ABSTRACT
Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.
Subject(s)
Animals , Mice , Colitis, Ulcerative/drug therapy , Ursodeoxycholic Acid/adverse effects , Berberine/pharmacology , Interleukin-6 , Tumor Necrosis Factor-alpha/pharmacology , Drugs, Chinese Herbal/pharmacology , Colon , Nanoparticles , Dextran Sulfate/adverse effects , Disease Models, Animal , Colitis/chemically inducedABSTRACT
cancer in patients with primary sclerosing cholangitis/ulcerative colitis? Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of intra-and extrahepatic bile ducts. About 70 percent of patients with CEP have idiopathic ulcerative colitis (IUC). PSC is considered a premalignant condition with an increased risk of colorectal cancer (CC). Individuals with PSC and IUC have higher risk of developing CC than IUC patients. There are different positions between American and European experts in the fields of hepatology and inflammatory bowel disease regarding the use of ursodeoxycholic acid (UDCA) in PSC and IUC as a chemo preventive. Studies have shown mixed results about the use of UDCA in preventing CC. The following is an update on the role of UDCA as a chemo preventive in this group of patients.
La colangitis esclerosante primaria (CEP) es una enfermedad crónica hepática colestásica caracterizada por inflamación y fibrosis de ductos biliares intra y extrahepáticos. Alrededor de 70 por ciento de los pacientes con CEP presenta colitis ulcerosa idiopática (CUI). La CEP es considerada una condición premaligna con un incremento del riesgo de cáncer colorrectal (CCR). Individuos con CEP más CUI tienen mayor riesgo de desarrollar CCR que pacientes con sólo CUI. Existen distintas posturas a nivel mundial entre expertos americanos y europeos tanto en el área de la hepatología como en el área de las EII (enfermedades inflamatorias intestinales) frente al uso de ácido ursodeoxicólico (AUDOC) en CEP y CUI como quimioprotector. Estudios han mostrado resultados contradictorios para el uso de AUDOC en la prevención de CCR. Se expone una revisión actualizada sobre el rol de AUDOC como quimioprotector en este grupo de pacientes.
Subject(s)
Humans , Ursodeoxycholic Acid/therapeutic use , Cholangitis, Sclerosing/pathology , Colorectal Neoplasms/prevention & control , Ursodeoxycholic Acid/adverse effects , Colitis, Ulcerative/pathologyABSTRACT
Antecedentes/objetivos: En pacientes sometidos a trasplante hepático ortotópico (TH), el rechazo celular agudo (RCA) constituye una de sus principales complicaciones, a pesar del mayor desarrollo de drogas inmunosupresoras. Por otra parte, el ácido ursodeoxicólico (AUC) es capaz de reducir la hiperexpresión de antígenos del complejo de histocompatibilidad mayor tipo I en hepatocitos, en la cirrosis biliar primaria. A su vez, reduce la producción periférica de interleukinas 2 y 4. Estos hallazgos podrían sugerir un eventual efecto beneficioso al AUC en reducir la injuria inmunológica, sin embargo, diversos estudios evidencian resultados contradictorios en la reducción de la incidencia de RCA. Pacientes y métodos: Entre noviembre 1993 y diciembre 2002 se evaluaron retrospectivamente a 58 pacientes sometidos a TH. Veinticinco de ellos recibieron AUC (15 mg/Kg) además de la inmunosupresión estándar, a lo menos por 1 año. El grupo control (n = 33), recibió el mismo tratamiento inmunosupresor, excepto AUC. El diagnóstico de RCA se fundamentó histológicamente. Resultados: No hubo diferencias en el número total de RCA en los dos grupos de pacientes; tampoco en la severidad o recurrencia. Ni la frecuencia de rechazo crónico como tampoco la de retrasplante hepático, fueron diferentes en ambos grupos de pacientes. Conclusiones: El presente estudio no mostró que la incidencia de RCA mejorara por la asociación de AUC a la triple terapia inmunosupresora estándar.