RESUMO
BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.
Assuntos
Constipação Intestinal/tratamento farmacológico , Fibras na Dieta/uso terapêutico , Intestinos/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Água/metabolismo , Animais , Aquaporina 3/genética , Aquaporina 3/metabolismo , Constipação Intestinal/sangue , Constipação Intestinal/genética , Constipação Intestinal/fisiopatologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fibras na Dieta/farmacologia , Fezes , Microbioma Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Dureza , Umidade , Polissacarídeos/química , Polissacarídeos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Transcrição Gênica/efeitos dos fármacos , Resultado do Tratamento , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/genéticaRESUMO
We investigated the efficacy and safety of a new type of dietary fiber (high specific volume polysaccharide) for use in treating constipation of different etiologies. Functional constipation patients and irritable bowel syndrome-constipation (IBS-C) patients were administrated high specific volume polysaccharide (HSVP) three times daily for a period of 2 wk to relieve their symptoms. Scores on a stool form scale, and patient reports of straining during a bowel movement, having sensations of an incomplete bowel movement or a blocked anorectum, and abnormal defecation intervals were recorded, graded, and scored by a functional constipation sample group. Similarly, a cohort of IBS-C patients reported their occurrence of abdominal discomfort or pain, abnormal stool formation, defecation frequency, and straining during a bowel movement. Additionally, both groups reported any adverse reactions associated with taking HSVP. All patients in both groups returned for follow-up visits, and no adverse reactions to treatment with HSVP were reported. In the functional constipation group, HSVP was effective for treating symptoms of constipation in 81.46% and 93.17% of patients after 7 and 14 d of dosing, respectively (both p<0.05). In the IBS-C group, symptoms of constipation were relieved in 71.67% and 88.34% of patients after 7 and 14 d of dosing, respectively (both p<0.05). High specific volume polysaccharide was shown be effective for treatment of functional constipation and IBS-C, without causing significant adverse events.
Assuntos
Constipação Intestinal/tratamento farmacológico , Defecação/efeitos dos fármacos , Fibras na Dieta/administração & dosagem , Síndrome do Intestino Irritável/complicações , Polissacarídeos/administração & dosagem , Adulto , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Fezes , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
In the title mol-ecule, C(24)H(17)N(3)O, the mean plane of the indolone ring forms dihedral angles of 112.0â (1) and 103.1â (1)° with the planes of the two indole rings. The dihedral angle between the mean planes of the two indole rings is 63.5â (1)°. In the crystal structure, mol-ecules are linked via inter-molecular N-Hâ¯O hydrogen bonds, forming a two-dimensional network parallel to the ab plane.