RESUMEN
Dioscin is a natural steroid saponin derived from plants of the genus Dioscoreaceae. Previous studies have proved its effects of antibacterial, anti-inflammatory and hypolipidemic. In this study, our aim was to explore the protective effect and preliminary mechanism of Dioscin on dextran sulfate sodium (DSS)-induced colitis in mice. The results showed that Dioscin reduced DSS-induced disease activity index (DAI) increase, colon length shortening and colon pathological damage. In addition, Dioscin reduced excessive inflammation by reversing the cytokines levels, reducing intestinal macrophage infiltration and promoting macrophage polarization to M2 phenotype. At the same time, Dioscin maintained the intestinal barrier function by increasing the expression of zonula occludens-1 (ZO-1), occludin and mucin (Muc)-2. Moreover, Dioscin inhibited NF-κB, MAPK signaling and nucleotide oligomerization domain-like receptor family pyrin domain ontaining 3(NLRP3) inflammasome pathway in DSS-induced colitis. These results suggest that Dioscin is a competent candidate for ulcerative colitis (UC) therapy in the future.
Asunto(s)
Colitis Ulcerosa/prevención & control , Colon/efectos de los fármacos , Diosgenina/análogos & derivados , Mucosa Intestinal/efectos de los fármacos , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/patología , Colon/inmunología , Colon/patología , Sulfato de Dextran/administración & dosificación , Sulfato de Dextran/toxicidad , Diosgenina/farmacología , Diosgenina/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Masculino , RatonesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ping weisan (PWS), a complex formulation used in traditional Chinese medicine, is first described in 1107 AD and published in the Prescriptions of Taiping Benevolent Dispensary. We have previously confirmed that PWS has the effect of alleviating DSS-induced chronic ulcerative colitis (UC) in mice. AIM OF THE STUDY: We aimed to examine whether PWS protects mice from chronic UC by regulating intestinal microbiota composition. MATERIALS AND METHODS: Chronic colitis was induced in C57BL/6 mice with 2.5% DSS in drinking water. PWS (8 g/kg) was orally administered throughout the experiment. Body weight changes, stool consistency and myeloperoxidase (MPO) activity were measured in these mice. Interleukin-17A (IL-17A) and interferon gamma (IFN-γ) mRNA levels were detected by qRT-PCR. The alterations of fecal microflora were investigated by 16S rRNA sequencing. Furthermore, intestinal tight junction protein including occludin, and serum lipopolysaccharide (LPS) level were also detected. RESULTS: PWS relieved DSS-induced loss of body weight, and improved stool consistency and MPO activity in mice. The levels of IL-17A and IFN-γ mRNA were also reduced after treatment with PWS. PWS not only regulated occludin level but also decreased serum LPS. We further showed DSS-induced changes in intestinal microbial composition and richness are significantly regulated by PWS. PWS treatment significantly decreased the abundance of Bacteroidetes, but increased the abundance of Firmicutes in chronic UC mice induced by DSS. CONCLUSIONS: Combining with our previous results, we found that PWS could exert anti-UC role by rebalancing intestinal bacteria.
Asunto(s)
Colitis/prevención & control , Colon/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Fármacos Gastrointestinales/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Enfermedad Crónica , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/microbiología , Colon/metabolismo , Colon/microbiología , Sulfato de Dextran , Modelos Animales de Enfermedad , Disbiosis , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Lipopolisacáridos/sangre , Masculino , Ratones Endogámicos C57BL , Ocludina/genética , Ocludina/metabolismo , Peroxidasa/metabolismo , Pérdida de Peso/efectos de los fármacosRESUMEN
Ripened Pu-erh tea extract contributes to reducing weight gain and fat accumulation; however, the role of gut microbiota on the antiobesity effect of ripened Pu-erh tea extract in obese mice remains unclear. This study aims to explore the role of alterations in gut microbes mediated by ripened Pu-erh tea extract in obese mice through 16S rRNA sequencing and a fecal transplant trial. Our results suggested that drinking water containing ripened Pu-erh tea extract could decrease weight gain, fat accumulation, adipose inflammation, the Firmicutes-to-Bacteroidetes ratio, and metabolic endotoxemia while, in the meantime, improving the intestinal barrier integrity in obese mice. Moreover, the fecal transplant trial indicated that feces from the donor mice treated with ripened Pu-erh tea extract could significantly modulate weight and metabolic syndrome in the recipient mice. Thus, our results indicated that gut microbiota can mediate the function of ripened Pu-erh tea extract against obesity; additionally, ripened Pu-erh tea extract can potentially prevent individuals from being obese through rebalancing the gut microbiota.
Asunto(s)
Microbioma Gastrointestinal , Obesidad/dietoterapia , Extractos Vegetales/metabolismo , Sustancias Protectoras/metabolismo , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , ADN Bacteriano/genética , Humanos , Intestinos/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Obesidad/microbiología , ARN Ribosómico 16S/genética , Té/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ping weisan (PWS), a famous traditional Chinese medicinal, is published in the Prescriptions of Taiping Benevolent Dispensary. PWS has been proven to be effective for many diseases, especially chronic diseases. AIM OF THE STUDY: The purpose of this study was to investigate the effect and potential mechanism of PWS on chronic colitis in mice. MATERIALS AND METHODS: Chronic colitis was induced in mice using 2.5% DSS for two cycles of 5 days, and different doses of PWS (2, 4, 8â¯g/kg) were administered throughout the experiment. The disease activity index (DAI), length of colon and pathological changes were measured. Cytokine levels in vivo and in vitro were detected by ELISA. The protein levels of TLR4, PPARγ and the key proteins in NF-κB pathway and NLRP3 inflammasome were measured by western blot. RESULTS: PWS decreased DSS-induced DAI, colon length shortening and colonic pathological damage. PWS also reduced TNF-α, IL-1ß and IL-12 production. In addition, PWS suppressed NF-κB pathway activation by regulating the expression of TLR4 and PPARγ. Our data also indicated that PWS could inhibit NLRP3 inflammasome activation. CONCLUSIONS: PWS treatment alleviated the degree of colitis caused by DSS, suggesting that PWS might be a novel agent for the treatment of chronic colitis.
Asunto(s)
Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Sulfato de Dextran , Medicamentos Herbarios Chinos/uso terapéutico , Animales , Antiinflamatorios/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Enfermedad Crónica , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7RESUMEN
Evodiamine (EVO), an extraction from the traditional Chinese medicine Evodia rutaecarpa, has been reported to possess anti-inflammatory, anti-tumor and other pharmacological activities. However, the effectiveness of EVO to relieve dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) has not been evaluated. In this study, the protective effects and mechanisms of EVO on DSS-induced UC mice were investigated. The results indicated that treatment with EVO ameliorated DSS-induced UC mice body weight loss, disease activity index (DAI), colon length shortening, colonic pathological damage, and myeloperoxidase (MPO) activity. The production of TNF-α, IL-1ß and IL-6 was also significantly inhibited by EVO. Further mechanistic results showed that EVO restrained the inflammation by regulating NF-κB signal and NLRP3 inflammasome. Furthermore, results also showed that EVO contributed to the tight junction (TJ) architecture integrity by modulating the expression of zonula occludens-1 (ZO-1) and occludin during colitis. Surprisingly, treatment with EVO reduced the concentration of plasmatic lipopolysaccharide (LPS) and re-balanced the levels of Escherichia coli and Lactobacillus. These findings suggested that EVO may have a potential protective effect on DSS-induced colitis and may be useful for the prevention and treatment of UC.
Asunto(s)
Colitis/metabolismo , Sulfato de Dextran/toxicidad , FN-kappa B/biosíntesis , Proteína con Dominio Pirina 3 de la Familia NLR/biosíntesis , Extractos Vegetales/uso terapéutico , Quinazolinas/uso terapéutico , Animales , Colitis/inducido químicamente , Colitis/prevención & control , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Extractos Vegetales/farmacología , Quinazolinas/farmacologíaRESUMEN
The purpose of this study was to investigate the protective effects and mechanisms of the essential oil of Zanthoxylum bungeanum pericarp (ZBEO) on dextran sulfate sodium (DSS)-induced experimental colitis in mice. ZBEO decreased DSS-induced body weight loss, the disease activity index, colon length shortening, colonic pathological damage, and myeloperoxidase activities. The production of pro-inflammatory mediators was significantly alleviated by ZBEO. Further mechanistic analysis showed that ZBEO inhibited inflammation by regulating NF-κB and PPARγ pathways. ZBEO also inhibited NLRP3 activation in colitis in mice. Furthermore, ZBEO contributed to the maintenance of tight junction architecture by regulating the expression of zonula occludens-1 during colitis. Surprisingly, treatment with ZBEO increased levels of the commensal bacteria containing Lactobacillus and Bifidobacteria but reduced Escherichia coli levels in the feces of mice. These results suggested that supplementation with ZBEO might provide a new dietary strategy for the prevention of ulcerative colitis.
Asunto(s)
Colitis/tratamiento farmacológico , Aceites Volátiles/administración & dosificación , Extractos Vegetales/administración & dosificación , Zanthoxylum/química , Animales , Colitis/inducido químicamente , Colitis/genética , Colitis/inmunología , Colon/efectos de los fármacos , Colon/inmunología , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/genética , FN-kappa B/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , PPAR gamma/genética , PPAR gamma/inmunologíaRESUMEN
Zanthoxylum bungeanum, which belongs to the Zanthoxylum genus of the Rutaceae family, is now wildly distributed in most parts of China and some Southeast Asian countries. The pericarp of Zanthoxylum bungeanum has been known to exhibit antibacterial, anti-inflammatory and other important therapeutic activities. The purpose of this study was to investigate the effects and mechanisms of Zanthoxylum bungeanum pericarp extract (ZBE) on DSS-induced experimental colitis in mice. The results demonstrated that the major flavonoid composition of ZBE includes rutin (32.36%), quercetin (13.61%) and isoquercitrin (24.89%). ZBE alleviated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, ZBE inhibited the expression of TNF-α, IL-1ß and IL-12 via the regulation of TLR4 and TLR4-related pathways in DSS-induced experimental colitis in mice and LPS-triggered inflammation in J774.1 cells. Our findings suggest that ZBE is effective in ameliorating experimental colitis, and further investigation is necessary on the use of ZBE as a new dietary strategy to lower the risk of ulcerative colitis (UC).