Abstract
Coumaric acid is a phenolic compound found in medicinal plants. Its use has been reported in the treatment of inflammatory diseases, prevention of alterations induced by oxidative stress, as well as acetaminophen-induced hepatotoxicity. Thus, this study evaluated coumaric acid as a potential treatment for liver fibrosis. Cell proliferation was assessed by the trypan blue exclusion technique and the cytotoxicity of coumaric acid was performed using an LDH assay. Mechanisms of cell apoptosis were evaluated by flow cytometry. The expression of genes associated with apoptosis, cell cycle control, and fibrosis was assessed by qPCR. The production of lipid droplets was quantified by oil red staining. The experiments performed showed that the treatment with coumaric acid was able to reduce cell proliferation without causing cell cytotoxicity or apoptosis. Coumaric acid was able to inhibit the expression of cyclin D1 and CDK’s (CDK2, CDK4, and CDK6), increasing p53 and p21, which could lead to cell cycle arrest. Treatment with coumaric acid was also able to revert the activated phenotype of GRX cells to their quiescent state. Thus, our results suggest that coumaric acid has a potential therapeutic effect against liver fibrosis.
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When requested, the authors provided the data and materials used for the development of the manuscript.
Change history
30 January 2023
A Correction to this paper has been published: https://doi.org/10.1007/s00210-023-02408-6
Abbreviations
- α-SMA:
-
Alpha smooth muscle actin
- CA:
-
Coumaric acid
- CCND1:
-
Cyclin D1
- CDK’s:
-
Kinase-dependent cyclins
- CDKI’s:
-
Kinase-dependent cyclins inhibitors
- CIS:
-
Cisplatin
- CLA:
-
Chlorogenic acid
- CLI:
-
Chronic liver injury
- Col-1:
-
Collagen
- DMEM:
-
Dulbecco’s Modified Eagle’s Medium
- EMC:
-
Extracellular matrix
- F1:
-
Fractions 1
- F2:
-
Fractions 2
- F3:
-
Fractions 3
- FBS:
-
Fetal bovine serum
- GA:
-
Gallic acid
- GFAP:
-
Glial fibrillary acidic protein
- GRX:
-
Hepatic stellate cell line
- HA:
-
Hydroxybenzoic acid
- HF:
-
Hepatic fibrosis
- HPLC:
-
High-performance liquid chromatography
- HSCs:
-
Hepatic stellate cells
- LDH:
-
Lactate dehydrogenase
- MP:
-
Moquiniastrum polymorphum subsp. Polymorphum
- NAC:
-
N-acetylcysteine
- PPAR-γ:
-
Proliferation-activated gamma receptor
- ORO:
-
Oil red-O
- TE:
-
Total extract
- TGF-β:
-
Transforming growth factor beta
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Funding
This study was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil; Financial Code 001), through a fellowship for the first author, and by National Council for Scientific and Technological Development (CNPq/Brazil) (Grant#311424/2018–0). License for Research on Brazil’s Biodiversity, CNPq#010852/2014–0 and Sistema Nacional de Gestão do Patrimônio Genético e do Conhecimento Tradicional Associado–SISGEN# ABAD620.
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JOR and ERS conceived and planned this project. MSB performed all experiments. BPC, GHV, and DM helped in phenotypic reversal and gene expression experiments. KHA performed the flow cytometry experiments. RMS helped during the gene expression experiments as well as in writing the manuscript. MSB analyzed the data and wrote the manuscript with review and contributions from JOR, ERS, and MFD. All authors approved the final manuscript.
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Bastos, M.S., Saalfeld, R.M., Costa, B.P. et al. Coumaric acid from M. polymorphum extracts reverses the activated state of hepatic stellate cells (GRX) and inhibits their proliferation by decreasing the p53/p21 pathway. Naunyn-Schmiedeberg's Arch Pharmacol 396, 925–937 (2023). https://doi.org/10.1007/s00210-022-02361-w
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DOI: https://doi.org/10.1007/s00210-022-02361-w