**1. Introduction**

Natural compounds have been used as treatments by ancient civilizations in drinks and flavorings. One of the most popular herbs, ginger, is used as a traditional medicine worldwide [1]. Ginger (*Zingiber o*ffi*cinale*) belongs to the family Zingiberaceae. Ginger is a perennial herb used for medicinal and culinary purposes. Ginger is used to treat a variety of ailments around the globe due to its varied phytochemical nature and health benefits [1]. Numerous phytoconstituents are present in ginger which have been divided in to volatile and non-volatile compounds [2]. During drying of ginger, Zingerone is produced directly and by thermal degradation. Zingerone (ZIN) [4-(3-methoxy-4-hydroxyphenyl)-butan-2-one] (Figure 1) is a vanillyl acetone which is a member of phenolic alkanone group [3]. ZIN is present in a significant amount in ginger and it is believed that the pharmacological activities of ginger is due to ZIN. It has a potent antioxidant, anti-inflammatory, anticancer, antidiabetic, antihypertensive, antimicrobial, antithrombotic, anxiolytic, anti-ulcer, and appetite stimulant properties [2].

**Figure 1.** Chemical structure of Zingerone [4-(3-methoxy-4-hydroxyphenyl)-butan-2-one].

Lipopolysaccharide (LPS) is a compound that forms part of Gram-negative bacteria, and is a major pathogenic factor in systemic inflammation or sepsis [4]. Gram-negative bacteria are the only species in existence that contain the endotoxic portion of LPS, and lipid. In septic conditions, LPS can activate the innate immunity as a pathogen-associated molecular pattern (PAMP), which mediates an inflammatory response locally or systemically. Also, LPS can activate non-immune cells and start the inflammatory process which is typically detrimental [5,6]. LPS releases inflammatory cytokines in numerous cell types, causing acute inflammatory response towards pathogens [7]. High doses of LPS triggers the release of pro-inflammatory cytokines which causes a detrimental condition known as oxidative stress [8]. Oxidative stress plays a major role in LPS-induced systemic inflammation and is believed to promote the production of reactive oxygen species (ROS). ROS are believed to be involved in the LPS toxicity mechanism [9,10]. The increased ROS level further encourages inflammatory processes and elevate pro-inflammatory cytokines [11]. The first line of ROS mediated inflammation defense mechanism includes multiple antioxidant enzymes, such as: Myeloperoxidase (MPO) and glutathione peroxidase (GSH). Biological compounds (quercetin, resveratrol, curcumin, thymoquinone, and lycopene) with antioxidant properties can help protect against LPS-induced ROS in the tissues and organs [12]. ZIN is one the natural phytoconstituent considered to be reducing oxidative stress due to its potent antioxidant potential [2,13]. Despite of its antioxidant capacity, ZIN can be used to treat these diseases as an e fficient medicine. This characteristic owes its potential to scavenge free oxidative radicals. ZIN can therefore suppress ROS and preserve the antioxidant properties. Thus the aim of the present investigation is to study the protective e ffect of zingerone against LPS-induced oxidative stress, DNA damage, cytokine storm, and histopathological alterations of di fferent organs in rats.
