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BACKGROUND:At present,a large number of studies have found that Liuwei Dihuang Pill can be used to treat osteoporosis,but there are few related studies on the differentiation and mineralization of osteoblasts induced by wear particles using Liuwei Dihuang Pill. OBJECTIVE:To investigate the positive effect of different concentrations of Liuwei Dihuang Pill-containing serum on titanium particle-induced mouse MC3T3-E1 osteoblast in vitro osteolysis model. METHODS:Drug-containing serum was extracted after oral administration of Liuwei Dihuang Pill.The best concentration of Liuwei Dihuang Pill-containing serum and titanium particles on the viability of MC3T3-E1 cells was screened.MC3T3-E1 cells were divided into three groups.The blank group was given osteoblastic differentiation culture.The model group was given titanium particles(5 μg/mL)ossification culture.The drug-containing serum group was given titanium particles(5 μg/mL)+ Liuwei Dihuang Pill-containing serum(10%,15%and 20%doses).Osteoblast viability was detected by CCK-8 assay.Cell alkaline phosphatase activity was detected by alkaline phosphatase staining.Cell mineralization was detected by silver nitrate(Von Kossa)and alizarin red staining.Expression levels of bone differentiation-related genes Runx-2,Osterix,Ocn,Axin,Alp,and Opn were detected by qRT-PCR.Wnt/β-catenin signaling pathways β-catenin,p-GSK-3β,GSK-3β,Runx2 and Osterix protein expression levels were detected by western blot assay. RESULTS AND CONCLUSION:(1)Liuwei Dihuang Pill-containing serum culture reversed the decrease in alkaline phosphatase activity of MC3T3E-1 cells induced by titanium particles,increased the alizarin red staining and calcification of MC3T3E-1 cells,increased the expression of osteogenesis-related genes in MC3T3E-1 cells,and increased the expression of proteins related to the Wnt/β-catenin signaling pathway.(2)These findings indicate that Liuwei Dihuang Pill-containing serum can reverse the inhibitory effect of titanium particles on the differentiation and mineralization of osteoblasts,upregulate the expression of osteogenesis-related genes,and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway,suggesting that Liuwei Dihuang Pill is expected to become an effective drug for preventing aseptic loosening of artificial joints.

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BACKGROUND:Most of the formulas for the clinical treatment of premature ovarian insufficiency have evolved from the basic formula of Liuwei Dihuang Pills,and have achieved good therapeutic efficacy.Currently,most of the experimental studies on Liuwei Dihuang Pills focus on morphological observations and physiological and biochemical detection of in vivo animal models,while fewer studies on molecular mechanisms have been reported. OBJECTIVE:To explore the molecular mechanism of Liuwei Dihuang Pills in the treatment of premature ovarian insufficiency based on the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species pathway. METHODS:Premature ovarian insufficiency model was established in mice by intraperitoneal injection of cyclophosphamide 120 mg/kg combined with busulfan 12 mg/kg,and then Liuwei Dihuang Pill suspension was used to intervene in premature ovarian insufficiency mice.After 12 weeks of intervention,the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,anti-Mullerian hormone,8-hydroxydeoxyguanosine,total antioxidant capacity and reactive oxygen species in serum of mice were detected by ELISA method.The morphological changes in mouse ovaries were observed by hematoxylin-eosin staining.The ultrastructure of mouse follicular granulosa cells and the apoptosis of granulosa cell mitochondria were observed by transmission electron microscopy.The expression levels of receptor gamma coactivator-1 alpha and mitochondrial transcription factor A in mouse ovarian granulosa cells were detected by immunohistochemistry. RESULTS AND CONCLUSION:Compared with the model group,serum levels of follicle-stimulating hormone,luteinizing hormone,reactive oxygen species,and 8-hydroxydeoxyguanosine were decreased in the experimental group(P＜0.05),and the levels of estradiol,anti-Mullerian hormone,and total antioxidant capacity were increased(P＜0.05).Hematoxylin-eosin staining showed that in the model group,there were more atretic follicles and corpus luteum forms,some secondary follicles,and interstitial fibrosis and hyperplasia;in the experimental group,a large number of atretic follicles,few corpus luteum forms,primordial follicles were observed at the edges but there were few secondary follicles and no mature follicles.Transmission electron microscopy showed that the organelles in ovarian granulosa cells of mice in the experimental groups were relatively intact.Immunohistochemical results showed that compared with the model group,the expression level of receptor gamma coactivator-1 alpha in the ovarian tissue of mice increased slightly in the experimental group at the 4th week,and there was no significant change at the 8th and 12th weeks.The expression level of mitochondrial transcription factor A in the ovarian tissues of mice in the experimental group was transiently increased at the 4th week,and then slightly decreased,which were all significantly different from those of the model group.To conclude,Liuwei Dihuang Pills inhibit ovarian granulosa cell apoptosis in mice with premature ovarian insufficiency to a certain extent through the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species signaling pathway,thereby improving the endocrine function of the ovary,enhancing the antioxidant capacity,and attenuating the degree of oxidative stress damage.

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Tyrosine kinase inhibitors (TKIs), as an important tumor therapy, can induce severe proteinuria that significantly affects anti-tumor therapy. Existing therapies against proteinuria induced by other etiologies are currently ineffective for TKI-induced proteinuria. It has been shown that various types of proteinuria are related to podocyte damage caused by changes in the RelA signaling pathway. Our experiments confirmed that TKIs activate the renal RelA signaling pathway, and induce death of podocytes and destruction of the glomerular filtration barrier. Here we found that Liuwei Dihuang Pill (LDP) attenuated the inflammatory injury of podocytes through inhibiting activation of RelA, and subsequently relieved TKI-related proteinuria and prevented the progression of TMA and FSGS. Our finding indicated that LDP may be effective for the treatment of TKI-induced proteinuria, which is clinically significant.

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Traditional Chinese medicine (TCM) compounds have recently garnered attention for the regulation of immune cell infiltration and the prevention and treatment of Alzheimer's disease (AD). The Liuwei Dihuang Pill (LDP) has potential in this regard; however, its specific molecular mechanism currently remains unclear. Therefore, we adopted a bioinformatics approach to investigate the infiltration patterns of different types of immune cells in AD and explored the molecular mechanism of LDP intervention, with the aim of providing a new basis for improving the clinical immunotherapy of AD patients. We found that M1 macrophages showed significantly different degrees of infiltration between the hippocampal tissue samples of AD patients and healthy individuals. Four immune intersection targets of LDP in the treatment of AD were identified; they were enriched in 206 biological functions and 30 signaling pathways. Quercetin had the best docking effect with the core immune target PRKCB. Our findings suggest that infiltrated immune cells may influence the course of AD and that LDP can regulate immune cell infiltration through multi-component, multi-target, and multi-pathway approaches, providing a new research direction regarding AD immunotherapy.

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BACKGROUND: Diabetic osteoporosis (DOP) is one of the chronic complications of diabetes mellitus, but without a standardized treatment plan till now. Liuwei Dihuang pill (LDP) has gradually exerted a remarkable effect on DOP in recent years; its specific mechanism is not clear yet. METHODS: We adopted network pharmacology approaches, including multi-database search, pharmacokinetic screening, network construction analysis, gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and molecular docking to elaborate the active components, signaling pathways and potential mechanisms of LDP in the treatment of DOP. RESULTS: Twenty-seven active ingredients and 55 related disease targets have been found through integrated network pharmacology. Functional enrichment analysis shows that five key active ingredients, including beta-sitosterol, stigmasterol, diosgenin, tetrahydroalstonine, and kadsurenone, may give full scope to insulin secretion estrogen-level raising and angiogenesis in biological process through the pivotal targets. In addition, the underlying effect of PI3K/AKT/FOXO and VEGF pathways is also suggested in the treatment. CONCLUSION: Based on systematic network pharmacology methods, we predicted the basic pharmacological effects and potential mechanisms of LDP in the treatment of DOP, revealing that LDP may treat DOP through multiple targets and multiple signaling pathways, which provide evidence for the further study of pharmacological mechanism and broader clinical thinking.

Asunto(s)

Diabetes Mellitus , Medicamentos Herbarios Chinos , Osteoporosis , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Osteoporosis/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas

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Introduction: Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury. Objectives: This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs. Methods: A literature search was carried out regarding our topic with the keywords of "atherosclerosis" or "Nrf2/HO-1" or "vascular endothelial cells" or "oxidative stress" or "Herbal medicine" or "natural products" or "natural extracts" or "natural compounds" or "traditional Chinese medicines" based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed. Results: These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies. Conclusion: Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

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Aterosclerosis , Preparaciones Farmacéuticas , Aterosclerosis/tratamiento farmacológico , Células Endoteliales/metabolismo , Hemo-Oxigenasa 1/metabolismo , Medicina de Hierbas , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo

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The effects of Liuwei Dihuang pill (LWDH) on diabetic nephropathy-related osteoporosis (DNOP) are unclear. The present study aimed to evaluate the effects of LWDH on KDM7A and Wnt/ß-catenin signaling pathway in DNOP rats and the high glucose-induced MC3T3-E1 cells. A DNOP model was prepared by streptozotocin in 9-week-old male Sprague-Dawley (SD) rats to evaluate the effects of LWDH. The cell viability and differentiation capacity of high glucose-induced MC3T3-E1 cells were determined by CCK-8 assay, Alizarin Red staining, and alkaline phosphatase (ALP) staining, respectively. Furthermore, the expressions of KDM7A and Wnt1/ß-catenin pathway-related proteins were determined by Western blot analysis. Treatment of DNOP rats with LWDH could significantly ameliorate the general state, degradation of renal function, and renal pathological changes. LWDH decreased the levels of TNF-α, IL-6, IL-8, IL-1ß, ALP, and TRAP, and increased the calcium, phosphorus in serum, as well as decreased the level of the calcium and phosphorus in the urine. Besides, LWDH significantly improved bone mineral density (BMD), bone volume (BV), and the bone microstructure of DNOP rats. Moreover, LWDH increased the levels of the elastic modulus, ultimate load, and bending strength in the femurs. In MC3T3-E1 cells, serum-containing LWDH significantly increases in cell viability and osteoblastic differentiation capability. The expression of α-SMA, vimentin, KDM7A, Wnt1 and ß-catenin were significantly down-regulated, and the E-cadherin, H3K9-Me2, H3K27-Me2, BMP-4, BMP-7, Runx2, osteocalcin, and Col1a1 were significantly up-regulated with LWDH treatment. The present study shows that LWDH has a therapeutic effect on DNOP, in part, through down-regulation of KDM7A and Wnt/ß-catenin pathway.

Asunto(s)

Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/complicaciones , Medicamentos Herbarios Chinos/farmacología , Osteoporosis/tratamiento farmacológico , Absorciometría de Fotón , Animales , Densidad Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Diabetes Mellitus Experimental/inducido químicamente , Nefropatías Diabéticas/inducido químicamente , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Módulo de Elasticidad/efectos de los fármacos , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Fémur/patología , Humanos , Histona Demetilasas con Dominio de Jumonji/metabolismo , Masculino , Ratones , Osteoporosis/diagnóstico , Osteoporosis/etiología , Osteoporosis/patología , Ratas , Ratas Sprague-Dawley , Estreptozocina/administración & dosificación , Estreptozocina/toxicidad , Vía de Señalización Wnt/efectos de los fármacos

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ETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin (CP) is the classical chemotherapeutic drug for various cancer, but it also accompanies reproductive toxicity and genotoxicity. Liuwei Dihuang Pill (LW) is the traditional Chinese medicine prescription for treating Kidney-Yin deficiency syndrome, which has been reported to prevent and treat various diseases. However, the protective effect of LW on CP-induced reproductive toxicity and genotoxicity has not been reported. AIM OF THE STUDY: To investigate the potential protective effect and mechanism of LW on CP-induced reproductive toxicity and genotoxicity in male mice. MATERIALS AND METHODS: Mice were given LW (0.4, 1.2 and 3.6 g/kg) or Vitamin C (0.1 g/kg) once daily by oral gavage for thirteen consecutive days. Then, CP (3.00 mg/kg) was given intraperitoneal injection once daily for five consecutive days starting on the ninth day. The protective effects of LW against CP-induced reproductive toxicity and genotoxicity were evaluated by body weight, testis ratio, sperm count, sperm viability, sperm abnormal morphology type, micronuclei test, testicular histopathology, serum malondialdehyde (MDA), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) level. RESULTS: The results demonstrated that LW could significantly increase CP-induced the reduction of sperm count and sperm viability, then decrease abnormal sperm type rate and micronucleus rate. Moreover, LW also could improve testicular abnormal histopathologic morphology induced by CP exposure. Meanwhile, LW decreased serum MDA level and increased T-SOD, GSH-Px and CAT level compared to CP group. CONCLUSION: our findings show that LW has protective effects on CP-induced reproductive toxicity and genotoxicity. LW decreases serum MDA level and increases T-SOD, GSH-Px and CAT level, which indicates that antioxidant activity may be the potential mechanism of LW to resist reproductive toxicity and genotoxicity.

Asunto(s)

Antioxidantes/farmacología , Cisplatino/efectos adversos , Medicamentos Herbarios Chinos/farmacología , Sustancias Protectoras/farmacología , Animales , Daño del ADN/efectos de los fármacos , Humanos , Infertilidad/inducido químicamente , Infertilidad/prevención & control , Masculino , Ratones , Pruebas de Micronúcleos , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/patología , Testículo/efectos de los fármacos , Testículo/patología

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OBJECTIVE: To investigate if the Liuwei Dihuang pill (LWDHP) can inhibit metastasis to the liver and lungs in mice bearing triple-negative breast cancer (TNBC), and the molecular mechanism underpinning this action. METHODS: Ninety-nine TNBC bearing-mice were distributed randomly to five groups: control (Con), paclitaxel (PTX), low-dose LWDHP (LLP, 2.3 g·kg－1·d－1), middle-dose LWDHP (MLP, 4.6 g·kg－1·d－1) and high-dose LWDHP (HLP, 9.2 g·kg－1·d－1). The LWDHP were administered (p.o.) to the agonal stage. The morphology of BC cells was observed by hematoxylin & eosin staining. Expression of axin-2, ß-catenin, T cell factor (TCF), cyclin- D1 and vascular endothelial growth factor (VEGF) was detected by western blotting or immunofluorescence. ß-catenin/TCF-1 interaction was measured using a co-immunoprecipitation assay. RESULTS: After LWDHP treatment, metastasis of BC cells to the lungs and liver was inhibited, expression of axin-2 was increased, expression of TCF-1, ß-catenin, cyclin-D1 and VEGF was decreased, and ß-catenin/TCF-1 interaction was disrupted. CONCLUSION: The LWDHP could inhibit metastasis of BC cells to the liver and lungs. The molecular mechanism underlying this action may be regulation of protein expression and ß-catenin/TCF-1 interactions in the Wnt pathway.

Asunto(s)

Medicamentos Herbarios Chinos/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Animales , Western Blotting , Modelos Animales de Enfermedad , Femenino , Técnica del Anticuerpo Fluorescente , Inmunoprecipitación , Ratones , Factores de Transcripción TCF/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo

RESUMEN

OBJECTIVES: To investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency. METHODS: In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. RESULTS: The mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. CONCLUSIONS: The CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.

Asunto(s)

Citocinas/genética , Medicamentos Herbarios Chinos/uso terapéutico , Quinasas Janus/metabolismo , Osteoporosis Posmenopáusica/tratamiento farmacológico , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Regulación hacia Arriba , Deficiencia Yin/tratamiento farmacológico , Citocinas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Femenino , Regulación de la Expresión Génica , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Deficiencia Yin/genética

RESUMEN

OBJECTIVE: To observe the contribution of Borneolum syntheticum to the intervention effect of Liuwei Dihuang Pill (, LDP) on experimental retinal degeneration, and initially investigate the mechanism of Borneolum syntheticum as meridian-lead-in drug. METHODS: A total of 180 sodium iodateinduced retinital degeneration rats were randomly divided into three groups, including distilled water group, LDP group, and LDP+Borneolum syntheticum (LDP+BS) group. Twenty normal rats were fed regularly without any treatment as normal control. On day 7 and 14 after treatment, histopathological study and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) test were performed to evaluate the retinopathy. Claudin-5 expression at blood-retina barrier (BRB) was detected by Western blot at different time points from 0.5 to 8 h after gavage. RESULTS: On day 7 and 14 after treatment, the retinal lesion grades were significantly different among the three groups (P<0.05). The grade in the LDP+BS group was significantly less than the LDP and distilled water groups (both P<0.05), no significant difference was observed between the LDP and distilled water groups (P>0.05). The apoptosis rates in the LDP+BS group was significantly less than the distilled water and LDP groups (both P<0.05), while there was no significant difference between LDP and distilled water groups (P>0.05). Expression of claudin-5 in LDP+BS group was significantly less than the other two groups at 0.5, 1 and 2 h after gavage (P<0.05). There was no apparent difference among the three groups at 4 and 8 h after gavage (P>0.05). CONCLUSION: Borneolum syntheticum could strengthen the effect of LDP on experimental retinal degeneration, indicated that Borneolum syntheticum might play the role of meridian-lead-in drug in the formula. The mechanism may be due to Borneolum syntheticum could promote the physiologically openness of bloodretina barrier through transiently affecting the expression of claudin-5.

Asunto(s)

Medicamentos Herbarios Chinos/uso terapéutico , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Claudina-5/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Ratas Sprague-Dawley , Degeneración Retiniana/patología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/patología , Factores de Tiempo

RESUMEN

<p><b>OBJECTIVES</b>To investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency.</p><p><b>METHODS</b>In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway.</p><p><b>RESULTS</b>The mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3.</p><p><b>CONCLUSIONS</b>The CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.</p>

Asunto(s)

Femenino , Humanos , Persona de Mediana Edad , Citocinas , Genética , Metabolismo , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Regulación de la Expresión Génica , Quinasas Janus , Metabolismo , Osteoporosis Posmenopáusica , Quimioterapia , Genética , ARN Mensajero , Genética , Metabolismo , Factores de Transcripción STAT , Metabolismo , Transducción de Señal , Regulación hacia Arriba , Deficiencia Yin , Quimioterapia , Genética

RESUMEN

<p><b>OBJECTIVE</b>To observe the contribution of Borneolum syntheticum to the intervention effect of Liuwei Dihuang Pill (, LDP) on experimental retinal degeneration, and initially investigate the mechanism of Borneolum syntheticum as meridian-lead-in drug.</p><p><b>METHODS</b>A total of 180 sodium iodateinduced retinital degeneration rats were randomly divided into three groups, including distilled water group, LDP group, and LDP+Borneolum syntheticum (LDP+BS) group. Twenty normal rats were fed regularly without any treatment as normal control. On day 7 and 14 after treatment, histopathological study and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) test were performed to evaluate the retinopathy. Claudin-5 expression at blood-retina barrier (BRB) was detected by Western blot at different time points from 0.5 to 8 h after gavage.</p><p><b>RESULTS</b>On day 7 and 14 after treatment, the retinal lesion grades were significantly different among the three groups (P<0.05). The grade in the LDP+BS group was significantly less than the LDP and distilled water groups (both P<0.05), no significant difference was observed between the LDP and distilled water groups (P>0.05). The apoptosis rates in the LDP+BS group was significantly less than the distilled water and LDP groups (both P<0.05), while there was no significant difference between LDP and distilled water groups (P>0.05). Expression of claudin-5 in LDP+BS group was significantly less than the other two groups at 0.5, 1 and 2 h after gavage (P<0.05). There was no apparent difference among the three groups at 4 and 8 h after gavage (P>0.05).</p><p><b>CONCLUSION</b>Borneolum syntheticum could strengthen the effect of LDP on experimental retinal degeneration, indicated that Borneolum syntheticum might play the role of meridian-lead-in drug in the formula. The mechanism may be due to Borneolum syntheticum could promote the physiologically openness of bloodretina barrier through transiently affecting the expression of claudin-5.</p>

Asunto(s)

Animales , Apoptosis , Claudina-5 , Metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Ratas Sprague-Dawley , Degeneración Retiniana , Quimioterapia , Patología , Epitelio Pigmentado de la Retina , Patología , Factores de Tiempo

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[Objective] To summarize the academic views and clinical experience of Professor HE Ruoping in the treatment of peri menopausal syndrome by using traditional Chinese medicine. [Method] From the clinical treatment, collecting the clinical information of the teacher, research and discuss the traditional Chinese medicine academic ideas and clinical experience of teacher HE in the treatment of perimenopausal syndrome, to summarize the traditional Chinese medicine of perimenopausal syndrome in dialectical characteristic.And further explain the characteristics of the treatment of teacher HE through case analysis. [Result] Teacher HE thinks that the main pathogenesis of perimenopausal syndrome is the deficiency of kidney Yin, and divides the patients into stagnation of liver-qi type, Qi stagnation and blood stasis, disharmony between heart and kidney, heart and spleen deficiency type, yin-yang deficiency type, a total of five kinds of syndrome types, according to their clinical manifestation.When confronted with such patients, teacher HE often chooses Liuwei Dihuang Pills to tonify kidney-yin and relieve liver for smooth Qi, promoting qi to activate blood, restoring normal coordination between heart and kidney, invigorating heart and spleen, tonify both Yin and Yang, gives patients more grooming solution at the same time to adjust their physical and mental state as a whole, so the patients could receive remarkable effect and avoid the potential risks of hormone replacement therapy.The case in this article has obtained good treatment results. [Conclusion] Teacher HE treats perimenopause syndrome by tonifying kidney-yin and taking accompanied symptoms and signs into account meanwhile, which has significant clinical effect and the value of popularization and application.

RESUMEN

@#A new method based on rat liver microsomes and chromatographic fingerprint comparison was established to investigate the possible herb-drug interactions between Liuwei Dihuang Pills(LDP)and nifedipine(NIF). LDP and NIF were incubated simultaneously with rat liver microsomes at 37 °C for 60 min in a shaking water bath. The separation was achieved on a C18 column using 0. 1% formic acid solution and acetonitrile as mobile phase with a liner gradient program. The flow rate was set at 1. 0 mL/min. Detection was achieved by UV light at 240 nm. To evaluate the interactions between LDP and NIF, the similarity of the fingerprinting chromatograms before and after co-incubation was calculated by similarity evaluation system for chromatographic fingerprint of TCM. Furthermore, pharmacokinetic experiments in rat suggested that there was no significant difference in the pharmacokinetic parameters of the typical components in LDP.

RESUMEN

AIM: To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice. METHODS: Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was administrated for 10 wk for improvement of insulin resistance. Body weight and food intake were measured every week. Blood samples were collected for assays of fasting blood glucose, insulin, insulin-like growth factor (IGF)-1, adiponectin and leptin. Stomach tissues were collected for histopathological analysis, immunohistochemical staining of Ki67, quantitative reverse transcription-polymerase chain reaction and western blotting. RESULTS: The incidence of MNU-induced gastric dysplasia was significantly elevated in diabetic (db/db) mice relative to the control (db/m) mice. The incidence of gastric dysplasia was significantly reduced by LDP with suppression of cell proliferation, as demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor mRNAs was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in the stomach tissues by LDP. In addition, adiponectin was increased and leptin was decreased in the serum by LDP. CONCLUSION: LDP decreased risk of gastric dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity and correction of adipokines disorders.

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Medicamentos Herbarios Chinos/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Adiponectina/sangre , Animales , Glucemia/análisis , Peso Corporal , Carcinogénesis , Transformación Celular Neoplásica , Diabetes Mellitus Experimental , Inmunohistoquímica , Insulina/sangre , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Antígeno Ki-67/sangre , Leptina/sangre , Masculino , Metilnitrosourea , Ratones , Neoplasias Gástricas/inducido químicamente

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OBJECTIVE:To obverse the efficacy and safety of Liuwei dihuang pill combined with TCM prescription acupoint application in the treatment of type 2 diabetic constipation. METHODS:120 patients with type 2 diabetic constipation were random-ly divided into control group(60 cases)and observation group(60 cases). All patients received controlling blood pressure and regu-lating blood lipids drugs,diet control combined with exercise,and fixed dose of Metformin hydrochloride tablet(0.5 g/times,2 times a day)and Acarbose tablet(100 mg/times,3 times a day);based on it,control group received 5 mg Mosapride citrate tablet, 3 times a day;observation group additionally received 8 Liuwei dihuang pills(3 times a day)combined with TCM prescription acu-point application (in double Tianshu Point,double Yongquan point,double Shenque Point and double Zusanli). 7 d was regarded as a treatment course,and it lasted 3 courses. Clinical efficacy,blood glucose [2 h postprandial glucose(2 h PG),blood glucose (FPG)],the clinical symptom indexes(defecation interval time,each defecation time,weekly defecation frequency)before and af-ter treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than in control group,and the difference was statistically significant (P0.05). After treatment,2 h PG and FPG in 2 groups were significantly lower than before,and obser-vation group was lower than control group;defecation interval time and each defecation time were significantly shorter than before, and observation group was shorter than control group;weekly defecation frequency was significantly higher than before,and obser-vation group was higher than control group,The differences were statistically significant (P0.05). CONCLUSIONS:Liuwei dihuang pill combined with TCM priscription acupoint ap-plication shows good efficacy in the treatment of type 2 diabetic constipation. It can effectively improve constipation,reduce defeca-tion interval time and each defecation time,increase weekly defecation frequency and have no influence on blood glucose control with small adverse reactions and high safety.

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Objective: To investigate the relationship among powder particle size, cell wall-breaking rate, and dissolution of Liuwei Dihuang Pill (LDP) in vitro. Methods: Particle size and cell wall-breaking rate of four kinds of LDP were measured by laser particle size instrument and optical microscope. The loganin and paeonol were taken as indexes, the feature of dissolution for the above four kinds of LDP was examined by grouting method. Results: There were significant differences in the distribution of particle size, wall-breaking rate, and dissolution among different crushing degrees of LDP. With the decrease of the powder particle size, the wall-breaking rate and relative cumulative dissolution of loganin and paeonol increased. The rate of characteristic cell wall-breaking in the micro powder of Corni Fructus, Alismatis Rhizoma, and Moutan Cortex could reach 100%. Conclusion: Moderately changing degree of smash could cause cell wall-breaking rate changes, so as to control effective ingredient the dissolution rate and extent of Chinese medicine.

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Objective To study the clinical effects of addition treatment of liver-kidney yin deficiency and postmenopausal osteoporosis with Liuwei Dihuang pill.Methods 120 patients suffering from postmenopausal osteopo-rosis who were determined to be subject to liver -kidney Yin deficiency by doctors of traditional Chinese medicine when they received treatment at the outpatient clinic of traditional Chinese medicine department of our hospital in the period from February 2010 to june 2013 were divided into three groups:group A,B and C,with the random number table.For group A:provided the honeyed pills made up by supplemented six -ingredient rehmannia pill,and taken two pills per day continuously for six months;For group B:provided 5mg of zoledronic acid injection for intravenous drip infusion;For group C:provided traditional Chinese medicine honeyed pills and zoledronic acid for treatment at the same time;all of the three groups take Calcium carbonate D3 at the same time;The three groups of cases until the 12th month were observed and followed -up.The clinical efficacy of three groups were compared.Results A,C group 3 months after treatment with estradiol levels compared with before treatment,the difference was statistically significant (t =2.54,P =0.05,t =2.07,P =0.06).A group 3 months after treatment,the VAS scores at 6 months respectively (3.75 ±1.32),(2.06 ±1.53)points before treatment,and the differences were statistically significant(t =10.18, P =0.00,t =9.26,P =0.00).A group 3 months after treatment,the SF -36 scores at 6 months were (90.82 ± 12.38),(105.82 ±9.06)% respectively,compared with that before treatment,the differences were statistically significant(t =8.40,P =0.00,t =5.21,P =0.00).A group 6 months after treatment of lumbar 1 -4 bone density-were (0.85 ±0.07)g/m2 ,and before treatment[(0.76 ±0.07)g/m2 ]comparison,the difference was statistically significant(t =7.56,P =0.00);A group 6 months after treatment of Wards bone density compared with before treatment,the difference was statistically significant(t =8.07,P =0.00).C group 6 months after treatment of lumbar 1 -4 bone density(0.91 ±0.07)g/m2 ,and B Group[(0.88 ±0.05)g/m2 ]comparison,the difference was statistical-ly significant(t =27.19,P =0.00);C group after treatment,the bone mineral density of Wards area for 6 months were (0.62 ±0.04)g/m2 .The difference was statistically significant (t =26.22,P =0.00),compared with the B group. The TCMsyndromes of TCMin the 6 months after treatment in A group were (5.42 ±2.13),and the difference was statistically significant (t =13.29,P =0.00),compared with the B Group (10.75 ±4.08).(t =13.29,P =0.00). Compared with B group,the difference was statistically significant(t =26.22,P =0.00).A group after the treatment of TCMsyndrome score was 6 months(5.42 ±2.13),and B Group[(10.75 ±4.08)],the difference was statistically significant(t =13.29,P =0.00).Conclusion The addition of Liuwei Dihuang pill can improve BMD,alleviate the ostealgia and improve life quality of patients suffering from postmenopausal osteoporosis,and has no obvious adverse effects.It can enhance curative effects through using with diphosphonate.

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OBJECTIVE: To improve the quality control method of Liuwei Dihuang Pills. METHODS: Morroniside and loganin from processed Fruetus Corni were identified by TLC. Morrniside, loganin and paeonol in Liuwei Dihuang Pills were determined by HPLC. The determination was performed on a Phenomenex Gemini 110A C18 column (4.6 mm×250 mm, 5 μm) maintained at 40℃ with gradient elution of acetonitrile (A) and 0.3% phosphoric acid aqueous solution (B) at a flow rate of 1 mL·min-1. The detective wavelength was set at 240 nm for morroniside and loganin and 274 nm for paeonol. RESULTS: The TLC spots were clear. Morrniside, loganin and paeonol showed good linear relationship in the range of 0.02078-1.039, 0.02034-1.017, and 0.04576-2.288 μg, respectively. The average recoveries (n=9) were 99.97%-100.99% with RSDs less than 2.3%. CONCLUSION: The method is simple, rapid, accurate and can be used to control the quality of Liuwei Dihuang Pill more effectively.