Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i>
Corneal opacification due to fibrosis is a leading cause of blindness worldwide. Fibrosis occurs from many causes including trauma, photorefractive surgery, microbial keratitis (infection of the cornea), and chemical burns, yet there is a paucity of therapeutics to prevent or treat corneal fibrosis....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/10/1447 |
| _version_ | 1827651330877947904 |
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| author | Vanessa Rozo Melinda Quan Theint Aung Jennifer Kang Sara M. Thomasy Brian C. Leonard |
| author_facet | Vanessa Rozo Melinda Quan Theint Aung Jennifer Kang Sara M. Thomasy Brian C. Leonard |
| author_sort | Vanessa Rozo |
| collection | DOAJ |
| description | Corneal opacification due to fibrosis is a leading cause of blindness worldwide. Fibrosis occurs from many causes including trauma, photorefractive surgery, microbial keratitis (infection of the cornea), and chemical burns, yet there is a paucity of therapeutics to prevent or treat corneal fibrosis. This study aimed to determine if andrographolide, a labdane diterpenoid found in <i>Andrographis paniculate</i>, has anti-fibrotic properties. Furthermore, we evaluated if andrographolide could prevent the differentiation of fibroblasts to myofibroblasts <i>in vitro</i>, given that the transforming growth factor beta-1(TGF-β1) stimulated persistence of myofibroblasts in the cornea is a primary component of fibrosis. We demonstrated that andrographolide inhibited the upregulation of alpha smooth muscle actin (αSMA) mRNA and protein in rabbit corneal fibroblasts (RCFs), thus, demonstrating a reduction in the transdifferentiation of myofibroblasts. Immunofluorescent staining of TGF-β1-stimulated RCFs confirmed a dose-dependent decrease in αSMA expression when treated with andrographolide. Additionally, andrographolide was well tolerated <i>in vivo</i> and had no impact on corneal epithelialization in a rat debridement model. These data support future studies investigating the use of andrographolide as an anti-fibrotic in corneal wound healing. |
| first_indexed | 2024-03-09T20:37:14Z |
| format | Article |
| id | doaj.art-b25aa442a4554baf925800805b7c2fe7 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:37:14Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b25aa442a4554baf925800805b7c2fe72023-11-23T23:08:48ZengMDPI AGBiomolecules2218-273X2022-10-011210144710.3390/biom12101447Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i>Vanessa Rozo0Melinda Quan1Theint Aung2Jennifer Kang3Sara M. Thomasy4Brian C. Leonard5Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USACorneal opacification due to fibrosis is a leading cause of blindness worldwide. Fibrosis occurs from many causes including trauma, photorefractive surgery, microbial keratitis (infection of the cornea), and chemical burns, yet there is a paucity of therapeutics to prevent or treat corneal fibrosis. This study aimed to determine if andrographolide, a labdane diterpenoid found in <i>Andrographis paniculate</i>, has anti-fibrotic properties. Furthermore, we evaluated if andrographolide could prevent the differentiation of fibroblasts to myofibroblasts <i>in vitro</i>, given that the transforming growth factor beta-1(TGF-β1) stimulated persistence of myofibroblasts in the cornea is a primary component of fibrosis. We demonstrated that andrographolide inhibited the upregulation of alpha smooth muscle actin (αSMA) mRNA and protein in rabbit corneal fibroblasts (RCFs), thus, demonstrating a reduction in the transdifferentiation of myofibroblasts. Immunofluorescent staining of TGF-β1-stimulated RCFs confirmed a dose-dependent decrease in αSMA expression when treated with andrographolide. Additionally, andrographolide was well tolerated <i>in vivo</i> and had no impact on corneal epithelialization in a rat debridement model. These data support future studies investigating the use of andrographolide as an anti-fibrotic in corneal wound healing.https://www.mdpi.com/2218-273X/12/10/1447andrographolidecorneal fibrosiscorneal wound healingmyofibroblast |
| spellingShingle | Vanessa Rozo Melinda Quan Theint Aung Jennifer Kang Sara M. Thomasy Brian C. Leonard Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i> Biomolecules andrographolide corneal fibrosis corneal wound healing myofibroblast |
| title | Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i> |
| title_full | Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i> |
| title_fullStr | Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i> |
| title_full_unstemmed | Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i> |
| title_short | Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i> |
| title_sort | andrographolide inhibits corneal fibroblast to myofibroblast differentiation i in vitro i |
| topic | andrographolide corneal fibrosis corneal wound healing myofibroblast |
| url | https://www.mdpi.com/2218-273X/12/10/1447 |
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