Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism

Abstract

Acute liver failure (ALF) is a serious clinical disorder with high fatality rates. Mahuang decoction (MHD), a well-known traditional Chinese medicine, has multiple pharmacological effects, such as anti-inflammation, anti-allergy, anti-asthma, and anti-hyperglycemia. In this study, we investigated the protective effect of MHD against ALF. In the lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced ALF mouse model, the elevated activities of the serum alanine and aspartate transaminases as well as the liver pathological damage were markedly alleviated by MHD. Subsequently, a metabolomics study based on the ultrahigh performance liquid chromatograph coupled with Q Exactive Orbitrap mass spectrometry was carried to clarify the therapeutic mechanisms of MHD against ALF. A total of 36 metabolites contributing to LPS/D-GalN-induced ALF were identified in the serum samples, among which the abnormalities of 27 metabolites were ameliorated by MHD. The analysis of metabolic pathways revealed that the therapeutic effects of MHD are likely due to the modulation of the metabolic disorders of tricarboxylic acid (TCA) cycle, retinol metabolism, tryptophan metabolism, arginine and proline metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan synthesis, as well as cysteine and methionine metabolism. This study demonstrated for the first time that MHD exerted an obvious protective effect against ALF mainly through the regulation of TCA cycle and amino acid metabolism, highlighting the importance of metabolomics to investigate the drug-targeted metabolic pathways.

Flos Carthami Exerts Hepatoprotective Action in a Rat Model of Alcoholic Liver Injury via Modulating the Metabolomics Profile

“…The enrichment analysis of the hub metabolites indicated their involvement in nicotinate and nicotinamide metabolism, retinol metabolism, “alanine, aspartate, and glutamate metabolism,” and tryptophan metabolism. A previous study found that nicotinate and nicotinamide metabolism was impaired in acute liver failure and could be reversed by mahuang decoction [ 45 ], which similarly corroborates with our present findings. Altered retinol metabolism has been incriminated in diverse liver conditions such as hepatic fibrosis and nonalcoholic fatty liver disease [ 46 ]; here, we also found similar results.…”

Plasma metabolomic and lipidomic alterations associated with anti-tuberculosis drug-induced liver injury

“…Pathway enrichment analysis of differential metabolites and differential lipid molecules revealed that several metabolic pathways, including drug metabolism-other enzymes, niacin and nicotinamide metabolism, tyrosine metabolism, tryptophan metabolism, ferroptosis, and unsaturated fatty acid biosynthesis pathways ( Tables 3 , 5 ), are related to the occurrence of ATB-DILI. Mahuang Decoction can significantly protect against DILI by regulating the metabolic pathways of niacin and nicotinamide and the metabolism of tryptophan ( Liao et al, 2021 ). Tyrosine and tryptophan biosynthesis and phenylalanine and tyrosine metabolism were found to be significantly associated with DILI in a hydrazine-induced rat liver injury model ( An et al, 2018 ).…”

Study on the mechanism of cadmium chloride pollution accelerating skin tissue metabolism disorder, aging and inhibiting hair regeneration

“…Oxidative damage induced by mitochondrial ROS production is an important molecular basis for various pathophysiological conditions, including aging and cancer ( 34 ). It was found that the metabolism of fatty acids and amino acids is an important pathway of the tricarboxylic acid cycle ( 35 ). Our results revealed that fatty acid, bile acid, and amino acid metabolites and metabolic pathways were reduced in response to Cd 2+ intervention, and the differential metabolites and metabolic pathways were more affected in the High-dose group.…”