Quercetin, chrysin, caffeic acid and ferulic acid ameliorate cyclophosphamide-induced toxicities in SH-SY5Y cells

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ORIGINAL ARTICLE

Quercetin, chrysin, caffeic acid and ferulic acid ameliorate cyclophosphamide‑induced toxicities in SH‑SY5Y cells Adnan Ayna1   · Seda Nur Özbolat1 · Ekrem Darendelioglu2 Received: 4 August 2020 / Accepted: 3 October 2020 © Springer Nature B.V. 2020

Abstract Clinical use of cyclophosphamide (CP) causes apoptosis-induced cell death in the immune system, liver, heart and kidneys. To prevent the cells against side effects of CP and its metabolites, increasing antioxidant defence mechanism of the body with supplemental antioxidants is important. Therefore, there is a requirement for effective agents which could prevent the healthy cells from the harmful effects of drug-induced toxicities. Several antioxidants have been used in protecting or alleviating CP-induced cell death. However, no such study is reported in CP-induced SH-SY5Y cell toxicity. The aim of this study was to evaluate likelihood ameliorative effects of caffeic acid, chrysin, quercetin and ferulic acid against CP-induced toxicity in SH-SY5Y neuron cells. In this study protective effects of quercetin, chrysin, caffeic acid and ferulic acid against CP-induced cell toxicity in SH-SY5Y cells was evaluated by cell proliferation assay, lipid peroxidation (LPO) analysis to decipher antioxidant capacity, tunel assay and qRT-PCR experiments to examine anti-apoptotic activities of the antioxidants. The results showed that CP-induced cell toxicity in SH-SY5Y cells and treatments with the antioxidants suppressed the cell death. Our results suggests that these anti-oxidants protected SH-SY5Y cells via a decrease in LPO levels, downregulating the expression of Cas-3, Cyt c and Bax and upregulating expression of anti-apoptotic gene Bcl-2. The use of antioxidant as nutritional supplements, and in particular of caffeic acid, chrysin, quercetin and ferulic acid, reduce apoptotic effects of CP in SH-SY5Y cells that could add insight into therapeutic approaches to CP-induced cell injuries. Keywords  Cyclophosphamide · Ferulic acid · Quercetin · Chrysin · SH-SY5Y cells

Introduction Natural products have been used for therapeutic purposes for decades. Among the natural products, flavonoids are phenolic compounds that are abundantly found in plants, fruits and bee products. Their therapeutic effects in the ameliorating and treatment of several diseases including cancer, diabetes and neurodegenerative and cardiovascular diseases have well been studied [1]. Chrysin (Chr) is Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1103​3-020-05896​-4) contains supplementary material, which is available to authorized users. * Adnan Ayna [email protected] 1



Department of Chemistry, Faculty of Arts and Sciences, Bingol University, Bingol, Turkey



Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bingol University, Bingol, Turkey

2

a bioactive flavonoid with strong antioxidant, antiinflammatory and anticancer activities [2]. Hydroxycinnamic acid derivatives are among essential type of anti