RESUMO
Obesity is a multifaceted medical condition characterized by the pathological accumulation of excessive lipids in the body. We investigated the effects of morroniside, a bioactive compound derived from Cornus officinalis, on adipogenesis. We used a preadipocyte 3T3-L1 stable cell line and primary cultured adipose-derived stem cells (ADSCs) in vitro and ovariectomized (OVX) and a high-fat diet (HFD)-fed obese mouse model in vivo. Preadipocyte 3T3-L1 cells and ADSCs incubated with morroniside during adipocyte differentiation and obese mice subjected to OVX and HFD received oral morroniside treatment for 12 weeks. Morroniside treatment significantly reduced adipocyte differentiation and fatty acid accumulation and downregulated adipogenesis-related gene expression, concomitant with a decrease in triglyceride content and an increase in glycerol release in cells. The results of the in vivo study showed that morroniside ameliorated obesity-related phenotypes by reducing body weight gain, hepatic steatosis, and adipose tissue in obese mice. These findings suggest that morroniside is a promising compound for preventing and treating obesity.
Assuntos
Células 3T3-L1 , Adipogenia , Fármacos Antiobesidade , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Animais , Camundongos , Adipogenia/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Fármacos Antiobesidade/farmacologia , Feminino , Dieta Hiperlipídica/efeitos adversos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Glicosídeos/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Diferenciação Celular/efeitos dos fármacos , Camundongos Obesos , Triglicerídeos/metabolismo , Ovariectomia , Fígado Gorduroso/tratamento farmacológicoRESUMO
BACKGROUND: The overstoring of surplus calories in mature adipocytes causes obesity and abnormal metabolic activity. The anti-obesity effect of a Celosia cristata (CC) total flower extract was assessed in vitro, using 3T3-L1 pre-adipocytes and mouse adipose-derived stem cells (ADSCs), and in vivo, using high-fat diet (HFD)-treated C57BL/6 male mice. METHODS: CC extract was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs. After differentiation, lipid droplets were assessed by oil red O staining, adipogenesis and lipolytic factors were evaluated, and intracellular triglyceride and glycerol concentrations were analyzed. For in vivo experiments, histomorphological analysis, mRNA expression levels of adipogenic and lipolytic factors in adipose tissue, blood plasma analysis, metabolic profiles were investigated. RESULTS: CC treatment significantly prevented adipocyte differentiation and lipid droplet accumulation, reducing adipogenesis-related factors and increasing lipolysis-related factors. Consequently, the intracellular triacylglycerol content was diminished, whereas the glycerol concentration in the cell supernatant increased. Mice fed an HFD supplemented with the CC extract exhibited decreased HFD-induced weight gain with metabolic abnormalities such as intrahepatic lipid accumulation and adipocyte hypertrophy. Improved glucose utilization and insulin sensitivity were observed, accompanied by the amelioration of metabolic disturbances, including alterations in liver enzymes and lipid profiles, in CC-treated mice. Moreover, the CC extract helped restore the disrupted energy metabolism induced by the HFD, based on a metabolic animal monitoring system. CONCLUSION: This study suggests that CC total flower extract is a potential natural herbal supplement for the prevention and management of obesity.
Assuntos
Células 3T3-L1 , Adipócitos , Adipogenia , Fármacos Antiobesidade , Celosia , Dieta Hiperlipídica , Flores , Camundongos Endogâmicos C57BL , Obesidade , Extratos Vegetais , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Masculino , Camundongos , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/isolamento & purificação , Flores/química , Adipogenia/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Celosia/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacosRESUMO
Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10-7 (odds ratio = 1.72) and 1.1 × 10-7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.
Assuntos
Fraturas Ósseas , Osteoporose , Animais , Feminino , Camundongos , Densidade Óssea/genética , Fraturas Ósseas/genética , Osteogênese/genética , Osteoporose/genética , Osteoporose/metabolismo , Peixe-ZebraRESUMO
Obesity is characterized by the excessive accumulation of mature adipocytes that store surplus energy in the form of lipids. In this study, we investigated the inhibitory effects of loganin on adipogenesis in mouse preadipocyte 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) in vitro and in mice with ovariectomy (OVX)- and high-fat diet (HFD)-induced obesity in vivo. For an in vitro study, loganin was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs, lipid droplets were evaluated by oil red O staining, and adipogenesis-related factors were assessed by qRT-PCR. For in vivo studies, mouse models of OVX- and HFD-induced obesity were orally administered with loganin, body weight was measured, and hepatic steatosis and development of excessive fat were evaluated by histological analysis. Loganin treatment reduced adipocyte differentiation by accumulating lipid droplets through the downregulation of adipogenesis-related factors, including peroxisome proliferator-activated receptor γ (Pparg), CCAAT/enhancer-binding protein α (Cebpa), perilipin 2 (Plin2), fatty acid synthase (Fasn), and sterol regulatory element binding transcription protein 1 (Srebp1). Loganin administration prevented weight gain in mouse models of obesity induced by OVX and HFD. Further, loganin inhibited metabolic abnormalities, such as hepatic steatosis and adipocyte enlargement, and increased the serum levels of leptin and insulin in both OVX- and HFD-induced obesity models. These results suggest that loganin is a potential candidate for preventing and treating obesity.
Assuntos
Adipogenia , Fármacos Antiobesidade , Iridoides , Animais , Camundongos , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , PPAR gama/metabolismo , Aumento de Peso , Iridoides/farmacologiaRESUMO
Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast-osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.
Assuntos
Osteogênese , Osteoporose , Feminino , Animais , Camundongos , Iridoides , Osteoblastos , Osteoporose/tratamento farmacológicoRESUMO
Methods: Polyphenolic and iridoid constituents of extracts were analyzed qualitatively and quantitatively using the ultraperformance liquid chromatography system coupled with a quadrupole-time of flight mass spectrometry. Primary cultured osteoblasts isolated from mouse calvarias and osteoclast-lineage primary cultured monocytes isolated from mouse bone marrow were used for the assessment of osteoblast and osteoclast differentiation. In the osteoblast culture, cellular viability, alkaline phosphatase (ALP) activity, ALP staining, and mRNA expression of Alpl and Runx2 were examined. In the osteoclast culture, the examined parameters were cellular viability, tartrate-resistant acid phosphatase (TRAP) activity and staining, and mRNA expression of Nfatc1, Ctsk, and Acp. Results: A total of 41 main compounds of iridoids, anthocyanins, hydrolysable tannins, phenolic acids, and flavonols were identified in the three extracts. RED EXT1 contained most of the tested polyphenols and iridoids and was the only extract containing anthocyanins. YL EXT2 contained only one iridoid, loganic acid and gallic acid. YL EXT3 comprised a mixture of iridoids and polyphenols. RED EXT1, YL EXT 2, and to a lesser extent YL EXT3 promoted osteoblast differentiation increasing significantly ALP activity and the amount of ALP-positive stained cells. All extracts upregulated mRNA expression of Alpl and Runx2. RED EXT1 caused the most significant decrease in TRAP activity and the numbers of TRAP-positive multinucleated cells. RED EXT1 caused also the most significant downregulation of mRNA expression of osteoclast related genes Nfatc1, Ctsk, and Acp5. Extracts from yellow fruits, mostly YL EXT2 caused lower, but still significant inhibitory effect on TRAP and osteoclast related genes. Conclusions: The main conclusion of our study is that all three extracts, especially RED EXT1 from red cornelian cherry fruits, possess the antiosteoporotic potential and may be a promising phytomedicine candidate for the prevention and treatment of osteoporosis.
Assuntos
Cornus , Fosfatase Alcalina , Animais , Antocianinas/farmacologia , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core , Cornus/química , Flavonóis , Frutas/química , Ácido Gálico/análise , Iridoides/química , Iridoides/farmacologia , Camundongos , Osteoblastos , Osteoclastos , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Polifenóis/química , RNA Mensageiro , Taninos , Fosfatase Ácida Resistente a Tartarato/análiseRESUMO
Background and Objectives: Traditional herbal medicines are becoming more popular as a complementary medication as they have the advantages of being mostly harmless and safe, causing fewer side-effects than conventional medications. Here, we demonstrate the inhibitory effects of the combination of Ulmus davidiana (UD) and Cornus officinalis (CO) extracts on osteoporotic bone loss. Materials and Methods: This study presented osteogenic effects in primary cultured osteoblasts, pre-osteoblastic MC3T3-E1 cell lines, and osteoclastogenic effects in osteoclasts derived from bone marrow monocytes, and finally, protective effects on bone loss in an ovariectomy (OVX)-induced osteoporotic animal model. Results: A significant increase in alkaline phosphatase (ALP) activity was observed following treatment with UD and CO mixtures (8:2, 7:3, and 5:5 ratios) and individual UD and CO extracts, with the highest ALP activity being detected for the treatment with UD and CO extracts at a 5:5 ratio. An optimal ratio of UD and CO (UC) extract promoted osteoblast differentiation in both pre-osteoblastic cells and primary osteoblasts by increasing osteoblastic markers such as Alpl, Runx2, and Bglap. However, treatment with the UC extract inhibited osteoclast differentiation with a decreased expression of osteoclastogenesis-related genes, including Ctsk, Acp5, Mmp9, and Nfatc1. In addition, UC treatment prevented osteoporotic bone loss in OVX mice and improved impaired skeletal structure parameters. Conclusions: This study suggests that combined UD and CO extracts may be a beneficial traditional medicine for the prevention of postmenopausal osteoporosis.
Assuntos
Cornus , Osteoporose Pós-Menopausa , Ulmus , Animais , Diferenciação Celular , Feminino , Humanos , Camundongos , Osteoclastos , Osteoporose Pós-Menopausa/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ulmus/químicaRESUMO
Osteoarthritis (OA) is the progressive destruction of articular cartilage with severe symptoms, including pain and stiffness. We investigated the anti-osteoarthritic effects of Prunella vulgaris (PV) and Gentiana lutea (GL) extract in primary cultured chondrocytes RAW 264.7 cells in vitro and destabilization of the medial meniscus (DMM)-induced OA mice in vivo. Primary chondrocytes were induced with IL-1ß, and RAW 264.7 cells were treated with LPS and co-incubated with either individual extracts of PV and GL or different ratios of PV and GL mixture. For the OA animal model, the medial meniscus (DMM) was destabilized in 9-week-old male C57BL/6 mice. Treatment of individual PV and GL and combination of PV and GL extracts inhibited the mRNA expression level of COX2 in chondrocytes and RAW 264.7 cells. The optimized inhibitory effect was attained with a PV and GL combination at an 8:2 ratio (PG) without cytotoxic effects. PG extracts prevented the expression of catabolic factors (COX2, Mmp3, Mmp9, and Mmp13) and inflammatory mediator levels (PGE2 and collagenase). In addition, PG decreased subchondral sclerosis and increased BMD in the subchondral region of DMM-induced OA mice with protection of articular cartilage destruction by inhibiting inflammatory processes. This study suggests that PG may be an alternative medicinal herb for treatment of OA.
RESUMO
Neurofibromatosis type 1 (NF1) is an autosomal dominant human genetic disorder. The progression of benign plexiform neurofibromas to malignant peripheral nerve sheet tumors (MPNSTs) is a major cause of mortality in patients with NF1. Although elevated epidermal growth factor receptor (EGFR) expression plays a crucial role in the pathogenesis of MPNST, the cause of EGFR overexpression remains unclear. Here, we assessed EGFR expression levels in MPNST tissues of NF1 patients and NF1 patient-derived MPNST cells. We found that the expression of EGFR was upregulated in MPNST tissues and MPNST cells, while the expression of neurofibromin was significantly decreased. Manipulation of NF1 expression by NF1 siRNA treatment or NF1-GAP-related domain overexpression demonstrated that EGFR expression levels were closely and inversely correlated with neurofibromin levels. Notably, knockdown of the NF1 gene by siRNA treatment augmented the nuclear localization of phosphorylated SP1 (pSP1) and enhanced pSP1 binding to the EGFR gene promoter region. Our results suggest that neurofibromin deficiency in NF1-associated MPNSTs enhances the Ras/ERK/SP1 signaling pathway, which in turn may lead to the upregulation of EGFR expression. This study provides insight into the progression of benign tumors and novel therapeutic approaches for treatment of NF1-associated MPNSTs.
Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Neurofibromatose 1/metabolismo , Neurofibromina 1/metabolismo , Fator de Transcrição Sp1/metabolismo , Regulação para Cima , Proteínas ras/metabolismo , Linhagem Celular Tumoral , Receptores ErbB/biossíntese , Receptores ErbB/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Humanos , Neurofibromatose 1/genética , Neurofibromina 1/genética , Fator de Transcrição Sp1/genética , Proteínas ras/genéticaRESUMO
Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.
RESUMO
Bone remodeling is a continuous process of bone synthesis and destruction that is regulated by osteoblasts and osteoclasts. Here, we investigated the anti-osteoporotic effects of morroniside in mouse preosteoblast MC3T3-E1 cells and mouse primary cultured osteoblasts and osteoclasts in vitro and ovariectomy (OVX)-induced mouse osteoporosis in vivo. Morroniside treatment enhanced alkaline phosphatase activity and positively stained cells via upregulation of osteoblastogenesis-associated genes in MC3T3-E1 cell lines and primary cultured osteoblasts. However, morroniside inhibited tartrate-resistant acid phosphatase activity and TRAP-stained multinucleated positive cells via downregulation of osteoclast-mediated genes in primary cultured monocytes. In the osteoporotic animal model, ovariectomized (OVX) mice were administered morroniside (2 or 10 mg/kg/day) for 12 weeks. Morroniside prevented OVX-induced bone mineral density (BMD) loss and reduced bone structural compartment loss in the micro-CT images. Taken together, morroniside promoted increased osteoblast differentiation and decreased osteoclast differentiation in cells, and consequently inhibited OVX-induced osteoporotic pathogenesis in mice. This study suggests that morroniside may be a potent therapeutic single compound for the prevention of osteoporosis.
Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Cornus/química , Glicosídeos/administração & dosagem , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoporose/etiologia , Osteoporose/terapia , Ovariectomia/efeitos adversos , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Animais , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos ICR , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismoRESUMO
Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1ß)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1ß-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.
Assuntos
Cornus/química , Glicosídeos/farmacologia , Inflamação/tratamento farmacológico , Meniscos Tibiais/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Animais , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Dinoprostona/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosídeos/química , Humanos , Interleucina-1beta/genética , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Meniscos Tibiais/patologia , Meniscos Tibiais/cirurgia , Camundongos , Osteoartrite/genética , Osteoartrite/patologia , Osteoartrite/cirurgia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cultura Primária de Células , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacosRESUMO
Arthritis is a common inflammatory disease that causes pain, stiffness, and joint swelling. Here, we investigated the ameliorative effects of loganin on arthritis in vitro and in vivo. A single bioactive compound was fractionated and isolated from Cornus officinalis (CO) extract to screen for anti-arthritic effects. A single component, loganin, was identified as a candidate. The CO extract and loganin inhibited the expression of factors associated with cartilage degradation, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMP-3), and matrix metalloproteinase 13 (MMP-13), in interukin-1 beta (IL-1ß)-induced chondrocyte inflammation. In addition, prostaglandin and collagenase levels were reduced following treatment of IL-1ß-induced chondrocytes with loganin. In the destabilization of the medial meniscus (DMM)-induced mouse model, loganin administration attenuated cartilage degeneration by inhibiting COX-2, MMP-3, and MMP-13. Transverse micro-CT images revealed that loganin reduced DMM-induced osteophyte formation. These results indicate that loganin has protective effects in DMM-induced mice.
RESUMO
Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.
Assuntos
Iridoides/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoporose/patologia , Substâncias Protetoras/farmacologia , Administração Oral , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Modelos Animais de Doenças , Gentiana/química , Iridoides/administração & dosagem , Iridoides/química , Iridoides/isolamento & purificação , Camundongos , Osteoblastos/patologia , Osteoclastos/patologia , Ovariectomia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Obesity is a medical condition that presents excessive fat accumulation with high risk of serious chronic diseases. The aim of this clinical trial is to investigate the anti-obesity effects of Cornus officinalis (CO) and Ribes fasciculatum (RF) on body fat reduction in Korean overweight women. A total of 147 overweight female participants enrolled in double-blinded clinical trial for 12 weeks and 76 participants completed the clinical study. Participants were treated with four CO and RF mixture (COEC; 400 mg per tablet) or four placebo tablets once a day. Obesity associated parameters (body weight, body mass index (BMI), waist circumference, waist-to-hip ratio, body fat percentage and body fat mass) and safety assessment were analyzed. After 12 weeks of COEC treatment, primary outcomes such as body fat percentage (0.76% vs. 0.01%; p = 0.022) and mass (1.1 kg vs. 0.5 kg; p = 0.049) were significantly decreased. In addition, the results were statistically significant between the COEC and placebo groups, strongly indicated that COEC had anti-obesity effects on overweight women. Secondary outcomes-including body weight, waist and hip circumference, waist-to-hip ratio, body mass index and computed tomography measurement of visceral fat area, subcutaneous fat area, total abdominal fat area and visceral-to-subcutaneous fat ratio-were reduced in COEC-treated group, but no statistical differences were found between the COEC and placebo groups. The safety assessment did not differ between the two groups. These results suggest that treatment of COEC extract reduces body fat percentage and mass in Korean overweight women, indicating it as a protective functional agent for obesity.
RESUMO
Obesity is prevalent in modern human societies. We examined the anti-obesity effects of scopolin on adipocyte differentiation in preadipocyte 3T3-L1 cells and weight loss in an ovariectomy (OVX)-induced obese mouse model. Scopolin inhibited adipocyte differentiation and lipid accumulation in the preadipocyte cells by suppressing the transcription of adipogenic-related factors, including adiponectin (Adipoq), peroxisome proliferator-activated receptor gamma (Pparg), lipoprotein lipase (Lpl), perilipin1 (Plin1), fatty acid-binding protein 4 (Fabp4), glucose transporter type 4 (Slc2a4), and CCAAT/enhancer-binding protein alpha (Cebpa). In OVX-induced obese mice, administration of scopolin promoted the reduction of body weight, total fat percentage, liver steatosis, and adipose cell size. In addition, the scopolin-treated OVX mice showed decreased serum levels of leptin and insulin. Taken together, these findings suggest that the use of scopolin prevented adipocyte differentiation and weight gain in vitro and in vivo, indicating that scopolin may be a potential bioactive compound for the treatment and prevention of obesity in humans.
Assuntos
Adipócitos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Obesidade , Ovariectomia , Transcrição Gênica/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/patologia , Animais , Feminino , Camundongos , Obesidade/metabolismo , Obesidade/patologia , Obesidade/prevenção & controleRESUMO
Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis.
Assuntos
Cumarínicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Glucosídeos/uso terapêutico , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Células 3T3 , Animais , Densidade Óssea/efeitos dos fármacos , Diferenciação Celular , Cumarínicos/farmacologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Glucosídeos/farmacologia , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacosRESUMO
Osteoporosis is a porous bone disease caused by bone density loss, which increases the risk of fractures. Cornus officinalis (CO) and Achyranthes japonica (AJ) have been used as traditional herbal medicine for various disorders in East Asia. Although the anti-osteoporotic effects of single extract of CO and AJ have already been reported, the synergistic effect of a combined mixture has not been studied. In this study, we investigated the effects of a CO and AJ herbal mixture on osteoporosis in in vitro and in vivo models. The results demonstrate that treatment with the CO and AJ mixture significantly promoted osteoblast differentiation of MC3T3-E1 mouse preosteoblasts through the upregulation of osteoblastic differentiation-associated genes such as alkaline phosphatase (Alpl), runt-related transcription factor 2 (Runx2), and bone gamma-carboxyglutamic acid-containing protein (Bglap), while the mixture significantly inhibited differentiation of osteoclasts isolated from primary-cultured mouse monocytes. In addition, oral administration of CO and AJ mixture significantly prevented bone mineral density loss and trabecular bone structures in an ovariectomy-induced osteoporotic mouse model. These results suggest that the combination treatment of CO and AJ mixture might be a beneficial therapy for osteoporosis.
RESUMO
Medicinal plants have been used worldwide as primary alternative healthcare supplements. Cornus officinalis (CO) and Ribes fasciculatum (RF) are traditional medicinal plants applied in East Asia to treat human diseases such as hepatitis, osteoporosis, oxidative stress and allergy. The aim of this study was to examine the anti-obesity effect of CO and RF on preadipocyte 3T3-L1 cells in vitro and high-fat diet (HFD)-induced obesity mice in vivo. Combination treatment of CO and RF in differentiated 3T3-L1 cells inhibited adipocyte differentiation through downregulation of adipogenesis-associated genes such as CCAAT/enhancer-binding protein alpha (Cebpa), fatty acid binding protein 4 (Fabp4), peroxisome proliferator-activated receptor gamma (Pparg) and sterol regulatory element binding protein (Srebp1). In vivo animal models showed that a mixture of CO and RF inhibited HFD-induced weight gain, resulting in decreased abdominal visceral fat tissues and fatty hepatocyte deposition. In addition, CO+RF treatment decreased HFD-induced adipogenesis-associated genes in abdominal white fat tissue. These results suggest that administration of a CO and RF mixture prevented adipocyte differentiation and lipid accumulation in preadipocyte cells and HFD-induced body weight in obesity mice. Therefore, combined therapy of CO and RF may be a protective therapeutic agent against obesity.
Assuntos
Adipogenia/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Cornus/química , PPAR gama/genética , Ribes/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Objective: Genetic factors play a critical role in pubertal progression; however, mutations associated with central precocious puberty (CPP) have been reported only in four genes: KISS1, KISS1R, DLK1, and MKRN3. This study aimed to identify novel, potentially pathogenic variants in patients with familial CPP via whole-exome sequencing (WES).Methods: WES analysis was applied in 28 patients (25 girls and three boys) belonging to 14 families, wherein all siblings were diagnosed with CPP. Data analysis aimed to select only very rare variants (minor allele frequency <1%). Nonsense, splice-site, and frameshift variants were considered the most ideal candidate variants. Additionally, non-synonymous missense variants predicted as being deleterious using in silico analysis tools were further considered.Results: The analysis of exome sequencing data resulted in the identification of rare mutations in two promising candidate genes (NOTCH2 and HERC2) in a family. Siblings with CPP exhibited two heterozygous missense mutations (p. Leu15Phe in NOTCH2 and p. Arg4081His in HERC2). Moreover, their parents without history of CPP had a missense variant in either NOTCH2 or HERC2.Conclusions: We identified new candidate genes with potential roles in pubertal development. Digenic inheritance of the two genetic mutations associated with the Notch signaling pathway may have a synergistic effect resulting in CPP.