism remains largely unknown. Here we report that BBR mimics insulin action by increasing glucose uptake ability by 3T3-L1 adipocytes and L6 myocytes in an insulin-independent manner, inhibiting phosphatase activity of protein tyrosine phosphatase 1B (PTP1B), and increasing phosphorylation of IR, IRS1 and Akt in 3T3-L1 adipocytes. In diabetic mice, BBR lowers hyperglycemia and improves impaired glucose tolerance, but does not increase insulin release and synthesis. The results suggest that BBR represents a different class of anti-hyperglycemic agents.
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Trans-cinnamaldehyde (CA) and its analogs 2-hydroxycinnamaldehyde and 2-benzoyloxycinnamaldehyde have been reported to possess antitumor activity. CA is also a known Nrf2 activator. In this study, a series of ortho-substituted cinnamaldehyde analogs was synthesized and screened for antiproliferative and thioredoxin reductase (TrxR)-inhibitory activities. Whereas CA was weakly cytotoxic and TrxR inhibiting, hydroxy and benzoyloxy substitutions resulted in analogs with enhanced antiproliferative activity paralleling increased potency in TrxR inactivation. A novel analog, 5-fluoro-2-hydroxycinnamaldehyde, was identified as exhibiting the strongest antitumor effect (GI(50) 1.6 microM in HCT 116 cells) and TrxR inhibition (IC(50) 7 microM, 1 h incubation with recombinant TrxR). CA and its 2-hydroxy- and 2-benzoyloxy-substituted analogs possessed dual TrxR-inhibitory and Nrf2-inducing effects, both attributed to an active Michael acceptor pharmacophore. At lethal concentrations, TrxR-inhibitory potencies correlated with the compounds' antiproliferative activities. The penultimate C-terminal selenocysteine residue was shown to be a possible target. Conversely, at sublethal concentrations, these agents induced an adaptive antioxidant response through Nrf2-mediated upregulation of phase II enzymes, including TrxR induction. We conclude from the results obtained that TrxR inactivation contributes at least partly to cinnamaldehyde cytotoxicity. These Michael acceptor molecules can potentially be exploited for use in different concentrations in chemotherapeutic and chemopreventive strategies.
Article
Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts express increased levels of collagen-degrading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo. Transcription factor AP-1 and alpha2beta1 integrin, which are key regulators of MMP-1 expression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and reduces fibroblast stretch, consistent with reduced mechanical tension, as observed in aged human skin. Limited fragmentation of three-dimensional collagen lattices with exogenous MMP-1 also reduces fibroblast stretch and mechanical tension. Furthermore, fibroblasts cultured in fragmented collagen lattices express elevated levels of MMP-1, AP-1, and alpha2beta1 integrin. Importantly, culture in fragmented collagen raises intracellular oxidant levels and treatment with antioxidant MitoQ(10) significantly reduces MMP-1 expression. These data identify positive feedback regulation that couples age-dependent MMP-1-catalyzed collagen fragmentation and oxidative stress. We propose that this self perpetuating cycle promotes human skin aging. These data extend the current understanding of the oxidative theory of aging beyond a cellular-centric view to include extracellular matrix and the critical role that connective tissue microenvironment plays in the biology of aging.
Article
Multicellular organisms are formed by specialized cells assembled in tissues. Individual cells contact and interact with other cells and with the extracellular matrix--a network of secreted proteins and carbohydrates that fills the intercellular spaces. The extracellular matrix helps cells to bind together and regulates a number of cellular functions, such as adhesion, migration, proliferation, and differentiation. It is formed by macromolecules, locally secreted by resident cells. The two main classes of macromolecules are polysaccharide glycosaminoglycans, usually covalently linked to proteins in the form of proteoglycans, and fibrous proteins of two functional types, structural (collagen, elastin) and adhesive (fibronectin, laminin, vitronectin, etc.). Receptors for extracellular matrix macromolecules are present in virtually all of the cells studied. They belong to the superfamily of integrins, alpha beta heterodimers, which, in most cases, recognize the Arg-Gly-Asp sequence of extracellular matrix proteins. On the exterior side of the cell, integrins link an extracellular matrix macromolecule, whereas in the cytosol, they bind the cytoskeleton, thereby forming a membrane bridge between extracellular and intracellular fibers. This structure enables the cell to adhere to the substratum. Similar to hormone- or growth factor-receptor binding, the interaction of the integrin with its specific ligand induces immediate signal transduction and influences cellular activities.
Article
Fibroblasts cultivated in three-dimensional tissue-like matrices are characterized by a slowed metabolism and a decrease of protein synthesis, unless they are submitted to physical tensions. We checked the effects of insulin like growth factor-I (IGF-I), known as a potent stimulator of mitogenesis and protein synthesis for many cell types, in various models of cultures: confluent monolayers, collagen lattices, non-retracting or retracting fibrin lattices. IGF-I (1-100 ng.ml-1) had no effect on cell divisions in lattice cultures. It was able to stimulate collagen lattice retraction when the medium was supplemented with low concentrations of serum. IGF-I at 10 or 100 ng.ml-1 stimulated collagen and non-collagen syntheses in all culture systems, but stimulation of collagen synthesis only began at the highest concentration (100 ng.ml-1) in retracted lattices. Northern blot and dot-blot analyses of mRNAs extracted from monolayer cultures of fibroblasts showed that IGF-I stimulated pro alpha 1(I) collagen synthesis at the pretranslational level. Cycloheximide (7.5 micrograms.ml-1) completely inhibited pro alpha 1(I) collagen gene expression induced by IGF-I. These results show that IGF-I is a potent stimulus for protein synthesis and collagen gene expression in monolayers and tridimensional cultures of fibroblasts, but that it exerts no mitogenic activity in tridimensional lattices. Synergistic associations of IGF-I with other growth factors will have to be found in order to reverse the quiescent status of fibroblasts in lattices.
Article
Previous studies of the age-related changes in interstitial collagens, have suggested that the proportion of type III collagen compared with type I decreases with age. In this study collagen concentration and the proportion of types were measured in heart, lung and skin of male Lewis rats aged between 1 day and 2 years. Collagen concentration, based on hydroxyproline levels, increased in all tissues up until 6 months of age, thereafter it increased in heart and lung, yet decreased in skin. The relative proportions of types I and III collagen were assessed after cyanogen bromide digestion of the tissue and separation of the resultant peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. At 2 weeks of age collagen type III represented about one-third of types I and III in all tissues. After this age the proportion of type III increased up to 1 year in both heart (53.9 +/- 1.8%) and lung (47.7 +/- 2.8%), whereas it decreased in skin (18.6 +/- 1.5%). These data show that there are age-related changes in both collagen concentration and the relative proportions of types I and III collagen, but that the direction of these changes differs between tissues.
Article
The collagen superfamily of proteins now contains at least 19 proteins formally defined as collagens and an additional ten proteins that have collagen-like domains. The most abundant collagens form extracellular fibrils or network-like structures, but the others fulfill a variety of biological functions. Some of the eight highly specific post-translational enzymes involved in collagen biosynthesis have recently been cloned. Over 400 mutations in 6 different collagens cause a variety of human diseases that include osteogenesis imperfecta, chondrodysplasias, some forms of osteoporosis, some forms of osteoarthritis, and the renal disease known as the Alport syndrome. Many of the disease phenotypes have been produced in transgenic mice with mutated collagen genes. There has been increasing interest in the possibility that the unique post-translational enzymes involved in collagen biosynthesis offer attractive targets for specifically inhibiting excessive fibrotic reactions in a number of diseases. A number of experiments suggest it may be possible to inhibit collagen synthesis with oligo-nucleotides or antisense genes.
Article
Bioactive compound(s) extracted from cinnamon potentiate insulin activity, as measured by glucose oxidation in the rat epididymal fat cell assay. Wortmannin, a potent PI 3'-kinase inhibitor, decreases the biological response to insulin and bioactive compound(s) from cinnamon similarly, indicating that cinnamon is affecting an element(s) upstream of PI 3'-kinase. Enzyme studies done in vitro show that the bioactive compound(s) can stimulate autophosphorylation of a truncated form of the insulin receptor and can inhibit PTP-1, a rat homolog of a tyrosine phosphatase (PTP-1B) that inactivates the insulin receptor. No inhibition was found with alkaline phosphate or calcineurin suggesting that the active material is not a general phosphatase inhibitor. It is suggested, then, that a cinnamon compound(s), like insulin, affects protein phosphorylation-dephosphorylation reactions in the intact adipocyte. Bioactive cinnamon compounds may find further use in studies of insulin resistance in adult-onset diabetes.
Article
The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of IGF-I and IGF-II. The IGFs play a critical role in promoting development, stimulating growth and organogenesis via mitogenic, antiapoptotic and chemotactic activity. Recent research has focused on the events that occur intracellularly upon receptor activation. Several pathways have been shown to be important. The insulin-receptor substrate (IRS), SHC, GRB2, CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell. This review outlines some of the signalling pathways believed to be important in converting IGF-IR activation into changes in cell behavior and metabolism.
Article
Helicobacter pylori has been associated with the pathogenesis of antral gastritis, duodenal ulcer, and gastric lymphoma. Eradication of H. pylori has been shown to reverse or prevent relapse of these diseases. Antimicrobials employed in the eradication of H. pylori are not without adverse effects. Newer treatment modalities, therefore, are required. In vitro studies have shown the effectiveness of cinnamon extract against H. pylori and its urease. In this pilot study, we tested the activity of an alcoholic extract of cinnamon in a group of patients infected with H. pylori. Fifteen patients (11 women, 4 men) aged 16 to 79 years were given 40 mg of an alcoholic cinnamon extract twice daily for 4 weeks; eight patients aged 35 to 79 (7 women, 1 man) received placebo. The amount of H. pylori colonization was measured by the 13C urea breath test before and after therapy. The mean urea breath test counts in the study and control groups before and after therapy were 22.1 and 23.9 versus 24.4 and 25.9, respectively. The cinnamon extract was well tolerated, and side effects were minimal. We concluded that cinnamon extract, at a concentration of 80 mg /day as a single agent, is ineffective in eradicating H. pylori. Combination of cinnamon with other antimicrobials, or cinnamon extract at a higher concentration, however, may prove useful.
Article
The insulin-like growth factors (IGFs) are a ubiquitous family of growth factors, binding proteins and receptors that are involved in normal growth and development. They are also implicated in numerous pathological states, including malignancy. IGF-II is a commonly expressed growth factor in many tumors and may enhance tumor growth, acting via the overexpressed IGF-I receptor, a cell-surface tyrosine kinase receptor. The IGF-I receptor may be overexpressed due to mutations in tumor suppression gene products such as p53 and WT-1 or growth factors such as bFGF and PDGF. Thus, this family of growth factors, especially the IGF-I receptor, may present an excellent target for new therapeutic agents in the treatment of cancer and other disorders of excessive cellular proliferation.
Article
trans-Cinnamaldehyde and trans-cinnamic alcohol have been commonly reported to cause allergic contact dermatitis (ACD) in humans. Cinnamaldehyde is a more potent skin sensitizer than cinnamic alcohol. It has been hypothesized that cinnamic alcohol is a "prohapten" that requires metabolic activation, presumably by oxidoreductase enzymes such as alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1), to the protein-reactive cinnamaldehyde (a hapten). In this study, the in vitro percutaneous absorption and metabolism of cinnamaldehyde and cinnamic alcohol (78 micromol dose) has been examined using freshly excised, metabolically viable, full-thickness breast and abdomen skin from six female donors. Penetration rates and total cumulative recoveries of cinnamic compounds that were present in receptor fluid, extracted from within the skin, evaporated from the skin surface, or remained unabsorbed on the skin surface after 24 h were quantified by reversed-phase high-performance liquid chromatography. Biotransformation of cinnamaldehyde to both cinnamic alcohol and cinnamic acid was observed. Topically applied cinnamic alcohol was converted to cinnamaldehyde (found on the skin surface only) and cinnamic acid. To establish whether these biotransformations were enzymatic, experiments were performed in the absence and presence of varying concentrations (80-320 micromol) of the ADH/CYP2E1 inhibitors pyrazole or 4-methylpyrazole. The observation that pyrazole significantly reduced (p < 0.05) the total penetration of cinnamic metabolites into receptor fluid, following either cinnamaldehyde or cinnamic alcohol treatment, but did not significantly affect parent chemical penetration, suggests that we are measuring cutaneous metabolic products of ADH activity. The skin absorption and metabolism of cinnamaldehyde and cinnamic alcohol will play an important role in the manifestation of ACD following topical exposure to these compounds.
Article
These studies investigated the ability of a hydroxychalcone from cinnamon to function as an insulin mimetic in 3T3-LI adipocytes. Comparative experiments were performed with the cinnamon methylhydroxychalcone polymer and insulin with regard to glucose uptake, glycogen synthesis. phosphatidylinositol-3-kinase dependency, glycogen synthase activation and glycogen synthase kinase-3beta activity. The phosphorylation state of the insulin receptor was also investigated. MHCP treatment stimulated glucose uptake and glycogen synthesis to a similar level as insulin. Glycogen synthesis was inhibited by both wortmannin and LY294002, inhibitors directed against the PI-3-kinase. In addition, MHCP treatment activated glycogen synthase and inhibited glycogen synthase kinase-3beta activities, known effects of insulin treatment. Analysis of the insulin receptor demonstrated that the receptor was phosphorylated upon exposure to the MHCP. This supports that the insulin cascade was triggered by MHCP. Along with comparing MHCP to insulin, experiments were done with MHCP and insulin combined. The responses observed using the dual treatment were greater than additive, indicating synergism between the two compounds. Together, these results demonstrate that the MHCP is an effective mimetic of insulin. MHCP may be useful in the treatment of insulin resistance and in the study of the pathways leading to glucose utilization in cells.
Article
Protein tyrosine phosphatases (PTPs) are a large family of enzymes that catalyze the hydrolytic removal of the phosphoryl group from phosphotyrosyl (pY) proteins. PTP inhibitors provide potential treatment of human diseases/conditions such as diabetes and obesity as well as useful tools for studying the function of PTPs in signaling pathways. In this work, we have shown that certain aryl-substituted aldehydes act as reversible, slow-binding inhibitors of modest potency against PTP1B, SHP-1, and a dual-specificity phosphatase, VHR. Attachment of the tripeptide Gly-Glu-Glu to the para position of cinnamaldehyde resulted in an inhibitor (Cinn-GEE) of substantially increased potency against all three enzymes (e.g., K-1* = 5.4 muM against PTP1B). The mechanism of inhibition was investigated using Cinn-GEE specifically labeled with C-13 at the aldehyde carbon and H-1-C-13 heteronuclear single-quantum coherence spectroscopy. While Cinn-GEE alone showed a single cross-peak at delta 9.64 (H-1) and delta 201 (C-13), the PTP1B/Cinn-GEE complex showed three distinct cross-peaks at delta 7.6-7.8 (H-1) and 130-137 (C-13). Mutation of the catalytic cysteine (Cys-215 in PTP1B) into alanine had no effect on the cross-peaks, whereas mutation of a conserved active-site arginine (Arg-221 in PTP1B) to alanine abolished all three cross-peaks. Similar experiments with Cinn-GEE that had been labeled with C-13 at the benzylic position revealed a change in the hybridization state (from sp(2) to sp(3)) for the benzylic carbon as a result of binding to PTP1B. These results rule out the Possibility of a free aldehyde, aldehyde hydrate, or hemithioacetal as the enzyme-bound inhibitor form. Instead, the data are consistent with the formation of an enamine between the aldehyde group of the inhibitor and the guanidine group of Arg-221 in the PTP1B active site. These aldehydes may provide a general core structure that can be further developed into highly potent and specific PTP inhibitors.
Article
Human skin, like all other organs, undergoes chronological aging. In addition, unlike other organs, skin is in direct contact with the environment and therefore undergoes aging as a consequence of environmental damage. The primary environmental factor that causes human skin aging is UV irradiation from the sun. This sun-induced skin aging (photoaging), like chronological aging, is a cumulative process. However, unlike chronological aging, which depends on the passage of time per se, photoaging depends primarily on the degree of sun exposure and skin pigment. Individuals who have outdoor lifestyles, live in sunny climates, and are lightly pigmented will experience the greatest degree of photoaging. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms that bring about chronological aging and photoaging. This emerging information reveals that chronological aging and photoaging share fundamental molecular pathways. These new insights regarding convergence of the molecular basis of chronological aging and photoaging provide exciting new opportunities for the development of new anti-aging therapies. This article reviews our current understanding and presents new data about the molecular pathways that mediate skin damage by UV irradiation and by the passage of time.
Article
In response to tissue injury connective tissue synthesis occurs either normally or abnormally, which is mediated by transforming growth factor-beta (TGF-beta) and other growth factors. This article will be primarily concerned with the response of injured tissues at the gene level of Type I procollagen synthesis in response to TGF-beta. This leads to provisional repair, which in turn may lead to involution, remodeling, regeneration, and ultimately repair. Alternately, continuation of provisional repair may lead to fibrosis and ultimately scarring. Scarring of internal organs such as the liver and the lung leads to loss of function and ultimately death. In the case of scarring of skin, this is a cosmetic problem and can be rectified by surgery. Type I procollagen is synthesized by two genes, proalpha1 (Type I) and proalpha2 (Type I) collagen genes. This article will focus on DNA binding sites on these two genes, which regulate the transcription of the specific gene. This article will also define specific cell signaling pathways for the turning on of the proalpha1 and proalpha2 (Type I) collagen genes. This article will address several questions. First, what is the major cytokine acting extracellularly which stimulates the transcription of the proalpha1 and proalpha2 (Type I) collagen genes during tissue fibrosis? Secondly, how are the signals transmitted by the extracellular profibrotic cytokine TGF-beta from the cellular membrane to the nucleus for transcription of the proalpha1 (Type I) and proalpha2 (Type I) collagen genes? Thirdly, what signaling pathways cross-talk with the signaling pathways resulting in the expression of the Type I collagen genes? Fourthly, how does TGF-beta affect extracellular matrix homeostasis? Fifthly, what are the nuclear factors corresponding to the DNA elements required for the promotion of the proalpha1 (Type I) and proalpha2 (Type I) collagen genes? Finally, how are the proalpha1 (Type I) and proalpha2 (Type I) collagen genes coordinately regulated? Strategies will also be presented for reducing fibrosis, which is the result of overexpression of TGF-beta.
Article
Cassia bark or cortex cinnamomi, the dried stem bark of Cinnamomum cassia Presl. (Lauraceae), is a popular natural spice and a commonly used herb in traditional Chinese medicine. However, adulterants are frequently found in the market. In this study, 44 samples of Cassia bark including bark from seven related Cinnamomum species were collected from fields and market. Four characteristic components, cinnamaldehyde, cinnamic acid, cinnamyl alcohol, and coumarin were determined by RP-HPLC, and a fingerprint comprised of five markers was established. These results showed that cassia barks contained high contents of cinnamaldehyde (13.01-56.93 mg/g). The highest content of cinnamaldehyde (up to 93.83 mg/g) was found in debarked cortex, which is traditionally regarded as having the best quality in local herb shops. In contrast, the adulterants from the other Cinnamomum species, C. wilsonii Camble, C. japonicum Sieb., C. mairei Levl. and C. burmanii (Nees) Blume, contained low contents of cinnamaldehyde (<2.00 mg/g). The content of cinnamaldehyde in C. loureirii Nees was comparable to that in C. cassia. It is suggested that five characteristic peaks by HPLC are suitable for distinguishing genuine cassia bark from the adulterants and could be applied in the quality control of this commodity.
Article
We have previously demonstrated that mechanical loading of cardiac fibroblasts leads to increased synthesis and gene expression of the extracellular matrix protein collagen. We hypothesised that the upregulation of procollagen gene expression in cardiac fibroblasts, in response to cyclic mechanical load, is mediated by one or more members of the MAP kinase family. To test this hypothesis, the effect of mechanical load on the activation of extracellular signal-regulated kinase (ERK) 1/2, p46/54JNK, and p38MAPK was examined in rat cardiac fibroblasts. Peak phosphorylation of ERK 1/2, p38MAPK kinases, and p46/54JNK was observed following 10-20 min of continuous cyclic mechanical load. Mechanical load significantly increased procollagen alpha1(I) mRNA levels up to twofold above static controls after 24 h. This increase was completely abolished by the MEK 1/2 inhibitor U0126, with no effect on basal levels. In contrast, SB203580, a specific inhibitor of p38MAPK, enhanced both basal and stretch-stimulated levels of procollagen mRNA. Consistent with this finding, selective activation of the p38MAPK signalling pathway by expression of MKK6(Glu), a constitutive activator of p38MAPK, significantly reduced procollagen alpha1(I) promoter activity. SB203580-dependent increase in procollagen alpha1(I) was accompanied by ERK 1/2 activation, and inhibition of this pathway completely prevented SB203580-induced procollagen alpha1(I) expression. These results suggest that mechanical load-induced procollagen alpha1(I) gene expression requires ERK 1/2 activation and that the p38MAPK pathway negatively regulates gene expression in cardiac fibroblasts. These pathways are likely to be key in events leading to matrix deposition during heart growth and remodelling induced by mechanical load.
Article
A toxicologic and dermatologic review of cinnamaldehyde when used as a fragrance ingredient is presented.
Article
The important role of IGF and insulin-related signaling pathways in the control of longevity of worms and insects is very well documented. In the mouse, several spontaneous or experimentally induced mutations that interfere with GH biosynthesis, GH actions, or sensitivity to IGF-I lead to extended longevity. Increases in the average life span in these mutants range from approximately 20-70% depending on the nature of the endocrine defect, gender, diet, and/or genetic background. Extended longevity of hypopituitary and GH-resistant mice appears to be due to multiple mechanisms including reduced insulin levels, enhanced insulin sensitivity, alterations in carbohydrate and lipid metabolism, reduced generation of reactive oxygen species, enhanced resistance to stress, reduced oxidative damage, and delayed onset of age-related disease. There is considerable evidence to suggest that the genetic and endocrine mechanisms that influence aging and longevity in mice may play a similar role in other mammalian species, including the human.