Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant-like effect of Wuling mycelia powder in rat

Biomed Pharmacother. 2016 Mar:78:60-65. doi: 10.1016/j.biopha.2015.12.016. Epub 2016 Jan 11.

Abstract

Context: Wuling mycelia powder is the dry powder of rare a fungi Xyla ria sp., Carbon species, with a long history of medicinal use in Chinese medicine. Recently it has shown a powerful antidepressant activity in clinic.

Objective: The present study explores the antidepressant activity of Wuling mycelia powder in chronic unpredictable mild stress (CUMS) rats and its possible involvement of l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway.

Materials and methods: Experiments were performed in the rat CUMS model. CUMS rats were treated with Wuling mycelia powder (0.5, 1.0 or 2.0 g/kg, i.g.) to test behavioral changes including the sucrose preference, the crossing number and food consumption. Further, L-arginine (substrate for nitric oxide) (750 mg/kg), 7-nitroindazole (a specific neuronal nitric oxide synthase inhibitor) (25 mg/kg), sildenafil (phosphodiesterase 5 inhibitor) (5 mg/kg) and methylene blue (direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase) (10 mg/kg) were treated for 60 min before each test to detect the possible mechanism of antidepressant-like effect of Wuling mycelia powder.

Results: After 4 weeks of administration, both 1.0 or 2.0 g/kg Wuling mycelia powder suppressed the behavioral changes including the sucrose preference [F(3, 31)=50.87, p<0.001], the crossing number [F(3, 31)=68.98, p<0.05], and food consumption [F(3, 31)=19.04, p<0.05] in the CUMS rats. The antidepressant-like effect of Wuling mycelia powder was prevented by pretreatment with l-arginine and sildenafil. Pretreatment of rats with 7-nitroindazole and methylene blue potentiated the effect of Wulin mycelia powder.

Discussion and conclusion: Our findings demonstrate that Wuling mycelia powder has an antidepressant-like effect in the CUMS rats, and possible involvement of L-arginine-nitric oxide-cyclic GMP signaling pathway in its antidepressant effect.

Keywords: 7-Nitroindazole; Methylene; Sildenafil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Arginine / metabolism*
  • Cyclic GMP / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry*
  • Feeding Behavior / drug effects
  • Food Preferences
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Indazoles / chemistry
  • Male
  • Methylene Blue / chemistry
  • Mycelium / chemistry*
  • Nitric Oxide / metabolism*
  • Powders
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Sildenafil Citrate / chemistry
  • Stress, Psychological / drug therapy
  • Sucrose

Substances

  • Antidepressive Agents
  • Drugs, Chinese Herbal
  • Indazoles
  • Powders
  • wuling
  • Nitric Oxide
  • Sucrose
  • Arginine
  • Sildenafil Citrate
  • Cyclic GMP
  • Methylene Blue
  • 7-nitroindazole