Abstract
In recent years, the incidence of diseases associated with hepatic injury has increased in prevalence. Targeting the mitochondria to protect liver function has gained momentum due to their central role in energy production, apoptotic cell death, oxidative stress, calcium homeostasis, and lipid metabolism. In this study, we employed a hepatic mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method (CM-HMC) to identify hepatic mitochondria ligands from medicinal herbs (MHs) including Notopterygii Rhizoma et Radix (NRR) that possess hepatic-protective effects. A total of 4 newly identified mitochondrial ligands were successfully identified by CM-HMC. The mitochondria-regulating activities of 3 of the 4 hits were confirmed using isolated mitochondria. The hepatic-protective effects of one of these hits were validated in carbon tetrachloride-damaged human liver L02 cell models. We have thus identified new natural hepatic-protectants that enhance our understanding of the hepatic-protective mechanisms of MHs. CM-HMC was proven to efficiently screen for mitochondrial ligands from MHs.
Highlights
The occurrence of liver injury and liver-related morbidity has increased in recent years [1]
A growing body of evidence suggests that mitochondrial disorders result in liver injury through an array of pathways [8,9,10] including the inhibition of mitochondrial β-oxidation and respiratory chain function, collapse of the mitochondrial membrane potential (∆Ψm) through mitochondrial membrane permeability transition protein opening, and damage to the antioxidant defense system
chromatography/mass spectrometry method (CM-HMC) was developed through the coupling of centrifugal ultrafiltration (CU) with liquid chromatography/mass spectrometry (LC/MS) to directly identify hepatic mitochondria (HM)-targeted constituents from complex medicinal herbs (MHs) samples [17]
Summary
The occurrence of liver injury and liver-related morbidity has increased in recent years [1]. Liver damage is mainly caused by external factors, including viruses, alcohol, and drugs, which induce the production of free radicals and cytokines and enhance lipid peroxidation. The culmination of these effects promotes hepatocyte apoptosis and liver fibrosis, resulting in liver cirrhosis and carcinoma [2,3,4]. Mitochondria play an important role in energy production, apoptotic cell death, oxidative stress, calcium homeostasis, and lipid metabolism [7]. They would be better altering the order of the mitochondria-related functions/ consequences. Methods to recover normal mitochondrial function represent clinically favorable therapies to cure liver injury
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