I-Tiao-Gung extract through its active component daidzin improves cyclophosphamide-induced bladder dysfunction in rat model

Neurourol Urodyn. 2018 Nov;37(8):2560-2570. doi: 10.1002/nau.23815. Epub 2018 Sep 3.

Abstract

Aims: We explored the therapeutic potential of intragastric administration traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung, ITG) extract and its active component Daidzin on cyclophosphamide (CYP)-induced cystitis and bladder hyperactivity in rats.

Methods: Female Wistar rats were divided into control, CYP (200 mg/kg), CYP + ITG (1.17 g/kg/day), CYP + Daidzin (12.5 mg/kg/day), and 1 week of ITG preconditioning with CYP (ITG + CYP) groups. We determined the trans cystometrogram associated with external urethral sphincter electromyogram, and the expression of M2 and M3 muscarinic and P2 × 2 and P2 × 3 purinergic receptors by Western blot in these animals.

Results: ITG extract contains 1.07% of Daidzin and 0.77% of Daidzein by high-performance liquid chromatography. Daidzin was more efficient than Daidzein in scavenging H2 O2 activity by a chemiluminescence analyzer. CYP induced higher frequency, shorter intercontraction interval, lower maximal voiding pressure, lower threshold pressure, and Phase-2 emptying contraction with a depressed external urethral sphincter electromyogram activity, and hemorrhagic cystitis in the bladders. The altered parameters by CYP were significantly improved in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. The P2 × 2 and P2 × 3 expressions were significantly upregulated in CYP group, but were depressed in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. The M2 expression was not significantly different among these five groups. The M3 expression was significantly upregulated in CYP group, but was significantly depressed in CYP + ITG, CYP + Daidzin, and ITG + CYP groups.

Conclusions: These data suggest that ITG extract through its active component Daidzin effectively improved CYP-induced cystitis by the action of restoring Phase 2 activity and inhibiting the expressions of P2 × 2, P2 × 3, and M3 receptors.

Keywords: I-Tiao-Gung; cyclophosphamide; daidzin; muscarinic receptor; overactive bladder; purinergic receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclophosphamide / toxicity
  • Cystitis / chemically induced
  • Cystitis / physiopathology
  • Drugs, Chinese Herbal / pharmacology*
  • Electromyography
  • Female
  • Isoflavones / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M2 / drug effects
  • Receptor, Muscarinic M2 / metabolism
  • Receptor, Muscarinic M3 / drug effects
  • Receptor, Muscarinic M3 / metabolism
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / metabolism
  • Urethra / drug effects
  • Urethra / physiopathology
  • Urinary Bladder / drug effects*
  • Urinary Bladder / metabolism
  • Urinary Bladder / physiopathology
  • Urinary Bladder, Overactive / chemically induced
  • Urinary Bladder, Overactive / physiopathology
  • Urination / drug effects

Substances

  • Drugs, Chinese Herbal
  • Isoflavones
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Receptors, Purinergic P2
  • daidzin
  • daidzein
  • Cyclophosphamide