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BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. RESULTS: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSCCMs. CONCLUSION: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications.
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Proteínas Quinasas Activadas por AMP , Cardiotoxicidad , Cirsium , Doxorrubicina , Miocitos Cardíacos , Extractos Vegetales , Animales , Humanos , Masculino , Ratones , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis/efectos de los fármacos , Cardiotoxicidad/tratamiento farmacológico , Línea Celular Tumoral , Cirsium/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, is widely used to treat various types of cancer; however, prolonged treatment induces cardiomyotoxicity. Although studies have been performed to overcome DOX-induced cardiotoxicity (DICT), no effective method is currently available. This study investigated the effects and potential mechanisms of Poncirus trifoliata aqueous extract (PTA) in DICT. Changes in cell survival were assessed in H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells. The C57BL/6 mice were treated with DOX to induce DICT in vivo, and alterations in electrophysiological characteristics, serum biomarkers, and histological features were examined. The PTA treatment inhibited DOX-induced decrease in H9c2 cell viability but did not affect the MDA-MB-231 cell viability. Additionally, the PTA restored the abnormal heart rate, R-R interval, QT interval, and ST segment and inhibited the decrease in serum cardiac and hepatic toxicity indicators in the DICT model. Moreover, the PTA administration protected against myocardial fibrosis and apoptosis in the heart tissue of mice with DICT. PTA treatment restored DOX-induced decrease in the expression of NAD(P)H dehydrogenase quinone acceptor oxidoreductase 1 in a PTA concentration-dependent manner. In conclusion, the PTA inhibitory effect on DICT is attributable to its antioxidant properties, suggesting the potential of PTA as a phytotherapeutic agent for DICT.
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Miocitos Cardíacos , Poncirus , Ratas , Ratones , Humanos , Animales , NAD/metabolismo , Poncirus/metabolismo , Regulación hacia Arriba , Estrés Oxidativo , Ratones Endogámicos C57BL , Doxorrubicina/toxicidad , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Oxidorreductasas/metabolismo , Quinonas/farmacologíaRESUMEN
Purpose: Pediatric palliative care is a rapidly developing multidisciplinary approach that supports children with life-limiting conditions and their families. However, there is limited evidence on how to effectively support bereaved parents and siblings. The purpose of this study is to explore the therapeutic impact of art therapy for bereaved families, in accordance with John Bowlby's four-stage theory of mourning. Methods: This single-case study employed the consensual qualitative research method. Art therapy records of bereaved families were reviewed individually, and records from one case were selected. Verbal statements made during the art therapy sessions and photocopies of the artworks were analyzed to understand the mourning process of the family. Results: A total of 113 statements and 12 artworks from 19 art therapy sessions were analyzed. As the art therapy progressed, each family member exhibited a pattern of engaging in more positive and healthy conversations in daily life, demonstrating the final stage of mourning reorganization and recovery. The family dynamics also revealed that they reconstructed their inner world and redefined the meaning of loss, which is the final stage of mourning. The art therapy provided a safe environment for the family, allowing them to fulfill their wishes and regain the strength needed for recovery. Conclusion: This study suggests that art therapy supports bereaved families in alleviating their psychological difficulties, engaging in a healthy mourning process, and functioning as members of society. Further research is needed to better understand the effect of art therapy as a bereavement support tool in pediatric palliative care.
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Medical and economic developments have allowed the human lifespan to extend and, as a result, the elderly population has increased worldwide. Osteoporosis is a common geriatric disease that has no symptoms and even a small impact can cause fractures in patients, leading to a serious deterioration in the quality of life. Osteoporosis treatment typically involves bisphosphonates and selective estrogen receptor modulators. However, these treatments are known to cause severe side effects, such as mandibular osteonecrosis and breast cancer, if used for an extended period of time. Therefore, it is essential to develop therapeutic agents from natural products that have fewer side effects. Gleditsiae fructus (GF) is a dried or immature fruit of Gleditsia sinensis Lam. and is composed of various triterpenoid saponins. The antiinflammatory effect of GF has been confirmed in various diseases, and since the antiinflammatory effect plays a major role in inhibiting osteoclast differentiation, GF was expected to be effective in osteoclast differentiation and menopausal osteoporosis; however, to the best of our knowledge, it has not yet been studied. Therefore, the present study was designed to examine the effect of GF on osteoclastogenesis and to investigate the mechanism underlying inhibition of osteoclast differentiation. The effects of GF on osteoclastogenesis were determined in vitro by tartrateresistant acid phosphatase (TRAP) staining, pit formation assays, filamentous actin (Factin) ring formation assays, western blotting and reverse transcriptionquantitative PCR analyses. Furthermore, the administration of GF to an animal model exhibiting menopausal osteoporosis allowed for the analysis of alterations in the bone microstructure of the femur using microCT. Additionally, assessments of femoral tissue and serum were conducted. The present study revealed that the administration of GF resulted in a reduction in osteoclast levels, Factin rings, TRAP activity and pit area. Furthermore, GF showed a dosedependent suppression of nuclear factor of activated Tcells cytoplasmic, cFos and other osteoclastogenesisrelated markers.
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Enfermedades Óseas Metabólicas , Osteoporosis , Preparaciones de Plantas , Animales , Femenino , Humanos , Actinas , Antiinflamatorios , Frutas/química , Osteogénesis , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Proteínas Proto-Oncogénicas c-fos/genética , Calidad de Vida , Preparaciones de Plantas/farmacología , Gleditsia/químicaRESUMEN
This study used various approaches and databases to evaluate the molecular processes and identify miRNA sponges and drugs associated with the pathophysiology of stroke caused by heavy metals and their combinations. We found that the genes ALB (albumin), IL1B (Interleukin-1ß), F2 (coagulation factor II), APOA1 (apolipoprotein A1), IL6 (Interleukin 6), and NOS2 (nitric oxide synthase 2) were linked to the development of strokes by 18 chemicals and a combination of cadmium, copper, and lead. These results may point to the significance of detoxification and neuroinflammation in stroke as well as the potential for targeting these genes in future stroke therapies. ALB and IL1B were the most common and significant genes. The "selenium micronutrient network," "vitamin B12 metabolism," and "folate metabolism" were shown to be the most significant pathways connected to the risk of stroke brought on by combined heavy metals. The two main cellular elements that may increase the risk of stroke caused by heavy metals were discovered to be "blood microparticle" and "endoplasmic reticulum lumen." We also observed an important chromosome (chr7p15.3), two transcription factors (NFKB2 [nuclear factor kappa B subunit 2] and NR1I2 [nuclear receptor subfamily 1 group, member 2]), and four microRNAs (hsa-miR-26a-5p, hsa-miR-9-5p, hsa-miR-124-3p, and hsa-miR-155-5p) associated with stroke caused by combined heavy metals. Additionally, for these miRNAs, we created and examined in silico microRNA sponge sequences. Triflusal and andrographolide have been identified as potential treatments for heavy metal-induced stroke. Taken together, heavy metals may be a significant contributor to the pathophysiology of stroke, but further investigation into the precise molecular pathways implicated in stroke pathophysiology is required to corroborate these findings.
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Metales Pesados , MicroARNs , Selenio , Oligoelementos , MicroARNs/genética , MicroARNs/metabolismo , Metales Pesados/toxicidad , CobreRESUMEN
BACKGROUND: We aimed to assess the interactions between mixed heavy metals, genes, and miRNAs implicated in depression development and to design and create miRNA sponges. METHODS: The key data-mining approaches in this study were the Comparative Toxicogenomics Database (CTD), MIENTURNET, GeneMania, Metascape, Webgestalt, miRNAsong, and Cytoscape software. RESULTS: A mixture of cadmium, lead, mercury, and arsenic was related to the development of depression. Even though the genes acquired from the heavy metals of depression studied were different, the "selenium micronutrient network", "vitamin B12 and folate metabolism", and "positive regulation of peptidyl-serine phosphorylation" pathways were highlighted. The heavy metal mixture altered the genes SOD1, IL6, PTGS2, PON1, BDNF, and ALB, highlighting the role of oxidative stress, pro-inflammatory cytokines, paraoxonase activity, neurotrophic factors, and antioxidants related to depression, as well as the possibility of targeting these genes in prospective depressive treatment. Chr1q31.1, five transcription factors (NR4A3, NR1H4, ATF3, CREB3L3, and NR1I3), the "endoplasmic reticulum lumen," "blood microparticle," and "myelin sheath", were found to be important chromosomal locations, transcription factors, and cellular parts linked to depression and affected by mixed heavy metals. Furthermore, we developed a network-based approach to detect significant genes, miRNA, pathways, and illnesses related to depression development. We also observed eight important miRNAs related to depression induced by mixed heavy metals (hsa-miR-16-5p, hsa-miR-132-3p, hsa-miR-1-3p, hsa-miR-204-5p, hsa-miR-206, hsa-miR-124-3p, hsa-miR-146a-5p, and hsa-miR-26a-5p). In addition, we created and evaluated miRNA sponge sequences for these miRNAs in silico. LIMITATIONS: A toxicogenomic design in silico was used. CONCLUSIONS: Our findings highlight the importance of oxidative stress, notably SOD1 and the selenium micronutrient network, in depression caused by heavy metal mixtures and provide additional insights into common molecular pathways implicated in depression pathogenesis.
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Arsénico , Mercurio , MicroARNs , Selenio , Humanos , Cadmio , Depresión , Estudios Prospectivos , Superóxido Dismutasa-1 , MicroARNs/genética , Factores de Transcripción , ArildialquilfosfatasaRESUMEN
Codonopsis lanceolata (C. lanceolata) has been commonly utilized as a therapeutic plant in traditional medicine. In this study, we examined variations in metabolites in C. lanceolata roots grown in different regions using ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Multivariate analysis showed that the metabolite profiles of plants grown in Hoengseong and Jeongseon were more similar to each other than to that of C. lanceolata grown in Jeju. Most primary metabolites were present at higher levels in C. lanceolata grown in Jeju. In contrast, C. lanceolata grown in Hoengseong and Jeongseon had high levels of secondary metabolites such as phenylpropanoids and triterpenoid saponins, respectively. In addition, the bioactive compound content and antioxidant capacity of in C. lanceolata grown in Hoengseong and Jeongseon were observed to be higher than those of C. lanceolata grown in Jeju. This study suggests that metabolomics is an effective approach to investigate the difference of metabolite profiling in C. lanceolata from different geographical origins, and is useful for evaluating its pharmacological potential.
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The inner shell of the chestnut (Castanea crenata) has long been used in Asia as a medicinal herb for improving digestion and blood circulation, and treating diarrhea. However, most chestnut shells are now treated as waste materials in industrial peeling processes. In this study, we examined the metabolite variation among major cultivars of C. crenata shells using mass spectrometry. Among five representative cultivars, Okkwang, Porotan, and Ishizuuchi had higher levels of bioactive compounds, such as ellagic acid derivatives, ellagitannins, flavonoids, and gallic acid derivatives. Their antioxidant capacity was positively correlated with their chemical composition. The byproducts (whole shells) from the industrial peeling process were re-evaluated in comparison with the inner shell, a rich source of phenolic compounds. The phenolic acids and flavonoid glucoside derivatives were significantly higher in the whole shells, whereas the levels of flavonoids were higher in the inner shells. In addition, the whole shell extracts significantly reduced cellular reactive oxygen species production compared to the inner shell extracts. This study demonstrated the different biochemical benefits of different C. crenata cultivars through metabolic profiling and suggests that the whole shell could be used as a functional ingredient, as it has the highest levels of bioactive products and antioxidant effects.
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Antioxidantes , Fagaceae , Antioxidantes/química , Nueces/química , Extractos Vegetales/química , Fenoles/análisis , Flavonoides/química , Fagaceae/químicaRESUMEN
BACKGROUND AND AIMS: There is growing evidence that thiamine supplementation could reverse non-communicable diseases such as diabetes and cardiovascular diseases. However, the role of thiamine in metabolic syndrome (MetS) remains unclear. We hypothesized whether an increased intake of thiamine diminishes the risk of MetS in the Korean population with various comorbidities. This study aimed to assess the association between thiamine intake and MetS among adults with comorbidities. METHODS: 57,523 eligible participants aged over 18 years between 2009 and 2019 were recruited to obtain data on sociodemographic characteristics, medical history, current medications, lifestyle, and family history. A 24-h recall was used to determine thiamine intake. Odds ratio (OR) for MetS was calculated for log2-transformed thiamine intake values, subsequently predicting the risk of MetS based on the marginal effect. RESULTS: The risk of MetS was significantly higher in subjects with comorbidities than in those without comorbidities. A doubling of daily thiamine intake was significantly associated with a decrease in MetS among adults with comorbidities by 7% (OR 0.93; 95%CI 0.89-0.97). CONCLUSIONS: The potential health benefits result from the intake of thiamine through an ordinary diet in the clinical management of MetS. Therefore, there is an ongoing need to look into these links between thiamine supplementation and MetS in well-characterized cohorts of participants with comorbidities.
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Síndrome Metabólico , Adulto , Pueblo Asiatico , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/prevención & control , Persona de Mediana Edad , República de Corea/epidemiología , Factores de Riesgo , TiaminaRESUMEN
BACKGROUND: We aim to identify the association between a mixture of vitamin B1, B2, and B3 intakes and depression. METHODS: Daily intake of vitamins was measured by a one-day 24 h recall. Multivariate logistic regression, weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were used. RESULTS: Of 9,848 adults included in the final analysis, 4.38% had depression. In the logistic regression model, daily vitamin B1 and B3 intakes were associated with depression, and significant trends were observed for these vitamin intake tertiles (p < 0.001). The WQS index was significantly associated with depression (OR = 0.24, 95% CI: 0.23-0.24). The gqcomp index also found a significant association between a mixture of vitamin B1 and B3 intake and depression (OR = 0.67, 95% CI: 0.44-0.98). Vitamin B1 intake was the most heavily weighed vitamin intake in this model. In BKMR analysis, the overall effects of vitamin B1 and B3 intake mixture were negatively associated with depression. Vitamin B1 and B3 intake showed negative trends and was observed as the most important factor associated with depression. The cutoff levels for B vitamin intake levels related to depression were reported. LIMITATIONS: A 24-hour recall and cross-sectional design were used. CONCLUSIONS: Given the rising prevalence of depressive symptoms in Korea, an increase in daily intake of vitamin B1 and/or B3 through regular diets may help to reduce the risk of depression. Therefore, there is an ongoing need to investigate these associations between B vitamin supplementation and depression, either separately or jointly, in well-characterized cohorts of depression population.
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Depresión , Tiamina , Adulto , Teorema de Bayes , Estudios Transversales , Depresión/epidemiología , Humanos , Vitamina B 12 , VitaminasRESUMEN
Atopic dermatitis (AD) is a chronic inflammatory allergic skin disease, characterized by pruritic and eczematous skin lesions. Lycopus lucidus Turcz (LLT) is a perennial herb that has been reported to have various biological properties, including effects on blood circulation, as well as antiinflammatory, antioxidant, antivascular inflammation and woundhealing effects. However, whether LLT improves dermatitis and the underlying mechanisms has yet to be determined. The aim of the present study was to determine whether LLT can improve 2,4dinitrochlorobenzene (DNCB)induced dermatitis and to verify the inhibitory effect of LLT on the expression of chemokines and proinflammatory cytokines in the HaCaT immortalized keratinocyte cell line. In addition, the antiinflammatory function of LLT in RAW264.7 mouse macrophages was investigated. In the DNCBinduced AD mouse model, LLT inhibited infiltration by mast cells, eosinophils and CD8+ cells in the dorsal skin tissue of AD mice, and suppressed the expression of IgE and IL6 in serum. In addition, LLT inhibited the phosphorylation of ERK and JNK, as well as NFκB in skin tissue. In the HaCaT cell model induced by TNFα/IFNγ, LLT inhibited the expression of thymus and activationregulated chemokine, granulocytemacrophage colonystimulating factor, monocyte chemoattractant protein1, TNFα and IL1ß, whilst inhibiting the phosphorylation of NFκB. In addition, in the lipopolysaccharideinduced RAW 264.7 cell inflammation model, LLT inhibited the expression of TNFα and IFNγ, the nuclear translocation of NFκB and the phosphorylation of ERK and JNK. These results suggested that LLT may be a promising candidate for the treatment of inflammatory dermatitis.
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Quimiocinas/metabolismo , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/metabolismo , Lycopus/química , Macrófagos/metabolismo , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Linfocitos T CD8-positivos/metabolismo , Dinitroclorobenceno , Modelos Animales de Enfermedad , Eosinófilos/metabolismo , Células HaCaT , Humanos , MAP Quinasa Quinasa 4/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Masculino , Mastocitos/metabolismo , Medicina Tradicional China , Ratones , Ratones Endogámicos BALB C , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Piel/patología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
OBJECTIVE: To determine the associations between metabolic syndrome (MetS) during menopause and serum heavy metal levels and vitamin and curry consumption. METHODS: A data set of 7,131 pre- and postmenopausal women aged ≥ 20âyears collected between 2009 and 2017 was used to obtain information on sociodemographic, lifestyles, family histories, food intakes, and serum heavy metal levels and MetS. Logistic regression was used to identify associations between the presence of MetS and risk factors and to predict risks of MetS based on marginal effects. RESULTS: Our results show that postmenopausal women had a higher risk of MetS than premenopausal women. During postmenopause elevations in the levels of serum cadmium by one unit increased the risk of MetS by 33% (OR 1.33; 95% CI, 1.03-1.72, Pâ=â0.028). Risks of MetS in pre- and postmenopausal women, when serum Hb levels increased by 1 unit increased 21% (OR 1.21; 95% CI, 1.09-1.33, Pâ<â0.001) and 26% (OR 1.26; 95% CI, 1.16-1.38, Pâ<â0.001), respectively. Furthermore, the risk of MetS risk in pre- and postmenopausal women was increased 2.49-fold and 2.79-fold by a 1% increase in HbA1c level (OR 2.49; 95% CI, 1.97-3.16, Pâ<â0.001) and (OR 2.79; 95% CI, 2.30-3.38, Pâ<â0.001), respectively. High curry consumption reduced the risk of MetS significantly more than low curry consumption (OR 0.60; 95% CI, 0.39-0.91, Pâ=â0.017) in premenopausal women. Furthermore, an increase in daily vitamin B2 intake by 1 mg reduced the risk of MetS by 45% (OR 0.55; 95% CI, 0.32-0.94, Pâ=â0.028) in postmenopausal women. CONCLUSION: Vitamin B2 and curry supplementation may protect against MetS. Further work is needed to reduce risk factors associated with heavy metals and determine the effects of vitamins and curry consumption on MetS during menopause.
Video Summary:http://links.lww.com/MENO/A791 .
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Síndrome Metabólico , Metales Pesados , Estudios Transversales , Femenino , Humanos , Menopausia , Síndrome Metabólico/epidemiología , República de Corea/epidemiología , Factores de Riesgo , VitaminasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae thunbergii Bulbus (FT), knowns as "Jeolpaemo ()" in Korean traditional medicine, is a perennial plant belonging to the Liliaceae family and has been used to treat symptoms such as cough, sputum formation, and purulent pneumonia. Owing to its effects of lowering heat, removing sputum, and reducing swelling, the plant has also been used as an external prescription medicine to treat inflammation. AIM OF THE STUDY: To analyze the anti-inflammatory effects of FT-ethanol extract (FT-Et) and FT-chloroform fraction extract (FT-Cl) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in vivo and in vitro. MATERIALS AND METHODS: The effect of FT-Et and FT-Cl on AD was observed using an AD-like skin lesion model induced by DNCB in vivo. HaCaT and RBL2H3 cells were used to determine the effects of FT-Et and FT-Cl in vitro. After inducing AD-like skin lesions in vivo, FT was topically applied to the skin lesion for 35 days. Epidermal thickness, dermal thickness, scratching behavior, infiltration of inflammatory cells, and expression of skin barrier proteins were measured. TARC, MDC, and IL-4 levels were analyzed using ELISA in HaCaT cells. Beta-hexosaminidase and IL-4 levels were measured in RBL2H3 cells. The expression of filaggrin (FLG), loricrin (LOR), involucrin (INV), and aquaporin-3(AQP-3) was measured by PCR. Phosphorylation of MAPKs was analyzed using Western blot technique. RESULTS: FT-Cl significantly reduced ear swelling, scratching behavior, SCORAD index, epidermal thickness, infiltration of inflammatory cells, and loss of skin barrier proteins. FT-Et inhibited the infiltration of mast cells and CD8+ cells and decreased the loss of skin barrier proteins. In TNF-α/IFN-γ-stimulated HaCaT cells, FT-Cl inhibited TRAC, MDC, and IL-4 expression and upregulated the expression of FLG, INV, and AQP-3, whereas FT-Et inhibited the expression of TRAC and MDC and increased the expression of FLG, INV, and AQP-3 at high concentrations. In RBL2H3, FT-Cl downregulated ß-hexosaminidase and IL-4 expression. In addition, FT-Cl inhibited the phosphorylation of ERK and p-38 in HaCaT and RBL2H3 cells. CONCLUSIONS: Collectively, FT-Cl showed better effect than FT-Et in vivo and in vitro. These results suggest that a specific component present in FT-Cl acted against AD. Future research should focus on the analysis of components contained in FT-Cl and the anti-inflammatory effects of the active ingredient.
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Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Dinitroclorobenceno/toxicidad , Liliaceae/química , Fitoterapia , Extractos Vegetales/farmacología , Animales , Línea Celular , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patologíaRESUMEN
Lycii radicis cortex (LRC) has been used to regulate high blood pressure, body temperature, pain and bone disorders in East Asia. Glucocorticoids (GCs), also known as steroids, are potent immunity regulators widely used in the treatment of inflammatory diseases. However, despite their effectiveness, GC usage is strictly controlled due to severe sideeffects, such as osteoporosis. However, further research is required as to date, at least to the best of our knowledge, there is no appropriate model to overcome secondary osteoporosis as a sideeffect of GC use. Thus, the aim of the present study was to establish an experimental model of osteoporosis induced by GC. Furthermore, the present study aimed to establish the research methodology for medical evaluations of the effectiveness and sideeffects of GCs. A secondary osteoporosis animal model was established, and the animals were divided into two groups as follows: The allergic contact dermatitis (ACD)induced group and the nonACDinduced group. In the ACDinduced group, a GC topical application group was compared with a GC subcutaneous injection group. The results revealed that the presence of ACD affected the induction of GCmediated osteoporosis. Therefore, the group exhibiting induced ACD that was treated with a topical application of GC was selected for examining the sideeffects of GCs. The effects of LRC on secondary osteoporosis were confirmed in vivo and in vitro. The results indicated that LRC regulated dexamethasoneinduced osteoblast apoptotic markers, including caspase6, caspase9, Xlinked inhibitor of apoptosis, apoptosis inhibitor 1 and apoptosis inhibitor 2, and increased the expression of osteoblast differentiationrelated genes, such as Runtrelated transcription factor 2 and bone morphogenetic protein 2 in the MC3T3E1 cell line. LRC also significantly reduced GCinduced osteoporosis and exerted antiinflammatory effects in vivo. In addition, LRC inhibited the reduction of calbindinD28k in the kidney. Overall, the results of the present study suggest that the use of LRC alleviates GCinduced secondary osteoporosis.
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Proteína Morfogenética Ósea 2/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Osteoporosis/prevención & control , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteína Morfogenética Ósea 2/metabolismo , Calbindinas/genética , Calbindinas/metabolismo , Calcio/metabolismo , Línea Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/genética , Dermatitis Alérgica por Contacto/prevención & control , Dinitroclorobenceno/toxicidad , Modelos Animales de Enfermedad , Regulación hacia Abajo/genética , Medicamentos Herbarios Chinos/análisis , Cromatografía de Gases y Espectrometría de Masas , Glucocorticoides , Humanos , Masculino , Ratones Endogámicos ICR , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoporosis/inducido químicamente , Osteoporosis/genéticaRESUMEN
The present study aimed to determine thiamine intake levels and the association between thiamine intake, diabetes, cardiovascular diseases and mental health. Participants were interviewed to obtain data on socio-demographic characteristics, lifestyle, current medications, medical and family history. The daily intake of thiamine was assessed by a 24-h recall. The mean age of the 34 700 study subjects was 42â 9 years (sd 22â 8, min-max: 1-80) and 19 342 (55â 7 %) were women. The levels of thiamine intake were 1â 126 mg (2016), 1â 115 mg (2017) and 1â 087 mg (2018) for women, which were equal to or only slightly above the recommended intake of 1â 10 mg/d for women. The levels of thiamine intake from 2014-15 and 2016-18 significantly decreased. The estimated percentage of insufficient thiamine intake was 37â 8 % (95 % CI 37â 3, 38â 4). Multivariable regression analysis adjusted for potential confounders showed that thiamine intake was critically associated with lower risks of hypertension, MI or angina, type 2 diabetes, depression and dyslipidemia. The daily thiamine intake from food can reversal the risks of hypertension (OR 0â 95; 95 % CI 0â 90, 0â 99), MI or angina (OR 0â 84; 95 % CI 0â 74, 0â 95), type 2 diabetes (OR 0â 86; 95 % CI 0â 81, 0â 93), depression (OR 0â 90; 95 % CI 0â 83, 0â 97) and dyslipidemia (OR 0â 90; 95 % CI 0â 86, 0â 95), respectively. Further works are needed to identify the effects of thiamine and non-communicable diseases (NCDs) and mental health. A preventive thiamine supplementation strategy should be adopted to target NCDs and mental health and risk factors associated with thiamine deficiency. The optimisation of NCD control and mental health protection is also a vital integral part of Korea's public health system.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Dieta , Tiamina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Niño , Preescolar , Estudios Transversales , Depresión/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Dislipidemias/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Lactante , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Adulto JovenRESUMEN
Bone homeostasis is maintained by osteoclasts that absorb bone and osteoblasts that form bone tissue. Menopausal osteoporosis is a disease associated with aging and hormonal changes due to menopause causing abnormal activation of osteoclasts, resulting in a decrease in bone density. Existing treatments for osteoporosis have been reported to have serious side effects, such as jawbone necrosis and breast and uterine cancer; therefore, their use by patients is decreasing, whilst studies focusing on alternative treatments are increasingly popular. Solanum nigrum Line (SL) has been used as a medicinal plant that possesses several pharmacological effects, such as antiinflammatory and hepatotoxic protective effects. To the best of our knowledge, however, its effects on osteoporosis and osteoclasts have not been demonstrated previously. In the present study, the antiosteoporotic effect of SL was investigated using a postmenopausal model of osteoporosis in which SpragueDawley rat ovaries were extracted. In addition, the inhibitory effects on osteoclast differentiation and function of SL was confirmed using an osteoclast model treated with receptor activator of NFκB ligand (RANKL) on murine RAW 264.7 macrophages. In vivo experiments showed that SL reduced the decrease in bone mineral density and improved changes in the morphological index of bone microstructure, such as trabecular number and separation. In addition, the number of tartrate resistant acid phosphatasepositive cells in the femur and the expression levels of nuclear factor of activated Tcells cytoplasmic 1 (NFATc1) and cathepsin K protein were inhibited. In vitro, SL suppressed RANKLinduced osteoclast differentiation and bone resorption ability; this was mediated by NFATc1/cFos, a key transcription factor involved in osteoclast differentiation, ultimately inhibiting expression of various osteoclastassociated genes. These experimental results show that SL may be an alternative treatment for osteoporosis caused by abnormal activation of osteoclasts in the future.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Densidad Ósea/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/prevención & control , Extractos Vegetales/farmacología , Solanum nigrum/química , Actinas/metabolismo , Administración Oral , Animales , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/química , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Hueso Esponjoso/efectos de los fármacos , Hueso Esponjoso/metabolismo , Catepsina K/metabolismo , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Osteoblastos/efectos de los fármacos , Osteoclastos/citología , Osteoclastos/metabolismo , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/patología , Ovariectomía/efectos adversos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/metabolismo , Células RAW 264.7 , Ratas Sprague-Dawley , Factores de Transcripción/metabolismoRESUMEN
Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density (BMD), which results in an increased risk of fracture. Melandrium firmum (Siebold & Zucc.) Rohrbach (MFR), 'Wangbulryuhaeng' in Korean, is the dried aerial portion of Melandrii Herba Rohrbach, which is a member of the Caryophyllaceae family and has been used to treat several gynecological conditions as a traditional medicine. However, to the best of our knowledge, the effect of MFR on osteoclast differentiation and osteoporosis has not been assessed. To evaluate the effects of MFR on osteoclast differentiation, tartrateresistant acid phosphatase staining, actin ring formation and bone resorption assays were used. Additionally, receptor activator of nuclear factorκB ligandinduced expression of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) and cFos were measured using western blotting and reverse transcriptionPCR. The expression levels of osteoclastrelated genes were also examined. To further investigate the antiosteoporotic effects of MFR in vivo, an ovariectomized (OVX) rat model of menopausal osteoporosis was established. Subsequently, the femoral head was scanned using microcomputed tomography. The results revealed that MFR suppressed osteoclast differentiation, formation and function. Specifically, MFR reduced the expression levels of osteoclastrelated genes by downregulating transcription factors, such as NFATc1 and cFos. Consistent with the in vitro results, administration of MFR water extract to OVX rats reduced BMD loss, and reduced the expression levels of NFATc1 and cathepsin K in the femoral head. In conclusion, MFR may contribute to alleviate osteoporosislike symptoms. These results suggested that MFR may exhibit potential for the prevention and treatment of postmenopausal osteoporosis.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Osteoclastos/efectos de los fármacos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Silene/química , Actinas/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/toxicidad , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Calcificación Fisiológica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/patología , Ovariectomía/efectos adversos , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/toxicidad , Ratas Sprague-Dawley , Factor 6 Asociado a Receptor de TNF/metabolismo , Fosfatasa Ácida Tartratorresistente/metabolismoRESUMEN
Osteoporosis is characterized by a decrease in bone microarchitecture with an increased risk of fracture. Long-term use of primary treatments, such as bisphosphonates and selective estrogen receptor modulators, results in various side effects. Therefore, it is necessary to develop alternative therapeutics derived from natural products. Crataegus pinnatifida Bunge (CPB) is a dried fruit used to treat diet-induced indigestion, loss of appetite, and diarrhea. However, research into the effects of CPB on osteoclast differentiation and osteoporosis is still limited. In vitro experiments were conducted to examine the effects of CPB on RANKL-induced osteoclast differentiation in RAW 264.7 cells. Moreover, we investigated the effects of CPB on bone loss in the femoral head in an ovariectomized rat model using microcomputed tomography. In vitro, tartrate-resistant acid phosphatase (TRAP) staining results showed the number of TRAP-positive cells, and TRAP activity significantly decreased following CPB treatment. CPB also significantly decreased pit formation. Furthermore, CPB inhibited osteoclast differentiation by suppressing NFATc1, and c-Fos expression. Moreover, CPB treatment inhibited osteoclast-related genes, such as Nfatc1, Ca2, Acp5, mmp9, CtsK, Oscar, and Atp6v0d2. In vivo, bone mineral density and structure model index were improved by administration of CPB. In conclusion, CPB prevented osteoclast differentiation in vitro and prevented bone loss in vivo. Therefore, CPB could be a potential alternative medicine for bone diseases, such as osteoporosis.
RESUMEN
Cone of Pinus densiflora (CP), or Korean red pinecone, is a cluster of Pinus densiflora fruit. CP has also been verified in several studies to have anti-oxidation, anti-fungal, anti-bacterial, and anti-melanogenic effects. However, anti-inflammatory effects have not yet been confirmed in the inflammatory responses of pinecones to allergic contact dermatitis. The purpose of this study is to prove the anti-inflammatory effect of CP on allergic contact dermatitis (ACD) in vitro and in vivo. CP inhibited the expression of TSLP, TARC, MCP-1, TNF-α, and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells and MCP-1, GM-CSF, TNF-α, IL-6, and IL-8 in PMACI (phorbol-12-myristate-13-acetate plus A23187)-stimulated HMC-1 cells. CP inhibited the phosphorylation of mitogen-activated protein kinase (MAPKs), as well as the translocation of NF-κB on TNF-α/IFN-γ stimulated in HaCaT cells. In vivo, CP decreased major symptoms of ACD, levels of IL-6 in skin lesion, thickening of the epidermis and dermis, infiltration of eosinophils and mast cells, and the infiltration of CD4+ T cells and CD8+ T cells. This result suggests that CP represents a potential alternative medicine to ACD for diseases such as chronic skin inflammation.
Asunto(s)
Antiinflamatorios/farmacología , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Pinus/química , Extractos Vegetales/farmacología , Animales , Transporte Biológico/efectos de los fármacos , Dermatitis Alérgica por Contacto/etiología , Dinitroclorobenceno , Modelos Animales de Enfermedad , Eosinófilos/efectos de los fármacos , Epidermis/efectos de los fármacos , Células HaCaT , Humanos , Interferón gamma/metabolismo , Mastocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cervical cancer is the fourth most common cancer among women worldwide. Though several natural products have been reported regarding their efficacies against cervical cancer, there has been no review article that categorized them according to their anti-cancer mechanisms. In this study, anti-cancerous natural products against cervical cancer were collected using Pubmed (including Medline) and google scholar, published within three years. Their mechanisms were categorized as induction of apoptosis, inhibition of angiogenesis, inhibition of metastasis, reduction of resistance, and regulation of miRNAs. A total of 64 natural products suppressed cervical cancer. Among them, Penicillium sclerotiorum extracts from Cassia fistula L., ethanol extracts from Bauhinia variegate candida, thymoquinone obtained from Nigella sativa, lipid-soluble extracts of Pinellia pedatisecta Schott., and 1'S-1'-acetoxychavicol extracted from Alpinia conchigera have been shown to have multi-effects against cervical cancer. In conclusion, natural products could be attractive candidates for novel anti-cancer drugs.