Pharmacological potential of Chinese botanical drugs in managing chronic kidney disease by targeting mitochondrial quality control

Abstract

Chronic kidney disease (CKD) is a multifactorial health issue characterized by structural and functional impairments of the kidneys, with significant incidence and mortality rates in global populations. Mitochondrial quality control (MQC) comprises cellular mechanisms that maintain mitochondrial health, and imbalances in the MQC system, including abnormalities in mitochondrial oxidative stress, dynamics, biogenesis, autophagy, and apoptosis, have been implicated in the onset and progression of CKD. In addition, the interplay between gut microbiota, microbial metabolites, and mitochondrial integrity has gained increasing attention in CKD research. Consequently, therapeutic strategies targeting MQC have attracted considerable research interest. Chinese botanical drugs (CBD), known for their multi-component, multi-target profiles and favorable safety, demonstrate considerable potential in slowing CKD progression by modulating MQC. This review systematically summarizes current evidence on CBD metabolites and formulations that ameliorate CKD through MQC regulation. Firstly, we outline the mechanisms of action of MQC system, with a focus on its role in CKD. We then discussed the pivotal role of the gut microbiota-microbial metabolites-mitochondria axis in the progression of CKD. Finally, we provide a summary of CBD metabolites and formulations that target the MQC system for CKD treatment to date, and explore their specific therapeutic mechanisms. Despite promising preclinical findings, we also critically assess limitations within the available literature, such as methodological variability and a lack of clinical validation. By integrating current knowledge and identifying key research gaps, this review aims to inform future studies and advance the development of CBD-based therapies for CKD.