RESUMEN
AIMS: The current study aims to investigate the effect of Yupingfeng (YPF) powder on immunosuppression, and explore the possible mechanisms. MAIN METHODS: Firstly, the monomer components of YPF powder were analyzed by UPLC-QTOF-MS combined with UNIFI automatic analysis platform, then the mechanism of YPF on immunosuppressive treatment was investigated using network pharmacological method, and finally the prediction was verified in a Candida albicans (Can)-induced immunosuppressive BALB/c mouse model. KEY FINDINGS: 98 monomer compounds in YPF were obtained. Through virtual analysis and screening on the oral utilization and drug likeness properties of the components, 47 effective components were got. 9 core targets obtained were enriched in IL-17 signaling pathway. In the mouse model, YPF could reduce the number of Can and alleviate Can-induced inflammation in the kidney effectively, upregulate Can-induced low proportion of CD4+/CD8+ of splenic lymphocytes, and increase Can-induced low activity of IL-17 pathway. SIGNIFICANCE: These results demonstrate that YPF could improve the immunity of Can-induced immunosuppression in BALB/c mice through upregulating the activity of IL-17 pathway.
Asunto(s)
Candida albicans/inmunología , Candidiasis , Medicamentos Herbarios Chinos , Tolerancia Inmunológica/efectos de los fármacos , Animales , Candidiasis/tratamiento farmacológico , Candidiasis/inmunología , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Evaluación de Medicamentos , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos BALB C , PolvosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jiaolong capsule (JLC) was approved for the therapy of gastrointestinal diseases by the State Food and Drug Administration (SFDA) of China. It has a satisfactory curative effect in the treatment of patients with inflammatory bowel disease, however, the mechanism remains to be elucidated. AIM OF THE STUDY: In current study, the effects and possible mechanisms of JLC on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated. MATERIALS AND METHODS: Sulfasalazine and JLC were administrated orally and initialized 6 h after TNBS enema, once a day for seven consecutive days. The effect of JLC on intestinal microbial populations and LPS/TLR-4/NF-κB pathway was observed and assessed. Thirty female SD rats were distributed into six groups randomly and equally, namely, control, TNBS, TNBS + sulfasalazine (625 mg/kg), and TNBS + three different doses of JLC (25, 50, and 100 mg/kg) groups. RESULTS: The effect of JLC on restoring normal structures of colorectum and repairing colonic damage were superior to that of sulfasalazine. JLC showed a positive effect in re-balancing intestinal bacteria population of colitis, and suppressed the activation of LPS/TLR-4/NF-κB pathway. CONCLUSION: The results suggest that JLC demonstrated a beneficial effect on treating colitis in a rat model. The possible mechanisms may be through the regulatory effect of intestinal commensal bacteria and down-regulation of LPS/TLR-4/NF-κB pathway.
Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Fármacos Gastrointestinales/farmacología , Sustancias Protectoras/farmacología , Ácido Acético/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Colitis Ulcerosa/inducido químicamente , Colon/efectos de los fármacos , Colon/patología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Fármacos Gastrointestinales/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Endogámicos ICR , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Sustancias Protectoras/química , Sustancias Protectoras/uso terapéutico , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Sulfasalazina/farmacología , Sulfasalazina/uso terapéutico , Receptor Toll-Like 4/biosíntesis , Receptor Toll-Like 4/efectos de los fármacos , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Ácido Trinitrobencenosulfónico/toxicidadRESUMEN
Alcoholic fatty liver disease (AFLD), a major public health problem, has drawn clinical and scientific attention. The study aims to investigate the effect of Ganmeijian [crude extract of malt root, phosphoesterase complex (Pho)] on AFLD, and explore the possible mechanisms. An AFLD rat model was made. 30 and 60 mg/kg Pho were administrated through intestinal fistula for 5 weeks. Compared with those in model group, AST, LDL-C and TC in 30 mg/kg Pho group and TC in 60 mg/kg Pho group decreased. The mRNA level of Fas, Gpat1 and Srebp-1c in Pho groups was significantly reduced. The level of GSH-Px was increased, mitochondrial activity was improved, and the level of MDA and ROS was reduced in Pho groups. Pho shows a beneficial effect on AFLD. The mechanisms are possibly related to Pho inhibiting the expression of fat synthesis genes, protecting the function and increasing the activity of mitochondria in hepatocytes, then reducing the accumulation of ROS and the level of oxidative stress in the liver.