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1.
Pharm Biol ; 59(1): 884-892, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34219593

RESUMO

CONTEXT: Laurolitsine is an aporphine alkaloid and exhibits potent antihyperglycemic and antihyperlipidemic effects in ob/ob mice. OBJECTIVE: To investigate the pharmacokinetics, tissue distribution and excretion of laurolitsine. MATERIALS AND METHODS: A LC-MS/MS method was established and validated to determine laurolitsine concentrations in the biological matrix of rats (plasma, tissue homogenate, urine and faeces). 10 Sprague-Dawley (SD) rats were used for plasma exposure study: 5 rats were injected with 2.0 mg/kg of laurolitsine via the tail vein, and the other 5 rats were administered laurolitsine (10.0 mg/kg) by gavage. 25 SD rats used for tissue distribution study and 5 SD rats for urine and faeces excretion study: rats administered laurolitsine (10.0 mg/kg) by gavage. After administered, serial blood, tissue, urine and faeces were collected. Analytical quantification was performed by a previous LC-MS/MS method. The pharmacokinetics, bioavailability, tissue distribution and excretion of laurolitsine were described. RESULTS: The pharmacokinetic parameters of oral and intravenous administration with Tmax were 0.47 and 0.083 h, t1/2 were 3.73 and 1.67 h, respectively. Oral bioavailability was as low as 18.17%. Laurolitsine was found at a high concentration in the gastrointestinal tract, liver, lungs and kidneys (26 015.33, 905.12, 442.32 and 214.99 ng/g at 0.5 h, respectively) and low excretion to parent laurolitsine in urine and faeces (0.03 and 1.20% in 36 h, respectively). CONCLUSIONS: This study established a simple, rapid and accurate LC-MS/MS method to determine laurolitsine in different rat samples and successful application in a pharmacokinetic study.


Assuntos
Aporfinas/farmacocinética , Cromatografia Líquida/métodos , Litsea/química , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Aporfinas/isolamento & purificação , Disponibilidade Biológica , Meia-Vida , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
2.
Pharm Biol ; 59(1): 1415-1424, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34689683

RESUMO

CONTEXT: Tadehaginoside, an active ingredient isolated from Tadehagi triquetrum (Linn.) Ohashi (Leguminosae), exhibited various biological activities. However, the pharmacokinetics and tissue distribution which affect tadehaginoside's therapeutic actions and application remain elusive. OBJECTIVE: To clarify the metabolism of tadehaginoside in vivo. MATERIALS AND METHODS: The pharmacokinetics and tissue distribution of tadehaginoside and its metabolite p-hydroxycinnamic acid (HYD) were investigated using LC-MS/MS. Pharmacokinetic parameters were determined in 10 Sprague-Dawley rats divided into two groups, the intravenous group (5 mg/kg) and the oral group (25 mg/kg). For the tissue-distribution study, 20 rats were intravenously given tadehaginoside (5 mg/kg) before the experiment (n = 4). Biological samples were collected before drug administration (control group) and after drug administration. RESULTS: The linearity, accuracy, precision, stability, recovery and matrix effect of the method were well-validated and the results satisfied the requirements of biological sample measurement. Treatment with tadehaginoside via intragastric and intravenous administration, the calculated Cmax in rats was 6.01 ± 2.14 ng/mL and 109.77 ± 4.29 ng/mL, and Tmax was 0.025 ± 0.08 h and 0.08 h, respectively. The results indicated that the quick absorption of tadehaginoside was observed following intravenous administration, and tadehaginoside in plasma of rats with intragastric administration showed relatively low concentration may be due to the formation of its metabolite. Tissue-distribution study indicated that kidney and spleen were the major distribution organs for tadehaginoside in rats and there was no long-term accumulation in most tissues. DISCUSSION AND CONCLUSION: These results could provide clues for exploring the bioactivity of tadehaginoside based on its pharmacokinetic characteristics.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácidos Cumáricos/farmacocinética , Glucosídeos/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Ácidos Cumáricos/análise , Glucosídeos/análise , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Distribuição Tecidual
3.
Am J Chin Med ; 50(8): 2223-2244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36266753

RESUMO

The property theory is a unique principle instructing traditional Chinese doctors to prescribe proper medicines against diseases. As an essential part of it, the five-flavor theory catalogs various Chinese materia medicas (CMMs) into five flavors (sweet, bitter, sour, salty, and pungent) based on their taste and medical functions. Although CMM has been successfully applied in China for thousands of years, it is still a big challenge to interpret CMM flavor via modern biomarkers, further deepening its elusiveness. Herein, to identify the correlation between gut microbiota and CMM flavor, we selected 14 CMMs with different flavors to prepare their aqueous extracts, quantified the contained major chemical components, and then performed full-length 16S rRNA sequencing to analyze the gut microbiota of C57BL/6 mice administrated with CMM extracts. We found that flavones, alkaloids, and saponins were the richest components for sweet-, bitter-, and pungent-flavored CMMs, respectively. Medicines with merged flavors (bitter-pungent and sweet-pungent) displayed mixed profiles of components. According to gut microbial analysis, modulation of CMMs belonging to the same flavor on the taxonomic classification was inconsistent to an extent, while the functional sets of gut microbiota, co-abundance gene groups (CAGs), strongly and differentially responded to distinct flavors. Moreover, these correlations were in line with their pharmacological actions. Therefore, the gut microbial functional sets (CAGs) could act as the possible indicator to reflect CMM flavor, rather than the composition of microbial community.


Assuntos
Microbioma Gastrointestinal , Materia Medica , Camundongos , Animais , Medicina Tradicional Chinesa , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Camundongos Endogâmicos C57BL
4.
Medicine (Baltimore) ; 99(40): e22223, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019396

RESUMO

RATIONALE: Mixed gonadal dysgenesis is a rare disorder of sex development, and typically contains a mosaic 45,X/46,XY karyotype. PATIENT CONCERNS: We reported here a case of a 42-year-old man with infertility for 6 years and inability to ejaculate during intercourse. DIAGNOSIS: Physical examination confirmed that the external genitalia was male. The right testis of this patient was resected and the left testis had intrascrotal calcification. Hormone test showed that the level of follicle-stimulating hormone was 20.14 IU/L (normal range, 1.27-19.26 IU/L). No deletion or mutation was found on the sex-determining region Y. H&E staining revealed seminiferous tubule dysgenesis. The karyotyping in peripheral blood and testicular tissue was 45,X/46,XY and 45,X/47,XYY/46,XY, respectively. Based on these results, the patient was diagnosed with 45,X/46,XY or 45,X/47,XYY/46,XY mosaicism and gonadal dysgenesis. INTERVENTIONS: In vitro fertilization and embryo transfer technology were used to help his wife to achieve pregnancy. OUTCOMES: A normal baby boy was born at 36 weeks of gestation with a karyotype 46, XY. LESSONS: We reported a rare case of a karyotype 45,X/46,XY in blood cells and 45,X/47, XYY/46,XY in testicular tissue. In vitro fertilization and embryo transfer technology can help to achieve pregnancy.


Assuntos
Disgenesia Gonadal Mista/genética , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Feminino , Disgenesia Gonadal Mista/complicações , Disgenesia Gonadal Mista/diagnóstico , Humanos , Infertilidade Masculina/etiologia , Masculino , Mosaicismo , Gravidez , Resultado da Gravidez , Recuperação Espermática
5.
Mol Med Rep ; 20(5): 4193-4201, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545469

RESUMO

The present study aimed to investigate the role of lysosomal­associated transmembrane protein 5 (LAPTM5) in osteoclast differentiation induced by osteoblasts. The results demonstrated that the expression levels of LAPTM5 were downregulated following runt­related transcription factor 2 (RUNX2) silencing and upregulated following RUNX2 overexpression in ST2 cells. Chromatin immunoprecipitation analysis identified the binding of RUNX2 to the LAPTM5 promoter at the ­1176 to ­1171 position. Dual­luciferase reporter assays confirmed that RUNX2 directly activated the LAPTM5 gene. The concentration of receptor activator of nuclear factor­κB ligand (RANKL) protein in the cytoplasm and in the media was significantly increased following LAPTM5 knockdown. LAPTM5 silencing in ST2 cells enhanced osteoclastic differentiation of co­cultured RAW264.7 cells. The present study indicated that expression of LAPTM5 was regulated by the interaction of RUNX2 with its promoter region and that LAPTM5 was involved in the trafficking of RANKL. These findings suggested a possible coupling mechanism between osteogenesis and osteoclastogenesis in which RUNX2 may be involved in osteoclast differentiation through the regulation of the lysosome­associated genes that modulate RANKL expression.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas Imediatamente Precoces/genética , Proteínas de Membrana/genética , Osteoblastos/metabolismo , Ligante RANK/metabolismo , Ativação Transcricional , Animais , Biomarcadores , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Expressão Gênica , Regulação da Expressão Gênica , Proteínas Imediatamente Precoces/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Regiões Promotoras Genéticas , Ligação Proteica , Transporte Proteico , Ligante RANK/genética
6.
Asian Pac J Trop Med ; 8(3): 209-13, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25902163

RESUMO

OBJECTIVE: To explore effect of high glucose on expression of osteoprotegerin (OPG) and receptor activator of NF- κ B ligand (RANKE) in rat aortic vascular smooth muscle cells. METHODS: SD rats were intraperitoneally injected with streptozotocin, OPG and RANKL expression in rat thoracic aortas were detected by immunohistochemical staining. In cultured vascular smooth muscle cells (VSMCs) (A7r5), qRT-PCR and Western blot analysis were used to examine the mRNA and protein levels of OPG and RANKL. RESULTS: Our results demonstrated that OPG expression was increased in hyperglycemic rat aortic VSMCs, while RANKL expression was decreased. Besides, in vitro experiments high glucose induced OPG expression, but depressed RANKL expression by dose- and time-dependent manner in cultured A7r5. CONCLUSIONS: Our findings suggested that high glucose could promote the expression of OPG, and inhibit the expression of RANKL in VSMCs, which may be partly be the molecular mechanism of diabetic vascular calcification.

7.
Cytotechnology ; 62(6): 509-18, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20976554

RESUMO

Since the first human embryonic stem cell (hESC) line was generated by Thomson et al. (in Science 282:1145-1147, 1998), hundreds of hESC lines have been reported by different labs, providing resources for basic research and regenerative medicine as well. However it has been widely recognized that hESC lines varied on their properties, in terms of gene expression profile, epigenetic modify profile, and differentiation tendency. Generation of more hESC lines will largely enhance our knowledge of hESCs innate character. In this current work, we reported the generation of HN4, a hESC line derived from grade III IVF human embryo by using a mixture of human foreskin fibroblast (HFF) and mouse embryonic fibroblast (MEF) as feeder layers, and a whole-mechanical method in inner cell mass (ICM) isolation. HN4 satisfied the criteria of hESCs pluripotency, with high expression of hESC surface markers (SSEA-3, SSEA-4, TRA-1-60, TRA-1-81), transcription factors (OCT-4, NANOG, REX-1), and alkaline phosphatase. It is able to differentiate to three germ layer derivatives when cultured in vitro, or in teratoma formation. Moreover, it displayed promising potential in neural differentiation under a proper culture condition, suggesting the advantage of HN4 in further investigation. Additionally, the whole-mechanical protocol for ICM isolation facilitates hESC line generation for its ease to handle.

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