Synergistic Differential DNA Demethylation Activity of <i>Danshensu</i> (<i>Salvia miltiorrhiza</i>) Associated with Different Probiotics in Nonalcoholic Fatty Liver Disease
Amr Hassan,
Patrícia Rijo,
Tamer M. M. Abuamara,
Lashin Saad Ali Lashin,
Sherif A. Kamar,
Gabrielle Bangay,
Majid Mohammed Al-Sawahli,
Marina K. Fouad,
Mohammad A. Zoair,
Tamer I. Abdalrhman,
Dalia Elebeedy,
Ibrahim A. Ibrahim,
Aly F. Mohamed,
Ahmed I. Abd El Maksoud
Affiliations
Amr Hassan
Department of Bioinformatics, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat 32897, Egypt
Patrícia Rijo
CBIOS—Lusófona University’s Research Center for Biosciences and Health Technologies, 1749-024 Lisbon, Portugal
Tamer M. M. Abuamara
Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman 19111, Jordan
Lashin Saad Ali Lashin
Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman 19111, Jordan
Sherif A. Kamar
Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman 19111, Jordan
Gabrielle Bangay
CBIOS—Lusófona University’s Research Center for Biosciences and Health Technologies, 1749-024 Lisbon, Portugal
Majid Mohammed Al-Sawahli
Department of Pharmaceutics, College of Pharmacy, The Islamic University, Najaf 54001, Iraq
Marina K. Fouad
College of Biotechnology, Misr University of Science and Technology, Giza 12573, Egypt
Mohammad A. Zoair
Department of Physiology, Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt
Tamer I. Abdalrhman
Department of Histology, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt
Dalia Elebeedy
College of Biotechnology, Misr University of Science and Technology, Giza 12573, Egypt
Ibrahim A. Ibrahim
Department of Plant Biotechnology, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat 32897, Egypt
Aly F. Mohamed
Holding Company for Vaccine and Sera Production (VACSERA), Giza 22311, Egypt
Ahmed I. Abd El Maksoud
College of Biotechnology, Misr University of Science and Technology, Giza 12573, Egypt
Nonalcoholic fatty liver disease (NAFLD) is a major hepatic disorder occurring in non-alcohol-drinking individuals. Salvianic acid A or Danshensu (DSS, 3-(3, 4-dihydroxyphenyl)-(2R)-lactic acid), derived from the root of Danshen (Salvia miltiorrhiza), has demonstrated heart and liver protective properties. In this work, we investigated the antioxidant activity and hepatoprotective activity of Danshensu alone and in combination with different agents, such as probiotic bacteria (Lactobacillus casei and Lactobacillus acidophilus), 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 Danshensu combined with probiotics (L. casei and L. acidophilus) 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.
