The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity.

Abstract

BACKGROUND AND PURPOSE:

Apigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity.

EXPERIMENTAL APPROACH:

Male C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations.

KEY RESULTS:

When compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens.

CONCLUSIONS AND IMPLICATIONS:

Apigenin prevents systemic metabolic alterations, counteracts enteric inflammation and normalizes colonic dysmotility associated with obesity.

• Authors: Daniela Gentile, Matteo Fornai, Rocchina Colucci, Carolina Pellegrini, Erika Tirotta, Laura Benvenuti, Cristina Segnani, Chiara Ippolito, Emiliano Duranti, Agostino Virdis, Sara Carpi, Paola Nieri, Zoltán H Németh, Laura Pistelli, Nunzia Bernardini, Corrado Blandizzi, Luca Antonioli
• Journal: PloS one (PLoS One) Vol. 13 Issue 4 Pg. e0195502 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 29641549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonoids
• Interleukin-1beta
• Interleukin-6
• MicroRNAs
• Substance P
• Malondialdehyde
• Apigenin
• Nitric Oxide Synthase Type II

Topics

• Adipose Tissue (drug effects, pathology)
• Animals
• Apigenin (pharmacology)
• Body Weight (drug effects)
• Colon (drug effects, metabolism, pathology)
• Diet, High-Fat (adverse effects)
• Eosinophils (drug effects, immunology)
• Flavonoids (pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Inflammation (metabolism, pathology, physiopathology, prevention & control)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Male
• Malondialdehyde (metabolism)
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Motor Activity (drug effects)
• Muscle, Smooth (drug effects, physiopathology)
• Nitric Oxide Synthase Type II (metabolism)
• Obesity (chemically induced, metabolism, pathology, physiopathology)
• Organ Size (drug effects)
• Substance P (metabolism)