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Medicinas Complementárias
Métodos Terapéuticos y Terapias MTCI
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1.
Phytomedicine ; 123: 155145, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37976698

RESUMEN

BACKGROUND: Sesamol (SEM), a natural lignan compound isolated from sesame, has strong anti-oxidant property, regulating lipid metabolism, decreasing cholesterol and hepatoprotection. However, its anti-hepatic fibrosis effect and mechanisms have not been comprehensively elucidated. HYPOTHESIS/PURPOSE: This study aims to investigate the anti-hepatic fibrosis of SEM and its underlying mechanisms. METHOD: C57BL/6 mice with hepatic fibrosis were induced by TAA, then administrated with SEM or curcumin, respectively. HSCs were stimulated by TGF-ß or conditioned medium, and then cultured with SEM, GW4064, GW3965, Rapamycin (RA) or 3-methyladenine (3-MA), respectively. Mice with hepatic fibrosis also were administrated with SEM, RA or 3-MA to estimate the effect of SEM on autophagy. RESULTS: In vitro, SEM significantly inhibited extracellular matrix deposition, P2 × 7r-NLRP3, and inflammatory cytokines. SEM increased FXR and LXRα/ß expressions and decreased MAPLC3α/ß and P62 expressions, functioning as 3-MA (autophagy inhibitor). In vivo, SEM reduced serum transaminase, histopathology changes, fibrogenesis, autophagy markers and inflammatory cytokines caused by TAA. LX-2 were activated with conditioned medium from LPS-primed THP-1, which resulted in significant enhance of autophagy markers and inflammatory cytokines and decrease of FXR and LXRα/ß expressions. SEM could reverse above these changes and function as 3-MA, GW4064, or GW3965. Deficiency of FXR or LXR attenuated the regulation of SEM on α-SMA, MAPLC3α/ß, P62 and IL-1ß in activated LX-2. In activated THP-1, deficiency of FXR could decrease the expression of LXR, and vice versa. Deficiency of FXR or LXR in activated MΦ decreased the expressions of FXR and LXR in activated LX-2. Deficiency FXR or LXR in activated MΦ also attenuated the regulation of SEM on α-SMA, MAPLC3α/ß, P62, caspase-1 and IL-1ß. In vivo, SEM significantly reversed hepatic fibrosis via FXR/LXR and autophagy. CONCLUSION: SEM could regulate hepatic fibrosis by inhibiting fibrogenesis, autophagy and inflammation. FXR/LXR axis-mediated inhibition of autophagy contributed to the regulation of SEM against hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. SEM might be a prospective therapeutic candidate, and its mechanism would be a new direction or strategy for hepatic fibrosis treatment.


Asunto(s)
Benzoatos , Benzodioxoles , Bencilaminas , Hepatocitos , Cirrosis Hepática , Fenoles , Ratones , Animales , Medios de Cultivo Condicionados/efectos adversos , Medios de Cultivo Condicionados/metabolismo , Ratones Endogámicos C57BL , Cirrosis Hepática/metabolismo , Hepatocitos/metabolismo , Macrófagos , Citocinas/metabolismo , Autofagia , Células Estrelladas Hepáticas , Hígado
2.
J Ethnopharmacol ; 299: 115652, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36038092

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Mudan decoction (DMD) is a classic prescription for treating intestinal carbuncle from Zhang Zhongjing's "Essentials of the Golden Chamber" in the Han Dynasty. Recent studies also prove that DMD has a therapeutic effect on ulcerative colitis (UC), but its mechanism is still unclear. AIM OF STUDY: In this study, we aim to assess the therapeutic effect of DMD on DSS-induced chronic colitis in mice and deeply expound its underlying regulative mechanism. MATERIALS AND METHODS: The efficacy of DMD on mice with 2% DSS-induced chronic colitis was examined by changes in mouse body weight, DAI score, colon length changes, peripheral blood white blood cells (WBC) and red blood cells (RBC) counts, and hemoglobin (HGB) content, using mesalazine as a positive control. A small animal imaging system observed the FITC-Dextran fluorescence distribution in mice, and the contents of IL-22 and IL-17A in colon tissue homogenate supernatant and LPS in peripheral blood were detected by ELISA. Fluorescence in situ molecular hybridization and bacterial culture were used to investigate bacterial infiltration in intestinal mucosa and bacterial translocation in mesenteric lymph nodes and spleen. Mice immune function was further evaluated by analyzing the changes in spleen index, thymus index, and the ratio of peripheral blood granulocytes, monocytes, and lymphocytes. Meanwhile, the proportion of NCR+ group 3 innate lymphoid cells (ILC3), NCR-ILC3, and IL-22+ILC3 in colonic lamina propria lymphocytes of mice was detected by flow cytometry. The contents of effectors IL-22, IL-17A, and GM-CSF were detected by RT-PCR. We use cell scratching to determine the effect of DMD conditioned medium on the migration of Caco-2 cells by establishing an in vitro model of MNK-3 conditioned medium (CM) intervening Caco-2 cells. RT-PCR and WB detect the expression of tight junction ZO-1, Occludin, and Claudin-1. RESULTS: DMD restored the body weight, colon length, peripheral blood RBC numbers, and HGB content of chronic colitis mice and reduced peripheral blood WBC and colon inflammatory cell infiltration. Moreover, DMD decreased LPS content in serum, bacterial infiltration of colonic mucosa, and bacterial translocation in spleen and mesenteric lymph nodes. Simultaneously, DMD intensified the expression of ZO-1, Occludin, and Claudin-1, the ratio of NCR+ILC3 and IL-22+ILC3, and decreased the proportion of NCR-ILC3. In vitro studies also confirmed that the conditioned medium of DMD promoted the migration of Caco-2 cells and the expression of tight junction proteins. CONCLUSION: Our results confirm that DMD improves inflammation and restores intestinal epithelial function in mice with chronic colitis, and the mechanism may be related to regulating ILC3 function.


Asunto(s)
Colitis Ulcerosa , Colitis , Animales , Peso Corporal , Células CACO-2 , Claudina-1/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Medios de Cultivo Condicionados/efectos adversos , Medios de Cultivo Condicionados/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Inmunidad Innata , Interleucina-17/metabolismo , Mucosa Intestinal/metabolismo , Lipopolisacáridos/farmacología , Linfocitos/metabolismo , Mesalamina/efectos adversos , Ratones , Ratones Endogámicos C57BL , Ocludina/metabolismo , Proteínas de Uniones Estrechas/metabolismo
3.
Int Arch Allergy Immunol ; 116(1): 36-9, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9623507

RESUMEN

In order to further evaluate the role of cytokines in the induction of atopic pruritus, leukocytes from 10 atopic eczema patients or 10 nonallergic controls were stimulated in vitro with mite or birch pollen antigen for 1 and 4 days. Subjects were prick-tested with the supernatants, and whealing and itching were evaluated 20 and 60 min later. The supernatants were also examined for the contents of GM-CSF, IL-2, IL-6 and IL-8 by ELISA and TNFalpha. Two hours prior to testing, the antihistamine cetirizine (20 mg) or a placebo tablet were given to the patients according to a randomized, double-blind study protocol. After pricking with antigen-stimulated leukocyte supernatants, 6 of 10 patients but no controls reacted mostly at 20 min with whealing and/or pruritus. In the cetirizine-treated group, no decrease in these skin reactions was seen compared to placebo. Analysis for cytokines showed increased levels of IL-8 in allergen-stimulated samples, with no correlation to the induction of itching or whealing by these supernatants. IL-6 levels were low and variable, and GM-CSF, IL-2 and TNFalpha levels were always below standard values. These data show that leukocytes selectively release IL-8 in response to in vitro antigen stimulation. They furthermore provide additional support for the concept that as yet to be identified products play a role in atopic pruritus.


Asunto(s)
Citocinas/fisiología , Dermatitis Atópica/inmunología , Hipersensibilidad Inmediata/inmunología , Prurito/inmunología , Adolescente , Adulto , Alérgenos/inmunología , Alérgenos/farmacología , Animales , Antialérgicos/administración & dosificación , Antialérgicos/uso terapéutico , Antígenos/inmunología , Antígenos/farmacología , Cetirizina/administración & dosificación , Cetirizina/uso terapéutico , Estudios Cruzados , Medios de Cultivo Condicionados/efectos adversos , Medios de Cultivo Condicionados/química , Medios de Cultivo Condicionados/farmacología , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Interleucina-2/análisis , Interleucina-2/metabolismo , Interleucina-8/administración & dosificación , Interleucina-8/efectos adversos , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Ácaros/inmunología , Polen/inmunología , Prurito/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/inmunología , Pruebas Cutáneas , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismo
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