Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most lethal cancer types worldwide, and accumulating evidence has pointed to the association between oxidative stress and the development of hepatocellular carcinoma (HCC); the mechanisms and overall impacts remain uncertain (Fu and Chung, 2018)
olivetoric acid (OA) and physodic acid (PA) were isolated from P. furfuracea as we described in detail previously (Emsen et al, 2020; Emsen et al, 2021) using Soxhlet extraction and silica column chromatography
This study evaluated the effects of P. furfuracea secondary metabolites; OA and PA on normal human hepatocytes (THLE2) and human hepatocellular carcinoma (HepG2) cells
Summary
Hepatocellular carcinoma (HCC) is one of the most lethal cancer types worldwide, and accumulating evidence has pointed to the association between oxidative stress and the development of HCC; the mechanisms and overall impacts remain uncertain (Fu and Chung, 2018). Antioxidant enzymes play significant roles against oxidative stress. Cytosolic (SOD1) and mitochondrial superoxide dismutase (SOD2) act on superoxide radicals to produce hydrogen peroxide that would eventually be detoxified by catalase (CAT) and glutathione peroxidase (GPx) enzymes. Especially phenolics have high capacities to act on radicals. Phenolic compounds have many different types, such as gallic acid, rutin, phloridzin, syringic acid, ferulic acid, and almost all of them show very high antioxidant properties (Mohammed et al, 2020; Emsen and Kolukisa, 2021). Many different plant species containing these compounds have traditionally been used by the public to treat diseases and are still highly preferred, especially in Asian countries
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