*Article Hericium Erinaceus* **Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells**

**Ines Amara 1,2,**†**, Maria Scuto 2,**†**, Agata Zappalà 2, Maria Laura Ontario 2, Antonio Petralia 3, Salwa Abid-Essefi 1, Luigi Maiolino 3, Anna Signorile 4,\*, Angela Trovato Salinaro 2,\* and Vittorio Calabrese <sup>2</sup>**


Received: 10 February 2020; Accepted: 17 March 2020; Published: 20 March 2020

**Abstract:** *Hericium Erinaceus* (HE) is a medicinal plant known to possess anticarcinogenic, antibiotic, and antioxidant activities. It has been shown to have a protective effect against ischemia-injury-induced neuronal cell death in rats. As an extending study, here we examined in pheochromocytoma 12 (PC12) cells, whether HE could exert a protective effect against oxidative stress and apoptosis induced by di(2-ethylhexyl)phthalate (DEHP), a plasticizer known to cause neurotoxicity. We demonstrated that pretreatment with HE significantly attenuated DEHP induced cell death. This protective effect may be attributed to its ability to reduce intracellular reactive oxygen species levels, preserving the activity of respiratory complexes and stabilizing the mitochondrial membrane potential. Additionally, HE pretreatment significantly modulated Nrf2 and Nrf2-dependent vitagenes expression, preventing the increase of pro-apoptotic and the decrease of anti-apoptotic markers. Collectively, our data provide evidence of new preventive nutritional strategy using HE against DEHP-induced apoptosis in PC12 cells.

**Keywords:** Di (2-Ethylhexyl) pthalate; *Hericium erinaceus*; vitagenes; oxidative stress; apoptosis; mitochondrial respiratory complexes
