Contents lists available at ScienceDirect Biomedicine & Pharmacotherapy journal homepage: www.elsevier.com/locate/biopha Review Therapeutic effects of thymoquinone for the treatment of central nervous system tumors: A review Tahereh Farkhondeh a , Saeed Samarghandian b, ⁎ , Soroush Hozeifi c , Mohsen Azimi-Nezhad b,d a Innovative Medical Research Center, Faculty of Medicine, Mashhad Branch, Islamic Azad University, Mashhad, Iran b Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran c Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran d Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran ARTICLE INFO Keywords: Thymoquinone Tumors Anti-cancer CNS ABSTRACT Background: The aim of this study is to review the effects of thymoquinone (TQ) against central nervous systems (CNS) tumors. Methods: In this study, we extensively reviewed all articles on the terms of N. sativa, TQ, CNS tumors, and different disorders in PubMed, Science Direct, Scopus, and Google Scholar databases between the years 1990 and 2017. Results: The present study found that TQ has many therapeutic effects due to its antioxidant, anti-inflammatory, and anti-proliferative activities. Experimental studies indicated the protective effects of TQ against CNS tumors. The anti-tumor effects of TQ are mainly caused by inducing G2/M cell cycle arrest, apoptotic pathways, in- hibiting autophagy, angiogenesis, invasion, and migration and also by enhancing the efficacy of chemother- apeutic drugs. Although, the study observed no significant toxicity of TQ in the experimental models, more clinical studies are needed to confirm the safety and efficacy of TQ for human. Conclusions: The present review found that TQ treatment can be considered as a promising therapeutic strategy for human malignant CNS in future. 1. Introduction Malignant and non-malignant Primary brain and other central nervous system (CNS) tumors have an incidence of 22.36 per 100,000 [1]. Malignant primary brain tumors are recognized as the main cause of death from solid tumors in children and the third cause of death from cancer in adolescents and young adults aged 15–39 years old [2]. The different types of CNS tumors include astrocytic tumors, oligoden- droglial tumors, mixed gliomas, ependymal tumors, medulloblastomas, pineal parenchymal tumors, meningeal tumors, germ cell tumors, and craniopharyngioma [3]. The cause of CNS tumors has not fully under- stood, however; genetic background may increase the risk of CNS tu- mors [4]. Although the magnetic resonance imaging is essential for early diagnosis of the anatomic extent of the tumor; however, a biopsy is usually needed to confirm the brain tumors [5]. The different types of treatment for patients with CNS tumors consist of the standard (the currently used treatment) and tested in clinical trials [5].The current standard of treatment for CNS tumors includes of active surveillance, surgery radiation therapy, chemotherapy, and targeted therapy [5]. The complementary and alternative medicine are especially interested and have been studied on natural anticancer agents with low side effects [6]. These compounds are safely used at high doses as supplementary treatment in the chemotherapy regimens [6]. Thymoquinone (TQ) is observed in the seeds of Nigella Sativa, which is belonging to the Ranzmculaceae family[7].TQ was also found in the plants of the La- miaceae family such as Agastache, Coridothymus, Origanum, Monarda, Mosla, Satureja, Thymbra, and Thymus [8].TQ possesses beneficial properties such as antioxidant, anti-inflammatory, and chemother- apeutic effects [9]. The recent biomedical findings indicated that TQ may be effective against various disorders including Alzheimer’s dis- ease, Parkinson’s disease, Arthritis, Cardiovascular disease, Diabetes, and various types of cancers such as brain tumors [10]. TQ has been indicated to posse the antitumor effects against several cancer cells, including osteosarcoma, colon, lung, ovarian, pancreas and myelo- blastic leukemia [11–13]. The present review has been designed to review the protective effects of TQ against CNS tumors by gathering the scientific literature. https://doi.org/10.1016/j.biopha.2017.12.013 Received 19 September 2017; Received in revised form 26 November 2017; Accepted 4 December 2017 ⁎ Corresponding author. E-mail address: samarghandians@mums.ac.ir (S. Samarghandian). Biomedicine & Pharmacotherapy xxx (xxxx) xxx–xxx 0753-3322/ © 2017 Published by Elsevier Masson SAS. Please cite this article as: Farkhondeh, T., Biomedicine & Pharmacotherapy (2017), https://doi.org/10.1016/j.biopha.2017.12.013