Contents lists available at ScienceDirect Industrial Crops & Products journal homepage: www.elsevier.com/locate/indcrop Antioxidant and stress modulatory efficacy of essential oil extracted from plantation-grown Santalum album L. A. Mohankumar a, ⁎ , D. Kalaiselvi a , C. Levenson b , G. Shanmugam a , G. Thiruppathi a , S. Nivitha c , P. Sundararaj a, ⁎ a Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, Tamilnadu, 641046, India b Santalis Pharmaceuticals Inc., 18618 Tuscany Stone, Suite 100, San Antonio, Texas, 78258, USA c College of Science, Northeastern University, Boston, Massachusetts, 02115, USA ARTICLE INFO Keywords: Santalum album Essential oil Antioxidant Oxidative stress Caenorhabditis elegans Nrf2 ABSTRACT The East Indian sandalwood oil has been widely used as an Ayurvedic medicine and has multiple pharmaco- logical properties. However, antioxidant and antistress potency of East Indian sandalwood oil against oxidative stress-induced damages remain unexplored. Thus, the present study was aimed to investigate the in vitro and in vivo antioxidant and stress-protective properties of essential oil extracted from the heartwood of plantation- grown Santalum album L. (SEO). The SEO was extracted by traditional stream distillation method and the che- mical components were determined via gas chromatography-mass spectrometry (GC–MS) analysis. Nineteen chemical compounds were identified by GC–MS, accounting for 96.81% of total oil. The main components were α-santalol (41.77%), β-santalol (18.02%), (Z)-α-trans-bergamotol (8.50%), (Z)-lanceol (6.57%), and epi-β-san- talol (5.78%). The in vitro results suggests that SEO possess an excellent antioxidant activity as it was able to inhibits the intracellular reactive oxygen species (ROS) generation, reverse the morphological damages and effectively improves viability of neural cells under oxidative stress conditions. Moreover, SEO markedly in- creased the antioxidant enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. Western blotting results further confirmed that SEO protects neural cells against oxidative damages possibly by activating the nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) antioxidant me- chanism. The SEO also exhibited a strong in vivo antioxidant and stress modulatory activity on Caenorhabditis elegans. The SEO not only acts protective against oxidative stress but also prolongs the lifespan of mev-1 mutant C. elegans having shortened lifespan due to the over production of ROS. This data confirmed that SEO exert potent antioxidant and stress modulatory activities possibly by direct scavenging of free radicals and activation of antioxidant defense system, in vitro and in vivo. Together, these findings indicated that SEO has the potency to be utilized as a source of antioxidant for treating several degenerative and disease conditions caused by oxidative stress. 1. Introduction Santalum album L. is a small evergreen, hemiparasitic, heavily branched and high value industrial tree widely distributed in South Asia and Australia. The volatile oil derived from the heartwood of S. album known as sandalwood essential oil (hereafter SEO) has been used in religious rituals as a fragrance material and in aromatherapy as an antidepressant for more than 5000 years (Burdock and Carabin, 2008; Moy and Levenson, 2017). The Food and Drug Administration (FDA, USA) approved SEO as a natural flavoring agent and its use in combi- nation with flavors for human consumption was permitted (Burdock and Carabin, 2008). SEO has several other pharmacological properties due to their antioxidant (Misra and Dey, 2013), neuroprotective (Mohankumar et al., 2018), anti-inflammatory (Sharma et al., 2018), antimicrobial (Misra and Dey, 2012), and cancer preventive (Santha and Dwivedi, 2015) capabilities. However, antioxidant and antistress potency of SEO against oxidative stress-induced damages and its un- derlying protective mechanisms remain unexplored. Oxidative stress-induced cell damage has been confirmed as an etiology involved in a variety of human ailments. However, the damage induced by oxidative stress depends on the imbalance between reactive oxygen species (ROS) generation and antioxidant defenses (Andersen, 2004; Finkel and Holbrook, 2000; Reuter et al., 2010). Among others, hydrogen peroxide (H 2 O 2 ), an important contributor of ROS, is https://doi.org/10.1016/j.indcrop.2019.111623 Received 29 March 2019; Received in revised form 8 June 2019; Accepted 28 July 2019 ⁎ Corresponding authors at: Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, Tamilnadu, 641046, India. E-mail addresses: amkkmohan@gmail.com (M. A.), sunpalan@gmail.com (S. P.). Industrial Crops & Products 140 (2019) 111623 0926-6690/ © 2019 Elsevier B.V. All rights reserved. T