Article

Royal Jelly Increases Collagen Production in Rat Skin After Ovariectomy

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Abstract

Royal jelly (RJ) is a honeybee product that contains proteins, carbohydrates, fats, free amino acids, vitamins, and minerals. RJ has been reported to have antitumor, antibacterial, and wound-healing activities. We previously reported that RJ enhanced the migration of human dermal fibroblasts and altered the levels of cholesterol and sphinganine in an in vitro wound-healing model in addition to regulating skin photoaging following exposure to ultraviolet-B radiation. We established an animal model of skin aging in the context of estrogen deficiency and assessed the antiaging effects of RJ on skin. To establish an in vivo model of skin aging, bilateral ovariectomies were performed in 12-week-old virgin female Sprague-Dawley rats. Induction of osteoporosis was confirmed through two-dimensional images of the trabecular bone in the left femoral necks using microcomputed tomography. The protective effects of RJ ovariectomy-induced skin aging were examined by determining the protein expression of type I procollagen and matrix metalloproteinase (MMP)-1. The collagen content and epidermal thickness of skin tissue were measured by staining techniques. There was a significant difference in weight between sham-operated and ovariectomized groups. Food efficiency ratio did not differ significantly among the groups. The level of procollagen type I protein was increased in the dorsal skin of ovariectomized rats fed with a dietary supplement containing 1% RJ extract, but the level of MMP-1 was not altered. In particular, the amount of collagen recovered was close to the normal level. RJ may protect against skin aging by enhancing collagen production in rats with ovariectomy-induced estrogen deficiency.

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... RJ contains rich proteins, carbohydrates, fats, free amino acids, vitamins and minerals. 26 In particular, lipids in RJ are useful as preventive and supportive medicines with functionalities that include potential inhibitors of cancer growth, immune system modulators, alternative therapies for menopause, skin-aging protectors, neurogenesis inducers. 26 Park et al. 26 , also reported that RJ, in particular, caffeic acid phenethyl ester (CAPE) from Honeybee propolis has been known to have capacity of attenuating osteoclastogenesis and bone resorption in ovariectomized (OVX) mice. ...
... 26 In particular, lipids in RJ are useful as preventive and supportive medicines with functionalities that include potential inhibitors of cancer growth, immune system modulators, alternative therapies for menopause, skin-aging protectors, neurogenesis inducers. 26 Park et al. 26 , also reported that RJ, in particular, caffeic acid phenethyl ester (CAPE) from Honeybee propolis has been known to have capacity of attenuating osteoclastogenesis and bone resorption in ovariectomized (OVX) mice. 27 According to the results, with CAPE treatment, the microarchitecture of the tibia metaphysis was J MM significantly enhanced with a reduction of osteoclast formation as well bone mineral density (BMD). ...
... 26 In particular, lipids in RJ are useful as preventive and supportive medicines with functionalities that include potential inhibitors of cancer growth, immune system modulators, alternative therapies for menopause, skin-aging protectors, neurogenesis inducers. 26 Park et al. 26 , also reported that RJ, in particular, caffeic acid phenethyl ester (CAPE) from Honeybee propolis has been known to have capacity of attenuating osteoclastogenesis and bone resorption in ovariectomized (OVX) mice. 27 According to the results, with CAPE treatment, the microarchitecture of the tibia metaphysis was J MM significantly enhanced with a reduction of osteoclast formation as well bone mineral density (BMD). ...
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Human health problems due to long life are becoming major issues in society, and in particular greater interest collected on women's health after menopause. Many substances can be introduced to women's health, however, materials from the substances have not shown all of the safety and efficacy properties that are not easily found. Currently, it is known about the effects of the disease on the female insect-derived material that is capable of overcoming this problem significantly. When using the insect-derived material through the results of several studies suggest that it is possible to solve a hormonal imbalance and nutritional imbalance in the elderly. Here, we'd like to try to dissertate about the new trends for women's health improvement using novel materials-derived from insects.
... Beekeeping products have been deeply rooted as nutritional sources and medicines in the lives of different people and cultures worldwide for thousands of years. Honeybee products are used as a nutritional source in daily life and medicine [7][8][9][10][11][12][13]. The main products of beekeeping include honey, royal jelly (RJ), propolis, pollen, and bee larva produced or collected by Apidae. ...
... RJ, which the queen honeybee requires for its development, is mainly secreted by the mandibular and hypopharyngeal glands of worker honeybees (Apis mellifera). RJ is a complex substance comprising proteins, sugars, lipids, amino acids, vitamins, and minerals [9]. Previously, our research group found that orally administered RJ restored tear secretion capacity in a dose-dependent manner in a rat model of dry eye [16]. ...
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Background Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye. Methods and Findings We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20–60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (p = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (p = 0.0005) and volume in the placebo group (p = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands. Conclusion Our results suggest that RJ improves tear volume in patients with dry eye. Trial Registration Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446)
... Royal jelly (RJ) is a secretion product of the cephalic glands of honey bees (Apis mellifera L.) and is one of the most attractive functional foods. It is the specic food for the queen honey bee throughout her life period and it is involved in the fertility and longevity of the queen. 1 A multitude of pharmacological activities have been reported in experimental animals [2][3][4][5][6] and in clinical trials, 7-10 including antitumor, 2 anti-oxidant, 3 anti-inammatory, 4 antibacterial, 5 and anti-aging, 6 improvement of chills, 7 neck muscle strain, 8 tinnitus, 9 female menopausal symptoms, 10 age associated muscle strength decline, 11 and lipoprotein metabolism by lowering serum total cholesterol and leading to low-density lipoprotein levels, as well. 12 The chemical composition of RJ consists of: water (60-70%), proteins (9-18%), sugars (7.5-23%), lipids (3-8%), and other trace compounds. ...
... Royal jelly (RJ) is a secretion product of the cephalic glands of honey bees (Apis mellifera L.) and is one of the most attractive functional foods. It is the specic food for the queen honey bee throughout her life period and it is involved in the fertility and longevity of the queen. 1 A multitude of pharmacological activities have been reported in experimental animals [2][3][4][5][6] and in clinical trials, 7-10 including antitumor, 2 anti-oxidant, 3 anti-inammatory, 4 antibacterial, 5 and anti-aging, 6 improvement of chills, 7 neck muscle strain, 8 tinnitus, 9 female menopausal symptoms, 10 age associated muscle strength decline, 11 and lipoprotein metabolism by lowering serum total cholesterol and leading to low-density lipoprotein levels, as well. 12 The chemical composition of RJ consists of: water (60-70%), proteins (9-18%), sugars (7.5-23%), lipids (3-8%), and other trace compounds. ...
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The unique fatty acids in royal jelly (RJ), 10-hydroxy-2-decenoic acid and 10-hydroxydecanoic acid are expected to be associated with many health benefits, but little is known on the pharmacokinetics and metabolism. The aim of this study is to confirm the metabolism and pharmacokinetics of RJ fatty acids in humans. Twelve volunteers received RJ capsules or enzyme treated RJ (ETRJ) capsules (800 mg). The other group received two doses of ETRJ tablets (800 mg and 1600 mg). Plasma samples were collected up to 12 h after the RJ intake and urine samples were collected within 24 h after ETRJ tablet consumption. The samples were analyzed by LC/MS/MS. A multivariate analysis of the RJ dose plasma samples detected 2-decenedioic acid (2-DA), sebacic acid (SA), and 3-hydroxysebacic acid (3-HSA) with significantly different intensities (P < 0.05) before and after RJ intake. The area under the concentration (AUC) of 2-DA, SA, and 3-HSA was 2500.05 ± 569.58, 322.57 ± 137.36, and 242.98 ± 58.36 ng h mL ⁻¹ , respectively. By enzyme treatment, the AUC of 2-DA, SA, and 3-HSA was significantly increased (P < 0.05). The values of AUC and urinary excretion of these metabolites were dose-dependent. The major RJ fatty acids were metabolized to dicarboxylate, absorbed into the circulation and their absorption increased by enzyme treatment. This study provides useful information that will support studies aimed at clarifying the identity of bioactive RJ constituents and their biological effect, and further the development of RJ.
... Approximately 185 organic compounds have been detected in royal jelly, which has various benefits and biological activities such as in reproductive health, neurodegenerative diseases, and tumor treatment [1] [2] [3] [4]. New evidence of the effect of royal jelly in anti-dermatitis [5] [6], wound healing [7], collagen production [8] and anti-melanogenesis [9] have been accumulated in the last two decades. Thus, royal jelly is considered an ideal cosmetics and skin care product component. ...
... A few studies reported that postmenopausal osteoporosis was caused by decreased production of estrogen hormone and RJ has estrogenic effects to ameliorate postmenopausal 400 osteoporosis. Furthermore, RJ is effective on bone metabolism and collagen biosynthesis and enhances collagen production (Fujii et al. 1990;Kim et al. 2010;Park et al. 2012; Table 1). ...
Article
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Royal jelly (RJ) is a natural bee product with great potential for use in medicine. The chemical composition of RJ indicates the presence of various bioactive substances including 10-hydroxydecanoic acid and 24-methylenecholesterol. In addition, a number of biological and pharmacological activities of RJ have been documented. The aim of this study was to review the biological and medical effects of RJ. The search was conducted in articles from electronic and scientific literature databases such as Pub Med, Science Direct, Scopus, Medline, and ISI Web of Science published from 1990 to 2017 using keywords of pharmacological, biological, and clinical effects and royal jelly. Data were chosen after the primary survey of all abstracts and selected full articles. Comparison among related data was done by the authors. Literature has shown that RJ possesses many beneficial effects on biological systems. For example, the therapeutic uses of RJ have been reported in several diseases such as hypercholesterolemia, diabetes, hypertension, and cancers. It was also found to possess neurotrophic, hypotensive, immunomodulatory, antimicrobial, antioxidant, antidiabetic, antihypercholesterolemic, antitumor, and anti-inflammatory effects. Owing to the broad spectrum of biological effects and valuable clinical trials, evaluating the beneficial pharmaceutical effects of RJ in animal and human models seems to be important.
... Therefore , RJ has been long-used as a supplement for nutrition, anti-aging or infertility. RJ has been demonstrated to possess many pharmacological activities in experimental animals, including anti- tumor [3], anti-oxidant [4], anti-inflammatory [5], antibacterial [6], anti-allergic [7], anti-aging [8] and antihypertensive properties [9]. In humans, its oral ingestion improves lipoprotein metabolism and reduces serum total cholesterol (TC) and low-density lipoprotein (LDL) levels [10] . ...
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Background Royal jelly is a widely ingested supplement for health, but its effects on humans are not well known. The objective was to evaluate the effects of long-term royal jelly ingestion on humans. Methods We conducted a randomized placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42-83 years were enrolled and were randomly divided into a royal jelly group (n = 31) and a control group (n = 30). Three thousand mg of royal jelly (RJ) or a placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes were changes in anthropometric measurements and biochemical indexes from baseline to 6 months after intervention. Results Thirty subjects in the RJ group and 26 in the control group were included in the analysis of endpoints. In an adjusted mean change of the variables from the baseline, significant differences between the two groups could be found in red blood cell counts (+0.16x106 /μL for the RJ group vs. -0.01x106 /μL for the control group, P = 0.0134), hematocrit (+0.9% vs. -0.8%, P = 0.0251), log (fasting plasma glucose) (+0.01 ± 0.01 log mg/dL vs. +0.05 ± 0.01 log mg/dL, P = 0.0297), log (insulinogenic index) (+0.25 vs. -0.13, P = 0.0319), log dehydroepiandrosterone sulfate (DHEA-S) (+0.08 log μg/dL vs. +0.20 log μg/dL, P = 0.0483), log testosterone (T) (+0.12 ± 0.04 log ng/mL vs. -0.02 ± 0.05 log ng/mL, P = 0.0416), log T/DHEA-S ratio (+0.05 ± 0.05 vs. -0.23 ± 0.59, P = 0.0015), and in one of the SF-36 subscale scores, mental health (MH) (+4 vs. -7, P = 0.0276). Conclusions Six-month ingestion of RJ in humans improved erythropoiesis, glucose tolerance and mental health. Acceleration of conversion from DHEA-S to T by RJ may have been observed among these favorable effects.
... 15 The effect has been attributed to the regulation of transforming growth factor (hTGF-β) and other relative growth factors. 16 Diosgenin has been found to increase the secretion of collagen from ovariectomized estrogen-deficient rats 17 and the dermal thickness of hairless mice due to its structure similar to that of 17β-estradiol. 18 Reducing the size to the nano/submicrometer scale is believed to enhance the bioavailability of nutrients. ...
Article
Nano/submicrometer scaled yam particles have been prepared by using media milling. The particle size of media-milled yam was confirmed by laser light scattering method and scanning electron microscope. Influences of media-milled yam on skin fibroblast cells (WS1) were evaluated. The size reduction did not significantly alter the proximate composition and the presence of nano particles was not toxic to WS1 cells. The contents of bioactive compounds (diosgenin, stigmasterol, and beta-sitosterol) were significantly increased by media milling, which enhanced the secretion of hTGF-beta and inhibited the formation of MMP-1. Thus, the collagen secretion from WS1 was significantly increased by size reduction. Diosgenin was employed as a positive control. Nevertheless, media-milled yam exhibited greater effects on WS1 cells than diosgenin. It appeared that both diosgenin and size reduction were helpful for enhancing the secretion of collagen by WS1 cells. In addition, the irritancy of yam was eliminated by media-milling.
... Extrinsic aging is caused by environmental factors, mainly ultraviolet (UV) radiation, which is called photoaging, and is characterized by wrinkles and dryness. (Anandan et al., 2013;Mukherjee et al., 2011;Berneburg et al., 2008;Papakonstantinou et al., 2012;Park et al., 2012). ...
Article
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Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP-1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor-β1. Our data indicate that GA is a potential candidate for the prevention of UVB-induced premature skin aging. Copyright © 2014 John Wiley & Sons, Ltd.
... RJ is a complex substance containing a unique combination of proteins (12-15%), sugars (10-12%), lipids (3-7%), amino acids, vitamins, and minerals [18]. RJ has also been demonstrated to possess many pharmacological activities in experimental animals, including antitumor [19], antioxidant [20,21], anti-inflammatory [22], antibacterial [23], antiallergic [24], antiaging [25], and antihypertensive properties [26]. Recently, many authors have reported that the antioxidant effect is important for wound healing [27][28][29]. ...
Article
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Purpose. One of the common side effects experienced by head and neck cancer patients on chemoradiotherapy is mucositis. Severe mucositis may be controllable by limiting cancer therapy, but it has resulted in decreasing the completion rate of chemoradiotherapy. The efficacy of royal jelly (RJ) as prophylaxis against chemoradiotherapy-induced mucositis was evaluated through clinical scoring of oral and pharyngeal mucositis. Methods. In this randomized, single-blind (physician-blind), clinical trial, 13 patients with head and neck cancer requiring chemoradiation were randomly assigned to two groups. Seven patients assigned to the study group received RJ, and 6 patients were assigned to the control group. RJ group patients took RJ three times per day during treatment. The patients in both groups were evaluated twice a week for the development of mucositis using Common Terminology Criteria for Adverse Events version 3.0. Results. A significant reduction in mucositis was seen among RJ-treated patients compared with controls ( P < 0.001 ). Conclusion. This study demonstrated that prophylactic use of RJ was effective in reducing mucositis induced by chemoradiotherapy in head and neck cancer patients. However, further studies are needed because of the small sample size and the absence of double blinding.
... The skin aging is mainly genetically determined but also clinically associated with an increased fragility and loss of elasticity [3]; in addition, oxidative stress is an important contributor to the pathophysiology of various pathological conditions [4]. In fact, reactive oxygen species (ROS) are well-known as a cause of aging. ...
... Diet: According to Modern medicine and TPM, a healthy diet can have an important role to prevent aging in the body and skin (7)(8)(9). For example, honey and royal jelly consumption have anti-cancer effect and promote skin collagen formation incredibly (54)(55)(56)(57). Long-term continuous drinking of goat milk can prevent skin drying and adding honey with a piece of ginger to a glass of boiling milk improves its property significantly (16,17,19,21,23). ...
Article
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Context: Traditional persian medicine (TPM) is an ancient temperamental medicine with a rich literature about aging mechanism. Temperament has an important function in maintaining the ideal healthy status of human body. Aging process and skin aging could be postponed by applying herbal medicine and some specific traditional rules. Evidence Acquisition: The aim of this review study was gathering and discussing the mechanism of whole body aging and skin aging from perspective of TPM and introducing remedies to prevent it. Skin aging is caused by external and internal factors. According to TPM, loss of fat and water content in different skin layers is the main cause of skin aging and it could be avoided by considering simple essential commands. Results: Skin aging begins with whole body aging process and entire body gets cold and dry in elderly. Wrinkle formation is highly associated with loss of " skin natural moisture ". In the management, specific food supplements, simple massage therapy as well as herbal drugs were suggested. The current investigation was performed to show the knowledge of ancient Iranian scientists on aging process and related interventions. Conclusions: Reported herbal drugs might be beneficial for further studies for the management of skin aging and aging process.
... The profound effects of RJ on development and physiology of honey bees has stimulated many studies assessing whether its beneficial effects can transcend species barriers. RJ has been reported to increase lifespan in mice [13] and C. elegans [14]; decrease fatigue [15] in mice; increase collagen production [16], reduce hypertension [17] and modulate oxidative stress and tissue injury repair [18] in rats; slow testicular decline in hamsters [19]; inhibit the production of pro-inflammatory cytokines by activated mouse macrophages [20] and inhibit bisphenol Ainduced proliferation of human breast cancer cells [21]. RJ is a popular nutritional supplement in humans [22] and has been reported to have beneficial effects on glucose tolerance, mental health, and lipoprotein metabolism [23,24]. ...
Article
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Royal Jelly (RJ) is a product made by honey bee workers and is required for queen differentiation and accompanying changes in queen body size, development time, lifespan and reproductive output relative to workers. Previous studies have reported similar changes in Drosophila melanogaster in response to RJ. Here, we quantified viability, development time, body size, productivity, lifespan and genome wide transcript abundance of D. melanogaster reared on standard culture medium supplemented with increasing concentrations of RJ. We found that lower concentrations of RJ do induce significant differences in body size in both sexes; higher concentrations reduce size, increase mortality, shorten lifespan and reduce productivity. Increased concentrations of RJ also consistently lengthened development time in both sexes. RJ is associated with changes in expression of 1,581 probe sets assessed using Affymetrix Drosophila 2.0 microarrays, which were enriched for genes associated with metabolism and amino acid degradation. The transcriptional changes are consistent with alterations in cellular processes to cope with excess nutrients provided by RJ, including biosynthesis and detoxification, which might contribute to accelerated senescence and reduced lifespan.
... Tel: 82-63-238-2896, E-mail: sangmih@korea.kr ARTICLE healing (Park et al., 2012), and anti-photoaging (Park et al., 2011) properties in vivo and in vitro. We demonstrated in a previous study that RJ reduces melanin synthesis by down-regulating tyrosinase mRNA transcription (However, RJ has been linked to allergic contact dermatitis, acute asthma and anaphylaxis in countries with high consumption of RJ (Rosmilah et al., 2008). ...
Article
Royal jelly has been widely used as a health supplement worldwide. However, royal jelly has been implicated in allergic reactions, and we developed a water-soluble royal jelly (WSRJ) without the allergy inducing protein. In this study, we aimed to identify the anti-melanogenic efficacy of WSRJ. B16F1 melanoma cells were first treated with 10 nM alpha-melanocyte stimulating hormone (alpha-MSH) and then with various doses of WSRJ. In addition, we investigated the mRNA and protein expression of melanogenesis-related genes such as tyrosinase, tyrosinase related protein-1 (TRP-1) and TRP-2 by reverse transcription-polymerase chain reaction and western blotting. WSRJ directly inhibited tyrosinase and cellular tyrosinase activity, which decreased melanin synthesis in a-MSH stimulated B16F1 melanoma cells a level comparable to that observed with arbutin. WSRJ decreased the mRNA and protein expressions of tyrosinase, TRP-1, and TRP-2, which was comparable to that observed with arbutin. WSRJ has strong anti-melanogenic activity, which invoice direct inhibition of tyrosinase enzyme activity and suppression of expression of melanogenesis related genes. Results from this study suggests that WSRJ is a potential candidate for the treatment of skin pigmentation.
... RJ shows numerous pharmacological activities including antioxidant, anti-inflammatory, antihypercholesterolemic, antitumor, as well as hypotensive and vasodilative dermaprotective properties (Nagai & Inoue 2004;Guo et al. 2007;Park et al. 2012; Kashima et al. 2014). Previous studies have indicated that the hypocholesterolemic effect of dietary proteins and peptides are associated with its bile acid binding capacity and its metabolism (Nagaoka et al. 2010;Kashima et al. 2014). ...
Article
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Context: Royal jelly (RJ) has been reported for its health promoting factors such as antioxidant, anti-inflammatory and lipid lowering activities. Objective: The present randomized, placebo-controlled study examines the hypolipidemic beneficial effect of RJ through evaluating anthropometric measurements, lipid profile and various hormone levels in mildly hypercholesterolemic participants. Materials and methods: Forty subjects with mild hypercholesterolemia (180–200 mg/dL) were randomly selected and divided into two groups as experimental or placebo, who requested to intake nine capsules (350 mg/capsule) of RJ or placebo/day, respectively, for three months with one month of follow-up without any supplementation. Results: No significant changes were noted in any of the anthropometric parameters like body weight, waist and body fat. The serum total cholesterol (TC; 207.05–183.15 mg/dL) and low-density lipoprotein cholesterol (LDL-c; 126.44–120.31 mg/dL) levels were reduced significantly (p < 0.05) after administration of RJ. However, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c) levels were not considerably altered. Moreover, three months of RJ consumption significantly ameliorated (p < 0.05) the concentration of sex hormones like dehydroepiandrosterone sulphate (DHEA-S; 1788.09–1992.31 ng/mL). Also, intake of RJ did not elicit any hepatic or renal damage. Discussion and conclusion: Intervention with RJ for three months considerably lowered the TC and LDL-c levels through improving the levels of DHEA-S and thus alleviates the risk of cardiovascular disease (CVD).
... On the other hand, royal jelly (RJ) is a complex substance comprises a wonderful mixture of vitamins, minerals, amino acids, proteins (12-15%), sugars (10-12%) and lipids (3-7%) [8] . RJ has many beneficial biological functions in experimental animals such as antioxidant [9,10] , antibacterial [11] , antiinflammatory [12] , antiallergic [13] , antiaging [14] , antihypertensive [15] , and anticancerous properties [16] . Also, RJ contains steroids, phenols, acetylcholine and other unknown substances thus it is used in cosmetics for its alleged tonic and biostimulating effects [17] . ...
Article
Background Ethanol is the most commonly used and abused xenobiotic in the world. Royal jelly (RJ) has been considered as an antioxidant that protects against different agents. Aim of the work This study aimed to investigate the effect of ethanol on the rat tongue and the possible protective role of royal jelly. Material and methods Twenty five adult male rats were used in this study and were divided into 4 groups. Group I: 10 rats were divided equally into negative and positive controls. Group II: 5 rats received RJ at a dose of 100 mg/kg body weight by gastric tube daily for 30 days. Group III: 5 rats received ethanol at a dose of 10 ml/kg body weight from 30% v/v ethanol solution in distilled water by a gastric tube daily for 30 days. Group IV: 5 rats received both RJ and ethanol as the same previous doses by gastric tube for 30 days. Tongue sections were histologically prepared and examined. Results The results revealed that group II was nearly as group I. Group III revealed by LM dorsal surface of the tongue was covered by irregularly arranged, short and long lingual papillae. Some papillae were thin, with blunted tips and others were completely absent. The epithelial lining of the ventral surface also showed an apparent reduction in thickness. The keratin layer of the ventral surfaces of the tongue appeared in some regions discontinuous and detached. Some skeletal muscle fibers revealed separations and vacuolations. Scanning electron microscope (SEM) examination revealed a noticeable atrophy of lingual papillae from being short to being absent in focal areas. They were irregularly arranged in different directions. Group IV revealed amelioration of these changes. Conclusion Ethanol has damaging effects on the lingual papillae and muscles and royal jelly has a protective role for these effects. Key words: Lingual papillae, Ethanol, Royal jelly.
... 15 Studies indicate that royal jelly can potentially protect the skin against UVB-induced photo and skin aging by increasing collagen production. 15,16 Like those bee products, honey also exhibits many beneficial effects on the skin, such as effects of softening, moisturizing, and soothing,keeping the skin young and delaying the formation of wrinkles; regulating the skin pH; and preventing pathogen infections. 17 This study aimed to develop a prototype skincare formulation based on bee venom, propolis, honey, and royal jelly to effectively protect skin aging by analyzing various quality, stability, and safety parameters. ...
Article
Full-text available
This study aimed to develop a prototype skincare product with bee venom, propolis, honey, beeswax, and royal jelly. The prototype formulation contained 0.1 % bee venom, 0.3 % propolis extract, 0.45 % honey, and 1.0 % royal jelly. The prototype body cream was analyzed for stability, antioxidant activity, dermatological response, and cytotoxicity. In addition, a panel test evaluated the prototype for the claims such as skin smoothness, feelings of nourishment, moisturizing, skin tone, brightness, and visibility of wrinkles. According to the stability test, the prototype was stable for up to 90 days at room temperature and +40 °C. The formulation was found to have a high antioxidant capacity at 85.45%. Cell viability detected over 70% indicated that the prototype body cream was not cytotoxic. The dermatological analysis revealed no irritation or allergic reaction in non‐allergic individuals. Panel test showed that the prototype makes skin silky smooth, contributes to hydration, brightens and nourishes the skin, evens the skin tone, reduces the visibility of wrinkles, improves skin elasticity, and smoothes wrinkles. This prototype formulation requires further research to evaluate its effectiveness against skin aging on different skin types. Nevertheless, the side effects of such products need particular attention in developing a commercial product containing bee venom in susceptible individuals.
... 10-HDA is only found in RJ so it has been used as a quality marker of royal jelly products [10,11]. Several pharmacological activities of RJ have already been confirmed by animal experiments, and the pharmacological activities including anti-oxidation [12,13], anti-inflammation [14], anti-tumor [15,16], antiagenesis [17], antibacterial [18][19][20], vasodilative [21,22], hypertensive [21,22], anti-hypercholesterolemic [23], nephroprotective [24] and skin-whitening effects [25]. Based on its nutritional value and its benefit for human health there are more and more commercial RJ products are available in the markets. ...
Article
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Background It has been reported that royal jelly would reduce melanin synthesis and inhibit the expression of melanogensis related proteins and genes. In this study, we evaluate the anti-melanogenic and depigmenting activity of 10-hydroxy-2-decenoic acid (10-HDA) from royal jelly of Apis mellifera. Methods In this study, we assesses the 10-HDA whitening activity in comparison with the changes in the intracellular tyrosinase activity, melanin content and melanin production related protein levles in B16F1 melanoma cells after treating with 10-HDA. Furthermore, the skin whitening effect was evaluated by applying a cream product containing with 0.5%, 1% and 2% of 10-HDA onto the skin of mice (C57BL/6 J) for 3 week to observe the effect of DL*-values. Results The results showed that 10-HDA inhibited the MITF protein expression (IC50 0.86 mM) in B16F1 melanoma cells. Western blot analysis revealed that 10-HDA inhibited the activity of tyrosinase and the expression of tyrosinase-related protein 1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF) in B16F1 melanoma cells. In addition, the 10-HDA was applied on the skin of mice show significantly increased the average skin-whitening index (L value). Conclusions The validation data indicated the potential of 10-HDA for use in suppressing skin pigmentation. The 10-HDA is proposed as a candidate to inhibit melanogenesis, thus it could be developed as cosmetics skin care products.
... [39,40] Royal jelly is a complex matter and a product of honey bee that contains protein, sugars, fats, amino acids, vitamins, and minerals and also gamma globulin and elements needed for maintaining good health with various biological activities in body cells and tissues. [41,42] Furthermore, as a part of a beneficial diet, royal jelly contains many known useful minerals. [39] It also affects the process of collagenization and the activity of skin fibroblasts. ...
Article
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Background: Menopause and its complications could disturb the sense of well-being and health and affect the quality of life. The present study was performed to review the conducted interventional study related to the quality of life in menopausal women in Iran. Methods: In the present systematic review, to achieve the intended studies, Iranian Registry for Clinical Trials and Magiran, SID, Google Scholar, Scopus, PubMed, Proquest, ScienceDirect, and Web of Science databases were searched using: menopause" and "quality of life" keywords without any time limitations. Based on Jadad criteria, studies with a score of 3 or more were enrolled in the study. Results: From all the achieved studies at primary search, 12 were selected and enrolled in the study. Reviewing the results of the studies showed that participating physical exercise, using products containing phytoestrogens and isoflavones and participating in educational and counseling sessions have an effective role in the improvement of quality of life in menopausal women. Conclusions: Evidence indicated that from the existing strategies to improve the menopausal quality of life, using complementary medicine is an efficient method and could be more effective when consumed along with performing physical exercises and participating in educational programs.
... [11] Furthermore, RJ has long been used as a dietary, anti-aging or infertility supplement as atherapeutic medicine. [12] In laboratory animals, RJ has been shown to have several pharmacological functions, like antitumor, [13] antioxidant, [4] anti-inflammatory, [14] antibacterial, [15] anti-allergic, [16] anti-aging [17] and anti-hypertensive properties. [18] For humans, its oral consumption facilitates the metabolism of lipoproteins and decreases the levels of total serum cholesterol (TC) and low density lipoprotein (LDL). ...
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Royal Jelly (RJ) is most wanted healthy food supplement that makes lots of health benefits. One of the benefits include that it can act as potent supplement for healthy egg to help women with infertility. This review is focused on the recent developments in use of RJ in the treatment of infertility and boon for them to give a dream child. The healthy egg is very phenomenal key factor for the in vitro fertilization to be successful in sexing with sperm. RJ is traditionally used as health supplement for infertility treatment from the ancient time in Indian traditional system. The recent literature revealed that, scientific and traditional findings are proven it RJ is one of the therapeutic molecule and act as a food supplements that can be used it in to improve egg cell physiology. Although, there is no clinical research studies have been reported yet on RJ. Hence, in this review explored the comprehensive report on health benefits of RJ and its impact on reproductive aspects in particular in egg development of women during ovulation. This article will be the key step to the researchers and scientists who are involved in searching alternative, cost effective and without side effect for treating infertility in global scenario.
... It impacts on the estrogen and gon-adotropin effects in cells (Suzuki et al., 2008). RJ reduces such eye problems as conjunctivitis, corneal burn and blepharitis high eye blood pressure in old people (Park et al., 2012). It promotes the building of collagen in cell cultures and prevents the development of such skin lesions as atopic dermatitis and itching (Oribe et al., 2012;Kim et al., 2010). ...
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Royal jelly (RJ) has been known for centuries, but in the last 5-6 decades its systematic production and consumption has increased. RJ is secreted by the hypopharyngeal and mandibular glands of worker honeybees ( Apis mellifera ). This thick and milky substance contains water, proteins, carbohydrates, lipids, minerals, vitamins and such bio-active compounds as acetylcholine, peptides, the hormones testosterone, progesterone, prolactin, estradiol, (hydroxydecanoic acid) (HAD), adenosine monophosphate (AMP)-N1Oxide, polyphenols, flavonoids and adenosine. Because of its bioactive compounds, RJ can be considered as a functional and nutraceutical food. The main goal of this review is to summarize and update its physicochemical properties, bio-active ingredients, storage stability and shelf life. The functional properties are antioxidative activity, insulin-like action, improvement against diabetes, liver protection, antitumoral action, neurotrophic action, antibiotic effect, anti-inflammatory action and wound healing, hypotensive effect and blood regulatory actions, anti-aging effect and skin protection, effects on the reproductive system and fertility and also fortifying, tonic action and immunomodulating and anti-alergic activity. RJ may cause allergic reactions, asthma and even fatal anaphylaxis in some humans. Therefore, RJ should be orally ingested as nutreaceutical agent or food-ingredient only after an allergy test.
... RJ has been reported to have several pharmacological properties, such as antioxidant [15], hypocholesterolaemic [16], anti-inflammatory [17], anti-malignant [18], antibacterial [19] and antiageing [20] properties, in animals. Additionally, RJ in ovo injection has been concluded to improve chick body weight [21], internal organ weight and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion without adverse effects on hatchability [22]. ...
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The hypothesis of the present work was that the effects of in ovo injection may differ in different chicken strains. The influence of in ovo royal jelly (RJ) injection on hatching, growth and blood parameters in two chicken strains (Dokki-4 and El-Salam as example for different strains) was evaluated. A total of 1080 eggs were used. On the seventh day of incubation, the eggs were randomly allocated into six experimental groups in a 2 × 3 arrangement that included the two chicken strains and three concentrations of RJ (0, 0.25 and 0.5 mL RJ/egg). Injection with 0.5 mL RJ/egg improved hatchability compared to the other treatments. The El-Salam strain exhibited significantly higher body weight and body weight gain than the Dokki-4 strain. Injection with 0.5 mL RJ/egg significantly (p < 0.05) improved chicken body weight and daily weight gain compared to the control treatment. RJ injection decreased blood lipid profile parameters and the numbers of monocytes and eosinophils and increased total protein, globulin, haemoglobin (Hb) and lymphocyte levels compared to the control treatment. The Dokki-4 strain showed significantly higher antibody titres against avian influenza virus (AIV) (p < 0.05) and sheep red blood cells (SRBCs) (p < 0.0001) than the El-Salam strain and RJ injection enhanced antibody titres against AIV, Newcastle disease virus (NDV) and SRBCs. Therefore, the Dokki-4 strain was superior to the El-Salam strain for the tested parameters and injection with 0.5 mL RJ/egg produced the best hatching parameters, growth performance and health-related traits. RJ in ovo injection was much more effective in the Dokki-4 strain than in the El-Salam strain, which supported the hypothesis of the study that varying the chicken strain could alter the response to the in ovo injection with RJ.
... Royal jelly (RJ) is secreted from the hypopharyngeal and mandibular glands of worker honey bees to develop queen honey bees (Apis mellifera) and contains proteins, sugars, lipids, vitamins, minerals, amino acids, and other component [1]. RJ has various bioactivities such as anti-oxidant [2], antiinflammatory [3], anti-aging [4,5], lifespan extension [6], and neurogenesis [7] activities, and thus, it has been widely consumed as a nutritional supplement. ...
Article
Royal jelly (RJ) is used as a dietary supplement for human health promotion. Recently, a clinical trial has reported that RJ improved mental health. The present study was conducted to experimentally support the clinical effect of RJ on mental health and to further elucidate the mechanisms of action of RJ. RJ and an ethanol extract of RJ, which contains fatty acids but not proteins, inhibited an unpredictable chronic mild stress (UCMS)-induced increase in immobility time, a depression-like behavior, in the tail suspension test. DNA microarray analysis of the adrenal grand revealed that the expression of genes involved in cholesterol metabolism was up-regulated in response to UCMS exposure and that RJ suppressed expression of genes related to cholesterol synthesis and transport. These results suggested that RJ improves stress-induced depression-like behavior by regulating adrenal steroidogenesis and that fatty acids contained in RJ partly contribute to the antidepressant effect of RJ.
... Studies that used rats and mice as test subjects to examine the antibacterial, fungal, antiviral and antiparasitic effects of royal jelly have demonstrated estrogenic and gonadotropic effects (10)(11)(12), effect on growth and development (13)(14)(15), impact on increased life expectancy (16), role in preventing hypoxia and increasing oxygen carrying capacity (17)(18)(19), role in increasing fertility in male rabbits, rats and mice (20)(21)(22)(23), role in increasing reproductive capacity in sheep and rats (24)(25)(26)(27), association with high sperm quality, increased sperm concentration and motility (28), testicular protective effect (29), role in protecting the autoimmune system (30), preventing inflammation (31,32), protecting against cancer (33), protecting the cardiovascular system (34,35), minimizing neural damage, supporting memory (36), as well as antioxidative properties and role in mitigating osteoporosis, protecting the liver and preventing liver damage (18,(37)(38)(39). In a similar vein, studies that examined the effects of royal jelly on humans have demonstrated that it reduces fatigue, improves performance (10,40), has a positive impact on blood parameters with regards to cancer, allergies and wound healing (41)(42)(43)(44)(45)(46), causes a decrease in lipid metabolism, prevents cardiovascular occlusion, dilates the veins, regulates the blood pressure (47)(48)(49)(50), has an antioxidant effect and protects against radiation (51)(52)(53)(54), has positive effects on fertility in both men and women (55). However, there is limited information regarding the effect of short-term using the royal jelly, as 15-day intake, on serum testosterone levels in humans. ...
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This study with a placebo-controlled experimental design intends to investigate the effect of short-term Royal Jelly (RJ) on the testosterone levels in sedentary men at a dose of 1000 mg/day. For this purpose, a total of 20 adult sedentary men aged 21 to 23 were included in this study. The subjects visited the laboratory every day for 15 days between 08:00 and 10:00 to get their portion of royal jelly. The subjects were randomly divided into two groups, namely the experimental group (n = 10 individuals, 1000 mg/day of Royal Jelly) and the placebo group (n = 10 individuals, corn starch mixed with 1000 mg/day of water) and they took royal jelly in glass vials at the same time. Blood samples were taken from both groups of subjects one day before and one day after the study and analyzed to determine their testosterone levels. 2x2 mixed factor ANOVA and LSD tests were used to analyze data obtained from the experimental and the placebo group. A sharp increase in the testosterone levels of the experimental group that took RJ for a short time was found to be statistically significant (p<0.05). The pre-and post-test values of the placebo group were not found to be statistically significant (p>0.05). The study shows that a short-term 1000 mg/day dose of RJ supplements was effective in increasing testosterone levels in sedentary, healthy men.
... Water-soluble RJPHs, such as MRJP2, MRJP3, and MRJP7, induce the proliferation, differentiation, and migration of human epidermal keratinocyte cells to promote wound closure (112). Royal jelly increases collagen formation and shows anti-inflammatory properties (113). 10-HDA, defensin-1, and MRJP3, which are components of royal jelly, have an inhibitory effect on pro-inflammatory cytokines, such as IL-1 and IL-6, without harming the macrophages themselves. ...
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Inflammation is a defense process triggered when the body faces assaults from pathogens, toxic substances, microbial infections, or when tissue is damaged. Immune and inflammatory disorders are common pathogenic pathways that lead to the progress of various chronic diseases, such as cancer and diabetes. The overproduction of cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, is an essential parameter in the clinical diagnosis of auto-inflammatory diseases. In this review, the effects of bee products have on inflammatory and autoimmune diseases are discussed with respect to the current literature. The databases of Google Scholar, PubMed, Science Direct, Sci-Finder and clinical trials were screened using different combinations of the following terms: “immunomodulatory”, “anti-inflammatory”, “bee products”, “honey”, “propolis”, “royal jelly”, “bee venom”, “bee pollen”, “bee bread”, “preclinical trials”, “clinical trials”, and “safety”. Honey bee products, including propolis, royal jelly, honey, bee venom, and bee pollen, or their bioactive chemical constituents like polyphenols, demonstrate interesting therapeutic potential in the regulation of inflammatory mediator production as per the increase of TNF-α, IL-1β, IL-6, Il-2, and Il-7, and the decrease of reactive oxygen species (ROS) production. Additionally, improvement in the immune response via activation of B and T lymphocyte cells, both in in vitro, in vivo and in clinical studies was reported. Thus, the biological properties of bee products as anti-inflammatory, immune protective, antioxidant, anti-apoptotic, and antimicrobial agents have prompted further clinical investigation.
... Considering its potent antioxidant activity, major components of the RJ are flavonoids and phenolic compounds (Yang et al., 2019;Šedivá et al., 2018;Kocot et al., 2018). In recent years, studies have motivated on the antimicrobial (Coutinho et al., 2018;Park et al., 2019), anti-inflammatory (Yang et al., 2018), anti-diabetic (Khazaei et al., 2018), anti-oxidant (Danis et al., 1994;Asadi et al., 2019;Gu et al., 2018), anti-tumor (Filipič et al., 2015) and anti-aging (Park et al., 2012) activities of RJ from different origins. The physical properties and chemical composition of the bee products vary with the genotype of the bees according to the flora species and climatic conditions and this affects the anticancer, antioxidant and antimicrobial activities of the bee products (Kocot et al., 2018). ...
... Beside, changes in the skin collagen levels leads to a degreased skin elasticity and strength [75]. Royal jelly has been reported as a protective agent against skin aging that acts by enhancing collagen production in ovariectomized rats [76]. It was reported that after the administration of royal jelly 1% to estrogen-deprived females of Sprague-Dawley rats, the level of procollagen type I protein increased in the skin of the animals. ...
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Women’s life stages are based on their reproductive cycle. This cycle begins with menstruation and ends with menopause. Aging is a natural phenomenon that affects all humans, and it is associated with a decrease in the overall function of the organism. In women, aging is related with and starts with menopause. Also, during menopause and postmenopausal period, the risk of various age-related diseases and complaints is higher. For this reason, researchers were pushed to find effective remedies that could promote healthy aging and extended lifespan. Apitherapy is a type of alternative medicine that uses natural products from honeybees, such as honey, propolis, royal jelly, etc. Royal jelly is a natural yellowish-white substance, secreted by both hypopharyngeal and mandibular glands of nurse bees, usually used to feed the queen bees and young worker larvae. Over the centuries, this natural product was considered a gold mine for traditional and natural medicine, due to its miraculous effects. Royal jelly has been used for a long time in commercial medical products. It has been demonstrated to possess a wide range of functional properties, such as: antibacterial, anti-inflammatory, vasodilatative, hypotensive, anticancer, estrogen-like, antihypercholesterolemic, and antioxidant activities. This product is usually used to supplement various diseases such as cardiovascular disease, Alzheimer’s disease, sexual dysfunctions, diabetes or cancer. The main objective of this study is to highlight the effectiveness of royal jelly supplementation in relieving menopause symptoms and aging-related diseases. We also aimed to review the most recent research advances regarding the composition of royal jelly for a better understanding of the effects on human health promotion.
... Yang et al. (2018) also reported that10-HAD found in royal jelly shows bactericide and antiinflammatory activity in human colon cancer cells. Furthermore, royal jelly also shows multiple pharmacological activities as antitumor (Townsend et al., 1960), anti-oxidant (Nakajima et al., 2009), anti-inflammatory (Kohno et al., 2004), antibacterial (Tseng et al., 2011), anti-allergic (Okamoto et al., 2003), anti-aging (Park et al., 2012), and antihypertensive properties (Tokunaga et al., 2004). ...
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Honey bees play significant role in crop pollination. As, honeybee nutrition is raising global topic in beekeeping, it's essential nutrients, nutrient sources and role in honey bees are reviewed in this paper. Like other animals, honeybees also need carbohydrate, protein, vitamins, minerals and water. These nutrients are primarily supplemented by pollen, nectar, royal jelly or water. Adequate supplement of these nutrients play significant role in growth and development in honeybees and also development of immunity in honeybees. Knowledge of bee nutrition helps to manage nutrient in bee colony and prevents them from different diseases and pests.
... Royal jelly, a yellowish-white acidic highly viscous product secreted from the hypopharyngeal and mandibular glands in the head of worker honeybees (Apis mellifera), is involved in the sexual determination of the queen bee and used in the nutrition of larvae [18,19]. Royal jelly contains a complex composition of proteins, amino acids, phenols, carbohydrates, minerals, vitamins and unsaturated fatty acids [20,21]. Due to its complex composition, Royal jelly has a multitude of physiological effects such as anti-inflammatory, antitumor, anti-allergic, antibacterial, and antioxidant activities [22,23]. ...
... (2). This bee product stimulates cell proliferation, accelerates the migration of human fibrocytes (4), increases the level of sphingolipids and stimulates production of collagen and slows down the aging process (11). Thanks to these properties, royal jelly can be used to treat wounds and radiodermatitis. ...
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Royal jelly as a functional food has great potential to promote human health. As a unique ingredient in royal jelly, 10-hydroxy-2-decenoic acid (10-HDA) is a vital criterion to evaluate the quality of royal jelly. Current approaches for 10-HDA detection mainly rely on high-performance liquid chromatographic (HPLC), but it requires large-scale equipment and skilled laborers that are costly and time-consuming. Herein, we report a colorimetric sensing strategy for 10-HDA detection based on Ag(I) and tetramethylbenzidine (TMB), a widely used chromogenic reagent. Ag(I) can oxidize TMB to generate oxidized TMB (oxTMB) showing a light-blue color. Due to the chelation with Ag (I), the introduction of 10-HDA can prevent the generation of oxTMB that results in a color fading and a decrease in absorbance. This colorimetric sensing strategy enables highly sensitive detection of 10- HDA with a linear range from 1μM to 10 μM and a limit of detection of 0.13 μM. More importantly, this 10-HDA assay allows for a visual readout either by a smartphone or the naked eye with low cost, convenience, and rapid response that has been successfully applied for evaluating the quality of royal jelly in actual samples. The sensing strategy developed in this work provides a new colorimetric approach that holds great promise as a point-of-care platform for the food industry.
Article
Royal jelly (RJ) is an essential food for queen bees, and it reportedly has estrogen-like activity. The objective of this study was to evaluate the effect of RJ intake on bone quality with a focus on the posttranslational modifications of type I collagen. RJ was fed to ovariectomized (OVX) rats for 12 weeks. RJ intake did not affect OVX-induced reduction in bone volume at the femur epiphysis; however, the reduction of collagen crosslinks (pyridinoline and deoxypyridinoline), which represent an aspect of bone quality, were significantly mitigated. In cultured MC3T3-E1osteoblasts, RJ treatment did not affect cell proliferation, cell differentiation, matrix formation, or mineralization. However, RJ treatment did stimulate expression of plods, which encode lysyl hydroxylase isoforms that control the collagen crosslinking pathway, and it also affected collagen crosslinking. These results indicate that oral intake of RJ could improve bone quality by modulating the posttranslational modification of type I collagen.
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Royal jellies (RJs) possess moisturizing, emulsifying, and stabilizing properties, and several pharmacological activities have also been found to be present, which make them an ideal component for cosmetic and skin care products. However, despite the abundant efficacies, there is a lack of studies that explore the chemical composition of RJ using metabolome analysis. Furthermore, an evaluation of the chemical composition of Indonesian RJs collected from different regions has yet to be carried out. Therefore, the main objective of this study was to identify any differences in the chemical composition of such RJs. Chemical profiling was also carried out to enable more targeted utilization based on the actual compositions. Chemical profiling is also important given the rich Indonesian biodiversity and the high dependence of the RJ compositions on the botanical source. In this research, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used as part of an untargeted metabolomics approach. From the chemical profiling, >30 compounds were identified across four RJ samples. The major constituents of the samples were found to be oligosaccharides, fatty acids, and adenosine monophosphate derivatives. Meanwhile, sucrose and planteose were found to be highest in the samples from Banjarnegara and Kediri, whereas dimethyloctanoic acid was found to be unique to the sample from Banjarnegara. It was also discovered that the RJs from Demak and Tuban contained more organic fatty acids and oligosaccharides than the other samples. Although the sample from Demak demonstrated good potential for use in the cosmetic, skin care, and bio-supplement industries, the higher abundance of fatty acids and oligosaccharides in the sample from Tuban indicated that it is perhaps the most suitable RJ for use in this field.
Article
Epidermal hydration is maintained by the epidermal lipid barrier, of which ceramide (Cer) is the major constituent. We examined the dietary effect of royal jelly (RJ) on epidermal hydration in aged mice. Altered Cer metabolism was further determined by measuring epidermal levels of individual Cer, glucosylceramide (GC), and sphingomyelin (SM) species, and of Cer-metabolizing enzymes. Aged C57BL/6J mice were fed a control diet (group AGED) or diets with 1% RJ harvested from two different areas (groups AGED+RJ1:AGED+RJ2) for 16 weeks. Aged C57BL/6J mice with no dietary intervention (the control group: group C) represented the onset of aging. In group AGED, epidermal levels of hydration, Cer1/2/5/6/7, GC-A/B/C/D, SM1/2/3, and β-glucocerebrosidase (GCase) protein, an enzyme of GC hydrolysis for Cer generation, were lower than in group C; these levels, as well as those of Cer3/4 and acidic sphingomyelinase (aSMase) protein, an enzyme of SM hydrolysis for Cer generation, were higher in group AGED+RJ1 than in group AGED. Despite increases in GC-B, SM1/2/3, and serine palmitoyltransferase2 protein, an enzyme of de novo Cer synthesis, in group AGED+RJ2 to levels higher than in group AGED, epidermal levels of hydration, Cer1-7, GC-A/C/D, GCase, and aSMase proteins were similar in these two groups. Expression of GCase and aSMase mRNAs, and of Cer synthase3 and ceramidase proteins, enzymes of de novo Cer synthesis and degradation, did not differ among groups. Dietary RJ1 improved epidermal hydration by enhancing Cer metabolism with increased levels of all Cer, GC, and SM species, and of GCase and aSMase proteins.
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Ultraviolet (UV) irradiation reduces epidermal hydration, which is paralleled by the reduction of natural moisturizing factors (NMFs). Of various NMFs, free amino acids (AAs) are major constituents generated by filaggrin degradation. In this study, we attempted to determine whether dietary supplementation of royal jelly (RJ) in UV-irradiated mice can alters epidermal levels of hydration, filaggrins, and free AAs as well as of peptidylarginine deiminase-3 (PAD3), an enzyme involved in filaggrin degradation processes. Albino hairless mice were fed either a control diet (group UV+: UV irradiated control) or diets with 1% RJ harvested from different areas in Korea (groups RJ1, RJ2, and RJ3) or imported from China (group RJ4) for six weeks in parallel with UV irradiation. A normal control group (group UV-) was fed a control diet without UV irradiation for six weeks. Reduced epidermal levels of hydration, total filaggrins, and PAD3 were observed in group UV+; in group RJ1, these levels were increased to a level similar to that of group UV-. In addition, profilaggrins, two repeat intermediates (2RI), a precursor with two filaggrin repeats, and filaggrin were increased. Although no alteration of AAs was observed in any of the groups, and glutamate and serine, major AAs of NMF in group RJ1 were higher than in group UV+. Despite the increased levels of PAD3, epidermal levels of hydration, filaggrins, glutamate, and serine in groups RJ2, RJ3, and RJ4 were similar to those in group UV+. Dietary supplementation of RJ1 improves epidermal hydration in parallel with enhanced expression and degradation of filaggrin, but not by increased protein expression of PAD3, along with increased generation of glutamate and serine.
Chapter
In the bee world, the unit of life is the colony, not the bee. None of the three casts, i.e. queen, worker or drone, can survive alone nor reproduce itself. Swarming is a collective behavior by which the colony reproduces itself. For this purpose, the workers build special cells in which the queen deposits eggs. The hatching larvae are fed with a secretion of the worker bees, the royal jelly, which is necessary for the growth of the future queens. When laying eggs the queen is too heavy to fly; the bees then starve her to prepare her for swarming. When the queen cells are ready and the queen able to fly, about one-half of the bee population, together with the old queen, leaves the original nest to find another home.
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Food Yellow 4 (FY4) is a lemon-yellow-colored synthetic organic azo dye, which is used widely for imparting pleasant and attractive appearance to foods and cosmetics. The present study aimed at evaluating the possible mechanism underlying the FY4-induced reprotoxicity in rats, and the potential supportive role of royal jelly (RJ) or cod liver oil (CLO), which is a natural remedy with several pharmacological benefits, against induced toxicity. Forty-eight male rats were divided into different groups-the control group, the CLO group (0.4 mL/kg), the RJ group (300 mg/kg), the FY4 group (500 mg/kg b.w.), and the co-treated groups (FY4 + CLO or FY4 + RJ). Semen analysis, serum hormones, and enzyme activities were estimated. Immunohistochemical staining was performed using anti-PCNA, anti-Sox 9, anti-STRA8, anti-DMC1, and anti-ssDNA antibody. The FY4 group exhibited a significant decrease in sperm concentration and motility percentage (%) and a substantial reduction in the TES and LH levels. Testicular LDH, ACP, and SDH were observed to be inhibited. Furthermore, co-localization of DMC1 and ssDNA, which reflected apoptotic induction in the leptotene and zygotene spermatocytes, respectively, was observed to have markedly elevated in the FY4 treated rats, with fewer PCNA-positive and SOX9-positive cells and higher ssDNA-positive cells in the seminiferous epithelium in comparison to the control groups. Interestingly, co-treatment with CLO or RJ exhibited healthy sperms and restored their features, activated the enzyme production, and raised the levels of sexual hormones. In addition, both RJ and CLO restored the features of the testicular tissue as observed under a light microscope, and limited the apoptosis as observed through antibody staining. Collectively, the results of the present study revealed that the co-administration of RJ or CLO with FY4 improved the biochemical, hormonal, and structural aspects of the testicular tissue in rats. Therefore, CLO and RJ may be considered promising agents that would be able to improve the testicular structure and function in the FY4-exposed individuals.
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Royal jelly (RJ) is a honeybee product containing proteins, carbohydrates, fats, free amino acids, vitamins, and minerals. As its principal unsaturated fatty acid, RJ contains 10-hydroxy-2-decenoic acid (10-HDA), which may have antitumor and antibacterial activity and a capacity to stimulate collagen production. RJ has attracted interest in various parts of the world for its pharmacological properties. However, the effects of RJ on ultraviolet (UV)-induced photoaging of the skin have not been reported. In this study we measured the 10-HDA content of RJ by high-performance liquid chromatography and tested the effects of RJ on UVB-induced skin photoaging in normal human dermal fibroblasts. The effects of RJ and 10-HDA on UVB-induced photoaging were tested by measuring procollagen type I, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-1 after UVB irradiation. The RJ contained about 0.211% 10-HDA. The UVB-irradiated human skin fibroblasts treated with RJ and 10-HDA had increased procollagen type I and TGF-β1 productions, but the level of MMP-1 was not changed. Thus RJ may potentially protect the skin from UVB-induced photoaging by enhancing collagen production.
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Cirsium japonicum water extracts has been used to treat vascular related diseases. We have previously reported that Cirsium japonicum extracts activated estrogen receptors. It is widely known that estrogen increases the high density lipoprotein cholesterol and decrease the low density lipoprotein cholesterol on the lipid profile. But effects of Cirsium japonicum on lipid profile are not reported yet. Therefore, we have studied the effects of Cirsium japonicum on the lipid content in ovariectomized rats. Thirty Sprague-Dawley (SD) rats of were studied for 10 weeks. The rats were divided into five groups; (I) sham, no ovariectomized rats plus olive oil, (II) ovariectomized rats plus olive oil, (III) ovariectomized rats plus 0.5 mg/kg -estradiol (E2) in olive oil, (IV) ovariectomized rats plus 0.5 mg/kg Cirsium japonicum in olive oil, and (V) ovariectomized rats plus 5 mg/kg Cirsium japonicum in olive oil. Treatment with Cirsium japonicum or E2 induced significant reduction in total cholesterol, low density lipoprotein cholesterol/total cholesterol, total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol compared to control group as well as increase in uterine weight. However, changes in triglycerides levels were different. Our results suggest that Cirsium japonicum is functionally similar to E2 in vivo as well as in vitro.
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Royal jelly (RJ) is a honeybee product containing proteins, carbohydrates, fats, free amino acids, vitamins, and minerals. As its principal unsaturated fatty acid, RJ contains 10-hydroxy-2-decenoic acid (10-HDA), which may have antitumor and antibacterial activity and a capacity to stimulate collagen production. RJ has attracted interest in various parts of the world for its pharmacological properties. However, the effects of RJ on ultraviolet (UV)-induced photoaging of the skin have not been reported. In this study we measured the 10-HDA content of RJ by high-performance liquid chromatography and tested the effects of RJ on UVB-induced skin photoaging in normal human dermal fibroblasts. The effects of RJ and 10-HDA on UVB-induced photoaging were tested by measuring procollagen type I, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-1 after UVB irradiation. The RJ contained about 0.211% 10-HDA. The UVB-irradiated human skin fibroblasts treated with RJ and 10-HDA had increased procollagen type I and TGF-β1 productions, but the level of MMP-1 was not changed. Thus RJ may potentially protect the skin from UVB-induced photoaging by enhancing collagen production.
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Introduction: Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. Objectives: To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state. Methods: A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment. Results: The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 ± 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 ± 4.05, 22.4 ± 4.14 and 17.5 ± 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05). Conclusion: The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.
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Osteoporosis, a reduction in bone mineral density, represents the most common metabolic bone disease. Postmenopausal women are particularly susceptible to osteoporosis when their production of estrogen declines. For these women, fracture is a leading cause of morbidity and mortality. This study was conducted to evaluate the protective effects of olive oil supplementation against osteoporosis in ovariectomized (OVX) rats. We studied adult female Wistar rats aged 12-14 months, divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized rats supplemented with extravirgin olive oil (Olive-OVX) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. At the end of the experiment, blood samples were collected. Plasma levels of calcium, phosphorus, alkaline phosphatase (ALP), malondialdehyde (MDA), and nitrates were assayed. Specimens from both the tibia and the liver were processed for light microscopic examination. Histomorphometric analysis of the tibia was also performed. The OVX-rats showed a significant decrease in plasma calcium levels, and a significant increase in plasma ALP, MDA, and nitrates levels. These changes were attenuated by olive oil supplementation in the Olive-OVX rats. Light microscopic examination of the tibia of the OVX rats revealed a significant decrease in the cortical bone thickness (CBT) and the trabecular bone thickness (TBT). In addition, there was a significant increase in the osteoclast number denoting bone resorption. In the Olive-OVX rats these parameters were markedly improved as compared to the OVX group. Examination of the liver specimens revealed mononuclear cellular infiltration in the portal areas in the OVX-rats which was not detected in the Olive-OVX rats. Olive oil effectively mitigated ovariectomy-induced osteoporosis in rats, and is a promising candidate for the treatment of postmenopausal osteoporosis.
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Royal jelly (RJ) excreted by honeybees and used as a nutritional and medicinal agent has estrogen-like effects, yet the compounds mediating these effects remain unidentified. The possible effects of three RJ fatty acids (FAs) (10-hydroxy-2-decenoic-10H2DA, 3,10-dihydroxydecanoic-3,10DDA, sebacic acid-SA) on estrogen signaling was investigated in various cellular systems. In MCF-7 cells, FAs, in absence of estradiol (E(2)), modulated the estrogen receptor (ER) recruitment to the pS2 promoter and pS2 mRNA levels via only ERβ but not ERα, while in presence of E(2) FAs modulated both ERβ and ERα. Moreover, in presence of FAs, the E(2)-induced recruitment of the EAB1 co-activator peptide to ERα is masked and the E(2)-induced estrogen response element (ERE)-mediated transactivation is inhibited. In HeLa cells, in absence of E(2), FAs inhibited the ERE-mediated transactivation by ERβ but not ERα, while in presence of E(2), FAs inhibited ERE-activity by both ERβ and ERα. Molecular modeling revealed favorable binding of FAs to ERα at the co-activator-binding site, while binding assays showed that FAs did not bind to the ligand-binding pocket of ERα or ERβ. In KS483 osteoblasts, FAs, like E(2), induced mineralization via an ER-dependent way. Our data propose a possible molecular mechanism for the estrogenic activities of RJ's components which, although structurally entirely different from E(2), mediate estrogen signaling, at least in part, by modulating the recruitment of ERα, ERβ and co-activators to target genes.
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Oral administration of royal jelly (RJ) promotes wound healing in diabetic mice. Concerns have arisen regarding the efficacy of RJ on the wound healing process of normal skin cells. In this study, a wound was created by scratching normal human dermal fibroblasts, one of the major cells involved in the wound healing process. The area was promptly treated with RJ at varying concentrations of 0.1, 1.0, or 5 mg/ml for up to 48 hrs and migration was analyzed by evaluating closure of the wound margins. Furthermore, altered levels of lipids, which were recently reported to participate in the wound healing process, were analyzed by HPTLC and HPLC. Migration of fibroblasts peaked at 24 hrs after wounding. RJ treatment significantly accelerated the migration of fibroblasts in a dose-dependent manner at 8 hrs. Although RJ also accelerated the migration of fibroblasts at both 20 hrs and 24 hrs after wounding, the efficacy was less potent than at 8 hrs. Among various lipid classes within fibroblasts, the level of cholesterol was significantly decreased at 8 hrs following administration of both 0.1 ug/ml and 5 mg/ml RJ. Despite a dose-dependent increase in sphinganines, the levels of sphingosines, ceramides, and glucosylceramides were not altered with any concentration of RJ. We demonstrated that RJ enhances the migration of fibroblasts and alters the levels of various lipids involved in the wound healing process.
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Vascular endothelial growth factor (VEGF) is reported to be a potent pro-angiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. Royal jelly (RJ) is a honeybee product containing various proteins, sugars, lipids, vitamins and free amino acids. 10-Hydroxy-2-decenoic acid (10HDA), a major fatty acid component of RJ, is known to have various pharmacological effects; its antitumor activity being especially noteworthy. However, the mechanism underlying this effect is unclear. We examined the effect of 10HDA on VEGF-induced proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Our findings showed that, 10HDA at 20 microM or more significantly inhibited such proliferation, migration and tube formation. Similarly, 10 microM GM6001, a matrix metalloprotease inhibitor, prevented VEGF-induced migration and tube formation. These findings indicate that 10HDA exerts an inhibitory effect on VEGF-induced angiogenesis, partly by inhibiting both cell proliferation and migration. Further experiments will be needed to clarify the detailed mechanism.
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Chronically diabetic rats prepared by a single i.v. injection of streptozotocin were used to study whether royal jelly (RJ) possesses a hypoglycemic reaction and whether it can augment wound healing. Oral RJ administration of 10, 100 and 1000 mg/kg/day did not show any insulin-like activity (the hypoglycemic reaction). RJ, however, showed some anti-inflammatory activity by decreasing exudation and collagen formation in granulation tissue formation in the cotton pellet method. RJ also shortened the healing period of desquamated skin lesions. Thus, RJ possesses an anti-inflammatory action and is able to augment wound healing, but does not have an insulin-like action in streptozotocin-diabetic rats.
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Dehydroepiandrosterone (DHEA) is a steroid hormone involved in physiological aging. When administered by oral route, it has been shown to positively affect skin condition on aged people. The purpose of this pilot study was to observe the in vivo effects on skin aging of topical DHEA (1%). The DHEA formulation (1%) or the vehicle was topically applied for 4 months to facial and hand skin, in two groups of 20 post-menopausal women. The efficacy of the treatment was evaluated on the basis of clinical and biophysical signs linked to skin aging. We showed that DHEA treatment increased the rate of sebum, which was perceived rather positively by a menopausal population usually affected with a declining sebum level. Topical DHEA tends to improve skin brightness, to counteract papery appearance of skin and epidermal atrophy, a characteristic feature of hormone-related skin aging. Topical DHEA could also act on skin process related to wrinkles, but this result remains to be confirmed. This pilot study showed beneficial effects on skin characteristics that are rarely provided by topical treatments. It raised some interesting clues towards the treatment of skin aging.
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In this report we show that royal jelly (RJ) increases collagen production by normal hamster fibroblasts in the presence of ascorbic acid (AA) or ascorbic acid 2-O-alpha-glucoside (AA-2G). The effects of a combination of RJ with AA-2G on collagen synthesis were much greater than those of the combination of RJ with AA. RJ showed significant TGFq-β inducing activity on fibroblasts in the presence of AA-2G. These results suggest a possible mechanism for TGF-β production induced by RJ and AA-2G, occurring in conjunction with collagen synthesis in normal hamster fibroblasts.
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Aging is a multifaceted biological process that affects all organs and organ systems of the body. This review provides an up-to-date analysis of this highly exciting, rapidly changing field of science. The aging process is largely under genetic control but is highly responsive to diverse environmental influences. The genes that control aging are those that are involved with cell maintenance, cell damage and repair. The environmental factors that accelerate aging are those that influence either damage of cellular macromolecules, or interfere with their repair. Prominent among these are chronic inflammation, chronic infection, some metallic chemicals, ultraviolet light, and others that heighten oxidative stress. Other environment factors slow the aging process. Included among these agents are resveratrol and vitamin D. In addition, dietary restriction and exercise have been found to extend human lifespan. The various mechanisms whereby all these agents exert their influence on aging include epigenetic modification, chromatin maintenance, protection of telomeres, and anti-oxidant defense, among others. The complex process of aging remains under continued, intense investigation.
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Estrogen deficiency may contribute to extracellular matrix turnover in skin. This has led previous authors to postulate that aged skin heals less efficiently when compared to younger skin. Also, cigarette smokers have been shown to heal less efficiently than nonsmokers. Matrix metalloproteinase (MMP)-13, an enzyme that participates in the degradation of the extracellular matrix, has been implicated in physiologic aging and wound healing. This study investigates the effects of smoke exposure and estrogen deficiency on MMP-13 in young and aged female mouse skin. Young and aged female C57Bl/6J mice were ovariectomized. They were then randomly administered either 17β-estradiol (E2) or placebo pellets. Half the animals in each age group were further randomized to exposure to cigarette smoke for a period of 6 months. Smoking and estrogen deficiency increased MMP-13 protein and activity in aged skin. The tissue inhibitors of metalloproteinases, which inhibit MMPs, activity was unchanged across all groups. E2 replacement decreased the actual level of MMP-13 protein and activity. We also found an increased collagen content and decreased ER receptor protein level in aged, smoke-exposed female mice. Our experimental data show that tobacco smoke exposure and estrogen deficiency are additive risk factors for promoting increased activity of MMP-13 in aged skin. These findings suggest that MMP-13 functions as a mediator of smoke-induced skin injury in susceptible, aged experimental female mice.
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Estrogen plays an important role in skin homeostasis, as demonstrated by the changes seen in the skin of post-menopausal women, changes reversed by HRT. Estrogen also has a role in wound healing, since estrogen deficiency as occurs post-menopausally and in ovariectomised animals, is associated with a reduced rate of wound healing. Estrogen appears to modulate all phases of wound healing with effects on inflammatory cells, epithelialization, angiogenesis, extracellular matrix deposition and tissue remodelling. This study was designed to investigate the effects of 17beta-estradiol on cultured human dermal fibroblasts using an in vitro wound-healing assay. The end points investigated were cell migration, proliferation, total collagen secretion and active TGF-beta1 secretion. 17beta-estradiol significantly increased the migration and proliferation of cultured dermal fibroblasts following mechanical wounding, although the secretion of total soluble collagen was not altered. An increase in TGF-beta1 was demonstrated by unwounded confluent dermal fibroblast monolayers in response to 17beta-estradiol, but paradoxically, a decrease in the secretion of TGF-beta1 was demonstrated in the mechanically wounded dermal fibroblasts. These results identify human dermal fibroblasts as estrogen target cells and provide further evidence for a role by which estrogen regulates this particular cell type as part of the wound-healing process. However, the paradoxical nature of the effect of estrogen on TGF-beta1 secretion following mechanical wounding suggests that the cellular mechanism of action is complex. A greater understanding of the cell-specific action of estrogen may help to develop therapies that will improve cutaneous wound healing in the future.
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Background: Wrinkling and sagging of the skin during photoageing is physiologically associated with diminished elasticity, which can be attributed to increased fibroblast-derived elastase activity. This degrades the dermal elastic fibres needed to maintain the three-dimensional structure of the skin. We previously reported that ovariectomy accelerates ultraviolet (UV)B-induced wrinkle formation in rat hind limb skin by altering the three-dimensional structure of elastic fibres. In this study, we used hairless mice to assess the effects of ovariectomy with or without chronic UVA or UVB radiation on sagging and wrinkling of skin, on the elasticity of skin, as well as on matrix metalloproteinase activities in the skin. Ovariectomies or sham operations were performed on 6-week-old female ICR/HR hairless mice. Even in the ovariectomy group without UV irradiation, the skin elasticity was significantly decreased during the 3-13 weeks after ovariectomy, which was accompanied by a significant increase in elastase activity in the skin. After UVA or UVB irradiation, skin elasticity was significantly decreased to a greater extent in the ovariectomy group than in the sham operation group, and this was accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV in the skin. Consistent with the decreased skin elasticity, UVA irradiation for 12 weeks elicited more marked sagging in the ovariectomy group than in the sham operation group. UVB irradiation for 12 weeks also induced more marked wrinkle formation in the ovariectomy group than in the sham operation group. These results suggest that ovariectomy alone is sufficient to accelerate skin ageing and to increase UV sensitivity, which results in the further deterioration of the skin and photoageing, and may account for the accelerated skin ageing seen in postmenopausal women.
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To demonstrate the effect of a deficiency of ovarian hormones on the process of wound contraction, using the oophorectomised rat model of the human menopause. A randomised controlled trial. Ninety-six adult Wistar rats were randomly allocated into either an oophorectomised group or a sham-oophorectomised control group. Having confirmed a significant reduction in plasma oestradiol levels in the oophorectomised rats, full-thickness excised lesions were made in the flank skin of the adult rats at either two weeks or four months after oophorectomy, so that the effects of two different durations of hormone deficiency could be assessed and compared with the sham-oophorectomised controls. Following wounding, the rats were left for 3, 5, 10 or 22 days; wound contraction was assessed from photographs of the wounds taken at these intervals after injury. In the rats wounded four months after oophorectomy there was a slower rate of wound contraction, resulting in larger wounds at days 3, 5, 10 and 22, compared with control rats. No significant difference was observed in rats wounded two weeks after oophorectomy, indicating that the effects of ovarian hormone deficiency on this process are delayed. Due to the pivotal role of wound contraction in the process of wound healing these findings may be of clinical relevance and could have an important impact on the administration of hormone replacement therapy.
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Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased.
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Clinical observations have suggested a relationship between osteoarthritis and a changed sex-hormone metabolism, especially in menopausal women. This study analyzes the effect of 17β-estradiol on expression of matrix metalloproteinases-1, -3, -13 (MMP-1, -3, -13) and tissue inhibitors of metalloproteinases-1, -2 (TIMP-1, -2) in articular chondrocytes. An imbalance of matrix metalloproteinases (MMPs) specialized on degradation of articular cartilage matrix over the respective inhibitors of these enzymes (TIMPs) that leads to matrix destruction was postulated in the pathogenesis of osteoarthritis. Primary human articular chondrocytes from patients of both genders were cultured in alginate beads at 5% O(2) to which 10(-11)M-10(-5)M 17β-estradiol had been added and analyzed by means of immunohistochemistry, immunocytochemistry and real-time RT-PCR. Since articular chondrocytes in vivo are adapted to a low oxygen tension, culture was performed at 5% O(2). Immunohistochemical staining in articular cartilage tissue from patients and immunocytochemical staining in articular chondrocytes cultured in alginate beads was positive for type II collagen, estrogen receptor α, MMP-1, and -13. It was negative for type I collagen, MMP-3, TIMP-1 and -2. Using real-time RT-PCR, it was demonstrated that physiological and supraphysiological doses of 17β-estradiol suppress mRNA levels of MMP-3 and -13 significantly in articular chondrocytes of female patients. A significant suppressing effect was also seen in MMP-1 mRNA after a high dose of 10(-5)M 17β-estradiol. Furthermore, high doses of this hormone led to tendentially lower TIMP-1 levels whereas the TIMP-2 mRNA level was not influenced. In male patients, only incubations with high doses (10(-5)M) of 17β-estradiol were followed by a tendency to suppressed MMP-1 and TIMP-1 levels while TIMP-2 mRNA level was decreased significantly. There was no effect on MMP-13 expression of cells from male patients. Taken together, application of 17β-estradiol in physiological doses will improve the imbalance between the amounts of MMPs and TIMPs in articular chondrocytes from female patients. Downregulation of TIMP-2 by 17β-estradiol in male patients would not be articular cartilage protective.
Article
The importance of the endocrine environment in the initiation of the ageing process has been elucidated in several in vivo and in vitro studies. Changes in endocrine pathways accompany healthy ageing, these include the growth hormone/insulin-like growth factor-I axis (somatopause) and that of sexual hormones, namely estradiol (menopause), testosterone (andropause), and dehydroepiandrosterone and its sulphate (adrenopause). The clinical significance of these changes is variable and results in morphological and functional alterations of all organ systems including the skin and the central nervous system. Moreover, the pathogenesis of age-associated diseases such as epithelial skin cancer and neurodegenerative diseases has been partly attributed to the lack of hormones. Several studies have been conducted in an attempt to reverse the ageing process and clinical signs by substitution of the serum hormone levels in older individuals, however the benefits of hormone replacement therapy, if any, are still controversial. On the other hand, recent data suggest that skin is a window to the human organism and represents an adequate model for ageing research, also implying the use of skin samples for evaluating the ageing status of the central nervous system.
Article
Our previous studies demonstrate that 17beta-estradiol limits chronic volume overload-induced hypertrophy and improves heart function in ovariectomized rats. One possible cardioprotective mechanism involves the interaction between estrogen, estrogen receptors, and proteins of the extracellular matrix (ECM). The impact of estrogen deficiency and replacement on left ventricular (LV) hypertrophy and ECM protein expression was studied using five female rat groups: intact sham-operated, ovariectomized sham-operated, intact with volume overload, ovariectomized with volume overload, and ovariectomized with volume overload treated with estrogen. After 8 wk, LV protein extracts were evaluated by Western blot analysis for matrix metalloproteinase-2 (MMP-2) and MMP-9, MT1-MMP, tissue inhibitors of MMPs (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4, collagens type I and III, and estrogen receptor alpha and beta expression. MMP proteolytic activity was assessed by zymography. All volume-overloaded groups exhibited LV hypertrophy, which was associated with a loss of interstitial collagen and perivascular fibrosis. After 8 wk of volume overload, 70% of ovariectomized rats developed heart failure, in contrast to only one intact rat. A downregulation of MMP-2, estrogen receptor-alpha (ERalpha), and ERbeta, and upregulation of MMP-9 and MT1-MMP were found in the volume-overloaded hearts of ovariectomized rats. Estrogen treatment improved TIMP-2/MMP-2 and TIMP-1/MMP-9 protein balance, restored ERalpha expression, and prevented MMP-9 activation, perivascular collagen accumulation and development of heart failure. However, estrogen did not fully restore ERbeta expression and did not prevent the increase of MMP-9 expression or loss of interstitial collagen. These results support that estrogen limits undesirable ECM remodeling and LV dilation, in part, through modulation of ECM protein expression in volume-overloaded hearts of ovariectomized rats.
Article
Genistein has been implicated in the beneficial effects of soy on human health, particularly in the context of ageing. In post-menopausal women reduced systemic estrogen leads to a range of age-associated pathologies, including delayed cutaneous wound healing. We have previously shown that this can be reversed by estrogen replacement. However, the effect of genistein on the skin is poorly understood and crucially the influence of genistein on wound healing has not been assessed. 10-week-old ovariectomised mice were systemically treated with 17beta-estradiol or genistein. Genistein substantially accelerated wound repair, associated with a dampened inflammatory response. Unexpectedly, co-treatment with the ER antagonist ICI had little impact on the anti-inflammatory, healing promoting effects of genistein. Thus genistein's actions are only partially mediated via classical estrogen receptor-dependent signalling pathways. Indeed, we report that alternative (cell-type specific) signalling mechanisms are activated in the skin in response to genistein treatment.
Article
Rheumatoid arthritis synovial fibroblasts (RASFs) are known to produce matrix metalloproteinases (MMPs) and cause joint destruction. The purpose of this study is to develop a potential medicine for rheumatoid arthritis (RA). To this end, first, the MMPs inhibition factor was purified from an alkali-solubilized fraction of RJ (Apis mellifera) by C18 reverse-phase column chromatography and identified as 10-hydroxy-2-decenoic acid (10H2DA) by LTQ XL analysis. Next, Experimental test 10H2DA how to inhibited the activities of MMPs: with RASFs isolated from rheumatoid tissues by enzymatic digestion, cultures in monolayers were treated with 10H2DA (0.5mM, 1mM, and 2mM) or PBS for 2h followed by stimulation with TNF-alpha (10 ng/ml) for 2h, mRNA. Protein levels of MMP-1 and MMP-3 were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), the DNA-binding activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB) by electrophoretic mobility shift assay (EMSA), and the protein kinase activity of p38, ERK and JNK by kinase assay. The molecular investigation revealed that the 10H2DA-mediated suppression was likely to occur through blocking p38 kinase and c-Jun N-terminal kinase-AP-1 signaling pathways. In contrast, 10H2DA had no effect on extracellular signal-regulated kinase activity, NF-kappaB DNA-binding activity and IkappaBalpha degradation. These results suggest that 10H2DA may be of potential therapeutic value in inhibiting joint destruction in RA.
Article
Angiotensin I-converting enzyme (ACE) inhibitory and hypotensive effects of 7 peptide fractions (Frs) of royal jelly protein hydrolysate (RJPH) were studied in comparison with those of RJPH alone. Fr 4 and Fr 5 were the highest in ACE inhibitory activity and yield, respectively. Molecular weights (MWs) of RJPH and Fr 1-Fr 7 were distributed from 100 to 5,000 and those of Fr 1-Fr 7 increased in order from Fr 1 to Fr 7. RJPH, Fr 3 and Fr 4 at doses of 10, 30 and 100mg/kg i.v. and Fr 5 and Fr 6 at doses of 30 and 100mg/kg i.v. caused transiently significant hypotensive effects in spontaneously hypertensive rats (SHR). Fr 3, Fr 4, Fr 5 and Fr 6 at a dose of 1,000mg/kg also caused significant hypotensive effects 3h, 4-5h, 7-8h and 8h after oral administration in SHR, respectively. RJPH caused a long-lasting hypotensive effect in proportion to the magnitude of the MWs of RJPH fractions. The hypotensive pattern of RJPH was similar to the combined pattern of Fr 3-Fr 6. From these results, it can be concluded that the long-lasting hypotensive effect of oral administration of RJPH is dependent on the MWs of its ACE inhibitory peptides and the time required to digest them.
Article
The coincidence of climacteric symptoms and the beginning of skin aging suggests that estrogen deficiency may be a common and important factor in the perimenopausal woman. Often hormones have been considered important in endogenous aging of the skin, but their role has not been clearly defined. Therefore, we investigated, whether topical treatment of the skin with estrogen could reverse some of the changes in the aging skin. The effects of 0.01% estradiol and 0.3% estriol compounds were compared in 59 preclimacteric women with skim aging symptoms. Monthly determinations of estrodiol (E2), follicle-stimulating hormone (FSH), and prolactin (PRL) were done and the monthly clinical monitoring was supplemented by measurements of skin hydration by corneometry and profilometry. In 10 patients, skin biopsies were taken for immunohistochemical determination of collagen types I and III. After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted.
Article
In this study, the influence of ovariectomy in rat skin and bone (trabecular and cortical) collagen fibrils is examined using electron microscopy. Structural changes (fibril architecture and diameter) were detected, at the ultrastructural level, in skin and bone specimens from ovariectomized rats. The overall collagen fibril architecture was disturbed as compared with normal animals. Treated collagen fibrils' mean diameter values were significantly smaller than those from controls, in all tissues examined. The banding patterns of fibrils were normal in all cases; however, measurements by a computerized method of measuring axial periodicity of fibrils indicated significantly lower values for treated samples than untreated samples. Our results show a correlation between the effects induced by ovariectomy in skin and bone collagen. But, the question of whether these changes play a role in the pathogenesis of ovarian hormone deficiency in osteoporosis remains to be demonstrated.
Article
We studied the effect of hormonal treatment on skin ageing in menopausal women. Twenty-four patients (45-68 years; mean age, 54.9 years) without hormone treatment for at least 6 months were included. Patients were assigned to three therapy groups: 1, oestrogen only (Estraderm TTS 50) (n=6); 2, transdermal oestrogen and progesterone (Estraderm TTS 50 and 0.4 mg progesterone vaginal suppository) (n=7); and 3, oral oestrogen and progesterone (2 mg Progynova and 0.4 mg progesterone vaginal suppository) (n=8). One group without therapy was included as a control group (n=3). Treatment was continued for 6 months. Three patients, one from group 2 and two from group 3, discontinued therapy before the study endpoint. The following skin parameters were measured at monthly intervals during treatment: skin surface lipids, epidermal skin hydration, skin elasticity and skin thickness. Concomitant clinical evaluation included a subjective clinical evaluation form, a patient questionnaire and laboratory tests for oestradiol, progesterone and follicle stimulating hormone. Mean levels of epidermal skin moisture, elasticity and skin thickness were improved at the end of treatment based on both subjective and objective evaluation in patients with hormone replacement therapy (HRT). Skin surface lipids were increased during combined HRT, which may reflect stimulatory effects of the progestagen component on sebaceous gland activity, while oestrogen alone has a sebum-suppressive action. In the HRT groups, the questionnaire for climacteric complaints demonstrated significant improvements, while laboratory tests showed increases in oestradiol and progesterone and decreases in FSH. HRT with the mentioned regimes significantly improved parameters of skin ageing.
Article
Although no formal recommendations appear in the literature, the majority of data suggest that, in addition to ameliorating many menopausal symptoms, HRT with estrogen can have beneficial effects on the skin. In particular, estrogens may improve fine wrinkling, dryness, elasticity, and collagen content of postmenopausal skin. Estrogen also may improve the rate of wound healing in older subjects. At the present time, data are insufficient regarding other hormones, such as testosterone, DHEA, and growth hormone, to recommend their routine use to improve cutaneous appearance.
Article
Cutaneous ageing is a complex biological phenomenon consisting of two components; intrinsic ageing, which is largely genetically determined and extrinsic ageing caused by environmental exposure, primarily UV light. In sun-exposed areas, these two processes are superimposed. The process of intrinsic skin ageing resembles that seen in most internal organs and is thought to involve decreased proliferative capacity leading to cellular senescence, and altered biosynthetic activity of skin derived cells. Extrinsic ageing, more commonly termed photoageing, also involves changes in cellular biosynthetic activity but leads to gross disorganisation of the dermal matrix. The molecular mechanisms underlying some of these changes are now beginning to be unravelled and are discussed. As these mechanisms are identified, further insights into the underlying processes of skin ageing should emerge and better strategies to prevent the undesirable effects of age on skin appearance should follow.
Article
The purpose of this study was to examine effects of osthole on postmenopausal osteoporosis using ovariectomized (OVX) rats. All of the rats were divided into sham and OVX groups. At 2 weeks post-operation, the sham-operated rats received solvent vehicle (97% corn oil and 3% ethanol, 1.0 ml/kg, subcutaneously); the OVX rats were divided into three groups which were treated with solvent vehicle (same the sham rats, 1.0 ml/kg, subcutaneously), 17beta-estradiol (30 microg/kg, subcutaneously) or osthole (9.0 mg/kg, orally) 5 d/week for 4 weeks, respectively. In OVX rats, the increases of body weight, spleen and thymus weight were significantly decreased and the atrophy of uterus was preserved by 17beta-estradiol treatment, but not by osthole. Treatment with either 17beta-estradiol or osthole significantly protected cancellous bone loss owing to estrogen deficiency and significantly increased the maximal load in the femoral neck of OVX rats. In addition, the increases of serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) levels caused by ovariectomy were all significantly suppressed by 17beta-estradiol. However, only urinary DPD was significantly reduced by osthole and no change was found in serum OC. Our results demonstrate that osthole may be just as effective as 17beta-estradiol in suppressing bone loss due to ovariectomy but osthole perhaps does not work through the estrogen pathway.
Article
Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Article
A prospective, randomized, double-blind study was conducted to determine if estradiol and glycolic acid creams produced a significant reversal of epidermal and dermal markers of aging and if the cumulative effect of the creams was greater than either alone. Sixty-five patients applied a cream containing 0.01% estradiol or 15% glycolic acid, alone or in combination, to one side of the face, and a vehicle cream to the opposite side, for 6 months. A 2-mm punch biopsy was obtained from the hairline of each patient and processed for analysis. The estradiol treatment produced a 23% increase in epidermal thickness (P = .00458); the glycolic acid, a 27% increase (P = .00467); and the combination, a 38% increase (P = .000181). All groups showed a statistically significant improvement in reversing markers (rete peg pattern, epidermal thickness) of skin aging. Although not statistically significant (P = .1), a cumulative effect was seen when estradiol and glycolic acid creams were used in combination.
Article
The dose-dependent effect of a 24 h treatment with estradiol (E(2)) (1, 2, 5, 10 nM) and raloxifene (Rx) (1, 5, 10, 20 microM) on ER alpha and ER beta mRNA expression, collagen bio-synthesis, prolidase activity, MMP-2, MMP-9, insulin-like growth factor I receptor expression (IGF-1R) and beta1-integrin expressions in cultured fibroblasts obtained from postmenopausal women were examined. Both ligands increased mRNA expression of ER compared to control. Rx at 5 and 10 microM concentrations had greater stimulative effect on collagen biosynthesis, prolidase activity and IGF-1R expression compared to E(2) at 2 and 5 nM concentration. Both studied ER ligands had no effect on beta1-integrin receptor expressions. MMP-2 expression was not detected in human skin fibroblast culture. In contrast to estradiol raloxifene inhibited the expression of MMP-9. Raloxifene had stronger positive stimulative effects on collagen biosynthesis, through different biochemical mechanisms, than estradiol in human skin fibroblasts and might reverse some of the postmenopausal changes in skin or connective tissue. Increase of collagen synthesis induced by raloxifene may be activated by both estrogen receptor dependent and independent pathways such as up-regulation of estrogen receptors, up-regulation of IGF receptor, transcriptional regulation of collagen genes by estrogen receptor-raloxifene complex, increasing of prolidase activity or finally by inhibition of MMP-9 expression.
Article
We have previously shown that royal jelly (RJ) promoted collagen production by skin fibroblasts in the presence of ascorbic acid-2-O-alpha-glucoside (AA-2G). In this study, we purified the honeybee RJ-derived collagen production-promoting factor (HBRJ-CPF) from an alkali-solubilized fraction of RJ by C18 reverse-phase column chromatography. The elution profile by the C18 column chromatography and the molecular mass of the purified HBRJ-CPF material coincided with those of 10-hydroxy-2-decenoic acid (10H2DA). We then examined the collagen production-promoting activities of several commercially available fatty acids contained in RJ. We found that 10H2DA and 10-hydroxydecanoic acid increased the collagen production in a dose-dependent manner. Furthermore, 10H2DA induced the fibroblast cell line, NHDF, to produce transforming growth factor-beta 1 (TGF-beta 1) which is an important factor for collagen production. As expected, the collagen production-promoting activity of 10H2DA was neutralized by the anti-TGF-beta 1 antibody. These result suggest that HBRJ-CPF identified as 10H2DA promoted the collagen production of AA-2G-treated fibroblasts by inducing TGF-beta 1 production.
Article
Skin collagen content and bone mass decrease with aging. Loss of collagen from the skin might decrease its elasticity. We investigated associations between skin elasticity, bone mineral density (BMD), age, and menopausal hypoestrogenism. Thirty-eight healthy Japanese postmenopausal women were studied (mean age, 55.7 +/- 5.9 yr; range, 48 to 71). Skin elasticity was measured using a suction device applied to the dorsal right forearm. BMD values of L2 to 4 vertebral bodies were measured by dual-energy X-ray absorptiometry. Age showed significant negative correlations with both skin elasticity and BMD (r = -0.57, p<0.001 and r = -0.40, p<0.05, respectively). Years since menopause also showed significant negative correlations with both skin elasticity and BMD (r = -0.51, p<0.01 and r = -0.41, p<0.05, respectively). We also found a positive correlation between skin elasticity and BMD in these postmenopausal women (r = 0.44, p<0.01). In conclusion, we demonstrated declining skin elasticity and bone mass in postmenopausal women to possibly be age- and estrogen-related. Additionally, decreased skin elasticity might serve as a predictor of bone loss in postmenopausal women.
Article
Royal jelly (RJ) from honeybees (Apis mellifera) is traditionally thought to improve menopausal symptoms. The potential estrogenic activities of RJ were investigated using various approaches. RJ competed for binding of 17beta-estradiol to the human estrogen receptor alpha and beta but its affinities were weak compared with diethylstilbestrol and phytoestrogens. The reporter gene expression assays suggested that 0.1-1 mg/ml RJ activated estrogen receptors, leading to enhanced transcription of a reporter gene through an estrogen-responsive element. 1 mg/ml RJ stimulated the mRNA expression of estrogen-responsive pS2 and vascular endothelial growth factor (VEGF) by increasing gene transcription in MCF-7 cells. Treatment with RJ at concentrations ranging from 0.5 to 1 mg/ml enhanced MCF-7 cell proliferation, but concomitant treatment with 1 microM tamoxifen blocked this effect. In vivo studies using ovariectomized rats showed that 17beta-estradiol (20 mg/kg, s.c.) treatment restored VEGF expression in both uterus and brain, whereas RJ (1 g/kg, s.c.) restored it in uterus but not in brain. These findings provide evidence that RJ has estrogenic activities through interaction with estrogen receptors followed by endogenous gene expressions.
Article
Using the cross-sectional images taken with the zoom-in micro-tomography technique, we measured trabecular thicknesses of femur bones in postmortem rats. Since the zoom-in micro-tomography technique is capable of high resolution imaging of a small local region inside a large subject, we were able to measure the trabecular thickness without extracting bone samples from the rats. For the zoom-in micro-tomography, we used a micro-tomography system consisting of a micro-focus x-ray source, a 1248 x 1248 flat-panel x-ray detector and a precision scan mechanism. To compensate for the limited spatial resolution in the zoom-in micro-tomography images, we used the fuzzy distance transform for the calculation of the trabecular thickness. To validate the trabecular thickness measurement with the zoom-in micro-tomography images, we compared the measurement results with those obtained from the conventional micro-tomography images of the extracted bone samples. The difference between the two types of measurement results was less than 2.5%.
Article
The role of female hormones in estrogen-dependent cancers has been debated for years. This is particularly true of breast cancer. Retrospective, case, and cohort control studies usually have suggested no influence. The Women's Health Initiative study in 2002, a prospective double-blind study, noted an increased risk of breast cancer if estrogen plus progesterone was given. In the estrogen-only arm of that study, a decreased (not significant) risk of breast cancer was noted. With this controversy, can estrogen be given safely to a woman who has been treated for breast cancer? The relation between endometrial cancer and unopposed estrogen is well established. With clear-cut evidence of this relation, is there evidence to suggest a role for replacement therapy in women who have been treated for endometrial cancer? Several case-control and cohort studies have noted either no increased risk or actually less risk of recurrence in women taking estrogen after therapy after breast cancer. Although the general consensus is that such a recommendation is contraindicated, the data do not support this admonition. The current data suggest that replacement therapy can be given to the woman who has been treated for endometrial cancer. There seems to be little if any risk in giving hormone replacement therapy to women who have had breast or endometrial cancer. There are no data to suggest that hormone replacement therapy is contraindicated in women who have been treated for cervical or ovarian cancer.
Article
Unlabelled: Aging is a complex, multifactorial process resulting in several functional and esthetic changes in the skin. These changes result from intrinsic as well as extrinsic processes, such as ultraviolet radiation. Recent advances in skin biology have increased our understanding of skin homeostasis and the aging process, as well as the mechanisms by which ultraviolet radiation contributes to photoaging and cutaneous disease. These advances in skin biology have led to the development of a diversity of treatments aimed at preventing aging and rejuvenating the skin. The focus of this review is the mechanism of photoaging and the pathophysiology underlying the treatments specifically designed for its prevention and treatment. Learning objectives: At the conclusion of this learning activity, participants should be familiar with the mechanism of photoaging, the treatments for photoaging, and the data that supports the use of these treatments.
Article
Skin aging is a complex biological process that is a consequence of both intrinsic or genetically programmed aging that occurs with time, and extrinsic aging caused by environmental factors. The dramatic increase in the aging population and the psychosocial impact of skin aging has created a demand for effective interventions. The advances that have been made in the past 25 years in our understanding of the clinical, biochemical, and molecular changes associated with aging have led to the development of many different approaches to reduce, postpone, and in some cases, repair the untoward effects of intrinsic programmed aging and extrinsic environmental injury.
Article
Estrogens have a profound influence on skin. The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging. Estrogens prevent skin aging. They increase skin thickness and improve skin moisture. Beneficial effects of hormone replacement therapy (HRT) on skin aging have been well documented, but HRT cannot obviously be recommended solely to treat skin aging in menopausal women. Topical estrogen application is highly effective and safe if used by a dermatologist with expertise in endocrinology. The question of whether estrogen alternatives such as phytoestrogens and selective estrogen receptor modulators are effective estrogens for the prevention of skin aging in postmenopausal women remains unanswered. However, preliminary data indicate that such treatment may be of benefit for skin aging treatment.
Article
Recent studies have shown that apigenin not only inhibits bone resorption by osteoclasts but also induces osteoclast apoptosis. However, the influence of apigenin on osteoporosis in animals is relatively unknown. The purpose of this study was to examine the bone-protective effects of apigenin in estrogen-deficient ovariectomized rats. Three-month-old female Sprague-Dawley rats were either sham-operated or ovariectomized and fed AIN-93G diet for 7 weeks to induce bone loss. To confirm bone loss, we used a newly developed non-invasive technique involving zoom-in micro-computed tomography. Apigenin was administered at a dose of 10 mg/kg three times a week for 15 weeks. Our results indicate that apigenin not only increased the mineral content and density of the trabecular bone at the neck of the left femur, but also decreased body weight and dietary consumption. Moreover, our biochemical results indicate that apigenin has a positive effect on bone turnover. The present data suggest that apigenin should be considered for use in the treatment of osteoporosis.
Article
The present study was carried out to investigate the effects of biomedicinal agents on Ca2+, P and alkaline phosphatase (ALP) levels in ovariectomized rats. Rats were ovariectomized bilaterally and were fed up with Ca2+ and P-free diet during 8(9,10) weeks to induce osteoporosis. Osteoporosis was determined by the extent of bone density and by lowering the concentrations of serum Ca2+, P and ALP activity every week. Rats in antler, safflower, ipriflavon, or co-administrated with estrogen groups were administrated with feed supplement for 5 weeks to elucidate the protective and therapeutic effects against osteoporosis. The bone tissue was examined with electron microscope to determine the effects of each treatment on osteoporosis. 1. The levels of serum Ca2+ and P in osteoporosis-induced rats, administrated with antler, ipriflavon and estrogen groups, were little higher than those of control rats. However, the levels of serum Ca and P in ovariectomized rats were significantly higher than those of control group (p<0.05). 2. The activities of serum ALP in osteoporosis-induced rats, administrated with antler extract, safflower, ipriflavon, or co-administrated with estrogen, were little increased in comparing with those of control group, but were significantly decreased in with combination of estrogen for 5 weeks. However, The connections were interrupted and the bone matrix was destroyed in the osteoporosis-induced rats. 3. The inter-trabecular connections were examined under electron microscope. The connections were well maintained and bone loss was without in the administration with antler, safflower, and ipriflavon with combination of estrogen for 5 weeks. However, The connections were interrupted and the bone matrix was destroyed in the osteoporosis-induced rats.
Expression of procollagen type I and matrix metallopro-FIG. 5 (continued) PROTECTIVE EFFECT OF ROYAL JELLY AGAINST SKIN AGING 573 r2 Photoaging: Mechanisms and repair
  • Aj Mamelak
  • Pj Mcelgunn
  • Wl Morison
  • Sauder
Expression of procollagen type I and matrix metallopro-FIG. 5 (continued) PROTECTIVE EFFECT OF ROYAL JELLY AGAINST SKIN AGING 573 r2. Rabe JH, Mamelak AJ, McElgunn PJ, Morison WL, Sauder DN: Photoaging: Mechanisms and repair. J Am Acad Dermatol 2006; 55:1–19
Ovariectomy is sufficient to accelerate spontaneous skin ageing and to stimulate 574 PARK ET AL. ultraviolet irradiation-induced photoageing of murine skin
  • K Tsukahara
  • H Nakagawa
  • S Moriwaki
Tsukahara K, Nakagawa H, Moriwaki S, et al.: Ovariectomy is sufficient to accelerate spontaneous skin ageing and to stimulate 574 PARK ET AL. ultraviolet irradiation-induced photoageing of murine skin. Br J Dermatol 2004;151:984–994.