Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation <i>In Vitro</i>.
Vanessa RozoMelinda QuanTheint AungJennifer KangSara M ThomasyBrian C LeonardPublished in: Biomolecules (2022)
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.
Keyphrases
- wound healing
- transforming growth factor
- optical coherence tomography
- epithelial mesenchymal transition
- smooth muscle
- poor prognosis
- cataract surgery
- systemic sclerosis
- minimally invasive
- idiopathic pulmonary fibrosis
- binding protein
- oxidative stress
- acute coronary syndrome
- microbial community
- machine learning
- electronic health record
- data analysis
- protein protein