RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Restoring the mucus layer is a potential strategy for treating ulcerative colitis (UC). Previous studies reported that a Chinese medicine formula Shaoyao Decoction (SYD) effectively improved UC. However, the role and mechanism of SYD in restoring the mucus layer are still vague. AIM OF THE STUDY: This study aimed to research the therapeutical effects and unravel the involved mechanism of SYD on DSS-evoked UC. MATERIALS AND METHODS: First, the constituents of SYD were detected by UPLC-QTOF-MS/MS. Then, the DSS-induced UC model was introduced to investigate the pharmacologic action and molecular mechanism of SYD on UC. Pharmacodynamic indicators were assessed including body weight, colon length, ulcerations, disease activity index (DAI), inflammatory cytokines and histological parameters. To investigate the integrality and functions of the mucous layer, AB-PAS stain and UEA-1 stain were used to evaluate the completeness of mucous layer, as well as the maturation of goblet cells (GCs). The bacterial invasion was detected by fluorescence in situ hybridization. As to mechanism exploration, the expressions of Notch/Hes1 pathway were investigated by using agonists in lipopolysaccharides (LPS) -stimulated LS174T cell. RESULTS: After modeling in mice, SYD remarkedly ameliorated the symptoms of mouse colitis, the expression of pro-inflammatory factors declined, and increased IL-10 expression was observed in SYD-treated mice. Besides, SYD repaired the structure of the mucus layer and prevented bacterial invasion. Mechanism investigation discovered that SYD promoted GCs differentiation by inhibiting the Notch pathway, which was consistent with the results in LPS-challenged LS174 cell. CONCLUSIONS: These findings demonstrated that SYD could restore the mucus layer to prevent UC via suppressing the Notch signaling pathway, which provided evidences for the UC treatment of SYD in the clinic.
Assuntos
Colite Ulcerativa , Colite , Medicamentos de Ervas Chinesas , Animais , Camundongos , Espectrometria de Massas em Tandem , Lipopolissacarídeos/farmacologia , Hibridização in Situ Fluorescente , Medicamentos de Ervas Chinesas/farmacologia , Colite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Colo , Transdução de Sinais , Muco/metabolismo , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
BACKGROUND: Previous studies reported that Aloe vera ameliorated DSS-induced colitis and promoted mucus secretion. However, the effect of Aloin A (AA), a major compound of Aloe vera, on colitis and its exact mechanism remains uncovered. METHODS: C57BL/6 mice were successively subjected to 3% DSS solution for 5 days and distilled water for 2 days. Concurrently, AA (25, 50 mg/kg) and 5-aminosalicylic (500 mg/kg) were administrated intragastrically from day 1 to day 7. Colitis was evaluated by disease active index (DAI), colon length, inflammation response, and intestinal barrier function. In vitro LS174T cells challenged with 50 ng/ml of lipopolysaccharides (LPS) were used to validate the modulatory action of AA on the Notch signaling pathway. RESULTS: Our results showed that oral administration with AA prominently prevented DSS-induced colitis symptoms in terms of decreased DAI, prevention of colon shortening, and reduced pathological damage. AA mitigated the inflammatory response evidenced by the decreased proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and increased anti-inflammatory cytokine (IL-10). Besides, AA inhibited apoptosis and facilitated proliferation in colons. Moreover, AA treatment up-regulated the expression of tight junction (TJ) proteins (ZO-1, Occludin) and promoted the secretion of MUC2 to decrease colon permeability. Mechanistically, AA inhibited the Notch pathway to promote the secretion of MUC2, which was consistent with LPS-challenged LS174 cells. CONCLUSION: These results suggested that AA could prevent colitis by enhancing the intestinal barrier function via suppressing the Notch signaling pathway. Thus, AA might be a prospective remedy for ulcerative colitis.
Assuntos
Colite Ulcerativa , Colite , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/prevenção & controle , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Emodina/análogos & derivados , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Estudos Prospectivos , Transdução de Sinais , Proteínas de Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , ÁguaRESUMO
OBJECTIVE: To investigate the application of traditional Chinese medicine (TCM) syndrome differentiation in identification of body constitution of hypertensive and diabetic patients. METHODS: A total of 110 hypertensive patients with diabetes treated in our hospital were enrolled in this study, and were divided into a study group (SG, n=60) and a control group (CG, n=50) according to different intervention methods. Patients in the CG received conventional western medical intervention for hypertension and diabetes, while patients in the SG received body constitution-identified TCM syndrome differentiation intervention additionally. The changes of blood pressure and plasma glucose during the intervention were compared between the two groups, the clinical effect and quality of life of the two groups were evaluated, and multivariate stepwise Logistic regression analysis on influencing factor of TCM body constitution was conducted. RESULTS: Compared with that before intervention, the proportion of gentleness constitution in the SG showed a significant increase (P<0.05) after intervention. Dynamic analysis during the intervention showed that patients in the SG had lower systolic blood pressure (SBP), diastolic blood pressure (DBP), lower level of fasting plasma glucose (GLU) and 2-h postprandial plasma glucose (2hPG) than the CG from 1 to 12 months after intervention (P<0.05). Patients in the SG scored higher than the CG on all SF-36 dimensions after intervention (P<0.05). Multivariate stepwise Logistic regression analysis showed that dampness-heat constitution, blood-stasis constitution, Yin-deficiency constitution and phlegm-dampness constitution were the main risk factors for hypertension with diabetes (P<0.05). CONCLUSION: Body constitution-identified TCM syndrome differentiation treatment for hypertensive patients with diabetes is effective, which can significantly improve the plasma glucose and blood pressure indices of patients. Dampness-heat constitution, blood-stasis constitution, Yin-deficiency constitution and phlegm-dampness constitution are the risk factors for hypertension with diabetes.