RESUMEN
Radix Asteris, the root of Aster tataricus L. f., is historically significant in East Asian medicine for treating respiratory conditions. Yet, its implications on bone health remain uncharted. This research investigated the impact of an aqueous ethanol extract of Radix Asteris (EERA) on osteoclast differentiation and its prospective contribution to osteoporosis management. We discerned that EERA retards osteoclast differentiation by inhibiting receptor activator of nuclear factor kappa-B ligand (RANKL) expression and obstructing RANKL-induced osteoclastogenesis. EERA markedly suppressed RANKL-induced expression of NFATc1, a pivotal osteoclastogenic factor, via modulating early RANK signaling. EERA's therapeutic potential was underscored by its defense against trabecular bone degradation and its counteraction to increased body and perigonadal fat in ovariectomized mice, mirroring postmenopausal physiological changes. In the phytochemical analysis of EERA, we identified several constituents recognized for their roles in regulating bone and fat metabolism. Collectively, our findings emphasize the potential of EERA in osteoclast differentiation modulation and in the management of osteoporosis and associated metabolic changes following estrogen depletion, suggesting its suitability as an alternative therapeutic strategy for postmenopausal osteoporosis intertwined with metabolic imbalances.
Asunto(s)
Osteoclastos , Osteoporosis , Humanos , Femenino , Ratones , Animales , Osteoclastos/metabolismo , Etanol , Estudios Prospectivos , Factores de Transcripción NFATC/metabolismo , Osteoporosis/tratamiento farmacológico , Osteogénesis , FN-kappa B/metabolismo , Diferenciación Celular , Ligando RANK/metabolismo , OvariectomíaRESUMEN
Anethum graveolens L., known as European dill, is a versatile herb widely used in both traditional medicine and culinary practices. Despite its long-standing history, the potential impact of the water extract of A. graveolens seeds (WEAG) on bone health remains unexplored. In this study, we investigated the influence of WEAG on osteoclast differentiation and assessed its potential as an anti-osteoporotic agent. WEAG hindered osteoclast differentiation through the suppression of receptor activator of nuclear factor-κB ligand (RANKL) expression in osteoclast-supporting cells and by directly targeting osteoclast precursor cells. WEAG significantly reduced the expression of key osteoclastogenic transcription factors, namely c-Fos and NFATc1, typically induced by RANKL in osteoclast precursors. This reduction was attributed to the suppression of both MAPKs and NF-κB pathways in response to RANKL. In vivo experiments further revealed that WEAG administration effectively reduces trabecular bone loss and weight gain triggered by ovariectomy, mimicking postmenopausal osteoporosis. Furthermore, our comprehensive phytochemical analysis of WEAG identified a range of phytochemical constituents, associated with bone health and weight regulation. Notably, we discovered a specific compound, isorhamnetin-3-O-glucuronide, within WEAG that exhibits anti-osteoclastogenic potential. Overall, this research elucidated the beneficial effects and mechanistic basis of WEAG on osteoclast differentiation and bone loss, indicating its potential as a viable alternative to address bone loss in conditions like postmenopause.
Asunto(s)
Anethum graveolens , Resorción Ósea , Humanos , Femenino , Anethum graveolens/metabolismo , Diferenciación Celular , Factores de Transcripción NFATC/metabolismo , Osteoclastos , Osteogénesis , FN-kappa B/metabolismo , Fitoquímicos/farmacología , Ligando RANK/metabolismo , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Resorción Ósea/metabolismo , OvariectomíaRESUMEN
Euonymus alatus (Thunb.) Siebold, a traditional medicinal plant, has been used in China and several other Asian countries to address a variety of health concerns. The extensive research conducted on E. alatus is driven by its diverse pharmacological applications. However, its biological effects on osteoclastogenesis and osteoporosis have not been previously studied. In this research, we investigated the impact of an ethanolic extract of E. alatus (EEEA) on osteoclast differentiation and function as well as estrogen deficiency-induced bone loss. We found that EEEA inhibits osteoclast differentiation by downregulating the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoclast-supporting cells and by directly impeding RANKL-mediated signaling pathways for osteoclastogenesis in precursor cells. In addition, EEEA inhibited the bone-resorptive function of mature osteoclasts in vitro. Furthermore, oral administration of EEEA significantly alleviated bone loss in an ovariectomy-induced osteoporosis mouse model. Additionally, we identified phytochemicals in EEEA that have suppressive effects on osteoclast differentiation and bone loss. Collectively, these results suggest that EEEA holds potential as a biotherapeutic candidate for anti-postmenopausal osteoporosis.
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Lophatherum gracile Bronghiart, used in traditional herbal medicine, has many biological properties including antiviral, antipyretic, antitumor, vasorelaxation, and neutrophilic inflammatory effects. However, its modulatory effects on bone metabolism have not been investigated previously. In this study, we examined the effects of a water extract of the leaves of L. gracile (WELG) on osteoclast differentiation and bone loss, and explored its underlying mechanisms. We found that WELG inhibits osteoclastogenesis by suppressing both receptor activator of nuclear factor-κB ligand (RANKL)-induced early activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB)- and RANKL-induced modulation of the positive and negative regulators of osteoclastogenesis in osteoclast precursors. In vivo study demonstrated that WELG protects against bone loss, weight gain, and fat accumulation without affecting uterine atrophy in an ovariectomy-induced postmenopausal osteoporosis mice model. In addition, photochemical analysis of WELG identified active constituents known to have bone-protective effects. Overall, the results of this study suggest that WELG can be a potential candidate for therapy and prevention of postmenopausal osteoporosis.
Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Osteoporosis , Humanos , Ratones , Animales , Femenino , FN-kappa B/metabolismo , Osteogénesis , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/prevención & control , Osteoporosis Posmenopáusica/metabolismo , Ligandos , Conservadores de la Densidad Ósea/farmacología , Osteoporosis/etiología , Osteoporosis/prevención & control , Ovariectomía/efectos adversosRESUMEN
Human visitors affect the behavior of captive animals, which is the so-called visitor effect. The number and behavior of visitors may influence stress-related behaviors in captive animals, such as self-scratching, yawning, and visitor-directed vigilance. A social group setting can be applied to alleviate such negative visitor effects and facilitate social behavior and interactions between individuals. In this study, we examined how the number and behavior of visitors are related to stress-related behaviors of a captive mixed-species gibbon pair comprising a yellow-cheek gibbon (Nomascus gabriellae) and a white-handed gibbon (Hylobates lar). The two gibbons were separated during the study period, and we examined whether the social isolation stimulated the visitor effect. The frequency of stress-related behaviors of the gibbons increased and the social playing between them decreased proportionally to visitor number. In the indoor enclosure, the gibbons increased their visitor-directed vigilance when visitors shouted or struck the glass partition. Our findings indicate that the number and behavior of visitors negatively affect captive gibbons and that a mixed-species social setting can help gibbons reduce visitor-induced stress. Future studies with larger sample sizes will improve the understanding of the visitor effect and the social setting in the captivity.
Asunto(s)
Conducta Animal , Hylobates , Aislamiento Social , Animales , Conducta SocialRESUMEN
Pyrrosia lingua (Thunb.) Farw is a common plant that has been widely used as a traditional herbal medicine in China and Korea to treat patients suffering from pain, vaginal bleeding and urolithiasis. However, the pharmacological effects of P. lingua on bone remain unknown. We investigated the anti-osteoporotic effects of an ethanolic extract of P. lingua (EEPL). We found that EEPL suppressed osteoclast differentiation by directly acting on osteoclast precursor cells. EEPL suppressed the expression of receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor of activated T cells 1, a major transcription factor for osteoclastogenesis, by inhibiting RANKL-induced expression of aryl hydrocarbon receptor/c-Fos, and activation of nuclear factor-κB and mitogen-activated protein kinases. Moreover, administration of EEPL inhibited trabecular bone loss and weight gain in ovariectomized mice. Furthermore, we identified phytochemicals in EEPL that are known to exert anti-osteoclastogenic or anti-osteoporotic effects using ultra-high-performance liquid chromatography-tandem mass-spectrometry analysis. Overall, the results of this study suggest that EEPL is effective therapeutic candidate that can be used to prevent or treat postmenopausal osteoporosis.
Asunto(s)
Osteoclastos/efectos de los fármacos , Extractos Vegetales/farmacología , Polypodiaceae , Ligando RANK/efectos de los fármacos , Animales , Hueso Esponjoso/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , FN-kappa B/efectos de los fármacos , Osteoporosis/patología , Ovariectomía , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacos , Receptores de Hidrocarburo de Aril/efectos de los fármacos , Aumento de Peso/efectos de los fármacosRESUMEN
Mentha arvensis L., is an aromatic herb that belongs to the Lamiaceae family and is widely used in medicinal applications, essential oil applications, and food flavoring. The extract of M. arvensis has been reported to exert sedative-hypnotic, anti-inflammatory, anti-fungal, and anti-bacterial effects. However, its effects on bone metabolism have not yet been studied. Here, we investigated the effects of the water extract of M. arvensis (WEMA) on osteoclast formation in vitro and bone loss in an ovariectomized mouse model. We found that WEMA inhibited osteoclast differentiation by directly acting on osteoclast precursor cells. WEMA inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced the expression of cellular oncogene fos (c-Fos) and nuclear factor of activated T cells c1 (NFATc1), crucial transcription factors for osteoclast differentiation, by suppressing RANKL-induced activation of early signaling pathways such as those of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). In addition, oral administration of WEMA suppressed ovariectomy-induced trabecular bone loss in mice. We additionally identified phytochemicals in WEMA that are known to have anti-osteoclastogenic or anti-osteoporotic properties. Collectively, these results suggest that WEMA is a promising herbal candidate that can be used to prevent or treat postmenopausal osteoporosis.
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In traditional oriental medicines, Commiphora myrrha and its resinous exudate (i.e., myrrh) are used as herbal remedies to treat various inflammatory and metabolic disorders. Until now, C. myrrha-derived herbal products are considered useful source for bioactive compounds to manage numerous human diseases. This study investigated the effects of water extract of C. myrrha resin (WCM) and its polysaccharide (WCM-PE) on modulatory effects of osteoclast differentiation and/or ovariectomized-induced bone loss. Oral administration of WCM (200 and 500 mg/kg/day for four weeks) notably decreased trabecular bone loss and lipid accumulation in the bone marrow cavity. WCM and WCM-PE dose-dependently inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells, cytoplasmic 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, DC-STAMP and cathepsin K) expression. Thus, our results suggest that WCM and WCM-PE are promising nutraceutical candidates for the management of osteoporosis in postmenopausal women.
RESUMEN
In Asia, Amomum tsao-ko has long been used as a spice or seasoning in food to stimulate digestion. In the present study, we evaluated the effects of ethanol extract of Amomum tsao-ko (EEAT) on menopausal osteoporosis and obesity. After the administration of EEAT in ovariectomy (OVX) mice models for five weeks, microcomputed tomography and a histological analysis were performed to assess, respectively, the trabecular structure and the fat accumulation in adipose, liver, and bone tissues. We also examined the effects of EEAT on a bone marrow macrophage model of osteoclastogenesis by in vitro stimulation from the receptor activator of nuclear factor-kappa Β ligand (RANKL) through real-time PCR and Western blot analysis. In addition, ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with authentic standards was applied to characterize the phytochemical profiling of EEAT. We found that EEAT significantly decreased OVX-induced body weight gain and fat accumulation, significantly prevented OVX-induced deterioration of bone mineral density and microstructure of trabecular tissues, and significantly inhibited osteoclast differentiation by downregulating NF-κB/Fos/NFATc1 signaling in osteoclasts. Furthermore, UHPLC-MS/MS identified eight beneficial phytochemicals in EEAT. Collectively, these results suggest that EEAT might be an effective nutraceutical candidate to attenuate menopausal osteoporosis by inhibiting osteoclastogenesis and to prevent obesity by suppressing fat accumulation.
Asunto(s)
Amomum/química , Hueso Esponjoso/metabolismo , Etanol/química , Lipogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Hueso Esponjoso/patología , Femenino , Ratones , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis/etiología , Osteoporosis/metabolismo , Osteoporosis/patología , Ovariectomía , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacos , Aumento de Peso/efectos de los fármacosRESUMEN
Estrogen deficiency in postmenopausal women causes homeostatic imbalance of bone, resulting in bone loss and osteoporosis. Agastache rugosa, a plant belonging to the Lamiaceae family, is an aromatic herb, and the leaves of this herb are widely used as food ingredients. Extracts of A. rugosa have various bioactivities including anti-HIV integration, anti-inflammatory, and anti-atherogenic properties. However, the beneficial effect of A. rugosa on bone has not been studied. Therefore, we investigated the effects of water extract of A. rugosa (WEAR) on osteoclast differentiation and estrogen deficiency-induced bone loss in ovariectomized (OVX) mice as an animal model for postmenopausal osteoporosis. The oral administration of WEAR remarkably improved OVX-induced trabecular bone loss and fat accumulation in the bone marrow. WEAR suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in osteoclast precursor cells, subsequently inhibiting resorption activity on a bone mimetic surface. WEAR inhibited the expression of cellular oncogene fos (c-Fos) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), key osteoclastogenic transcription factors, by decreasing RANKL-induced activation of mitogen-activated protein kinases (MAPKs), and nuclear factor-κB (NF-κB) pathways. We also identified seventeen phytochemicals present in WEAR, including five phenols and twelve flavonoids, and found eleven bioactive constituents that have anti-osteoclastogenic effects. Collectively, these results suggest that WEAR could be used to treat and prevent postmenopausal osteoporosis by suppressing osteoclastogenesis.
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In Asia, extracts of Lysimachia christinae have been used for liver or urinogenital system-related diseases in traditional medicine. In this study, we investigated the effects of the water extract of L. christinae (WELC) on receptor activator of nuclear factor-kappa Β ligand (RANKL)-induced osteoclastic differentiation of bone marrow macrophages, and on osteoporosis and obesity in ovariectomy mice. RANK signaling pathways related to osteoclast differentiation were examined by real-time polymerase chain reaction (PCR) and western blot analysis. Additionally, we performed micro-computed tomography to assess trabecular bone loss, histological analysis for fat accumulation in adipose, liver, and bone tissues, and phytochemical profiling for WELC characterization. WELC significantly inhibited osteoclast differentiation by downregulating RANKL-induced mitogen-activated protein kinase (MAPK)/c-Fos/nuclear factor of activated T-cells (NFAT) signaling in osteoclast precursors and ovariectomy-induced trabecular loss by suppressing osteolcastic bone resorption. WELC markedly decreased ovariectomy-induced body weight gain and fat accumulation in adipose, liver, and bone tissues. Furthermore, ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) identified 16 phytochemicals in WELC when compared with the mass fragmentation of standard chemicals. Collectively, these results suggest that WELC might possess beneficial effects on postmenopausal osteoporosis by inhibiting osteoclast differentiation and obesity by suppressing fat accumulation.
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Tejido Adiposo/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Extractos Vegetales/farmacología , Primulaceae , Agua/farmacología , Animales , Resorción Ósea , Hueso Esponjoso/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Femenino , Ratones , Osteoclastos/efectos de los fármacos , Osteoporosis/etiología , Ovariectomía , Ligando RANK/metabolismo , Transducción de Señal/efectos de los fármacos , Espectrometría de Masas en Tándem , Aumento de Peso/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
Nelumbo nucifera, more commonly known as the Indian lotus, is an important plant that has been incorporated into traditional herbal remedies along the years. Even today, lotus leaves are considered reservoirs for bioactive compounds that can be used as nutritional supplements to treat various human diseases. However, despite the wide ranging biological activities of lotus polysaccharides, limited information is available regarding the anti-osteoporotic effects of these substances. The aim of this study was to investigate the beneficial effects of pectinase-assisted extractable polysaccharides from lotus leaves (LLEP) on estrogen deficiency-induced bone loss and osteoclast differentiation in bone marrow-derived macrophages. We found that LLEP markedly inhibited receptor activator of the nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner. It also revoked RANKL-induced activation of osteoclastogenic signals such as the expression of key transcription factors (i.e., c-Fos and nuclear factor of activated T cells cytoplasmic 1), resulting in a decrement in osteoclast-specific marker gene expressions. Microcomputed tomography and morphometric analysis revealed that a four-week oral administration of LLEP notably decreased trabecular bone loss. Taken together, our results suggest that LLEP can mitigate estrogen deficiency-induced bone loss by suppressing osteoclastogenesis, which makes it an excellent candidate for combating osteoporosis.
Asunto(s)
Lotus/química , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Hojas de la Planta/química , Polisacáridos/farmacología , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Diferenciación Celular/efectos de los fármacos , Femenino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Osteoporosis/metabolismo , Ligando RANK/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismoRESUMEN
Estrogen deprivation in postmenopausal women causes disruption of bone homeostasis, resulting in bone loss and osteoporosis. Conventional therapies can exert adverse effects. The sclerotum of Poria cocos has been used in traditional medicine and as a nutritional supplement and to treat various diseases. However, the effects of P. cocos on the bone remain largely undetermined. In this study, we examined the effects of P. cocos hydroethanolic extract (PC) on osteoclast differentiation and estrogen-deprivation-induced bone loss in an ovariectomized mouse model of postmenopausal osteoporosis. PC-mediated inhibition of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and resorption activity suppressed RANKL-induced expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which is a crucial transcription factor for osteoclast differentiation. In ovariectomized mice, PC markedly alleviated trabecular bone loss and reduced the accumulation of lipid droplets in the bone marrow. We additionally identified ten triterpenoid constituents of PC using UPLC-MS/MS analysis. Our results indicate that PC negatively regulated osteoclast differentiation and function, and can potentially be used to manage postmenopausal osteoporosis.
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Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Extractos Vegetales/farmacología , Wolfiporia , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Osteoporosis Posmenopáusica/etiología , Ovariectomía/efectos adversosRESUMEN
Deinococcus actinosclerus BM2T (GenBank: KT448814) is a radio-resistant bacterium that is newly isolated from the soil of a rocky hillside in Seoul. As an extremophile, D. actinosclerus BM2T may possess anti-inflammatory properties that may be beneficial to human health. In this study, we evaluated the anti-inflammatory effects of BM2U, an aqueous extract of D. actinosclerus BM2T, on lipopolysaccharide (LPS)-mediated inflammatory responses in RAW264.7 macrophage cells. BM2U showed antioxidant capacity, as determined by the DPPH radical scavenging (IC50 = 349.3 µg/ml) and ORAC (IC50 = 50.24 µg/ml) assays. At 20 µg/ml, BM2U induced a significant increase in heme oxygenase-1 (HO-1) expression (p < 0.05). BM2U treatment (0.2-20 µg/ml) significantly suppressed LPS-induced increase in the mRNA expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 (p < 0.05). BM2U treatment also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. BM2U treatment also inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs): JNK, ERK, and p-38 (p < 0.05). Collectively, BM2U exhibited anti-inflammatory potential that can be exploited in attenuating inflammatory responses.
Asunto(s)
Antiinflamatorios/farmacología , Deinococcus/química , Lipopolisacáridos/toxicidad , Animales , Antiinflamatorios/química , Antioxidantes/farmacología , Ciclooxigenasa 2/genética , Citocinas/genética , Deinococcus/aislamiento & purificación , Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
In traditional oriental medicine, nutgalls of Rhus chinensis have been used to treat various gastrointestinal and respiratory disorders. This study aimed to investigate the benefits of nutgalls of R. chinensis on bone loss and obesity in ovariectomized mice fed with a high-fat diet. Following surgical menopause induction, nutgalls of R. chinensis was orally administered for 4 weeks. Body weight gain and organ weights were measured. Histopathological examinations and UHPLC-MS/MS analysis were performed. Nutgalls of R. chinensis remarkably decreased obesity, gonadal fat, and bone loss in ovariectomized mice fed with a high-fat diet. Nutgalls of R. chinensis inhibited adipocyte differentiation of multipotent bone marrow stromal cells and reduced fat accumulation in gonadal fat, liver, and bone tissues. In UHPLC-MS/MS analysis, 27 phytochemicals containing gallotannin derivatives and flavonoids were identified by comparison with mass fragmentation of authentic standards. Taken together, the results demonstrate the beneficial effects of nutgalls of R. chinensis and its phytochemicals to manage postmenopausal bone disorders and obesity.
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Adipogénesis/efectos de los fármacos , Obesidad/tratamiento farmacológico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Rhus/química , Adipocitos/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Osteoporosis Posmenopáusica/diagnóstico por imagen , Ovariectomía , Fitoquímicos/química , Extractos Vegetales/química , Microtomografía por Rayos XRESUMEN
In traditional oriental medicine, the fruit of Forsythia suspensa has been used as a nutritional supplement to alleviate inflammation and treat gastrointestinal diseases. However, there is no information available on its beneficial effects on bone. We investigated the beneficial effects of F. suspensa water extract (WFS) on osteoclast differentiation and bone loss. The microarchitecture of trabecular bone was analyzed by micro-computed tomography. Osteoclast differentiation was evaluated based on tartrate-resistant alkaline phosphatase activity, and bone resorption activity was examined on a bone-like mineral surface. The mechanism of action of WFS was assessed by evaluating the expression and activation of signaling molecules. Phytochemical constituents were identified and quantitated by ultrahigh-performance liquid chromatography-tandem mass spectrometry. WFS reduced ovariectomy-induced trabecular bone loss and inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and resorption activity. WFS suppressed RANKL-induced expression of nuclear factor of activated T cells cytoplasmic 1, a crucial transcription factor for osteoclast differentiation by decreasing c-Fos protein levels and suppressing the activation of p38 and c-Jun-N-terminal kinase. We also identified 12 phytochemicals in WFS including lignans, phenylethanoids, and flavonoids. Collectively, these results suggest that WFS inhibits osteoclast differentiation and can potentially be used to treat postmenopausal osteoporosis.
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Resorción Ósea/tratamiento farmacológico , Forsythia/química , Fitoterapia/métodos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Animales , Resorción Ósea/etiología , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Humanos , Medicina Tradicional de Asia Oriental/métodos , Ratones , Osteoclastos/efectos de los fármacos , Ovariectomía/efectos adversos , Ligando RANK/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
In traditional oriental medicine, Drynaria roosii Nakaike is widely used in treating bone diseases. Postmenopausal women are strongly associated with osteoporosis and obesity. This study aimed to investigate the effects of the water extract of D. roosii (WDR) on bone loss and obesity in ovariectomized (OVX) mice fed a high-fat diet (HFD). Body weight, gonadal fat weight, histological findings, and morphometric parameters in trabecular bone were evaluated after OVX mice were treated with WDR and HFD for four weeks. The receptor activator of nuclear κ-B ligand (RANKL)-induced osteoclast differentiation in bone marrow-derived macrophages (BMMs) was examined. Phytochemical identification of WDR using ultrahigh-performance liquid chromatography-tandem mass spectrometry was performed. WDR reversed the changes in body weight gain, gonadal fat mass, and trabecular bone parameters by ovariectomy. However, ovariectomy-induced uterine atrophy was not affected by WDR. WDR decreased adipocyte size and pro-inflammatory cytokines (interleukin (IL)-1ß and IL-6) in gonadal fats and lipid accumulation in the bone marrow, which were induced by ovariectomy. WDR significantly decreased RANKL-induced osteoclast differentiation in BMMs. Fifteen phytochemicals were identified in WDR: Seven and nine with anti-osteoporotic and anti-adipogenic activities, respectively. Our findings suggest that WDR may have beneficial effects on postmenopausal osteoporosis and obesity.
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Adipogénesis/efectos de los fármacos , Dieta Alta en Grasa , Ovariectomía , Extractos Vegetales/farmacología , Polypodiaceae/química , Animales , Biomarcadores , Diferenciación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Citocinas/metabolismo , Femenino , Ratones , Estructura Molecular , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoporosis/diagnóstico por imagen , Osteoporosis/tratamiento farmacológico , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Espectrometría de Masas en Tándem , Microtomografía por Rayos XRESUMEN
Vascular inflammation has been suggested to play a key role in the initiation and progression of atherosclerosis. Hyperoside (HPS) is a plant-derived quercetin 3-d-galactoside reported to have anti-inflammatory, anti-oxidant, anti-cancer, anti-hyperglycemic, anti-coagulant, and cardioprotective activities. However, the effects of HPS on vascular inflammation have not been studied. Therefore, in this study, we investigated the suppressive effect of HPS on tumor necrosis factor-α (TNFα)-dependent inflammatory responses in MOVAS-1â¯cells, a murine vascular smooth muscle cell (VSMC) line. HPS did not show any significant cytotoxicity up to 10⯵g/mL over 24â¯h. TNFα challenge of VSMCs significantly increased the mRNA (3-fold) and protein expression (20-fold) of vascular cell adhesion molecule-1 (VCAM-1). However, these increases were abolished in the presence of HPS. Additionally, HPS significantly decreased monocyte adhesion to TNFα-stimulated VSMCs in a dose-dependent manner. Further, TNFα challenge induced activation of mitogen-activated protein kinases (MAPKs), such as p38â¯MAPK (38.0⯱â¯3.08 fold), JNK (51.6⯱â¯2.26 fold), and ERK (14.1⯱â¯0.77 fold); expression of nuclear factor-κB (NF-κB; â 4-fold) and TNF receptor 1 (TNFR1; 2.7⯱â¯0.198 fold) were also increased. Notably, the TNFα-induced expression of these molecules was also significantly inhibited by the presence of HPS. Given that p38â¯MAPK, JNK, ERK, NF-κB, and TNFR1 all play regulatory roles in the expression of VCAM-1, this study provides insight into the mechanism of action of HPS. In summary, HPS can inhibit TNFα-mediated vascular inflammatory responses and has potential as a new anti-atherosclerotic drug.
Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Quercetina/análogos & derivados , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Animales , Adhesión Celular/efectos de los fármacos , Línea Celular , Peroxidación de Lípido/efectos de los fármacos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Quercetina/química , Quercetina/farmacología , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Angelica tenuissima root has historically been used as a traditional medicine in Korea. Previous studies have identified the anti-melanogenic effects of the extract of A. tenuissima root fermented by Aspergillus oryzae (FAT). This study investigated the protective effects of FAT against ultraviolet light B exposure (UVB; 30 mJ/cm2) in HaCaT (human keratinocyte) or Hs68 (human foreskin fibroblast) skin cells. FAT treatment was able to stimulate wound healing rate at the basal condition. FAT also favored the maintenance and/or improvement of extracellular matrix impairment caused by UVB irradiation through: 1) upregulation of procollagen Type-1 synthesis and secretion; 2) suppression of MMP-1 and elastase expression. FAT was able to play a role in the attenuation of inflammatory responses caused by UVB irradiation via upregulation of photo-protective hemeoxygease-1 and suppression of proinflammatory cyclooxygenase-2 expression. After further verification of the anti-photoaging potential of FAT, it could be utilized as an effective ingredient in anti-aging and anti-wrinkle cosmetics.
Asunto(s)
Angelica/química , Aspergillus oryzae/metabolismo , Alimentos Fermentados , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Protectores contra Radiación/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Línea Celular Transformada , Movimiento Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Queratinocitos/citología , Metaloproteinasa 1 de la Matriz/genética , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Estrés Oxidativo/efectos de la radiación , Elastasa Pancreática/genética , Elastasa Pancreática/metabolismo , Extractos Vegetales/química , Raíces de Plantas/química , Procolágeno/genética , Procolágeno/metabolismo , Rayos Ultravioleta/efectos adversos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n = 6; p < 0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n = 6; p < 0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n = 6; p < 0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.