Synergistic Differential DNA Demethylation Activity of Danshensu ( Salvia miltiorrhiza ) Associated with Different Probiotics in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a major hepatic disorder occurring in non-alcohol-drinking individuals. Salvianic acid A or (DSS, 3-(3, 4-dihydroxyphenyl)-(2 )-lactic acid), derived from the root of ( ), has demonstrated heart and liver protective properties. In this work, we investigated the antioxidant activity and hepatoprotective activity of alone and in combination with different agents, such as probiotic bacteria ( and ), against several assays. The inhibition mechanism of the methylation gene biomarkers, such as DNMT-1, MS, STAT-3, and TET-1, against DSS was evaluated by molecular docking and RT-PCR techniques. The physicochemical and pharmacokinetic ADMET properties of DSS were determined by SwissADME and pkCSM. The results indicated that all lipid blood test profiles, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were reduced after the oral administration of combined with probiotics ( and ) that demonstrated good, efficient free radical scavenging activity, measured using anti-oxidant assays. ADMET and drug-likeness properties certify that the DSS could be utilized as a feasible drug since DSS showed satisfactory physicochemical and pharmacokinetic ADMET properties.