The Metabonomic Study Of Salvianic Acid On Improving Acute Alcoholic Liver Injury

Objective: Salvianic acid(SA), the primary active component of Salvia miltiorrhiza, has been shown to play a significant role in antioxidant, reducing apoptosis and necrosis of liver cells, as well as promoting the proliferation of hepatic cell. So far, there has been little research regarding the effective effect and mechanism of the protective effect of SA on acute liver injury induced by alcohol. In the present study, we conducted 1H NMR-based metabolomics integrated with multivariate data analysis methods to identify the biochemical variations in metabolic profiles associated with acute alcohol exposure-induced liver damage and report the characterization of changes in acute liver damage models treated with SA, with the goal of shedding light on the underlying metabolic mechanisms of the effects of SA on acute alcoholic liver damage, providing a scientific basis for the clinical application of SA in treating acute alcoholic liver injury.Methods: In this study, we collected the plasma, urine and liver tissue samples of control group, acute alcoholic liver damage group(5g/kg ethanol ig.) and SA treatment group(20 mg/kg SA+5g/kg alcohol ig.). Then we systematically analysed the effect of SA on regulating the metabonomic changes induced by acute alcohol adminastration through using a 1H NMR-based metabonomics approach together with histopathological and clinical biochemistry assessments, shedding light on the underlying metabolic mechanisms of the effects of SA on acute alcoholic liver damage.Results: HE staining showed that the model rats presented acute alcoholic injury with a large area of edema, centrilobular inflammation and necrosis. SA treatment alleviated the hepatic damages. The clinical biochemistry examination results showed that SA treatment decreased the increased levels of serum ALT and AST induced by alcohol administration, which implying that SA promoted the recovery of liver function. Through the metabonomic study, we found that SA reversed the metabolic changes in the body fluid and tissue of model rats, the metabolic characteristics is closed to normal group.(1) SA treatment can reduce the levels of lactate, glycerol, acetate, creatine and ketone bodies in the plasma of model rats, but up-regultae the levels of glycine and TMAO/betaine.(2) SA treatment can decrease the urinary 3-hydroxybutyrate, creatine, creatinine, N-methyl nicotinamide and glycerol in model rats, as well as increase the levels of acetate, succinate, citrate, phenylalanine, TMAO, btaine and hippurate.(3) As for liver samples, SA can inhibit the increase of 3-hydroxybutyrate, lactate, alanine, tyrosine and acetate in model rats, up-regulate the levels of a number of amino acids(glycine, valine, leucine and isoleucine), succinate, choline, taurine, TMAO and betaine, and make them tend to normal levels.Conclusion: The histopathological and clinical biochemistry assessments demonstrated that SA treatment not only alleviated the hepatic damages but also promoted the recovery of liver function. Metabonomics study suggested that SA reverse such changes and perform its effect of therapeutic intervention mainly by regulating amino acid, glucolipid, nicotinamide and methylation metabolism, revealing the metabolic regulation mechanism of SA, providing a scientific basis for clinical application.