| Description: |
Oleanolic acid is a non-toxic, hepatoprotective triterpenoid found in Phytolacca Americana, which exerts antitumor, anti-inflammatory, antioxidant, and antiviral properties. Oleanolic acid exhibits anti-HCV activity at least partly through suppressing HCV NS5B RdRp activity as a noncompetitive inhibitor; it induces the upregulation of miR-132, which serves as an important regulator of neurotrophic actions, mainly through the activation of the hippocampal BDNF-ERK-CREB signalling pathways; can be employed as a lead in the development of potent NO inhibitors. Oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway.
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| In vitro: |
| Bioorg Med Chem Lett. 2014 Sep 1;24(17):4114-9. | | Oleanolic acid analogs as NO, TNF-α and IL-1β inhibitors: synthesis, biological evaluation and docking studies.[Pubmed: 25113933] | A series of oleanolic acid analogs, characterized by structural modifications at position C-3 and C-28 of oleanane skeleton were synthesized and assessed for antiinflammatory potential towards lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophages.
METHODS AND RESULTS:
Results revealed that all the synthesized analogs of oleanolic acid inhibit NO production with an IC50 of 2.66-41.7 μM as compared to the specific nitric oxide synthase (NOS) inhibitor, L-NAME (IC50=69.21 and 73.18 μM on RAW 264.7 and J774A.1 cells, respectively) without affecting the cell viability when tested at their half maximal concentration. The most potent NO inhibitors (2, 8, 9 and 10) at a concentration of 20 μg/mL also demonstrated mild inhibition (27.9-51.9%) of LPS-induced tumor necrosis factor alpha (TNF-α) and weak inhibition (11.1-37.5%) towards interleukin 1-beta (IL-1β) production in both the cells.
CONCLUSIONS:
The present study paves a direction that analogs of oleanolic acid can be employed as a lead in the development of potent NO inhibitors. Molecular docking studies also showed that 10 (with top Goldscore docking pose 19.05) showed similar interaction as that of co-crystallized inhibitor and, thereby, helps to design the potent inhibitors of TNF-α. | | Antiviral Res. 2013 Apr;98(1):44-53. | | Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity.[Pubmed: 23422646 ] | Hepatitis C virus (HCV) infects up to 170 million people worldwide and causes significant morbidity and mortality. Unfortunately, current therapy is only curative in approximately 50% of HCV patients and has adverse side effects, which warrants the need to develop novel and effective antivirals against HCV. We have previously reported that the Chinese herb Fructus Ligustri Lucidi (FLL) directly inhibited HCV NS5B RNA-dependent RNA polymerase (RdRp) activity (Kong et al., 2007).
METHODS AND RESULTS:
In this study, we found that the FLL aqueous extract strongly suppressed HCV replication. Further high-performance liquid chromatography (HPLC) analysis combined with inhibitory assays indicates that oleanolic acid and ursolic acid are two antiviral components within FLL aqueous extract that significantly suppressed the replication of HCV genotype 1b replicon and HCV genotype 2a JFH1 virus. Moreover, oleanolic acid and ursolic acid exhibited anti-HCV activity at least partly through suppressing HCV NS5B RdRp activity as noncompetitive inhibitors.
CONCLUSIONS:
Therefore, our results for the first time demonstrated that natural products oleanolic acid and ursolic acid could be used as potential HCV antivirals that can be applied to clinic trials either as monotherapy or in combination with other HCV antivirals. |
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