Glycine tomentella hayata extract and its ingredient daidzin ameliorate cyclophosphamide-induced hemorrhagic cystitis and oxidative stress through the action of antioxidation, anti-fibrosis, and anti-inflammation.

We explored the therapeutic potential of intragastric administration of traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung [ITG]) extract and its major component Daidzin on cyclophosphamide (CYP)-induced cystitis, oxidative stress, fibrosis, inflammation, and bladder hyperactivity in rats. Female Wistar rats were divided into control, CYP (200 mg/kg), CYP+ITG (1.17 g/kg/day), and CYP+Daidzin (12.5 mg/kg/day) groups. We measured the voiding function by the transcystometrogram and evaluated the pathology with the hematoxylin and eosin and Masson stain. We determined the bladder reactive oxygen species (ROS) amount by an ultrasensitive chemiluminescence analyzer, the expression of 3-nitrotyrosine (3-NT) and NADPH oxidase 4 (NOX4) by Western blot and the expression of multiple cytokine profiles, including matrix metalloproteinase (MMP)-8 and tissue inhibitor of metalloproteinase (TIMP)-1 through a cytokine array. ITG extract contains 1.07% of Daidzin through high-performance liquid chromatography. The effect of ITG extract and Daidzin in scavenging hydrogen peroxide activity was more efficient than distilled water. CYP-induced higher urination frequency, shorter intercontraction interval, and lower maximal voiding pressure in the bladders and these symptoms were significantly ameliorated in CYP+ITG and CYP+Daidzin groups. The amount of in vivo bladder ROS and the expression of 3-NT and NOX4 expressions were significantly increased in CYP group but were efficiently decreased in the CYP+ITG and CYP+Daidzin groups. CYP-induced fibrosis, hemorrhage, leukocyte infiltration, and edema in the bladders were significantly attenuated in the CYP+ITG and CYP+Daidzin groups. These results suggested that ITG extract and its active component Daidzin effectively improved CYP-induced oxidative stress, inflammation, and fibrosis through inhibiting the MMP-8, TIMP-1, and oxidative stress.

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

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.