Chebulagic acid and Chebulinic acid inhibit TGF-β1 induced fibrotic changes in the chorio-retinal endothelial cells by inhibiting ERK phosphorylation.

Abstract:

PURPOSE:Diabetic retinopathy (DR) is characterized by pro-inflammatory, pro-angiogenic and pro-fibrotic environment during the various stages of the disease progression. Basement membrane changes in the retina and formation of fibrovascular membrane are characteristically seen in DR. In the present study the effect of Alcoholic (AlE) extracts of Triphala an ayurvedic herbal formulation and its chief compounds, Chebulagic (CA), Chebulinic (CI) and Gallic acid (GA) were evaluated for TGFβ1-induced anti-fibrotic activity in choroid-retinal endothelial cells (RF/6A). METHOD:RF/6A cells were treated with TGFβ1 alone or co-treated with AlE, CA, CI or GA. The mRNA and protein expression of fibrotic markers (αSMA, CTGF) were assessed by qPCR and western blot/ELISA. Functional changes were assessed using proliferation assay and migration assay. To deduce the mechanism of action, downstream signaling was assessed by western blot analysis along with in silico docking studies. RESULT:AlE (50 μg/ml) CA and CI at 10 μM reduced the expression of pro-fibrotic genes (αSMA and CTGF) induced by TGFβ1, by inhibiting ERK phosphorylation. GA did not inhibit TGFβ1 mediated changes in RF/6A cells. In silico experiments shows that CA and CI has favourable binding energy to bind with TGFβ receptor and inhibit the downstream signaling, while GA did not. CONCLUSION:Hence this study identifies Triphala and its chief compounds CA and CI as potential adjuvants in the management of DR.

journal_name

Microvasc Res

journal_title

Microvascular research

authors

Shanmuganathan S,Angayarkanni N

doi

10.1016/j.mvr.2018.09.001

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

14-23

eissn

0026-2862

issn

1095-9319

pii

S0026-2862(17)30282-0

journal_volume

121

pub_type

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