Aims. Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organs, on detrusor contractility and bladder wall remodeling process. Methods. Partial BOO (pBOO) was created by urethral occlusion in female rats, followed by oral gavage of different dose of AS-IV or vehicle. Cystometric evaluation and contractility test were performed. Bladder wall sections were used in morphology staining, and bladder tissue lysate was used for ELISA assay. Primary smooth muscle cells (SMCs) derived from detrusor were used for mechanism studies. Results. Seven weeks after pBOO, the bladder compensatory enlarged, and the contractility in response to electrical or chemical stimuli was reduced, while AS-IV treatment reversed this effect dose-dependently. AS-IV also showed beneficial effect on reversing the bladder wall remodeling process, as well as reducing ROS level. In mechanism study, AS-IV activated mitophagy and alleviated oxidative stress via an AMPK-dependent pathway. Conclusion. Out data suggested that AS-IV enhanced the contractility of detrusor and protected the bladder from obstruction induced damage, via enhancing the mitophagy and restoring mitochondria function trough an AMPK-dependent way.
This study aims to evaluate the therapeutic potential of cationic liposomal neostigmine bromide (NB), a novel drug delivery system, for the treatment of detrusor underactivity. By comparing the characteristics of NB-liposomes (NLP), NB-β-cyclodextrin inclusion complex liposomes (NCLP), and NB-mesoporous silica nanoparticle@CaCO 3 liposomes (NMCLP), NMCLP is selected as the main research subject. It has an average particle size and zeta potential of 100 nm and +50 mV, and its encapsulation efficiency and loading capacity of NB are 14.75% and 12.8%, respectively. Most importantly, NMCLP shows the best in vitro release performance among the three liposomes, demonstrating its ability in sustained release of NB. During cell and animal assays, efficient cellular uptake of liposomes through liposome-specific pathways is observed, facilitating targeted drug delivery, and in vivo experiments demonstrate the efficacy of NMCLP in improving bladder function in mice. Urodynamic measurements show increased bladder capacity and reduced voiding pressure, indicating enhanced bladder muscle activity. Histological analysis reveals the distribution and deep penetration of NMCLP within bladder tissues, supporting its localized drug effect. Therefore, NMCLP holds promise as a targeted and effective therapeutic strategy for detrusor underactivity.
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