Comparison of gamma irradiation and heating treatment on cytotoxicity, insulinotropic activity, and molecular structure
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Comparison of gamma irradiation and heating treatment on cytotoxicity, insulinotropic activity, and molecular structure change of mistletoe viscothionin Jong-Heum Park1 • Jae-Kyung Kim1 • Beom-Seok Song1
Received: 31 March 2020 / Revised: 21 July 2020 / Accepted: 29 July 2020 Ó The Korean Society of Food Science and Technology 2020
Abstract Mistletoe offers health-promoting effects; however, it has toxicity, requiring careful application. Viscothionin is a polypeptide of mistletoe that while contributing to toxicity also demonstrates anti-cancer and anti-diabetic activities. The aim of this study was to evaluate whether gamma irradiation or heating treatment could selectively reduce viscothionin-mediated cytotoxicity. Gamma irradiation effectively inhibited viscothionin-induced cytotoxicity to RIN5mF cells, but heating treatment did not affect its cytotoxicity. Both heating and gamma irradiation further increased the insulinotropic activity of viscothionin, whereas the effect of gamma irradiation was dose-dependent and diminished above 20 kGy. Structural analysis showed that gamma irradiation significantly altered the ordered structure of viscothionin, unlike heating treatment, resulting in a change of its molecular properties, which could be linked to the observed changes in the cytotoxicity and insulinotropic activity of the polypeptide. These results suggest gamma irradiation as an alternative method for minimizing viscothionin toxicity without interfering with anti-diabetic effect. Keywords Polypeptide of mistletoe Toxicity Gamma irradiation Heating treatment Structural analysis
& Beom-Seok Song [email protected] Jong-Heum Park [email protected] Jae-Kyung Kim [email protected] 1
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk-do 56212, Republic of Korea
Introduction Plant-derived traditional herbal medicines are increasingly applied in modern medicine for the treatment of several conditions as alternatives to chemically synthesized drugs in both developed and developing countries, and now frequently observed in pharmacies as well as food stores (Ekor, 2014). Mistletoe has long been widely used as a complementary health supplement or an herbal folk medicine for the prevention and treatment of various diseases in Europe and East Asia owing to a variety of biological activities, including immunomodulatory properties and anti-cancer, anti-diabetes, and anti-hypertension effects (Bu¨ssing, 2000a; Drozdoff et al., 2018). The major constituents of mistletoe are lectin, alkaloids, polysaccharides, and viscothionin (Pfu¨ller, 2000). Viscothionin is a polypeptide mixture of approximately 6 kDa comprising 46 highly conserved amino acids with reported anti-cancer activity (Giudici et al., 2003; Tabiasco et al., 2002). However, there is minimal information on its biological effects or therapeutic efficacy in other contexts. Stein et al. (1999) have found that viscothionin activates human granulocytes, and Huber et al. (2006) reported that viscothionin-ri
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