Cy5 RNA br Conflict of interest statement br Introduction Hu

Conflict of interest statement
Introduction Human saliva contains many detoxifying and antioxidant Cy5 RNA like glutathione S-transferase, catalase, peroxidase, aldehyde dehydrogenase (ALDH), etc. [1]. Human salivary ALDH (hsALDH) protects individuals from toxic aldehydes contained in food as natural ingredients, preservatives or contaminants, or even those produced during lipid oxidation, as well as those generated by inhalation of cigarette smoke, pollutants and drugs [2]. HsALDH is mainly a single, dimeric isoenzyme, belonging to class 3 ALDH and classified as ALDH3A1 (EC 1.2.1.5) [3]. It is an enzyme of broad substrate specificity preferential for long/medium chain aliphatic aldehydes and aromatic aldehydes including toxic 4-hydroxy-2-nonenal, but is inactive towards acetaldehyde [4]. The best substrates of hsALDH belong to the aromatic group which are cinnamic aldehyde, benzaldehyde and anisaldehyde, both in terms of Km and Vmax/Km[4]. It undergoes reversible oxidation in thiol free medium. Dithiothretiol (DTT) or dithioerythritol are used to regenerate the oxidized enzyme in vitro[5]. The activity of hsALDH is highly variable in the healthy population, and depends on many factors such as age, cigarette smoking, alcohol consumption, pollution, diet, drug consumption, etc. [6], [7]. Lower activity of hsALDH results in reduced protection of the oral cavity against oxidative stress, which may make the individual susceptible to carcinogenesis [8]. Inducers of this enzyme has shown to prevent experimental carcinogenesis [2]. Individuals who ingests large amounts of coffee and broccoli were found to have elevated level of this enzyme in their saliva [7]. Many strategies have been employed to restore the activity of mutated ALDH, enhance the activity in vitro or to induce the enzyme level in vivo[9], [10], [11], [12], [13]. Specific activators of ALDH such as Alda-89, Alda-1, tamoxifen, etc., have been studied which have shown impressive results in mitigating ALDH related pathogenesis in cell lines and in animal models [9], [14], [15], [16]. Therefore, the knowledge about factors influencing the hsALDH activity seems to be important for food and drug safety as well as for nutritional research [7], [17]. The Nigella sativa (black cumin) is an annual flowering plant which has been frequently used in folk medicine for the treatment of various diseases for centuries, both as an herb as well as pressed into oil [18], [19]. It is used to treat ailments such as asthma, bronchitis, rheumatism and to fight parasitic infections and many other diseases [20]. Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1,4-quinone is the main active and the most abundant constituent of the volatile oil of the cumin seeds [21]. It has been shown to have many beneficial pharmacological effects such as anti-oxidant, anti-inflammatory, immunomodulatory, anti-microbial, anti-diabetic, anti-tumor, hepatoprotective, neuroprotective and gastroprotective effects, etc. [22], [23], [24], [25], [26]. TQ has been found to exhibit promising anti-carcinogenic, anti-neoplastic, anti-proliferative, anti-mutagenic and apoptosis inducing activities against various tumor cells [27], [28]. Many chronic diseases are caused by an alleviated level of oxidative stress in the body. To combat this, wide arrays of cytoprotective factors are activated. TQ has been reported to induce activation of these cytoprotective proteins, and hence it is involved in the cellular anti-oxidant defence or inactivation of electrophilic carcinogens, thus preventing oxidative stress [29]. Its anti-oxidative potential is related to the redox properties of the quinone molecule, unrestricted mobility to cross physiological barriers and easy approach to subcellular compartments [30]. The cumin seeds and TQ have been found to maintain the oral health [31]. They mitigate the toxicity induced by anticancer drug cyclophosphamide [32]. TQ has been shown to have a positive effect on the lipid peroxidation level, activity of antioxidant enzymes and also ameliorates the oxidative stress [33], [34]. Therefore, physiological function of hsALDH and the pharmacological activities of TQ in vivo are similar. If TQ is found to have a direct effect on the activity of hsALDH in vitro, its pharmacological effects and mechanism of action can be established.