Ellagic acid inhibits the formation of hypertrophic scars by suppressing TGF‐β/Smad signaling pathway activity

Abstract

Hypertrophic scar (HS) is a benign fibroproliferative skin disease, which lacks the ideal treatment and drugs. Ellagic acid (EA) is a natural polyphenol that prevents fibroblasts from proliferating and migrating. This study aimed to determine the role of EA in HS formation and its possible mechanism by in vitro experiments. HS fibroblasts (HSFs) and normal fibroblasts (NFs) were separated from HS tissue and normal skin tissue, respectively. HSFs were treated with 10 and 50 μM EA to assess their effect on HS formation. In particular, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and scratch assay were used to detect the viability and migration ability of HSFs. Quantitative reverse transcriptase real‐time polymerase chain reaction was used to measure the mRNA expression level of basic fibroblast growth factor (bFGF), extracellular matrix (ECM)‐related gene collagen‐I (COL‐I), and fibronectin 1 (FN1) in HSFs. Finally, Western blot was utilized to measure the expression level of TGF‐β/Smad signaling pathway–related proteins in HSFs. The viability of HSFs was significantly increased compared with NFs. 10 and 50 μM EA treatment markedly inhibition the cell viability and migration of HSFs. EA treatment upregulated the bFGF expression level and downregulated the COL‐I and FN1 expression level in HSFs. In addition, p‐Smad2, p‐Smad3, and transforming growth factor (TGF)‐β1 expression levels as well as p‐Smad2/Smad2 and p‐Smad3/Smad3 ratios remarkably decreased in HSFs after EA treatment. EA inhibited the formation of HSs by suppressing the viability and migration of HSFs and ECM deposition as well as by preventing the activation of TGF‐β/Smad signaling.

Potential of Plant-Derived Compounds in Preventing and Reversing Organ Fibrosis and the Underlying Mechanisms

“…A study conducted by Zhao and colleagues [ 63 ] in vitro using fibroblasts demonstrated that EA significantly reduced the expression of TGF-β1 and phosphorylation of Smad2 and Smad3, thereby preventing the activation of the canonical TGF-β/Smad2/3 signaling pathway. In addition, EA treatment decreased the viability and migration of fibroblasts and downregulated the expression of ECM components including collagen type I and fibronectin.…”

Ratlarda BPA ile Oluşturulan Böbrek Hasarında Ellajik Asit Uygulamasının DNA Hasarı ve Bazı Böbrek Fonksiyon Parametreleri Üzerine Etkisi

“…Gıda örneklerinde, çevre örneklerinde, insan kanında ve serumunda, plasentada, idrarda ve anne sütünde ve hatta kozmetik ürünlerde BPA tespit edilmiştir (37,38). Bir polifenol olan EA, ağırlıklı olarak meyvelerde, sebzelerde ve bazı bitkisel gıdalarda bulunan (22) farklı türdeki kronik hastalıklara karşı potansiyel biyoaktiviteye sahiptir (23). EA'nın oksidatif strese karşı belirgin zayıflatıcı etki yarattığı ve enflamasyona karşı önemli önleyici rol oynadığı ve organ toksisitesine ilişkin yüksek biyokimyasal belirteçlere (ör: kreatinin) karşı dikkate değer koruma sağladığı bildirilmiştir (24).…”

“…Bir polifenol olan EA (Ellajik asit), ağırlıklı olarak meyvelerde, sebzelerde ve bazı bitkisel gıdalarda bulunan (22) farklı türdeki kronik hastalıklara karşı potansiyel biyoaktivite özelliği taşıyan bir bileşendir (23). EA'nın oksidatif strese karşı belirgin zayıflatıcı etki yarattığı ve enflamasyona karşı önemli önleyici rol oynadığı ve organ toksisitesine ilişkin Med J West Black Sea 2024;8(1): 58-66 yüksek biyokimyasal belirteçlere karşı dikkate değer koruma sağladığı bildirilmiştir (24).…”