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1.
Adv Healthc Mater ; 12(23): e2300325, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37167574

RESUMEN

Surgical resection is the most common approach for the treatment of osteosarcoma. However, two major complications, including residual tumor cells and large bone defects, often arise from the surgical resection of osteosarcoma. Discovering new strategies for programmatically solving the two above-mentioned puzzles has become a worldwide challenge. Herein, a novel one-step strategy is reported for natural phenolic acid planted nanohybrids with desired physicochemical properties and steerable photothermal effects for efficacious osteosarcoma suppression and bone healing. Nanohybrids are prepared based on the self-assembly of chlorogenic acid and gold nanorods through robust Au-catechol interface actions, featuring precise nanostructures, great water solubility, good stability, and adjustable hyperthermia generating capacity. As expected, on the one hand, these integrated nanohybrids can severely trigger apoptosis and suppress tumor growth with strong hyperthermia. On the other hand, with controllable mild NIR irradiation, the nanohybrids promote the expression of heat shock proteins and induce prominent osteogenic differentiation. This work initiates a brand-new strategy for assisting osteosarcoma surgical excision to resolve the blockage of residual tumor cells elimination and bone regeneration.


Asunto(s)
Neoplasias Óseas , Hipertermia Inducida , Osteosarcoma , Humanos , Osteogénesis , Ácido Clorogénico/farmacología , Neoplasia Residual/terapia , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Regeneración Ósea , Neoplasias Óseas/tratamiento farmacológico
2.
Int J Biol Macromol ; 215: 23-35, 2022 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-35718143

RESUMEN

For Codonopsis Radix polysaccharides (CRPs), oral administration is generally considered the most convenient route for patients. However, the details of its absorption and transport mechanisms remain unclear. In this study, we aimed to evaluate the oral absorption of CPA (an inulin-type fructan extracted from CRPs) in mice and Caco-2 cells. It was labeled with fluorescein isothiocyanate, and the fluorescence derivative (FCPA) was used to trace the behavior of CPA. The results showed that FCPA could be absorbed after oral administration and has a wide tissue distribution, including in the stomach, intestine, kidneys, and liver. FCPA was poorly absorbed, and its internalization was time- and energy-dependent, as well as dependent on cholesterol- and dynamin-mediated endocytosis. Confocal laser scanning microscopy showed successful cellular internalization of FCPA from the cytoplasm to the nucleus. In addition, we found that FCPA was trafficked to endosomes and lysosomes, and that tubulin was required for its intracellular transport. These findings add new details to our knowledge of the internalization and transport mechanisms of CPA, which may prove useful to the development and application of oral formulations of CRPs.


Asunto(s)
Codonopsis , Polisacáridos , Animales , Células CACO-2 , Codonopsis/química , Endocitosis , Humanos , Ratones , Polisacáridos/farmacología
3.
Food Funct ; 13(7): 4130-4141, 2022 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-35316828

RESUMEN

The aim of this work has been to establish and validate a simple and efficient method to detect the concentration of inulin-type fructan CPA from the roots of Codonopsis pilosula (Franch.) Nannf. in biosamples, and then apply it to evaluate the pharmacokinetics behavior, distribution character in tissue and excretion in mice. In this work, fluorescein isothiocyanate (FITC) was used to label CPA. Then FCPA was intravenously and orally administered to mice at different doses. In both i.v and p.o administration, FCPA concentration slowly declined in the circulatory system with a much longer T1/2 and MRT. After p.o administration, the area under the time curve (AUC0-∞) was dose-dependently increased. Taken together, FCPA showed poor absorption and wide tissue distribution. These pharmacokinetic results yield helpful insights into the pharmacological actions of FCPA.


Asunto(s)
Codonopsis , Fructanos , Administración Intravenosa , Animales , Inulina , Ratones , Raíces de Plantas
4.
Front Pharmacol ; 12: 670054, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34054541

RESUMEN

Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive. Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot. Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells. Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.

5.
Inflammation ; 44(2): 645-658, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33125572

RESUMEN

To investigate the beneficial effects of oridonin, a diterpenoid compound isolated from Rabdosia rubescens, on the inflammatory response in TNBS-induced post-inflammatory irritable bowel syndrome (PI-IBS) model and the underlying mechanism. Using the PI-IBS rat model and Caco-2 cell lines, we found that intestinal barrier function reflected by lactulose/mannitol (L/M) ratio and tight junction protein level was significantly ameliorated by oridonin. We also demonstrated that oridonin abrogated inflammation through inhibiting the phosphorylation of NF-κBp65 as well as its downstream gene (iNOS, COX-2, IL-1ß, and IL-6) level. Molecular docking studies confirmed the good binding activity between oridonin and PXR. In Caco-2 cell lines, oridonin markedly inhibited LPS-induced NF-κB activation in a PXR-dependent manner. Meanwhile, PXR and its target genes CYP3A4 and P-gp were induced by oridonin, which was associated with the decreased expression of NF-κB and the recovery of intestinal barrier. This study indicated that the therapeutic effect of oridonin on experimental PI-IBS through repairing intestinal barrier function may be closely associated with the regulatory role of PXR/NF-κB signaling pathway. Oridonin may serve as a PXR ligand for the development of drugs in the therapy for PI-IBS.


Asunto(s)
Antiinflamatorios/uso terapéutico , Diterpenos de Tipo Kaurano/uso terapéutico , Inflamación/tratamiento farmacológico , Síndrome del Colon Irritable/tratamiento farmacológico , FN-kappa B/metabolismo , Receptor X de Pregnano/metabolismo , Animales , Antiinflamatorios/farmacología , Biomarcadores/metabolismo , Western Blotting , Células CACO-2 , Diterpenos de Tipo Kaurano/farmacología , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/fisiopatología , Síndrome del Colon Irritable/etiología , Síndrome del Colon Irritable/metabolismo , Masculino , Permeabilidad , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/efectos de los fármacos , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Resultado del Tratamiento , Ácido Trinitrobencenosulfónico
6.
Artículo en Inglés | MEDLINE | ID: mdl-33123210

RESUMEN

Postinflammatory irritable bowel syndrome (PI-IBS) is a common functional gastrointestinal disorder, which is characterized by abdominal pain, low-grade inflammation, and visceral hypersensitivity. Shaoyao-Gancao decoction (SGD) has been used to improve the clinical symptoms of abdominal spasmodic pain accompanying acute gastroenteritis, but the underlying therapeutic mechanism has not been fully elucidated. In the present study, a rat model of PI-IBS was established via rectal administration of TNBS. Rats were scored daily for 28 days using disease activity index (DAI). Abdominal withdrawal reflex (AWR) was used to measure the pain threshold. After SGD (6.25, 12.5, and 25 g/kg/d) treatment for 14 days, rat colonic tissue was collected for histopathological grading, enterochromaffin (EC) cell count, and 5-HT content measurement. RT-qPCR and western blot analyses were employed to detect the gene and protein level of tryptophan hydroxylase (TPH), serotonin reuptake transporter (SERT), and transient receptor potential vanilloid 1 (TRPV1). To further validate the effect of SGD on TRPV1, another experiment was performed in cells. The results revealed that visceral hyperalgesia, reflected by increased DAI, AWR, pathological injury score, 5-HT content, and EC cell count in PI-IBS rats, was significantly ameliorated by SGD. In cells, SGD markedly inhibited the expression and function of TRPV1. Moreover, the expression levels of TPH were also repressed by SGD. The findings of the present study indicated that the therapeutic effect of SGD on visceral hyperalgesia may be closely associated with the regulatory role of TRPV1 and 5-HT signaling pathways.

7.
J Sep Sci ; 42(15): 2534-2549, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31144455

RESUMEN

A simple and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, liquiritin, liquiritigenin, glycyrrhetinic acid, and glycyrrhizin in rat plasma after oral administration of Shaoyao-Gancao decoction, which is traditionally used in the treatment of polycystic ovary syndrome. The plasma samples were pretreated with methanol as precipitant. The method exhibited good linearity (correlation coefficient (R2 ) > 0.99) with lower quantification limits of 0.595-4.69 ng/mL for all analytes. Intra- and interbatch precision, accuracy, recovery, and stability of the method were all within accepted criteria. The results showed that the pharmacokinetic behaviors of the seven compounds were altered in the pathological status of polycystic ovary syndrome. Furthermore, a total of 36 metabolites were structurally identified based on their accurate masses and fragment ions. The major metabolic pathway involves phase I metabolic reactions (such as hydroxylation), phase II metabolic reactions (such as sulfation and glucuronidation conjugation) as well as the combined multiple-step metabolism. This study is the first report on the pharmacokinetic and metabolic information of Shaoyao-Gancao decoction in both normal and model rats, which would provide scientific evidences for the bioactive chemical basis of herbal medicines and also promote the clinical application of Shaoyao-Gancao decoction for treating polycystic ovary syndrome.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Administración Oral , Animales , Hidrocarburos Aromáticos con Puentes/sangre , Hidrocarburos Aromáticos con Puentes/metabolismo , Hidrocarburos Aromáticos con Puentes/farmacocinética , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacocinética , Femenino , Flavanonas/sangre , Flavanonas/metabolismo , Flavanonas/farmacocinética , Glucósidos/sangre , Glucósidos/metabolismo , Glucósidos/farmacocinética , Ácido Glicirretínico/sangre , Ácido Glicirretínico/metabolismo , Ácido Glicirretínico/farmacocinética , Ácido Glicirrínico/sangre , Ácido Glicirrínico/metabolismo , Ácido Glicirrínico/farmacocinética , Monoterpenos/sangre , Monoterpenos/metabolismo , Monoterpenos/farmacocinética , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem
8.
Biosci Rep ; 39(1)2019 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-30573529

RESUMEN

Shaoyao-Gancao Decoction (SGD) has been widely used for the treatment of gynopathy. The present study aimed to evaluate the therapeutic effect and potential mechanism of SGD on hyperandrogenism in polycystic ovary syndrome (PCOS) rats. In the present work, SGD was orally administrated to the PCOS rats at the dose of 12.5, 25, and 50 g/kg/d for 14 consecutive days. UPLC-MS/MS was performed to identify the main chemical components of SGD. Body weight, ovarian weight, cystic dilating follicles, and serum levels of steroid hormones were tested to evaluate the therapeutic effect of SGD. In order to further clarify the underlying mechanism, we also measured mRNA and the protein levels of NF-κB, NF-κB p65, P-NF-κB p65, and IκB by RT-qPCR and Western blotting techniques. Our results showed that SGD treatment significantly alleviated hyperandrogenism in PCOS rats as evidenced by reduced serum levels of T and increased E2 and FSH levels. In addition, SGD effectively reduced the phosphorylation of NF-κB p65 and increased the expression of IκB. Results of the present study demonstrated that SGD could ameliorate hyperandrogenism in PCOS rats, and the potential mechanism may relate to the NF-κB pathway.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Hiperandrogenismo/tratamiento farmacológico , FN-kappa B/genética , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hiperandrogenismo/inducido químicamente , Hiperandrogenismo/genética , Hiperandrogenismo/patología , Quinasa I-kappa B/genética , Letrozol/toxicidad , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/patología , Ratas , Factor de Transcripción ReIA/genética
9.
Can J Physiol Pharmacol ; 96(12): 1328-1336, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30383974

RESUMEN

The enterohepatic circulation of bile acids (BAs) critically depends on BA transporters and enzymes, which can be affected by inflammatory bowel disease. Diarrhea in colitis is believed to result in part from BA malabsorption. The work aimed to investigate whether diarrhea in colitis was associated with the expression of BA transporters, enzymes, and nuclear receptors. RT-qPCR and Western blot techniques were used to evaluate the gene and protein levels of Cyp7a1, Asbt, SHP, FXR, Ostß in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of colitis. The total BAs (TBAs) levels were assayed using ELISA kits, and the individual BAs were measured by LC-MS/MS. Results showed that the fecal excretions of TBAs were significantly increased by 1.6-fold in acute stage of colitis. In ileum, Asbt was significantly decreased; however, there was a compensatory increase in Cyp7a1 level in liver. Moreover, FXR has a decreased tendency and the downstream target gene SHP was downregulated. Contrary to acute stage, molecular changes were completely reversible during the remission phase. Our results indicated that the expression of Asbt and Cyp7a1 were altered in acute colitis, which performed vital roles in maintaining BA homeostasis. Early medical manipulation of BA transporters and enzymes may help prevent diarrhea.


Asunto(s)
Ácidos y Sales Biliares/metabolismo , Colitis/metabolismo , Diarrea/metabolismo , Enfermedad Aguda , Animales , Colesterol 7-alfa-Hidroxilasa/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/fisiología , Homeostasis/fisiología , Íleon/metabolismo , Hígado/metabolismo , Masculino , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Ratas , Ratas Sprague-Dawley , Simportadores/metabolismo
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