A Review Study of Antioxidants and The Cinnamon Oil Effects

The aim of the study to estimate the antioxidant action and protecting effect of ethanolic cinnamon extract against CCl4 induced toxicity in male rats. To determine the effect of different concentrations of ethanolic cinnamon extract on male rats that fed a high cholesterol diet that induced hyperlipidemia. The experiment has been conducted in the present study., aimed to evaluate the hepatoprotective, role of Cinnamomum zeylanicum ethanolic extract in carbon tetrachloride (CCl4) induced hepatotoxic male rats, The cinnamon and its oil reported to have many beneficial uses in food preservation due to antioxidant of cinnamon. The Phenolic compounds extracted from cinnamon such as hydroxyl cinnamaldehyde and the hydroxycinnamic acid act as scavengers of peroxide radicals and avoid oxidative damage (Mathew and Abraham, 2006; Leela, 2008). Ranjbar et al, (2006) observed individuals consuming cinnamon tea showed increased total serum antioxidant status, increased thiols such as glutathione, NADPH, NADH, SOD, and decreased lipid peroxidation.


INTRODUCTION
Antioxidant means "against oxidation", antioxidants work to guard lipids, proteins and nucleic acids from peroxidation by radicals. They hinder or interval the oxidation of other particles by stopping the initiation or spread of oxidizing chain reactions. Antioxidants are effective because they are ready to give up their possess electrons to free radicals. After a free radical gains the electron from an antioxidant it no lengthier needs to attack the cell and the chain reaction of oxidation is destroyed (Dekkers et al., 1996).
Medical plants are the oldest friends of humanity. They not only provided food and shelter but also served the mankind to cure different aliments, and according to the world health organization (WHO) traditional systems of medicines always played important role in the global health. In the traditional health medicinal plants providing a new areas of drug research (Verma et al., 2014).
'Cinnamon', Cinnamomum zeylanicum (Lauracea), locally known as Qerfah or Darsin is an older and essential spice with wide-ranging requests in flavoring, perfumery, drinks and drugs (Jayaprakasha et al., 2002). In some previous studies, an essential oil of cinnamon is identified to have antibacterial (Jirovetz et al., 2002), antifungal (Misra et al., 2000), Previously, some studies also suggested that cinnamon owns strong free radical scavenging capability (Bafna and Balaraman, 2004), antioxidant and antimutagenic (Jayaprakasha et al., 2007) activities cholesterol-lowering properties (Khan et al., 2003;Subash et al., 2007). Oxygen, necessary for maintaining life, sometimes becomes toxic, resultant in the generation of most aggressive agents such as reactive oxygen species (ROS), aerobic organisms service a battery of defense mechanisms such as antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) to inhibit oxidative tissue damage (Halliwell and Gutteridge,1989).
Free radicals are made in normal and/or pathological cell metabolism. Oxidation is necessary too many living organisms for the manufacture of energy to fuel biological processes. However, the uncontrolled creation of oxygen-derived free radicals is complex in the beginning of many diseases such as cancer, rheumatoid arthritis, Copyright © The Author(s) cirrhosis and arteriosclerosis as well as in degenerative processes related with ageing (Baghiani et al.,2012).

Antioxidants
The antioxidants are group of organic molecules that prevent the progress of lipid oxidation. The main causes of food deterioration is oxidation, due to free radical production from its components, especially lipids. To prevent oxidation of foods, several synthetic antioxidants have been used widely by the food industry (Cubero et al., 2002). However, scientific evidence that synthetic antioxidants produce toxic effects on consumers has led to the search of natural antioxidants sources. The origins of antioxidant are natural components such as flavonoids, phenolic acids, tannins, coumarins, lignans and their derivatives, and they show strong antioxidant activity (Potterat, 1997;Cao et al., 1998).
The antioxidants comprise many materials that have important in guarding biological systems to avoid the toxic effects of oxidative stress on carbohydrates, lipids, proteins and DNA Figure (

Classification of antioxidant
There are several classifications of antioxidants, including endogenous antioxidants and exogenous antioxidant. (Jeppsson et al.,2007).

Oxidative stress
The oxidative stress is defined as an imbalance between oxidants and antioxidants in valid of the oxidants, potentially leading to damage (Sies, 1991). However, oxidative damage that cause weakens in physiological functions of cellular compounds. ROS is reactive oxygen species or RNS is reactive nitrogen species (Sies, 1991;Halliwell and Gutteridge, 2007).

Oxidative stress damage Oxidative damage of proteins
Proteins are targeted by oxidative damage inside the cells, because they have widely abundance and rapid interaction with radicals and excited-state species, including single oxygen (Sivalokanathan et al., 2006). The vast modifications made protein oxidation. Backbone cleavage and protein cross linking to more subtle modifications such as side chain oxidation, altered electrical changes and increase susceptibility to proteolysis. (Gracanin et al., 2009).

Oxidative damage of lipid Lipid peroxidation
Lipid peroxidation abbreviated as LPO defined as free radical intermediated chain reaction that can deactivated components of the cell. This process is associated with some complications like carcinogenesis (Beevi et al., 2007).

Malondialdehyde
Malondialdehyde (MDA) is a three-carbon atom, low-molecular weight aldehyde, produced by lipid peroxidation. It reacts with nucleophilic amine groups like lysine, arginine and the amino termini of amino acids. It also reacts with any ketones as aldehydes from other sources, for example; attached sugars or glycation products (Marnett, 1999). Because of their very short life time so that difficult in detection of ROS in vivo; In tissues and blood, MDA exists in two forms; bounded and unbounded to-NH 2 and SH groups of nucleic acid, protein and lipoproteins (Draper et al., 2000).

Glutathione
Glutathione is considered an intracellular peptide that have physiological functions such as detoxification of xenobiotics and/or their metabolites (Hayes and Strange, 2000). It have antioxidant of endogenous structure created to stabilize free radical (Jackson and Loeb, 2001). The GSH has metabolic functions involved storage of cysteine, signal transduction and apoptosis (Main et al., 2012). GSH presented in cytosol at percentage about 90%, and 10% is present in mitochondria and endoplasmic reticulum (Hwang et al, 1992). Also, 85% of GSH is free and unbound and the remain is bound to certain proteins (Sies ,1999). As explained in figure (2-6) shows that H2O2= Hydrogen peroxide, ROOH=Carboxy radical, GSH= Reduced glutathione, GSSG= Oxidized glutathione, PSH= Protein sulf hydryl, ROH= Hydroxyl radical, NADPH= Nicotine-amid dinucleotide phosphate reduced, NADP= Nicotine -amid dinucleotide phosphate oxidized.

Catalase
Catalase (CAT) is tetrameric enzyme established of four serious tetrahydrally organized subunits of 60KDa (Mates et al.,1999). Catalase induced hydrogen peroxidase to water (H2O) and molecular oxygen(O 2 ) and untaken at the peroxisome organelle. It have important role in protected of cells against oxidative damage (Cui et al., 2003). Also, catalase control development of cells by stimulation of the extracellular indicators controlled the mechanism of kinase, important to increase the growth of cell that inhibited by oxidative stress (Hachiye and Akashi, 2005).

Oxidative damage to DNA
DNA nuclear and mitochondrial oxidative damage caused by ROS, leading to structural changes in DNA, such as base pair mutation, deletion and insertion. Oxidative DNA damage may be indirect through the rise of intracellular Ca ++

Free radicals
Free radicals (FR) are contain one or more unpaired electrons, an unpaired electron being one that is alone in an atomic, molecular oxygen is so important component for living organism. It helps in the process of oxidation, which is a basic component of aerobic life and of the metabolic process (Aiyegoro and Okoh, 2010). It makes this species very unstable and tends to react with other molecules to pair this electron and therapy generates more stable species. It is generated under physiological conditions during aerobic metabolism (Gueteens et al., 2002).
The highly reactive molecules include Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). ROS is a term collectively describing radicals and other non-radical reactive oxygen derivatives.
These intermediates may participate in reactions giving rise to free radicals or damaging to organic substances. RNS are radical nitrogen-based molecules that can act to facilitate nitrosylation reactions (Caimi et al., 2004).

Reactive oxygen species
Reactive oxygen species (ROS) are chemicallyreactive particles including oxygen ions and peroxides. ROS are highly reactive due to the presence of unpaired valence shell electrons. ROS form as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis (Devasagayam et al.,2004).

Sources of free radicals and ROS
Free radicals and ROS are generated from normal metabolic process and from external sources.

A: Internal source
Mitochondrial respiratory chain is the main source of free radicals, during this process of ATP production and which a single electron is leaking out of the respiratory chain, reacts with molecular oxygen to form superoxide anion (Kumar, 2011). The stimulation of phagocytes reflects contributor of ROS generation in the human body during the killing of bacteria, virus and other xenobiotics, In addition, cytochrome (P450), xanthin oxidase, peroxisomes and conditions of ischemia/reperfusion represent remarkable sources of free radicals (Babior, 2004).

B: External sources
ROS may generate by exposure to radiation, environmental pollutants, ultraviolet light, ozone, cigarette smoke, certain drugs, pesticides, industrial solution and anesthetics (Kumar, 2011).

Cinnamon oil Origin, uses and factors affecting
Essential oils are a rich source of biologically active compounds, cinnamon produces two different oils; cinnamon bark oil obtained from the dried inner bark, whereas cinnamon leaf oil is obtained from the leaves and twigs. It is important to distinguish between the two variations of cinnamon oil, cinnamon bark oil has a spicy smell whereas cinnamon leaf oil is said to smell like cloves; cinnamon leaf oil is considered to be considerably safer to use in aromatherapy (Jayaprakasha et al., 2000). The cinnamon bark oil, bark oleoresin and cinnamon leaf oil are important value added products from cinnamon. Cinnamon bark oil is used in the food and pharmaceutical industries while, oleoresin is used mainly for flavoring food product such as cakes and confectionary (Gu el at., 2004). Temperature, humidity, duration of daylight (radiation), and wind patterns all have a direct influence on volatile oil content, especially in those herbs that have superficial histological storage structures (e.g. glandular trichomes). When the localization is deeper, the oil quality is more constant (Lawrence, 2002;Rohloff, 2004).

Chemical composition
From different parts of cinnamon (bark, roots and leaves) essential oils with variations in the composition by especially geographic and technical reasons can be obtained (Schmidt, 2006). Twenty-six compounds constitutes 97% of the volatile oil from cinnamon flowers were characterized with (E)-cinnamyl acetate (42%), trans-αbergamotene (8%) and caryophyllene oxide (7%) as the major compounds (Jayaprakasha et al., 2000). The combinations about thirty-four indicating 98% of volatile oil from the buds of C. z. were characterized using GC and GC-MS (Gu et al., 2004). The important chemical constituents of C. z. oil are cinnamaldehyde and eugenol (Senanayake et al., 1977).

Biological activities Antioxidant activity
The cinnamon and its oil reported to have many beneficial uses in food preservation due to antioxidant of cinnamon. The Phenolic compounds extracted from cinnamon such as hydroxyl cinnamaldehyde and hydroxycinnamic acid act as scavengers of peroxide radicals and avoid oxidative damage (Mathew and Abraham, 2006;Leela, 2008). Ranjbar et al, (2006) observed individuals consuming cinnamon tea showed increased total serum antioxidant status, increased thiols such as glutathione, NADPH, NADH, SOD and decreased lipid peroxidation Antihyperlipidimic activity Khan et al, (2004) demonstrated that intake of cinnamon daily reduced serum glucose, triglyceride TG, LDL and total cholesterol in people with type II diabetes and thus showed clinically significant reduction in cardiovascular risk factor biomarkers. A study indicated that the cinnamon oils possess hypoglycemic, hypolipidemic and antioxidant effects rats (Al-Logmani et al., 2009).

Antidiabetic activity
The cinnamon could reduce glucose level of the blood in non-insulin dependent diabetics. Further, the cinnamaldehyde proved as antidiabetic agent. Furthermore, the soluble polymeric compounds extraced from cinnamon have insulin enhancing biological activity in the in vitro assay measuring the insulin dependent effects on glucose metabolism and also function as antioxidants, these results suggest that compounds present in cinnamon may have useful for treatment of diabetes (Anderson et al., 2004).

Nematicidal activity
Study by (Park et al., 2005) showed cinnamon oil had high nematicidal activity to the male, female and juveniles of pinewood nematode Bursaphelenchusxyl ophilus. The active ingredient in the oil represented by cinnamyl acetate at a concentration of 32.81μg/l resulted in 50% mortality of nematodes, further the rate of 0.2 % (weight by volume of soil) of stem bark of cinnamon powder used for soil amendment significantly reduced by 91.1% gall number of Meloidogyne incognita infection (root gall formation) of tomato seedling compared with control (Kim et al., 2003).

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Anti-inflammatory activity
The cinnamon have anti-inflammatory activity whereas ethanolic extract (70%) from cinnamon was effective on cute inflammation in mice (Lee et al., 2003). In other hand herbal ophthalmic with 0.5% cinnamon found very effective as anti-inflammatory agent on ocular inflammation in rabbits (Leela, 2008).

Antifungal activity
The antifungal properties of cinnamon have also drawn great attention from many researchers. The effect of cinnamon extract on mycelial growth inhibition of phytophtora capsici. Further studies on medicinal plant extracts were studied against development of mycelium of Phytophthora capsici, Rhizoctonia solani, Fusarium solani, Colletotrichumgloe osprorioides, and Botrytis cinerea (Nguyen et al., 2009). Similar effect was found by Tzortzakis (2008), against Botrytis cinerea affected by essential oil. In addition, Amiri et al., (2008), found that mixture of eugenol and soy lecithin reduced the disease incidence caused by Botrytis cinerea. Cinnamaldehyde and eugenol also demonstrated to have inhibitory properties against Aspergillus flavus, Aspergillus ochraceus, Aspergillus niger, Aspergillu sterreus, Aspergillus citrinum and Penicillium viridicatum (Singh et al., 2007).

Insecticidal activity
cinnamon extracts such as cinnamaldehyde is a potent insecticide against adults of Sitophilusorycae and Callosobruches chinensis. The oil isolated from leaves of Artemisia princeps and seeds of cinnamon have repellent and insecticidal activities (Kim et al., 2003).

Antibacterial activity
Valero and Salmeron (2003) reported that cinnamon extracts found to be effective against bacteria whereas oils of cinnamon have antibacterials activity to inhibit growth of Bacillus cereus. In other hand, alcoholic extracts of cinnamon found very effective against Helicobacter pylori (Tabak et al., 1996). Furthermore it was present accompanying of cinnamon and nisin increasing death range of Salmonella typhimurium and Escherichia coli O157:H7 in apple juice (Yuste and Fung, 2004).

Toxicity and side effects
Cinnamon is used as a spice in food material in Asia so its safety is quite obvious, have reported acute toxicity of cinnamon in the animals is very low ratio i.e. Benzaldehyde (LD50 orally, 1300 mg/kg rat), cinnamaldehyde (LD50 orally, 2220 mg/kg rat), linalool (LD50 orally, 2790 mg/kg rat), and salicylaldehyde (LD50 orally, 520 mg/kg rat) (Budavari et al., 1989). According to the United States Food and Drug Administration, cinnamon is generally recognized as safe (Generally recognized as safe-GRAS) when used in amounts commonly found in food (USFDA, 2006). The most common adverse effects reported with cinnamon were related to contact irritation or allergic reaction with the skin or mucus membranes, stomatitis (Nadiminti et al., 2005;Endo and Rees, 2006).

CONCLUSION
From the current study, it can be concluded that

Oxidative stress have an essential role in
CCl4 that induced hepatotoxicity through the normal medical regimes of treatment.

2.
Antioxidants have established to be active in enhancing CCl4-induced toxicity in several preclinical and clinical intermediations.

Cinnamomum zeylanicum extracts
have capability to dawn normalize free radicals raise, enhance liver, kidney and cholestatic biomarkers, perfect hepatic marker enzymes, decrease fibrosis severity and regularize the hepatic and kidney cells design.

Cinnamomum zeylanicum extracts
prior and co-administration with CCl4 providing immediate complete protections in biochemical, physiological and liver, kidney histological variations. 5. Ethanol cinnamon extract refer to the greatest effective because of its content of flavonoids, sterol, tannins, saponins and alkaloids.