Hazelnut (Corylus avellana L.) Shells Extract: Phenolic Composition, Antioxidant Effect and Cytotoxic Activity on Human Cancer Cell Lines

Abstract

Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract). Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%–2.93%, w/w). The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (EC50 = 31.7 μg/mL with respect to α-tocopherol EC50 = 10.1 μg/mL), and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 μg/mL, respectively). The expression of cleaved forms of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28) and human cervical cancer (HeLa) cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin), and phenol derivatives (gallic acid), showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.

Pleurotus spp. Cultivation on Different Agri-Food By-Products: Example of Biotechnological Application

“…Hazelnut husks are raw materials particularly rich in cellulose and hemicellulose, which could be potentially used for the production of food enzymes, biofuel, and various chemicals (acetic acid, furfural, and lignin degradation products) after bioprocessing [97]. Furthermore, Çöpür, et al [98] evaluated the chemical properties of hazelnut husks and showed that they could be used as a valuable material for the production of particleboards, while recent works focused the attention on the extraction and the effects of antioxidant compounds from hazelnut shells [99,100], highlighting their potential use as important functional ingredient in food technology or in pharmaceutical industry.…”

Design and Development of Spray-Dried Microsystems to Improve Technological and Functional Properties of Bioactive Compounds from Hazelnut Shells

“…The extract, as previously demonstrated, contains a high polyphenols content. The polyphenols possess several biological activities, such as antioxidant, antimicrobial, anti-inflammatory, anti-cancer, with beneficial effects on human health [8]. However, some of them (phenolic acids, flavonoids, neo-lignans), if exposed to environmental stress, are unstable, because they could undergo oxidation and degradation processes, which take place especially during the storage period [48].…”

“…HPLC-grade water (18 mΩ) was prepared by a Milli-Q50 purification system (Millipore Corp., Bedford, MA, USA). The hazelnut shells extract (HSE) was prepared with the extraction method previously reported [8].…”

“…The neolignan lawsonicin was identified as the HSE chemical marker. Moreover, the extract antioxidant and inhibitory effect inducing apoptosis on human melanoma and cervical cancer cell growth were demonstrated [8]. Due to its functional properties, the production of HSE represents an efficient way to re-use and up-cycle hazelnut shells, turning these by-products, destined for landfill, into a resource of human health-promoting molecules.…”

A new parameter of growth inhibition for cell proliferation assays

“…We emphasize that, using these parameters to compare drug efficacy between distinct cell populations (such as cell lines), cells that grow “faster” in culture will be inferred more sensitive than “slower” ones, and therefore these parameters lead to a misinterpretation of the results because of their dependency to the unique growth properties of each cell population. Despite PG partially overcomes this limitation, we provide in the first section of the results a detailed description of the dependency of R , and consequently the IC 50 , to cell proliferation rate because of its frequent usage in current anticancer drug discovery research (as few recent examples (Ben et al, ; Cabrera et al, ; Esposito et al, ; Hamed, Darwish, Herrmann, Abadi, & Engel, ; Indovina et al, ; Koul et al, ; Mathema, Chaijaroenkul, Karbwang, & Na‐Bangchang, ; Menderes et al, ; Mukunthan, Satyan, & Patel, ; Muñoz, Rosso, & Coveñas, ; Potenza et al, ; Ravi, Ramesh, & Pattabhi, ; Rimoldi et al, ; Said, Brouard, Quintana, & Estévez, ; Venkataramana Reddy et al, ; Wehbe et al, ; Zamora et al, ; Zhu et al, )). Subsequently, in the second section of the results, we show that PG is also dependent on the growth properties of the cells, because of their exponential and not linear proliferation in culture.…”