Thunbergia laurifolia extract minimizes the adverse effects of toxicants by regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression in HepG2 cells.
Thunbergia laurifolia (TL) is widely used as an antidote in Thai traditional medicine against toxic substances such as alcohol, pesticides, arsenic, and strychnine. We found that the lyophilized form of TL in 80% ethanol possessed the antioxidant levels within the range 23,163.9 ± 1457.4 Trolox equivalents mM/kg dry mass and 899.8 ± 14.5 gallic acid equivalents mM/kg dry mass using the oxygen radical absorbance capacity assay and the Folin Ciocalteu phenol assay, respectively. TL extract (TLE) at a high dose (3000 mg/L) induced cytotoxicity according to the neutral red assay and the MTT assay. However, TLE doses of 800-3000 mg/L could reduce intracellular oxidative stress in a dose-dependent manner (P < 0.05) using the dichlorodihydrofluorescein diacetate assay. TLE significantly enhanced the mRNA expression of CYP1A1, CYP1A2, CYP2B6, CYP3A4, and PPARg, but it significantly inhibited the mRNA expression of CYP3A7, CYP2D6, and CYP2E1 (P < 0.05) by reverse transcription-polymerase chain reaction. Moreover, TLE could increase the activity of a multidrug transporter, P-glycoprotein, which accelerated the excretion of toxic substances from HepG2 cells. It is suggested that TLE may be beneficial for detoxification by reducing oxidative stress, minimizing toxicity by regulating the expression CYP450 mRNAs for suitable production of CYP450 isoenzymes, and increasing PPARγ mRNA expression and P-glycoprotein activity in HepG2 cells, thereby maintaining xenobiotic biotransformation balance.
Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
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Rocejanasaroj
Center for Excellence in Omics-Nano Medical Technology Development Project, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
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Tencomnao
Center for Excellence in Omics-Nano Medical Technology Development Project, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand warin.s@chula.ac.th.
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Sangkitikomol
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D027901:Acanthaceae / Q000737:chemistry*; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D047495:PPAR gamma; D010936:Plant Extracts; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System