| In vitro: |
| Chem Biol Interact. 2012 Aug 30;199(2):112-9. | | Pimaric acid from Aralia cordata has an inhibitory effect on TNF-α-induced MMP-9 production and HASMC migration via down-regulated NF-κB and AP-1.[Pubmed: 22705379] | Many studies have indicated that activation of matrix metalloproteinase (MMP)-9 and smooth muscle cell (SMC) migration are involved in neointimal formation and atherosclerosis. In this study, we revealed that Pimaric acid (PiMA) purified from Aralia cordata had an inhibitory effect on MMP-9 production and migration of human aortic smooth muscle cells (HASMCs) induced by tumor necrosis factor (TNF)-α.
METHODS AND RESULTS:
Down-regulated MMP-9 mRNA transcription was detected in Pimaric acid-treated cells using RT-PCR and the luciferase-tagged MMP-9 promoter assay. Results of an electrophoretic mobility shift assay indicated that Pimaric acid-treated HASMCs showed decreased binding activity of nuclear factor (NF)-κB and activator protein-1 transcription factors. A Western-blot analysis using nuclear extract demonstrated that Pimaric acid reduced the levels of NF-κB p65, c-Fos, p-c-Jun, Jun-D, and p-ATF2 proteins in the nucleus. In addition, TNF-α stimulated mitogen activated protein kinase (MAPK) containing extracellular signal regulated kinase 1 and 2, p38, and c-Jun N-terminal kinase was inhibited by Pimaric acid. Using the Transwell system, we found that Pimaric acid inhibited TNF-α stimulated HASMC migration/invasion in a dose-dependent manner. To confirm whether MAPK mediated MMP-9 expression, we used MAPK inhibitors including U0126, SB253580, and SP600125 and found that those inhibitors reduced MMP-9 expression and HASMC migration/invasion.
CONCLUSIONS:
These results suggest that Pimaric acid has potent anti-atherosclerotic activity with inhibitory action on MMP-9 production and cell migration in TNF-α-induced HASMCs. | | Eur J Clin Microbiol Infect Dis. 2012 Feb;31(2):149-59. | | 4-epi-Pimaric acid: a phytomolecule as a potent antibacterial and anti-biofilm agent for oral cavity pathogens.[Pubmed: 21594714] |
METHODS AND RESULTS:
The present study focused on the antibacterial and biofilm inhibitory potential of 4-epi-Pimaric acid isolated from aerial parts (stem and leaves) of Aralia cachemirica L. (Araliaceae) against oral cavity pathogens. 4-epi-Pimaric acid exhibited minimum inhibitory concentration (MIC) in the range of 4-16 μg/ml and minimum bactericidal concentration (MBC) two- to four-folds higher than MIC. There was significant inhibition in the biofilm formation by Streptococcus mutans on the saliva coated surface (P < 0.05), and confocal microscopy revealed that 4-epi-Pimaric acid inhibited the clumping and attachment of S. mutans. At 8 × MIC concentration, it significantly prevented the pH drop and reduced S. mutans biofilms (P < 0.05). Increased propidium iodide staining and leakage of 260- and 280-nm absorbing material by 4-epi-Pimaric acid treated cells of S. mutans suggested that it probably causes disruption of the cytoplasmic membrane structure. It also exhibited significant suppression of TNF-α expression in human neutrophils, suggestive of its anti-inflammatory activity. Furthermore, the compound was found to be significantly safe (IC(50) >100 μg/ml) in the MTT assay on AML-12 cell lines.
CONCLUSIONS:
In conclusion, 4-epi-Pimaric acid showed promising antibacterial, anti-biofilm and anti-inflammatory potency and this compound can be exploited for therapeutic application in oral microbial infections. |
|
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
