ReferenceID 2523
Upregulation of UGT1A1 expression by ursolic acid and oleanolic acid via the inhibition of the PKC/NF-κB signaling pathway
Phytomedicine
BACKGROUND: Isomeric ursolic acid (UA) and oleanolic acid (OA) compounds have recently garnered great attention due to their biological effects. Previously, it had been shown that UA and OA can exert important pharmacolo
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 2523
- Evidence Id
- 19113
- Core Evidence Id
- 19113
- Source Reference Id
- 5043
- Herb2 Reference Id
- HBREF005840
- Subject Paper Key
- HBIN037940_34536821
- Pubmed Id
- 34536821
- Doi
- 10.1016/j.phymed.2021.153726
- Paper Title
- Upregulation of UGT1A1 expression by ursolic acid and oleanolic acid via the inhibition of the PKC/NF-κB signaling pathway
- Paper Abstract
- BACKGROUND: Isomeric ursolic acid (UA) and oleanolic acid (OA) compounds have recently garnered great attention due to their biological effects. Previously, it had been shown that UA and OA can exert important pharmacological action via the protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) signaling, and that they can induce the expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) in HepG2 cells. This study aims to investigate the role of PKC/NF-kappaB signaling in regulating the expression of UGT1A1 and examine how UA and OA induce UGT1A1 based on this signaling pathway. METHODS: HepG2 cells, hp65-overexpressed HepG2 cell and lentivirus-hp65-shRNA silenced HepG2 cells were stimulated with PKC/NF-kappaB specific agonists and inhibitors for 24 h in the presence or absence of UA and OA. The expression of UGT1A1, PKC, and NF-kappaB were determined by qRT-PCR, western blot, and dual-luciferase reporter gene assays. RESULTS: PKC/NF-kappaB activation downregulates UGT1A1 expression. This effect is countered by UA and OA treatment. Phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS), the agonists of PKC and NF-kappaB signaling, respectively, significantly inhibit hp65-mediated UGT1A1 luciferase activity. UA, OA, and the PKC/NF-kappaB inhibitors suppress this effect. PMA and LPS do not affect UGT1A1 activity in p65-silenced HepG2 cells; however, UA and OA mildly influence UGT1A1 expression in these cells. CONCLUSION: The activation of PKC/NF-kappaB signaling can significantly downregulate UGT1A1 expression. By inhibiting the PKC/NF-kappaB signaling pathway, UA and OA promote UGT1A1 expression in HepG2 cells.
- Journal
- Phytomedicine
- Publish Year
- 2021
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Upregulation of UGT1A1 expression by ursolic acid and oleanolic acid via the inhibition of the PKC/NF-κB signaling pathway
- Bilingual Status
- semi_complete