Journal of Environmental Pathology, Toxicology and Oncology, 38(1):83–96 (2019) 0731-8898/19/$35.00 © 2019 by Begell House, Inc. www.begellhouse.com 83 Reduction of Gamma Radiation–Induced Damage by Hydro-Alcoholic Extract of Nardostachys jatamansi Aditya Menon, a Tiju Chacko, b Praseetha R. Nair, b Teeju Majeed, b & Cherupally Krishnan Krishnan Nair b,c, * a Origin Diagnostics and Research, Vavakkavu, Karunagappally; b Mar Athanasious College for Advanced Studies, Tiruvalla; c St.Gregorios Dental College & Research Centre, Kothamangalam *Address all correspondence to: Cherupally Krishnan Krishnan Nair, Director of Research, St. Gregorios Dental College and Research Centre, Kothamangalam 686681, Kerala, India, E-mail: ckknair@yahoo.com ABSTRACT: The search for a nontoxic radioprotector has not yielded any promising results. Many antioxidant com- pounds, though efective under in vitro conditions as radioprotectors, have failed under in vivo settings due to their toxici- ty. The Indian medical system of Ayurveda uses a variety of plants with antioxidant potential, and these may be harboring molecules with radioprotective properties. In the present work, the radioprotective property of Nardostachys jatamansi was investigated. A hydro-alcoholic extract of this plant provided protection to the cellular DNA and membrane from 4 Gy gamma radiation. Depletion of cellular antioxidant status was also prevented by this extract. Molecular-level analysis in the intestines of mice revealed a lower bax/bcl2 ratio suggestive of a reduction of radiation-induced apoptosis. Expres- sion levels of the DNA repair gene atm were elevated, along with a reduction in the expression of the infammatory gene cox2. The extract also provided a survival advantage to mice exposed to lethal doses of gamma radiation. These results suggest a possible radioprotective role for Nardostachys jatamansi. KEY WORDS: Nardostachys jatamansi, radioprotector, bax/bcl2 ratio, antioxidant I. INTRODUCTION Ionizing radiation and radioactive isotopes have been widely used in several human activities such as diagnostic medicine, cancer therapy, and industry in addition to nuclear power generation and nuclear warfare and defense. 1,2 Because radioactive isotopes and radiation fnd application in various felds, the exposure of humans to ionizing radiation has in- creased. 3,4 Exposure to ionizing radiation can cause various types of cellular damage including mutation of genetic material and damage to the molecular con- stituents of cells through free-radical generation. 5,6 Systemic exposure to higher doses of ionizing radi- ation results in various conditions afecting the im- mune system, digestive system, and at higher doses, the nervous system, 7–9 thereby putting the organism under stress and in extreme cases leading to death. Protecting humans from the deleterious efects of ionizing radiation have always been the corner- stone of research in the feld of radiation biology. 10 Radiomodifers are compounds that can alter the efect of radiation on a mammalian system 11 ; among them, radioprotectors reduce or prevent the harm- ful efects of ionizing radiation. 12 Research on the development of radioprotectors commenced with the Manhattan Project in the United States, and researchers at the Walter Reed Army Research In- stitute came up with a sulfhydryl compound called ‘amifostine,’ which showed promising radioprotec- tive properties among the 4,500 compounds tested. 13 However, the radioprotective efect of amifostine is short-lived and is associated with many side efects such as nausea, vomiting, hypotension, hypocalce- mia, and nephro- and neuro-toxicities at clinically efective doses. 14 Plants with antioxidant properties have been shown to provide protection to a mammalian sys- tem from ionizing radiation–induced damage. 15 Various plants used in the Indian system of medi- cine, Ayurveda, have been screened and found ef- fective in this respect. 14 Nardostachys jatamansi is one such plant; it has been used in the Ayurvedic system of medicine from time immemorial, 16 espe- cially for treating neurological problems. 17,18 The extract of Nardostachys jatamansi is also possesses antioxidant properties and has been experimentally proven to alleviate various conditions arising from