Renoprotective potentials of small molecule natural products targeting mitochondrial dysfunction

Abstract

Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), have become critical clinical, socioeconomic, and public health concerns worldwide. The kidney requires a lot of energy, and mitochondria act as the central organelle for the proper functioning of the kidney. Mitochondrial dysfunction has been associated with the pathogenesis of AKI and CKD. Natural products and their structural analogs have been sought as an alternative therapeutic strategy despite the challenges in drug discovery. Many studies have shown that small-molecule natural products can improve renal function and ameliorate kidney disease progression. This review summarizes the nephroprotective effects of small-molecule natural products, such as berberine, betulinic acid, celastrol, curcumin, salidroside, polydatin, and resveratrol. Treatment with small-molecule natural products was shown to attenuate renal oxidative stress and mitochondrial DNA (mtDNA) damage and restore mitochondrial biogenesis and dynamics in the kidneys against various injury stimuli. Therefore, small-molecule natural products should be recognized as multi-target therapeutics and promising drugs to prevent kidney diseases, particularly those with mitochondrial dysfunction.

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

“…Stress affects the connection between BCL2 and BAX/BAK, increasing apoptosis [ 45 ]. During continued stress, BECN1 is cleaved by caspase and translocates to the mitochondria, increasing apoptosis [ 46 ]. Depending on its length, BECN1 can induce autophagy or apoptosis [ 43 ].…”

Natural products for kidney disease treatment: Focus on targeting mitochondrial dysfunction

“…Mitochondrial quality control (MQC) is an elaborate mechanism to maintain homeostasis, ensuring the enough numbers of functional mitochondria ( Pickles et al, 2018 ; Huang et al, 2022b ). Involving mitochondrial biogenesis, dynamics, and mitophagy, mitochondrial homeostasis is intimately correlated with normal kidney function ( Rahman et al, 2022 ) ( Figure 1 ). Large reports have shown mitochondrial dysfunction is closely related to the progression of kidney diseases ( Galvan et al, 2017 ).…”

“…Mitochondrial structure and morphology plays a key role in energy production. They are tightly controlled by mitochondrial dynamics and mitophagy ( Rahman et al, 2022 ). With a highly dynamic action, mitochondria frequently remodel themselves through fusion and fission cycles ( Forbes and Thorburn, 2018 ; Mu et al, 2020 ; Liang et al, 2021 ).…”

“…Excessive ROS could lead to the depolarization of IMM, the opening of mitochondrial permeability transition pore (mPTP), and the leakage of cytochrome c (Cytc) into the cytoplasm. Furthermore, caspase signaling pathway would be activated to induce cell apoptosis and the development of kidney diseases ( Sinha et al, 2013 ; Galvan et al, 2017 ; Mani et al, 2020 ; Zhang et al, 2021a ; Rahman et al, 2022 ).…”

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases

“…However, ARE-containing gene is extensively controlled by Nrf2 in association with glutathione (GSH) homeostasis, NAD(P)H quinone oxidoreductase 1 (NQO1), and UDP-glucosyltransferase (UDP) [ 47 , 48 ]. Multiple causes of chronic liver disease result in inflammatory responses and necrosis, which destroy liver tissue and lead ultimately to liver cirrhosis [ 49 , 50 ]. Liver fibrosis is a clinical stage of nearly all chronic liver illnesses preceding cirrhosis, and its histology is characterized by excessive accumulation of extracellular matrix and inflammatory responses that interfere with the normal liver function [ 51 ].…”