RESUMEN
Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE's anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Extractos Vegetales/uso terapéutico , Rosa , Sinoviocitos/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Artritis Reumatoide/metabolismo , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/farmacología , Humanos , Interleucina-6 , Lonicera , Fitoterapia , Cultivo Primario de Células , Ratas , Factor de Transcripción STAT3/metabolismo , Líquido Sinovial/metabolismoRESUMEN
BACKGROUND: Receptor activator of NF-κB ligand (RANKL) facilitates differentiation of osteoclast precursors into osteoclasts, resulting in bone erosion in rheumatoid arthritis (RA) patients. Fibroblast-like synoviocytes (FLS) are the main cells for producing RANKL. Signal transducer and activator of transcription 3 (STAT3) signaling is activated in FLS of RA patients (RA-FLS), which has been linked to RANKL production. A two-herb formula (RL) comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos is traditionally used for treating RA in China. We have found that a standardized ethanolic extract of RL (RLE for short) alleviates bone erosion in collagen-induced arthritis (CIA) rats. PURPOSE: This study aimed to determine whether RLE inhibits RANKL production and osteoclastogenesis in cell and rat models, and to explore the involvement of the STAT3 pathway in this inhibition. STUDY DESIGN AND METHODS: A CIA rat model, interleukin-6/soluble interleukin-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS and a co-culture system (IL-6/sIL-6R-stimulated RA-FLS/peripheral blood mononuclear cells) were used to evaluate the effects of RLE. Micro-computed tomography analysis was used to observe bone erosion in CIA rats. Tartrate-resistant acid phosphatase staining was used to evaluate osteoclastogenesis. Western blotting and ELISA assays were employed to examine protein levels. RT-qPCR was used to detect mRNA levels. STAT3-over-activated RA-FLS were used to investigate the involvement of STAT3 signaling in the anti-osteoclastogenic effects of RLE. RESULTS: RLE alleviated bone erosion in joints of CIA rats. In both synovial tissues of CIA rats and IL-6/sIL-6R-stimulated RA-FLS, RLE downregulated the protein level of RANKL. In the co-culture system, RLE significantly and dose-dependently inhibited IL-6/sIL-6R-induced osteoclastogenesis. Mechanistic studies revealed that RLE lowered the protein level of phospho-STAT3 (Tyr705) in synovial tissues of CIA rats. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited the activation/phosphorylation of a STAT3 upstream kinase Janus kinase 2 (Tyr1007/1008) and STAT3 (Tyr705), decreased the nuclear localization of STAT3, lowered mRNA levels of STAT3-transcriptionally regulated genes IL-1ß and TNF-α. RLE's inhibitory effects on RANKL production in RA-FLS gradually decreased when IL-6/sIL-6R doses increased. Over-activation of STAT3 diminished the inhibitory effects of RLE on RANKL production in IL-6/sIL-6R-stimulated RA-FLS, and attenuated the anti-osteoclastogenic effects of RLE in the co-culture system. CONCLUSION: We, for the first time, demonstrated that suppressing STAT3 signaling contributes to the inhibition of RANKL production and osteoclastogenesis, and thereby supports the mechanisms responsible for the reduction in bone erosion in RLE-treated CIA rats. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug, and supports the notion that targeting STAT3 signaling is a viable strategy for managing bone erosion.
RESUMEN
ETHNOPHARMACOLOGY RELEVANCE: Si-Jun-Zi-Tang (SJZT) is a traditional Chinese medicine formula used to treat chronic and debilitating diseases including melanoma. SJZT-based therapies have achieved good clinical outcomes in melanoma management. However, the pharmacological basis of SJZT for its clinical use in melanoma treatment is not fully understood. AIM OF THE STUDY: To investigate the anti-melanoma effects and mechanism of action of an ethanolic extract of SJZT. MATERIALS AND METHODS: SJZT was extracted using 50% ethanol. A murine B16 melanoma-bearing mouse model was employed to investigate the anti-melanoma effects of SJZT. microRNA (miRNA) and mRNA levels were examined by RT-qPCR, and protein levels were measured by Western blotting. RESULTS: SJZT significantly inhibited B16 tumor growth in mice. Mechanistic investigations revealed that SJZT elevated miR-34b (a tumor suppressing miRNA), and lowered c-Met (a miR-34b target gene) and ß-catenin (a downstream molecule of c-Met signaling) expression levels in the B16 tumors. CONCLUSIONS: In this study we found, for the first time, that SJZT exerts anti-melanoma effects and regulates the miR-34b/c-Met/ß-catenin pathway in a melanoma mouse model. Our findings provide pharmacological justifications for the clinical use of SJZT in treating melanoma.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Melanoma Experimental/tratamiento farmacológico , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , beta Catenina/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Masculino , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones Endogámicos C57BL , MicroARNs/genética , Proteínas Proto-Oncogénicas c-met/genética , Transducción de Señal , Carga Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: Chrysoeriol is a flavone found in diverse dietary and medicinal herbs such as Lonicerae Japonicae Flos (the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.). These herbs are commonly used for treating inflammatory diseases. Herbal extracts containing chrysoeriol have been shown to have anti-inflammatory effects and inhibit nuclear factor-kappa B (NF-κB) signaling. Some of these extracts can inhibit signal transducers and activators of transcription 3 (STAT3) signaling in cancer cells. PURPOSE: This study aimed to determine whether chrysoeriol has anti-inflammatory effects and whether NF-κB and STAT3 pathways are involved in the effects. STUDY DESIGN AND METHODS: A TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model and LPS-stimulated RAW264.7 cells were used to evaluate the effects of chrysoeriol. Griess reagent was used to measure the production of nitric oxide (NO). Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels. RT-qPCR analyses were used to detect mRNA levels. Haematoxylin and eosin (H&E) staining was employed to examine the pathological conditions in animal tissues. RESULTS: In the mouse model, chrysoeriol ameliorated acute skin inflammation, evidenced by reduced ear thickness, ear weight and number of inflammatory cells in inflamed ear tissues. The compound lowered protein levels of phospho-p65 (Ser536), phospho-STAT3 (Tyr705), inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in mouse swollen ears. In LPS-stimulated RAW264.7 cells, chrysoeriol also lowered levels of these proteins. In addition, chrysoeriol decreased the production of NO and prostaglandin E2; inhibited the phosphorylation of inhibitor of κB (Ser32), p65 (Ser536) and Janus kinase 2 (Tyr1007/1008); decreased nuclear localization of p50, p65 and STAT3; and down-regulated mRNA levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α that are transcriptionally regulated by NF-κB and STAT3 in the cell model. CONCLUSION: We for the first time demonstrated that chrysoeriol ameliorates TPA-induced ear edema in mice, and that inhibition of JAK2/STAT3 and IκB/p65 NF-κB pathways are involved in the anti-inflammatory effects of chrysoeriol. This study provides chemical and pharmacological justifications for the use of chrysoeriol-containing herbs in treating inflammatory diseases, and provides pharmacological groundwork for developing chrysoeriol as a novel anti-inflammatory agent.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Erupciones por Medicamentos/tratamiento farmacológico , Flavonas/farmacología , FN-kappa B/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Erupciones por Medicamentos/metabolismo , Erupciones por Medicamentos/patología , Regulación de la Expresión Génica , Proteínas I-kappa B/metabolismo , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos ICR , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/toxicidadRESUMEN
AIMS: Melanoma is lethal. Constitutively active signal transducer and activator of transcription 3 (STAT3) has been proposed as a pathogenic factor and a therapeutic target of melanoma. Brevilin A, a sesquiterpene lactone isolated from Centipeda minima (L.) A. Br. et Aschers., has been shown to exert antineoplastic effects and inhibit the STAT3 pathway in nasopharyngeal, lung, prostate and breast cancer cells. This study aimed to determine whether brevilin A has anti-melanoma effects, and whether STAT3 signaling is involved in the effects. MAIN METHODS: A mouse A375 xenograft model, as well as A375 and A2058 cell models were employed to assess the in vivo and in vitro anti-melanoma effects of brevilin A. A375 cells stably expressing STAT3C, a constitutively active STAT3 mutant, were used to determine the role of STAT3 signaling in brevilin A's anti-melanoma effects. KEY FINDINGS: Intraperitoneal injection of brevilin A dose-dependently inhibited melanoma growth in mice and suppressed STAT3 phosphorylation in the tumors. In cultured cells, brevilin A reduced cell viability, induced apoptosis, suppressed migration and invasion, decreased protein levels of phospho-JAK2 (Y1007/1008) and phospho-STAT3 (Tyr705), and restrained STAT3 nuclear localization. STAT3 over-activation diminished brevilin A's effects on cell viability and migration. Collectively, brevilin A exerts anti-melanoma effects and these effects are at least in part attributed to the inhibition of the JAK2/STAT3 pathway. SIGNIFICANCE: Our findings provide a pharmacological basis for developing brevilin A as a new phytotherapeutic agent against melanoma.
Asunto(s)
Crotonatos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Janus Quinasa 2/metabolismo , Melanoma/tratamiento farmacológico , Factor de Transcripción STAT3/metabolismo , Sesquiterpenos/farmacología , Animales , Apoptosis , Movimiento Celular , Proliferación Celular , Humanos , Janus Quinasa 2/genética , Masculino , Melanoma/metabolismo , Melanoma/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación , Factor de Transcripción STAT3/genética , Transducción de Señal , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Metastasized melanoma is extremely difficult to treat. Activation of C-C chemokine receptor type 7 (CCR7) has been linked to melanoma metastasis. CCR7 can be directly regulated by miR-let-7. We have previously shown that an ethanolic extract of an herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos (SLE) inhibits melanoma cell migration and invasion. PURPOSE: In this study, we determined whether SLE suppresses melanoma metastasis, and whether regulation of miR-let-7a/f-CCR7 signaling is involved in the effect. STUDY DESIGN AND METHODS: Small RNA sequencing was conducted to compare miRNA expression profiles of B16F10 tumors dissected from SLE-treated or untreated mice. Western blot and RT-qPCR analyses were employed to examine protein and miRNA levels, respectively. A B16F10 melanoma lung metastasis mouse model was used to evaluate the effects of SLE on melanoma metastasis. MiR-let-7a/f-knockdown and CCR7-overexpression cell models were used to investigate the involvement of miR-let-7a/f-CCR7 signaling in the anti-metastatic effects of SLE. RESULTS: It was found that SLE upregulated levels of miR-let-7a/f in B16F10 melanoma tissues. SLE significantly elevated levels of miR-let-7a/f, lowered the protein level of CCR7, inhibited the phosphorylation of CCR7 downstream molecules p38 and JNK in B16F10 and A375 melanoma cells. SLE inhibited B16F10 melanoma lung metastasis in mice. SLE upregulated levels of miR-let-7a/f, and lowered protein levels of CCR7, MMP-2, MMP-9, phospho-p38 (Thr180/Tyr182) and phospho-JNK (Thr183/Tyr185) in melanoma-invaded lung tissues. Knockdown of miR-let-7a/f diminished the effects of SLE on CCR7 signaling in, and invasion of, melanoma cells. Overexpression of CCR7 lessened the effects of SLE in inhibiting the phosphorylation of p38 and JNK in, and the invasive capability of, melanoma cells. CONCLUSION: We for the first time demonstrated that SLE inhibits melanoma metastasis in mice, and that regulation of the miR-let-7a/f-CCR7 pathway contributes to the anti-metastatic mechanisms of SLE. These findings provide a pharmacological basis for developing SLE as a modern agent for treating metastatic melanoma. Additionally and importantly, this study suggests that regulating the miR-let-7a/f-CCR7 pathway is a novel strategy for controlling melanoma metastasis.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Melanoma Experimental/tratamiento farmacológico , MicroARNs/metabolismo , Extractos Vegetales/farmacología , Receptores CCR7/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Lonicera , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Melanoma Experimental/patología , Ratones Endogámicos C57BL , Extractos Vegetales/química , Receptores CCR7/genética , Sophora/químicaRESUMEN
The aim of this paper was to investigate the effect of SIRT1/TSC_2 signal axis on leukemia stem cell senescence induced by ginsenoside Rg_1. CD34~+CD38~- leukemia stem cells(CD34~+CD38~-LSCs) was isolated by magnetic cell sorting(MACS) and divided into two groups. The control group cells were routinely cultured, 40 µmol·L~(-1) ginsenoside Rg_1 was added to the control group for co-culture in Rg_1 group. The effect of Rg_l to induce CD34~+CD38~-LSCs senescence were evaluated by senescence-associated ß-Galactosidase(SA-ß-Gal) staining, cell cycle assay, CCK-8 and Colony-Assay. The expression of senescence associated SIRT1, TSC_2 mRNA and protein was examined by Real-time fluorescence quantitative PCR(FQ-PCR) and Western blot. The results showed that the CD34~+CD38~-LSCs could effectively be isolated by MACS, and the purity of CD34~+CD38~-LSCs is up to(95.86±3.04)%. Compared with the control group, the percentage of positive cells expressed SA-ß-Gal in the Rg_1 group is increased, the senescence morphological changes were observed in the CD34~+CD38~-LSCs in the Rg_1 group. The proliferation inhibition rate and the number of cells entered G_0/G_1 phase in the Rg_1 group were increased, but the colony-formed ability was decreased, Rg_1 could significantly inhibit the proliferation and self-renewal ability of CD34~+CD38~-LSCs. The expression of SIRT1 and TSC_2 mRNA and protein were down regulated in the Rg_1 group compared with the control group. Our research implied that Rg_1 may induce the senescence of CD34~+CD38~-LSCs and SIRT1/TSC_2 signal axis plays a significant role in this process.
Asunto(s)
Senescencia Celular/efectos de los fármacos , Ginsenósidos/farmacología , Leucemia Mieloide Aguda , Células Madre Neoplásicas/efectos de los fármacos , Transducción de Señal , Sirtuina 1/metabolismo , Proteína 2 del Complejo de la Esclerosis Tuberosa/metabolismo , Humanos , Células Tumorales CultivadasRESUMEN
A traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was used for treating melanoma in ancient China. We have previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects and suppresses STAT3 signaling in vitro and in vivo. STAT3 has been linked to the development of melanoma immunosuppressive microenvironment. In this work, we investigated whether SLE inhibits melanoma growth by reprogramming the tumor microenvironment in mouse and co-culture cell models. In B16F10 melanoma-bearing mice, we found that intragastric administration of SLE (1.2 g/kg) dramatically inhibited tumor growth. This observation was associated with the downregulation of protein levels of phospho-STAT3 (Tyr 705) and STAT3-regulated immunosuppressive cytokines, and mRNA levels of STAT3-targeted genes involved in tumor growth and immune evasion. We also observed increased Th, Tc and dendritic cells in the melanomas and spleens in SLE-treated mice compared to that in control mice. In a co-culture system composed of B16F10 cells and mouse primary splenic lymphocytes, it was found that SLE not only inhibited STAT3 activation in B16F10 cells, but also downregulated mRNA levels of STAT3-targeted genes in the splenic lymphocytes. In this co-culture setting, SLE decreased the levels of STAT3-regulated immunosuppressive cytokines, increased the percentages of Th, Tc and dendritic cells as well. Furthermore, effects of SLE on STAT3 phosphorylation, cytokine levels and immune cell subtype percentages were significantly weaker in the B16STAT3C cells (stable cells harboring a constitutively active STAT3 variant STAT3C)/splenic lymphocytes co-culture system than in the B16V cells (cells stably transfected with the empty vector)/splenic lymphocytes co-culture system, indicating that STAT3 over-activation diminishes SLE's effects. In summary, our findings indicate that reprograming the immune microenvironment, partially mediated by inhibiting STAT3 signaling, contributes to the anti-melanoma mechanisms of SLE. This study provides further pharmacological groundwork for developing SLE as a modern agent for melanoma prevention/treatment, and supports the notion that reprograming immunosuppressive microenvironment is a viable anti-melanoma strategy.
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Antineoplásicos/farmacología , Melanoma Experimental/inmunología , Extractos Vegetales/farmacología , Factor de Transcripción STAT3/inmunología , Neoplasias Cutáneas/inmunología , Sophora , Microambiente Tumoral/efectos de los fármacos , Animales , Antineoplásicos/uso terapéutico , Técnicas de Cocultivo , Flores , Lonicera , Linfocitos , Masculino , Medicina Tradicional China , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Ratones Endogámicos C57BL , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/inmunología , Neovascularización Patológica/patología , Extractos Vegetales/uso terapéutico , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Microambiente Tumoral/inmunologíaRESUMEN
OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mLâ¢min-1â¢1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mLâ¢min-1â¢1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mLâ¢min-1â¢1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).
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Medicamentos Herbarios Chinos/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Adulto , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de SaludRESUMEN
This study aimed to compare the influence between Cimicifuga foetida extract and different hormone therapies on breast pain in early postmenopausal women. A prospective, randomized, controlled clinical trial was conducted among 96 early postmenopausal women. Participants were randomly assigned to three groups: group A received 1 mg/day estradiol valerate plus 4 mg/day medroxyprogesterone acetate on days 19-30; group B received 1 mg/day estradiol valerate plus 100 mg/day micronized progesterone on days 19-30; group C received C. foetida extract, 1talet (contains 33.3 mg extract), t.i.d. Breast pain diary and numerical rating scale was used to access the breast pain. For 6 months' treatment, the total incidence of breast pain in group A and B was significantly higher than that in group C (p < .05). The duration (day) of breast pain in each month decreased over time in group A and B while it was continuously low and without significant change in group C (p > .05). The intensity of breast pain was mild in most participants and did not differ among three groups (p > .05). During treatment of early postmenopausal women with C. foetida extract for 6 months, the incidence and duration of breast pain were lower than upon treatment with E2 plus cyclic MPA or m-P and did not change over time.
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Cimicifuga , Estradiol/uso terapéutico , Estrógenos/uso terapéutico , Mastodinia/tratamiento farmacológico , Acetato de Medroxiprogesterona/uso terapéutico , Extractos Vegetales/uso terapéutico , Posmenopausia , Progestinas/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Fitoterapia , Progesterona/uso terapéutico , Resultado del TratamientoRESUMEN
In this study, a novel glycoprotein with molecular weight of 22.0â¯kDa was isolated and purified from Fupenzi (a kind of unripe fruits of Rubus chingii Hu.) by means of anion-exchange (DEAE-52) and gel column chromatography (Sephadex G-100). The glycoprotein consists of a carbohydrate component (81.42⯱â¯0.96%) and protein component (14.56⯱â¯1.21%). The anti-aging capability was measured in dgalactose induced aging mice model, and the experimental data showed that the glycoprotein could significantly inhibit the formation of malondialdehyde (MDA) and raise the activities of superoxide dismutase (SOD) and catalase (CAT) in mice kidney and serum. The reverse transcription polymerase chain reaction (RT-PCR), quantitative real time polymerase chain reaction (Q-PCR) and western blots showed that the glycoprotein significantly increase the expression of anti-aging gene klotho in mice kidney. The results suggested that the anti-aging mechanism of FPZ might be achieved by improving the klotho gene expression and repairing the renal function. This study will provide a scientific basis for the view of traditional Chinese medicine that tonifying kidney is the basic way of anti-aging. In addition, the glycoprotein could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases in humans.
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Envejecimiento/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Glucuronidasa/metabolismo , Glicoproteínas/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Rubus/química , Animales , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Riñón/anatomía & histología , Proteínas Klotho , Malondialdehído/metabolismo , Ratones , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
With the growing population, aging, extended lifespans and anti-aging have become popular areas of research in the life and social sciences. With increasing age, the structure and function of the testes, the spermatogenetic and androgenproducing organ in the male reproductive system, gradually declines. Ginsenoside Rg1 is an extract of Panax ginseng in traditional Chinese medicine. The extract facilitates antiaging through its antiinflammatory and antioxidant properties. However, it has not been reported whether ginsenoside Rg1 delays testicular aging. The present study established Dgalactose (Dgal)induced aging mouse models to examine the protective effects of ginsenoside Rg1 on the structure and function of the testes, and the underlying mechanism. A total of 60 healthy specific pathogenfree male C57BL/6 mice were randomly divided into four groups: Control group; Rg1 group; Dgal + Rg1 group; and Dgal group. The tissues of the mice were used for further experiments. The present study further investigated the effects of Rg1 on the volume of serum testosterone, the testicular index, testicular microscopic structures, the senescence of spermatogenetic cells, the apoptosis of spermatogenetic cells, the activity of the antioxidant enzymes, the levels of inflammatory cytokines, and the levels of Sphase kinaseassociated protein (p19), cyclindependent kinase inhibitor 1 (p21) and cellular tumor antigen p53 (p53) in Dgalinduced aging mice. In general, compared with the Dgal group, the treatment of Rg1 increased the testis index, serum testosterone level and the active content of superoxide dismutase and the total antioxidant capacity. The percentage of senescenceassociated ßgalactosidasepositive cells, the level of apoptosis and the volume of methane dicarboxylic aldehyde, tumor necrosis factorα, interleukin (IL)1ß and IL6 in testicular tissues were significantly decreased, and the expression of p19, p53 and p21 was downregulated due to the treatment with Rg1. The results of the present study demonstrated that ginsenoside Rg1 was able to protect the testes against Dgalinduced aging in mice. In addition, the protective effect of Rg1 may be achieved via antioxidation and downregulation of the p19/p53/p21 signaling pathway.
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Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Senescencia Celular/efectos de los fármacos , Galactosa/efectos adversos , Ginsenósidos/farmacología , Testículo/metabolismo , Envejecimiento/patología , Animales , Galactosa/farmacología , Masculino , Ratones , Testículo/patologíaRESUMEN
BACKGROUND: Rhizoma Paridis (Chonglou) is a commonly used and precious traditional Chinese medicine. Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz. and Paris polyphylla Smith var. chinensis (Franch.) Hara are the two main sources of Chonglou under the monograph of Rhizoma Paridis in Chinese Pharmacopoeia. In the local marketplace, however, this medicine is prone to be accidentally contaminated, deliberately substituted or admixed with other species that are similar to Rhizoma Paridis in shape and color. Consequently, these adulterations might compromise quality control and result in considerable health concerns for consumers. This study aims to develop a rapid and sensitive method for accurate identification of Rhizoma Paridis and its common adulterants. METHODS: DNA barcoding coupled with high resolution melting analysis was applied in this research to distinguish Rhizoma Paridis from its adulteration. The internal transcribed spacer 2 (ITS2) barcode was selected for HRM analysis to produce standard melting profile of the selected species. DNA of the tested herbal medicines was isolated and their melting profiles were generated and compared with the standard melting profile of P. polyphylla var. chinensis. RESULTS: The results indicate that the ITS2 molecular regions coupled with HRM analysis can effectively differentiate nine herbal species, including two authentic origins of Chonglou and their seven common adulterants. Ten herbal medicines labeled "Chonglou" obtained from a local market were collected and identified with our methods, and their sequence information was analyzed to validate the accuracy of HRM analysis. CONCLUSIONS: DNA barcoding coupled with HRM analysis is a accurate, reliable, rapid, cost-effective and robust tool, which could contribute to the quality control of Rhizoma Paridis in the supply chain of the natural health product industry (NHP).
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OBJECTIVE: To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs). METHODS: From 2005 to 2008, 390 women with PMSs were recruited from 4 clinic centers. The inclusion criteria included ages 40 to 60 years, estradiol (E2) below 30 ng/L, and follicle stimulating hormone (FSH) above 40 IU/L, etc. The patients were randomly assigned to HYKT group or HT group by random number table method, administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months. During treatment, the patients were interviewed quarterly, Kupperman Menopausal Index (KMI) scores, hot flush scores, insomnia scores, Menopause-Specific Quality of Life (MENQOL) scores and adverse effects were used for evaluating drug efficacy and safety respectively. The last interview was made at the end of 12-month treatment RESULTS: After treatment, KMI scores of HYKT group and HT group were both significantly decreased compared with baseline (P <0.01) and there was no significant difference between groups (P >0.05), except that KMI of HYKT group was higher after 3-month treatment (P <0.05). After treatment, hot flush and insomnia scores were both improved significantly in two groups (P <0.01); and HT had a better performance than HYKT in improving hot flush (P <0.05). MENQOL were significantly improved in both groups after treatment (P <0.01); but there was no significant difference between two groups (P >0.05). The incidence of adverse event in the HYKT group was much lower than that in the HT group (P <0.01). CONCLUSIONS: HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions. Although HYKT exerted curative effects more slowly than hormone, it possessed better safety profile than hormone.
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Medicamentos Herbarios Chinos/administración & dosificación , Terapia de Reemplazo de Estrógeno , Perimenopausia , Adulto , Terapia Combinada , Femenino , Sofocos/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Perimenopausia/efectos de los fármacos , Calidad de Vida , Resultado del TratamientoRESUMEN
The hematopoietic system is one of the potential targets of lead intoxication. Recognition of the lead-related deleterious outcomes promotes us to explore the potential therapeutic intervention. Here, we show that ginsenoside Rg1 (Rg1), extracted from the Chinese herb Panax ginseng, remarkably ameliorates the lead acetate-caused hematological index distortion as well as advanced hematopoietic stem cells (HSCs) aging and aging associated inflammation response. Specifically, Rg1 administration alleviated the increment of aging associated p53-p21-Rb signaling in aged HSCs induced by lead acetate. It also led a reduction of the lead acetate-induced increased inflammation level in blood plasma, which also partly contribute the aged HSCs rejuvenation. In conclusion, our results indicate that ginsenoside Rg1 therapeutically alleviated the essential blood deficits and advanced HSCs aging by lead acetate exposure, by which it could be viewed as a potential candidate for lead acetate-caused blood toxicity treatment.
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Ginsenósidos/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Panax/química , Animales , Senescencia Celular/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Homeostasis/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/prevención & control , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.
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Medicamentos Herbarios Chinos/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Pruebas de Función Renal , Masculino , Medicina Tradicional China/métodos , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: Studies have demonstrated that Tai Chi exercise improves blood lipid level with inconsistent results. A meta-analysis was conducted to quantify the effects of Tai Chi on blood lipid profiles in humans. METHODS: We screened the databases of PubMed, EMBASE, Cochrane Library (Central), Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang data, and Clinicaltrials.gov for randomized controlled trials with Physiotherapy Evidence Database (PEDro) score more than 3 points up to June 2015. Six studies involving 445 subjects were included. Most trials applied 12-week Tai Chi intervention courses. RESULTS: In comparison with the control group, blood triglyceride (TG) level difference between follow-up and baseline was statistically significantly lower in the Tai Chi practicing group (weighted mean difference (WMD) -16.81 mg/dl; 95% confidence intervals (CI) -31.27 to -2.35 mg/dl; P=0.02). A trend to improving total cholesterol (TC) reduction was found with Tai Chi (WMD -7.96 mg/dl; 95% CI -17.30 to 1.39 mg/dl; P=0.10). However, no difference was found in blood low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C). CONCLUSIONS: Tai Chi exercise lowered blood TG level with a trend to decrease blood TC level. Our data suggest that Tai Chi has the potential to implement meaningful blood lipid modification and serve as an adjunctive exercise modality. The relationship between Tai Chi exercise regimen and lipid profile change might have a scientific priority for future investigation.