Pseudevernia furfuracea (L.) Zopf ve sekonder metabolitlerinin hepatosellüler karsinom hücreleri üzerindeki antioksidan potansiyeli: antioksidan enzimlerin düzenlenmesi

Öz

Dünyada kansere bağlı ölümlerin önde gelen nedenlerinden biri olan hepatosellüler karsinom (HCC) gibi çok sayıda hastalığın tedavisinde tıbbi bitkilerin ve sekonder metabolitlerin kullanımı artmaktadır. Oksidatif stres, karaciğer kanseri gelişimine katkıda bulunur ve antioksidan sistemlerin teşvik edilmesi, tedavi için daha iyi bilgiler sağlayabilir. Bu çalışmada, Pseudevernia furfuracea (L.) Zopf likeninin antioksidan potansiyeli araştırılıştır. Ayrıca, P.furfuracea'dan izole edilen ana sekonder metabolitler olan olivetorik asit (OA) ve fisodik asitin (PA) hepatik antioksidan enzimlerin gen ekspresyonları üzerindeki etkileri hem kanserli (HepG2) hem de sağlıklı (THLE2) insan karaciğer hücrelerinde değerlendirilmiştir. Sonuçlara göre, P. furfuracea'nın toplam fenolik içeriği etanolik ve sulu ekstraktlar için sırasıyla 71.52 µg/mg ve 8.16 µg/mg gallik asit eşdeğeri bulunmuştur. Aynı şekilde β-karoten ve likopen içerikleri de etanolik ekstraktlarda daha yüksek olarak belirlenmiştir. Bu antioksidan bileşenlerle uyumlu olarak, etanol özütünün DPPH (2,2-difenil-1-pikrilhidrazil) radikal süpürme aktivitesi (IC50: 158.79 mg/L), sulu ekstraktlar (IC50: 630.33 mg/L) ile karşılaştırıldığında oldukça yüksektir. OA ve PA, HepG2 hücrelerinde tüm antioksidan enzimlerin gen ifade düzeylerini arttırırken, sağlıklı THLE2 hücrelerinde ise sadece gpx ekspresyonu yukarı yönde regüle olmuştur. Bundan farklı olarak, her iki metabolit de THLE2 hücrelerinde cat, sod1 ve sod2 ekspresyonlarını baskılamıştır. Bu sonuçlar P. furfuracea'nın sadece yüksek antioksidan potansiyeline sahip olmadığını, aynı zamanda sekonder metabolitlerinin de karaciğer kanserinde onkogenezi ve tümör ilerlemesini önleyecek antioksidan enzimleri yukarı regüle ederek kanser hücrelerinde oksidatif stresi azaltabileceğini göstermektedir.

Anahtar Kelimeler

• Pseudevernia furfuracea
• olivetorik asit
• fisodik asit
• antioksidan potansiyeli
• antioksidan enzimler

Antioxidant potential of Pseudevernia furfuracea (L.) Zopf and its secondary metabolites on hepatocellular carcinoma cells: regulation of antioxidant enzymes

Öz

The use of medicinal plants and secondary metabolites increases in treating numerous diseases such as hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death worldwide. Oxidative stress contributes to the development of liver cancer, and promoting antioxidant systems might provide better insights for the treatment. In the present study, the antioxidant potential of Pseudevernia furfuracea (L.) Zopf lichen species were investigated. Besides, effects of major secondary metabolites, olivetoric acid (OA) and physodic acid (PA), which were isolated from P. furfuracea, on hepatic gene expressions of antioxidant enzymes, were evaluated in both cancerous (HepG2) and healthy (THLE2) human liver cells. According to the results, the total phenolic content of P. furfuracea was 71.52 µg/mg and 8.16 µg/mg gallic acid equivalent for ethanolic and aqueous extracts, respectively. Likewise, β-carotene and lycopene contents were also higher in ethanolic extracts. In line with these antioxidant ingredients, DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity of ethanol extract (IC50: 158.79 mg/L) was remarkably high as compared with its aqueous extracts (IC50: 630.33 mg/L). OA and PA strongly augment all antioxidant enzymes’ gene expressions in HepG2 cells, while only gpx expression was upregulated in healthy THLE2 cells. Conversely, these two metabolites suppress cat, sod1, and sod2 expressions in THLE2 cells. These results together suggest that P. furfuracea not only has high antioxidant potential, but its secondary metabolites might also reduce oxidative stress in cancer cells by upregulating antioxidant enzymes, which would prevent oncogenesis and tumor progression in liver cancer.

Anahtar Kelimeler

• Pseudevernia furfuracea
• Olivetorik acid
• Physodic acid
• Antioxidant potential
• Antioxidant enzymes

Kaynakça

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