The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

Andrzej Wróbel,Tomasz Kluz,Piotr Radziszewski,Ewa Poleszak,Daniela Gold,Łukasz Zapała,Klaudia Stangel-Wójcikiewicz,Jacek Sieńko,Artur Rogowski,Marcin Misiek,Kajetan Juszczak

doi:10.3390/ijms22115853

Abstract

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1β, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T–H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.

Highlights

Natural products have already attracted researchers’ attention for their use in many medical applications
A cyclophosphamide injection led to a significant increase in the following parameters in conscious cytometry: basal pressure (BP), detrusor overactivity index (DOI), non-voiding contraction amplitude (ANVC), non-voiding contraction frequency (FNVC), and the area under the pressure curve (Table 1)
In rats that received asiatic acid together with cyclophosphamide a major drop in BP, DOI, ANVC, FNVC, and AUC was observed when compared to the CYP group

Summary

Introduction

Natural products have already attracted researchers’ attention for their use in many medical applications. One of the new candidates is Centella asiatica, which represents a medicinal herb that may be a source of several natural agents, i.e., pentacyclic triterpenoid saponins, inclusively known as centelloids [1] An example of these chemical substances is asiatic acid (AA), an aglycone form of asiaticoside [2,3], found in other plants [4]. When analyzing the compound closely, it occurs that it exhibits a wide spectrum of biological activities, markedly anti-inflammatory and wound healing [6], as well as neuroprotective [7] or neuromodulatory properties [8]. Among its specific actions there are the modulation of oxidative stress and inflammatory cytokine production [9]

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