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

Area of Science:

• Pharmacology and Toxicology
• Urology
• Traditional Chinese Medicine

Background:

• Cyclophosphamide (CYP) is a chemotherapeutic agent known to induce hemorrhagic cystitis and bladder dysfunction.
• Bladder hyperactivity, characterized by increased urinary frequency and urgency, is a common and distressing side effect of CYP treatment.
• Current therapeutic options for CYP-induced cystitis are limited, highlighting the need for novel treatment strategies.

Purpose of the Study:

• To investigate the therapeutic efficacy of intragastric I-Tiao-Gung (ITG) extract and its active component Daidzin in a rat model of CYP-induced cystitis and bladder hyperactivity.
• To elucidate the underlying mechanisms, including the modulation of muscarinic and purinergic receptors, involved in the therapeutic effects of ITG and Daidzin.

Main Methods:

• Female Wistar rats were administered CYP to induce cystitis and bladder hyperactivity.
• Animals were treated with ITG extract, Daidzin, or a combination, including ITG preconditioning.
• Cystometrograms, external urethral sphincter electromyogram activity, and the expression of M2/M3 muscarinic and P2×2/P2×3 purinergic receptors were assessed.

Main Results:

• ITG extract, containing Daidzin and Daidzein, demonstrated significant antioxidant activity.
• CYP-induced bladder dysfunction, characterized by increased frequency, reduced voiding pressure, and hemorrhagic cystitis, was significantly ameliorated by ITG and Daidzin treatments.
• Treatment groups showed a significant downregulation of P2×2, P2×3, and M3 receptor expressions, while M2 expression remained unchanged.

Conclusions:

• Intragastric administration of ITG extract, primarily through its active component Daidzin, effectively treats CYP-induced cystitis and bladder hyperactivity in rats.
• The therapeutic effects are attributed to the restoration of normal bladder activity and the inhibition of P2×2, P2×3, and M3 receptor upregulation.
• ITG and Daidzin represent promising natural therapeutic agents for managing chemotherapy-induced bladder complications.