Effects of Chaga Medicinal Mushroom Inonotus obliquus (Agaricomycetes) Extracts on NOS-cGMP-PDE5 Pathway in Rat Penile Smooth Muscle Cells

Int J Med Mushrooms. 2020;22(10):979-990. doi: 10.1615/IntJMedMushrooms.2020035812.


Some medicinal mushrooms have effects on sexual dysfunctions. Nitric oxide synthase (NOS)-cyclic gua-nosine monophosphate (cGMP)-phosphodiesterase 5 enzyme (PDE5) pathway is one of the pathophysiological basis of erectile dysfunction (ED). The normal erectile function involves the synthesis of nitric oxide (NO), and the subsequent accumulation of cGMP, whereas cGMP degradation is specifically controlled by PDE5, which promotes corporal smooth muscle cell (SMC) tone and terminates erection. The antioxidant activities of Inonotus obliquus (chaga) water extracts (IO1) and water extraction and alcohol precipitation extracts (IO2) were compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and oxygen radical absorbance capacity (ORAC) method. Three subtypes of NOS (nNOS, iNOS, and eNOS) and PDE5 protein expressions were tested by Western blotting, and cGMP was determined by ELISA on a rat corporal primary SMC. The results revealed that IO2, which had a significantly higher polysaccharide content than IO1, showed a significantly higher ORAC value and a significantly lower half inhibitory concentration for DPPH scavenging activity than IO1. We observed that both IO1 and IO2 increased the expression of eNOS and iNOS significantly compared with the control. Furthermore, when compared with the control, IO1 increased PDE5 expression significantly, while IO2 showed no effect. The different impacts on PDE5 might be the reason that IO2, not IO1, showed significant inducible effect on cGMP compared with the control. This is to our knowledge, the first study exploring the effect of I. obliquus on NOS-cGMP-PDE5 pathway on SMC. The results provide a possible selection of I. obliquus for the treatment of ED.

MeSH terms

  • Agaricales / chemistry*
  • Animals
  • Cyclic GMP / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism*
  • Erectile Dysfunction / drug therapy
  • Erectile Dysfunction / genetics
  • Erectile Dysfunction / metabolism*
  • Erectile Dysfunction / physiopathology
  • Humans
  • Inonotus / chemistry*
  • Male
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Penis / metabolism
  • Penis / physiopathology
  • Plant Extracts / pharmacology*
  • Rats


  • Plant Extracts
  • Nitric Oxide Synthase
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Cyclic GMP