A selanylimidazopyridine (3-SePh-IP) reverses the prodepressant- and anxiogenic-like effects of a high-fat/high-fructose diet in mice

J Pharm Pharmacol. 2021 Mar 27;73(5):673-681. doi: 10.1093/jpp/rgaa070.

Abstract

Objective: While chronic feeding with high-fat or high-sugar diets is known related to obesity and type 2 diabetes, later data have indicated that it is also related to depression and anxiety appearance. In this regard, multi-target drugs raise considerable interest as promising therapeutic solutions to complex diseases. Considering the pharmacological effects of the imidazopyridine-derivative moiety imidazo[1,2-a]pyridine and the organoselenium molecules, the combination of both could be a feasible strategy to develop efficient drugs to handle obesity and related comorbidities, for example dyslipidemia and mood disorders.

Methods: The antidepressant- and anxiolytic-like properties of a selanylimidazopyridine compound, 2-Phenyl-3-(phenylselanyl)imidazo[1,2-a]pyridine (3-SePh-IP), were evaluated on high-fat/high-fructose diet (HFFD)-fed female Swiss mice.

Key findings: Our results showed that a short-term HFFD (16 days) could promote a significant body weight gain, hypercholesterolemia, glucose intolerance, and anxiety- and depressive-like behaviour in mice. Concomitant treatment with 3-SePh-IP (10 mg/kg; i.p.) attenuated the HFFD-induced increase in cholesterol levels and blunted the anxiety- and depressive-like behaviour in mice.

Conclusions: 3-SePh-IP holds multimodal pharmacological properties, which provide a rationale for further studies, for example to assess the underlying mechanisms linked to its anxiolytic- and antidepressive-like activities.

Keywords: behavioural; imidazopyridine; obesity; selenium.

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / drug therapy*
  • Behavior, Animal / drug effects
  • Depression / chemically induced
  • Depression / drug therapy*
  • Diet, High-Fat / adverse effects*
  • Drug Therapy, Combination
  • Female
  • Fructose / adverse effects*
  • Hindlimb Suspension
  • Imidazoles / pharmacology*
  • Mice
  • Organoselenium Compounds / pharmacology*
  • Pyridines / pharmacology*
  • Weight Gain / drug effects

Substances

  • Imidazoles
  • Organoselenium Compounds
  • Pyridines
  • imidazopyridine
  • Fructose