INTRODUCTION:

Herbs and spices have traditional importance as they are not only an important component of our diet having some nutritional values but also possess pharmacological properties. Different parts of plants, fruits, herbs, shrubs and spices contain many compounds which give many health benefits¹. Allopathic medicines have many side effects and not suitable for long term usage. That is why there was a need of natural medicines which are used for cure of many diseases without any side effects. Natural medicines are easily accessible, available and cheap in price. These medicinal plants are used as analgesic, antipyretic, healing of wounds and for the cure of various diseases. These medicinal plants and herbs are proved helpful in treatment of kidney failures, sexual, hormonal, liver, nerval and mental diseases².

Many important compounds like vitamins, flavonoids, carotenoids and other phenolic compounds are proved important antioxidants³. These compounds are also helpful in treatment of cardiac diseases, diabetes and tumors. These natural drugs are less toxic and have minimum side effects than allopathic drugs. Chemical drugs are replaced by natural drugs because the later are less toxic, have minimal side effects, easily available and cost effective².

Cinnamon (Cinnamon zeylanicum) is a perennial tree that is 10 – 15meters in height from the family of Lauraceae occurs in Sri Lanka, China, Eastern Asia, India and other tropical regions. It is commonly known as Ceylon⁴. Cinnamon is derived from Rou gui, a Greek word. This word has a meaning of sweet wood. It is obtained from core of bark and dried and converted into tubular or stick form⁵. Oldest Chinese literature (4000 years ago) and Bible also emphasize the importance of cinnamon as medicinal herb. Its annual production is 224,000 tons in world. It grows in clay, loamy and sandy soils especially well drained. Acidic soils are preferable for its growth however it can also grow in neutral soils. It mostly prefers moist and shady or non-shady places. Leaves, barks, seeds and fruits are its medicinal and edible parts. Different types of aldehydes, carboxylic acids, essential oils and salts are isolated from cinnamon. Eugenol, cinnamaldehyde, camphor and cinnamyl acetate are most important of them⁶.

Cinnamon is used as flavors in different types of food products mostly pickles and tea. It is also used as tobacco flavors. Oils isolated from bark of cinnamon is used in preparations of many pharmaceutical drugs and toothpastes. It is used as tranquilizers, aphrodisiac and breath or mouth sweeteners. It is used to cure flu, headache, joint pain, gastric, intestinal, respiratory and cardiac diseases. It helps in digestion and provide relief from gas in the alimentary tract. Cinnamon is used as fragrances in perfumes, insecticides and soaps. Industries are using essential oils of cinnamon for manufacturing of cosmetic products, paints and food preservatives. These essential oils are also used in textile industries⁷.

Cinnamon shows anti-inflammatory, anti-tyrosinase, anti-microbial, anti-carcinogenic, anti-mutagenic and cardiac protective properties due to the presence of an important component proanthocyanidins. These phenolic compounds help in cure of damages, disorders and diseases caused by diabetes. Proanthocyanidins boost the immune system and help in lowering of cholesterol and blood glucose^8,9. Cinnamaldehyde, Eugenol and their derivatives isolated from C. zeylanicum show activities against parasites, microbes, oxidants and free radical scavengers. They also lower glucose level in blood, cholesterol level in serum and provide relief against hypertension¹⁰. Cinnamon shows anti-bacterial, anti-fungal properties and helps in preservation of food. It is used to cure cough, sore-throats, diarrhea, respiratory and stomach disorders like flatulence, nausea and abdominal cramps¹¹. Anti-septic, anti-allergic and anti-viral activities make cinnamon a beneficial plant. Moreover, it warms the body, helps in contraction of tissues and purifies the blood¹². Reproductive organs of rats become healthy by long term consumption of cinnamon bark oil. Their sperm quality also increases by cinnamon bark oil.

During metabolic processes, many species are produced as by product which have reactive oxygen in them. These species played some vital roles in our body. But when these species are produced in excess cause oxidative stress and become the reason for aging, tumor formation, diabetes, cardiac diseases, inflammation and nerval disorders. Protection from these species require natural or synthetic antioxidants. Different polyphenolic compounds extract from cinnamon are rich source of antioxidants. Natural antioxidants play better role of free radical scavenging than artificial ones¹³. Antioxidants of cinnamon play important roles in protection of cell membranes from free radical damage. Present study emphasizes a review on antioxidant activities of Cinnamon zeylanicum.

Oxidative stress in biological systems:

The term “oxidative stress” means an increase of species which contains more reactive oxygen in them. These species are produced as by products during many metabolic processes. Among these hydroxyl radicals (OH^•) is most reactive oxidant than others because of its high reduction potential and relatively high velocity constants. These reactive oxygen species are extremely reactive. They have one or more unpaired electrons. They can cause oxidative damage to cells and propagate through the membrane as well. Formation of tumor cells, inflammatory and diabetic diseases, disorders which cause aging, cardiac and neural disorders are mainly caused by this oxidative stress^14,15. Structures and functions of many biomolecules are damaged which further cause many diseases like progressive nervous system disorder (Parkinson's disease) and Alzheimer disease¹⁶.

This oxidative stress happens when balance between antioxidant defense system and free radical formation gets disturb. In lipids, polyunsaturated fatty acids are more common in causing loss of nutrition, discoloration, off flavor development and oxidative deterioration due to the hydroperoxides formation because they are more easily oxidized by molecular oxygen¹⁷.

Importance of antioxidants in food:

If intake of lipid peroxides exceeds in the body, it may lead to adverse health effects. In order to reduce oxidative stress in the body there is a need of antioxidant defense system to stop over production of free radicals. The term “Antioxidant” refers to the substance required in low quantity that resists the action of oxidant in the body. These antioxidants inhibit oxidizable substrates such as fats, DNA and proteins to get oxidized. This compound plays a major role in our bodies as well as in foods¹⁸.

Antioxidants found naturally but can also be synthesized that are extensively used by industries to stop lipid peroxidation¹⁹ Mutagenesis and carcinogenesis are often caused by the toxic properties of these synthetic antioxidants. That is why their use is also considered dangerous for mankind²⁰. Therefore, there is a need to use antioxidants that are derived from natural sources in our food as they are more effective as compared to synthetic and don’t have any harmful side effects. Scientists are working on extraction, purification, characterization of natural antioxidants from plants to utilize them in food industry^{21, 22}.

Different Natural antioxidants such as tocopherols i.e. vitamin E, ascorbic acid, and flavonoids are used because these compounds exhibit antitumor, antimutagenic and anticarcinogenic activities and ability to preserve food. Phenolic compounds isolated from certain plants are regarded as natural antioxidants. Different studies are reported on the structure, composition and properties of these natural compounds acting as antioxidants²².

Phenolic compounds as antioxidants:

All parts of the plants contain phenolic compounds which have hydroxyl groups present on the aromatic ring. These are secondary plant metabolites from either shikimate/Phenylpropanoid pathway. They are easily soluble in water. These phenolic compounds, their derivatives and various subgroups of phenolic compounds contribute their major role in exhibiting antioxidant activity²³.

Phenolic compounds exhibit their antioxidant activity by rapidly donating their electrons or a hydrogen atom to free radical or molecule that is oxidized and get paired. They chelate metal ions that speed up the lipid peroxidation process. In this way, they terminate free radicals or making it less harmful and prevent them to cause lipid peroxidation²⁴.

Method used by Ismail et al. to determine phenolic compounds was Folin-Ciocalteu. Aluminium chloride colorimetric method was used to determine flavonoid content in water extract of five herbal plants. These compounds also inhibit the activities of different radicals like DPPH and 2,2’-azinobis. Antioxidant assay was conducted by using radical scavenging activities of DPPH as well as ABTS. Both these activities are interrelated with total phenolic and flavonoid contents. Highest value of phenolic as well as flavonoid contents shown by Cinnamon zeylanicum among various plants. Around 270mg GAE/100 of phenolic content while approx. 60mg CE/100 g of flavonoid content observed. Results of antioxidant assay showed that even a low concentration of compounds isolated from the cinnamon plants prevent reactive oxygen species. Around 10 μg/mL value of EC50 was calculated for DPPH. ABTS EC50 for Cinnamon zeylanicum was at around 80. Five major compounds in Cinnamon zeylanicum and their biological activities were reported. Compounds of coumarin exhibit properties against inflammation, hypertension, blood coagulation, tuberculosis, convulsion, obesity, reactive oxygen species, hyperglycemia, neural disorders, tumors, bacteria, fungal and viral species. Octadecanoic acid and methyl ester exhibit Anti-viral and anti-microbial activity. n-Undecane, Formic acid-2-propenyl ester and cinnamaldehyde are active compounds in Cinnamon zeylanicum that shows these activities mentioned above¹³.

Hamidpour et al. described a detailed analysis of the pharmacological activities and medicinal uses of cinnamon and its main constituents that are responsible for exhibiting various pharmacological activities. Cinnamon is considered effective natural remedy that is used for the treatment of diseases such as Type 2 diabetes by activating autophosphorylation of insulin receptor to enhance glucose uptake by a methyl hydroxyl chalcone polymer (that is extracted from cinnamon). Cinnamon is also effective in treatment of chronic digestive diseases, cardiac disorders, Alzheimer’s disease, flatulence, abdominal cramps, nausea, diarrhea and sore throats. It also slows down the spoilage process of food and displays antifungal, anti-cholesterol, antitumor, antibacterial and angiogenesis activity. Essential oils of cinnamon contain 60-80% cinnamaldehyde, a volatile component which provide flavor and aroma to this plant. While essentials oil extracted from leaves contain almost 70-75% eugenol. This study revealed that water extract of phenolic compounds of cinnamon play important role in reducing oxidative stress by inhibiting 5-lipoxygenase. The specific extract of Cinnamon i.e. 500mg/d for 12-week period have been proved effective in improving fasting blood sugar and systolic blood pressure. If cinnamon is taken in excess quantity, it can cause irritation in mucus membrane and on skin⁵.

Nanasombat et al. concluded that essential oils of cinnamon exhibit antioxidant and antimicrobial activities. Four basic methods are used for determining antioxidant activity. Cinnamon showed 61.46% AA in β-carotene bleaching test. Around 2mM/mg reducing capacity shown by cinnamon oil in ferric reducing antioxidant power assay. 85% antioxidant activity shown by cinnamon oil in superoxide anion scavenging activity assay. The three main constituents i.e. cinnamaldehyde or cinnamic acid, eugenol and phenolic compounds in essential volatile oil play vital role in exhibiting strong DPPH radical scavenging activity. Thus, they are favorable to use as natural preservatives²⁵.

Singh et al. compared activities of chemicals and essential oils isolated from Cinnamon zeylanicum. GC-MS was carried out to determine components in cinnamon plant. In leaves, 19 volatile oil components were reported, and eugenol was the major component (87.3%). While oleoresins have 25 components and eugenol was 87.2% present. In barks, major component was (E)-cinnamaldehyde and cadinene. Bark oleoresin showed effective results in lipid inhibitory activity as compared to other synthetic antioxidants and volatile oils. Volatile oils showed 31.2%, 51.2%, 43.6%, and 57.6% scavenging activity on hydroxyl radicals. Bark oleoresin showed excellent chelating effect. Reducing powers of these essential oils are in the range of 56.0-58.4. Hence, oleoresins showed better effect in primary and secondary oxidation products. Cinnamaldehyde and eugenol in cinnamon could provide many benefits related to health²⁶.

El-Baroty et al. isolated many essential oils from cinnamon and analyzed antioxidant and antimicrobial activities. TLC and GCMS are used to characterize essential oils while TLC-bio-autography assay was used to determine antioxidant compounds. In essential oils of cinnamon bark trans-cinnamaldehyde was found as the major constituent (45.62%) and it is also monoterpene rich natural source. These results suggest that these essential oils can serve as preservative source²⁷.

Suresh et al. produced reduced form of graphene oxides by using Cinnamon zeylanicum and determined antioxidant properties of these reduced form of graphene oxides. Graphene compounds are very important and should be produced in excess as they possess important applications particularly their role as biosensors, composites and drug delivery. However, its production through chemical reduction method involves harmful chemical reductants such as (hydrazines, borohydrides and hydroquinones). So, it is necessary to introduce simple and efficient green method to produce reduced graphene oxide (rGO). Cinnamon contains important compounds mostly eugenol and cinnamaldehyde. Due to presence of these compounds and their derivatives, cinnamon exhibit many medicinal properties. Top down method is used to prepare graphene from graphite flakes. By using XRD, TEM and UV-visible techniques, the reduction of GO was conﬁrmed. Reduced graphene oxide showed strong antioxidant activities. Therefore, cinnamon can be used to synthesize graphene in large scale because it is most convenient method of reduction¹⁰.

Juliani and James isolated essential oils from Madagascar aromatic plants. Chemical composition of essential oils, their antioxidant and antimicrobial studies were examined. It was found out that those plants that contained highest percentage of eugenol in their essential oils showed highest antioxidant activity. Their essential oils contained complex mixtures of components mainly phenolic rich compounds that are responsible for their activities against reactive oxygen species. ABTS screen method was used to determine the in vitro activities of these vital oils against reactive oxygen species. Cinnamon leaf oil (C. zeylanicum) with 59-64% eugenol TEAC 560-580 while the C. zeylanicum bark exhibited lower antioxidant activity with traces of eugenol, cinnamaldehyde 38%, cinnamyl acetate 14%, TEAC 22.9. Cinnamon zeylanicum leaf essential oil exhibited higher antioxidant activities than cinnamon bark (C. zeylanicum). Antioxidant activity of plants is correlated with eugenol levels. It was concluded that essential oils of cinnamon plants have a potential role to serve as natural antioxidants²⁸.

Jamshidi et al. experimentally studied the effects of irradiations on activity of cinnamon compounds against reactive oxygen species. Microwave and Gamma radiations are irradiated on the activities of these plants. The hydroalcoholic (EtOH 50%) extracts of Cinnamon zeylanicum was prepared. Microwave and Gamma rays of different doses are irradiated for duration of five minutes on these extracts. Four methods were used to determine antioxidant activities of these samples. During Gamma irradiation exposure no change in antioxidant activity of cinnamon was observed. However, radical scavenging activity (RSA) of cinnamon extract increases as dose from 10 kGy increases. Irradiations due to higher doses may involve in the changes in structures of acidic compounds of phenols. Products formed by Millard reaction showed radical scavenging activities. These products are formed by using amino acids and sugars present in cinnamon. FRP and TPC of samples also increased on increasing the irradiation dose. In β-carotene bleaching assay (BCB) no change was observed in antioxidant activities of treated samples and control. On the other hand, microwave irradiation did not cause any significant change in antioxidant activities of cinnamon. But this activity and phenolic compounds increase with gamma irradiation. Electromagnetic radiations of microwave rays generated heat which resulted in the breaking of covalent bonds present between phenolic compounds and as a result free phenolic compounds having low molecular weight released. So, heat is responsible for this phenomenon while in comparison gamma irradiation is cold treatment. Hence by using appropriate power of microwave irradiation antioxidant activity of herbal extracts can be increased²⁹.

Fathiazad et al. have also reported the study on antioxidant activities of Cinnamon zeylanicum. Effects of these activities on the serum testosterone of rats have been studied. As Cinnamon zeylanicum contains various polyphenolic compounds that play an important role in reducing oxidative stress also have great medical importance by treating serious diseases and disorders mostly in obese people. Cinnamon spices mainly consist of two flavonoid compounds that are important antioxidants. Kaempferol and quercetin have ability to reduce oxidative stress could be helpful to reduce the risk of male infertility as it is considered a quick and an appropriate remedy. Wistar albino species of rats were used in this experiment. This experiment was conducted on twenty male species. The weight of these 8 weeks old species was 240 - 260g. Gavage method was used to give dose of Cinnamon zeylanicum to the rats. As two groups were made, and dose was given to only one group while the other group was considered as control group. 75mg/kg dose was given to rats for duration of four weeks. It was found out that flavonoid and similar compounds present in Cinnamon zeylanicum concluded remarkable results. Total antioxidant capacity as well as serum total testosterone was enhanced significantly. Viability, number and motility of sperms was also increased. The flavonoid especially Phytoestrogens have been found very effective in inhibiting 17ß hydroxysteroid dehydrogenase. Metabolism and biosynthesis of steroids was also affected by different pathways. So, the reduction of reactive oxygen species (ROS) is necessary. Chances of fertilization, formation of sperms and improvements in the formation of sperm cells increased because of the reduction of reactive oxygen species. Thus, Cinnamon zeylanicum can be used to treat male infertility³⁰.

Shobana and Naidu reported the antioxidant activity and thermal stability of antioxidant potential of selected 7 Indian spices. Crude aqueous or alcoholic extracts were prepared. Cinnamon was one of those species. Prepared extracts of cinnamon showed successful inhibition of lipid peroxidation. This inhibition was due to the presence of one or more antioxidants in spice extracts. It was observed that antioxidant activities of cinnamon were higher than garlic, pepper, mint, onion and ginger. But lower values of antioxidant activities than clove. It was observed that activities against reactive oxygen species were same for both extracts, and same as present in spices in natural conditions. These natural antioxidants are much safe to use as compared to synthetic antioxidants. The antioxidant activity of Cinnamon zeylanicum and other spice extracts remained same even after boiling for 30 mins at 100°C. Components of spices were not denatured even by applying very high temperature. Antioxidant activity shown by these spices were even as high as were before boiling. In addition to impart flavor to the food they can also be used to provide health benefits by reducing lipid peroxidation³¹.

Gauthami et al. used Cinnamon zeylanicum bark extract to synthesize silver nanoparticles and determined their antioxidant properties. Synthesis of silver nanoparticles via chemical based methods proves to be harmful as they may interfere with metabolic systems as these nanoparticles are now widely used in drug delivery systems, artificial implants, gene delivery, imaging diseases at different stages and diagnostic agents so, it is necessary to synthesize silver nanoparticles via bio based method using plant extracts. Cinnamon zeylanicum bark exhibit high antioxidant activity and bark extract produced more silver nanoparticles as compared to cinnamon bark powder. SEM, UV-Vis Spectroscopy and XRD were some analytical techniques used to characterize these silver nanoparticles. A characteristic absorbance wavelength was observed in UV-Vis Spectroscopy. The XRD profile showed intense peaks of silver at 2θ values. 30-150nm were the size distribution ranges for cinnamon silver nanoparticles. Zeta potential value of particles were 32 that means these particles having dispersion ability. Silver nanoparticles derived from cinnamon bark extract showed higher absorbance with 82% radical scavenging activity as compared to crude cinnamon extract with 23% radical scavenging activity. Thus, cinnamon extracts can be used in synthesis of nanoparticles for its medical importance³².

Saleem et al. isolated many essential oils from Cinnamon zeylanicum and analyzed their antioxidant activities. Hydro and steam distillation as well as super critical fluid extraction were used to extract essential oils from bark of cinnamon plant. Oil samples obtained by these methods then analyzed by GC-MS. It was observed that 58 components in hydro distillation, 52 components in steam distillation and 33 components were present in SCFE. In hydro and steam distillation, direct heating or use of high temperature caused the decomposition of many compounds. Low temperature was used in super critical fluid extraction, so there was less decomposition of compounds due to low temperature. When yields of these three methods were compared, it was concluded that higher yields were obtained in SCFE. Seven compounds that were present in oil extracted by SCFE method were regarded as important compounds. Five methods were used to check the antioxidant activity of these important compounds. Range of TPC was found 0.07-0.91mg/g while range of TFC was found 0.9-1.87 mg/g. These values were maximum in hydro distillation, moderate in steam distillation while minimum in SCFE. Same order was observed in DPPH scavenging activity. 56 to 70% radical scavenging activity was exhibited by all essential oils. Inhibition of linoleic acid peroxidation by these essential oils was maximum in SCFE, moderate in steam distillation while minimum in hydro distillation. 2.0mg/mL concentration of essential oils was used for the measurement of reducing potential. The values of reducing potentials may range from 0.911 to 1.911. Higher antioxidant and antimicrobial activities were shown by important compounds and essential oils present in cinnamon bark. Cinnamaldehyde is one of the most important compounds present in cinnamon bark. Other than cinnamaldehyde various phenolic compounds in essential oils also provide protection against microbes⁷.

Muchuweti et al. isolated and prepared aqueous methanolic extracts of 9 spices. Cinnamon zeylanicum was one of those species. Chemical composition of phenolic compounds isolated from cinnamon plants was determined. Antioxidant properties of these extracts were also analyzed. Folin-Ciocalteu, HPLC and tannin binding assay are the methods and techniques used to determine phenolic compounds. Activities of these spices against reactive oxygen species were determined by reducing power assay, β-carotene linoleic acid model system and radical scavenging assay. Vitamin C (Ascorbic acid) was used as a control in all these antioxidant assays. Cinnamon contained highest concentration of polyphenolic compounds i.e. 13.66mg GAE. High reducing power was analyzed when 0.12 absorbance at 25mg mL^-1of cinnamon was observed. Highest radical scavenging activity and antioxidant activity was also observed. Difference in antioxidant activity may be due to different cultivation method, storage duration and different climatic growth conditions. Most spices contained phenolic compounds and therefore showed better antioxidant properties in vitro as compared to ascorbic acid. Reason behind variation in phenolic compounds among different spices includes factors such as cultivation areas and other environmental stresses. Phenolic compounds present in the form of polyphenolic compounds in plants. Poly-pyrolidone (PVPP) efficiently bonded to tannin and the concentration of tannin is highest in cinnamon after treating samples with PVPP. It was concluded that hydroxyl groups are substituted on different degrees and positions affected the antioxidant potential of these phenolic compounds. Hydroxyl groups on ortho and para positions contribute more as they stabilize the free radicals and hence increase the antioxidant activity as compared to meta position which contribute less in antioxidant activity. HPLC analysis was carried out to identify individual phenolic compounds in spices. The compounds of cinnamon include vanillic acid, caffeic acid and ferullic acid³³.

Mancini-Filho et al. analyzed antioxidant activities of extracts of cinnamon. These antioxidant values are compared with synthetic antioxidants. In an experiment two control groups one with synthesized antioxidant and other without antioxidant were used to compare the antioxidant activities. Antioxidant activity at 50°C was determined by β-carotene and linoleic acid system at every 15 min interval. Absorbance reading was 470nm for 120 min. The etheric cinnamon extract (0.69 mg) inhibited 68% oxidation process. Two spray reagents showed spots in TLC and blue colour indicated. 0.50 was the retardation factor value for phenolic compounds which was shown by blue colored spots. Thus, natural antioxidants derived from plants could prevent lipid oxidation³⁴.

Jayaprakasha et al. isolated cinnamon fruit extracts and identified chemical constituents in them and determined their antioxidant properties. Solvents with increasing polarities from benzene to water was used to extract cinnamon fruit powder. Phenolic compounds were maximum in water extract. These compounds showed higher antioxidant activity. Different methods of column chromatography were used to fraction the water extract. These fractions are used to isolate components and HLC was carried out to analyze their purities. Five compounds were identified by using extensive NMR and MS analysis. Activities of these components against reactive oxygen species and synthetic antioxidant BHA were determined by two important model systems. At 12.5 ppm concentration, protocatechuic acid exhibited 77.3%, cinnamtannin B-1 39.3%, urolignoside 30.4% and rutin 44.7% radical scavenging activities. Hydroxyl groups present on the phenolic rings in their structure are the main reasons for antioxidant activities. These compounds donate their hydrogen to free radical and by forming stable end products, they stop the chain of oxidation and prevent them to cause oxidation in lipids. So, it was concluded that it was the hydroxy groups in phenolic compounds which were responsible for radical scavenging activity. More the number of hydroxyl groups, more it will inhibit radical scavenging activity. Cinnamtannin B-1 was one of the compounds which contain 11 hydroxyl groups in their phenolic structure showed highest antioxidant activity. After cinnamtannin B-1, Rutin with four hydroxyl groups showed higher activity. Same tendency was in β-carotene assay method³⁵.

Schmidt et al. isolated essential oils from leaves of Cinnamon zeylanicum. Chemical composition of these oils was determined. Food was prepared and preserved by using different parts of cinnamon. Besides their use in food, they are also applicable in medicines as well. Essential oils obtained from various parts of cinnamon plant i.e. from bark, roots, leaves, and buds with various compositions and these variations could be due to geographical and technical reasons. Trans-cinnamaldehyde is the major component of C. zeylanicum barks and essential oils. Sesquiterpenes, eugenol and camphor were isolated from essential oils of leaves, roots and buds respectively. Antioxidant activities were shown by particularly phenolic compounds and those compounds which contain polyphenolic moieties in them. GCMS and GCFID were the techniques used to study the chemical composition of these compounds present in essential oils. Antioxidant activities of these essential oils were determined by five different methods. BHA and BHT essential oils even in lower concentrations than eugenol, exhibited radical scavenging activity against DPPH radical. With the increase in concentration cinnamon oil showed highest hydroxyl radical scavenging activity and it also chelated metal ions such as iron efficiently. Secondary products which are formed during lipid peroxidation inhibited when concentration of essential oil is equal to that of standard synthetic antioxidant BHA. As a result, formation of conjugated dienes was also inhibited³⁶.

Jayaprakasha et al. isolated volatile oils from the fruits and flowers of cinnamon. Antioxidant and antimutagenic activities were also determined. Dried fruits were extracted with different polar and non-polar solvents by using Soxhlet extractor. Folin-Ciocalteu method was used to determine the contents of phenolic compounds. Water extract was rich in phenolic content 44.5% while ethyl acetate extract has lowest 14.4% phenolic content. The antioxidant activity was determined by two important methods. In both model systems the order of extracts was from water to ethyl acetate. Antioxidant activity of cinnamon is mainly due to presence of phenolic compounds. Water extracts of cinnamon fruit contain maximum phenolic compounds as compared to other extracts. Therefore, it exhibited highest antioxidant activity³⁷.

Ozcan and Arsalan isolated essential oils from different plants. Cinnamon was the main plant of concern in them. Antioxidant activities of these essential oils were also determined and compared with the oils of other plants. Samples were prepared by adding essential oils to the oils at concentration of 0.25% and 0.5% and kept them at 50°C in darkness for storage for 14 days. BHA which is a synthetic antioxidant in 0.02% concentration was used as a standard for comparison. Periodic determination method was used to determine antioxidant activity of essential oils. Only those essential oils showed antioxidant effect which were stored for more than 10 days. After 10^thday 0.5% of all essential oils exhibited antioxidant activity at various degrees as compared to BHA. Cinnamon oil showed highest antioxidant effect than hazelnut and poppy oils³⁸.

Kitazuru et al. reported the effects of different rays radiated on natural compounds of Cinnamon zeylanicum which shows strong antioxidant activity. Ionizing radiation to food is a process called food irradiations. This process is used so that it can kill harmful pathogens and insects. If these pathogens are not killed it cause many problems. Germination of root crops was also inhibited by these pathogens. This irradiation process becomes the source of formation of free radicals in carbohydrates, lipids, proteins and other molecules in food. It helps in reducing the process of lipid oxidation in food antioxidants. These antioxidants are used to donate their hydrogen to free radicals. In order to study the effect of irradiation in cinnamon antioxidants, ⁶⁰Co is used to irradiate (50g each) cinnamon samples. These samples were packed in polyethylene sheets. 0, 5, 10, 15, 20, 25 kGy are different irradiation doses at room temperature for each sample. Solvents with increasing polarities from benzene to water are used for extraction of samples. For extraction different methods as well as different instruments can be used. β-carotene and linoleic system was used to measure the antioxidant activity. Antioxidant activity was shown by all irradiated extracts of cinnamon. Whereas it was highest in the case of ether extract at 400ppm concentration and their activity increases with increased concentration. Hence the irradiation process did not affect the cinnamon antioxidants³⁹.

Simsek et al. reported the isolation of essential oils of Cinnamon zeylanicum. Chemical compositions and antioxidant potentials of these compounds or essential oils were also determined. These determinations were made under normal and heat stressed conditions. The analysis of essential oil was done by GCMS. Hydro distillation was carried out to obtain essential oil from cinnamon bark. Twelve main compounds that account 99.2% of cinnamon oil were isolated. Cinnamaldehyde was the major compound present in these extractions. While benzyl alcohol and eugenol were also present in minor quantity. While glycol acetal, benzyl cinnamate, formic acid, benzaldehyde, p-xylene, α-terpineol, α-terpinolene, 1H- cycloprop[e]azulene and benzenepropanol were present in trace amounts. Fifteen days old, 180 quails were used for this experiment to evaluate antioxidant activity. 3 big groups were formed in which there were 6 small groups. Each small group had 10 birds. These divisions were based on balanced gender and initial weight. For 24 hours a day, birds of thermo neutral groups were placed at controlled room temperature 22⁰C in wire cages. Birds of heat stress groups were placed at high temperature 34⁰C for 8 hours a day while at 22⁰C for 16 hours a day. Experiment was performed by providing either 500 or 250ppm cinnamon oil to experimental groups. Liver, kidney and heart’s malondialdehyde levels increased because of heat stress. As a result, superoxide dismutase produced in liver and kidney. Heat stress condition also lowered the activity of glutathione peroxidase and glutathione level. Antioxidant enzyme activities were present in cinnamon oil. It was concluded that level of GSH in tissues in both conditions of environment was increased due to these antioxidant activities. These antioxidant activities also reduced harmful effects of heat stress by providing protection to internal organs⁴⁰.

Khaki et al. investigated that the antioxidant activities of Cinnamon zeylanicum improved the action of insulin. Effects on levels of serum antioxidants of male diabetic rats were studied. As Cinnamon is known to have various medicinal properties including improving the action of insulin in diabetes and reducing the risk of infertility. According to researchers, blood glucose level and infertility are correlated. Diabetes can cause complications in fertility as it is related to high blood sugar level when pancreas does not produce enough insulin. In diabetes, overproduction of free radicals occurs, and various factors contribute to this process including hyperglycemia, glucose autoxidation, nonenzymatic, enzymatic and mitochondrial pathways. In order to reduce this oxidative stress in diabetes natural antioxidant Cinnamon zeylanicum is used. In this experiment, four groups of 8 weeks old forty Wistar albino species of male rats having weights from 240 – 260g were made. One was control group; second one was diabetic group and third group received 75mg/kg cinnamon by gavage method called cinnamon group. After 30 days 5cc blood of rat was taken for antioxidant measurement and it was found out that in cinnamon group, superoxide dismutase and glutathione peroxidase levels increased and Serum malondialdehyde level decreased as compared to control and diabetic groups. Thus, cinnamon can be used as a remedy in diabetic male patients as it sufficiently increases serum antioxidant levels⁴¹.

Ranjbar et al. reported comparative analysis of antioxidative stress properties of Cinnamon zeylanicum. These potentials were studied in humans. Drink of cinnamon with regular tea is commercially available in Iran. Cinnamon’s antioxidant potentials were studied that was determined by analyzing blood sample of different groups. Subjects were total 54 normal humans with same age living in same urban areas. Three groups having 18 humans each were made. One was taking 100mg of cinnamon with 30 mL of regular tea for almost two weeks, other was taking regular tea without cinnamon and third was control group received only water. Two groups one who were taking cinnamon with tea and one who taking only regular tea showed better antioxidant potential than control group. Total thiols and antioxidant powers were increased by tea with or without cinnamon. When activities of regular as well as cinnamon tea were compared. It was observed that plasma TBARS were more less in cinnamon tea. While plasma thiols and antioxidant power of total plasma was more in cinnamon tea. Thus, diseases related to oxidative stresses can be cured by cinnamon tea⁴².

Pandey et al. isolated many biologically active fractions from bark and leaves of Cinnamon zeylanicum. Antifungal, antimicrobial and antioxidant activities of these fractions were also analyzed. Plants contain various metabolites that are responsible for their therapeutic effects. Extracts of Cinnamon zeylanicum were prepared by using petroleum ether (PE), benzene (BZ), chloroform (CH), acetone (AC), ethanol (ET) and distilled water (AQ) as solvents. Reducing power assay method was used to determine the antioxidant activity of these extracts. Ascorbic acid (vitamin C) was used as standard. As the concentration of extracts increases, antioxidant activity also increases. More polar solvents exhibit more antioxidant activity as compared to non-polar. In bark extract AC showed exhibited strongest activity followed by AQ and lower in case of ET fractions. In leaf extracts reducing power was in the order AQ>CH>ET>EA>AC>PE=BZ. In comparison with bark and leaves extracts, bark extracts exhibited more antioxidant potential. So, instead of chemical preservatives, this plant extracts can be used¹¹.

Abeysekera et al. isolated the extracts from Cinnamon zeylanicum. In vitro antioxidant properties of these extracts from leaf and bark determined. MeOH, EtOH and DCM were used for extraction. These antioxidant activities were determined by using in vitro antioxidant assays. DPPH, ORAC, FRAP, ABTS, TFC and TPC are some of the assay methods used to determine antioxidant activity. Both leaf and bark ethanolic extracts possess significant antioxidant potential in all antioxidant assays as compared to (DCM: M). Comparison is made between leaf and bark ethanolic extracts. It was concluded that DPPH radical scavenging activity shown by bark ethanolic extracts was highest whereas leaf ethanolic extracts showed highest FRAP activity and then ABTS. Almost same activity of ORAC and TPC was shown by leaf ethanolic extracts. Lower TFC activity was shown by leaf ethanolic extracts. Thus, both leaf and bark extracts of Cinnamon zeylanicum can be used in cure of oxidative-stress related diseases as they sufficiently prevent formation of reactive oxygen species⁴.

Rao and Gan presented review on different species of cinnamon, their chemical composition and their pharmacological activities. Cinnamon contains variety of compounds in different parts of plants i.e. leaves, roots, bark, root bark, fruit and flowers that are responsible for their different biological activities. Leaves contain cinnamaldehyde (1-5%) and eugenol (70-95%). Root bark contains camphor (60%). Fruit contains caryophyllene (9-14%) and trans-cinnamylacetate (42-54%). Bark contains cinnamaldehyde (65-80%) and eugenol (5-10%). Buds contain terpenehydrocarbons (78%), alpha-Copaene (23.05%), alpha-bergamotene (27.38%) and oxygenated terpenoids (9%). Flowers contain trans-alpha-bergamotene (7.97%), caryophylleneoxidewe (7.20%) and (E)-Cinnamylacetate (41.98%). Flavonoid compounds, phenolic compounds, alcoholic and aqueous extracts, cinnamaldehyde, eugenol, linalool and essential oils of cinnamon exhibit significant antioxidant activity. Out of these eugenol and essential oils were more effective in inhibiting lipid peroxidation by direct action on oxygen and nitric acid production⁶.

Wong et al. used Cinnamon zeylanicum to isolate essential oils. Two methods were discussed for the extraction of oils. These methods were based on the quantity of sample obtained, solvents that were used, time, temperature, percentage peaks of active compound and determined antioxidant and antimicrobial activity by different methods. TLC and GCMS techniques were used to characterize essential oil while HPLC used to identify chemical composition in essential oil. Antimicrobial and antioxidant activities were determined by TLC-bio-autography assays. Steam distillation and Soxhlet extraction method were used for extraction of essential oils from different parts of plants of Cinnamon zeylanicum. In these essential oils, many important compounds were identified. Among these many are biologically active compounds. Cinnamaldehyde is one of these active compounds. Soxhlet extraction was performed by using solvent mostly ethanol at high temperature. More production of extracted oil content i.e. 5.785g for 5 hours and 6.836g for 10 hours extraction was obtained. Cinnamaldehyde percentage was 62-73%, low percentage of peak area as it contained less cinnamaldehyde. It produced oil in crude form and extracted product was purified by rotary evaporator while in steam distillation water was used as a solvent, temperature was low, quantity of product was less i.e. 0.914g for 5 hours and 1.538g for 10 hours, cinnamaldehyde percentage was 90%, high percentage of peak area as it contained high amount of cinnamaldehyde. It used separatory funnel. Steam distillation was considered best for extraction of cinnamaldehyde because it never decomposes in this method due to low temperature, it gives pure product, faster and safer method, cheaper than other methods whereas in Soxhlet extraction thermal degradation may happen due to high temperature⁴³.

Ervina et al. reported the comparison between cinnamon bark infusion, extract, its fractions and determined phytochemical constituents that exhibit antioxidant activity. By water extraction, infusion was prepared. Ethanolic extracts were fractioned and then n-hexane, water and ethyl acetate fractions were made. DPPH method was used to determine in vitro antioxidant activity semi quantitatively. TLC-autography with several spray reagents was used to identify chemical constituents in them. It was found out that cinnamon bark infusion exhibited the highest antioxidant activity with IC50 value of 3.03, then ethanolic extract 8.36, water 8.89 and ethyl acetate- fractions 13.51µg/mL. Their antioxidant potential was found to be higher than rutin with IC50 of 15.27µg/mL. Main antioxidant compounds that were present include polyphenol (tannin, flavonoids) and phenolic volatile oil⁴⁴.

Faix et al. reported the isolation of essential oils from Cinnamon zeylanicum. The effect of these essential oils in diet supplements were analyzed. This was performed in order to check the antioxidant status of broiler chickens. For this purpose, 0%, 0.1%, 0.05% and 0.025% of essential oil was added in diets. Hybrid broilers (Ross 308) were used in this experiment. Those diets were fed to 32 these female broilers. Epitheliums from kidney, liver, duodenal and blood were collected to determine and examine the antioxidant status. It was concluded from results that malondialdehyde level in duodenal mucosa and plasma decreased significantly by using of only 0.1% essential oil. But this did not cause any effect in tissues of kidney and liver. Glutathione peroxidase (GPx) activities was found to be higher and blood phagocytic activity was increased as compared to the control group (0%). Activities of ALT in plasma sufficiently decreased with 0.025% and 0.05% of essential oils. 0.05% of essential oil in the diet caused much higher increase in activity of GPx in the liver and kidney. These activities are analyzed by comparing he values with control. Thus, Cinnamon zeylanicum essential oil exhibited antioxidant potential by activating antioxidant enzymes in broiler chickens and can be used as dietary supplements¹².

Dugoua et al. presented a systematic review to find the pharmacological activities of cinnamon. Moreover, efficacy and safety of these were also determined. Various medical conditions, antioxidant activity and effects of cinnamon on them were reported. Type 2 diabetes is one of these medical conditions. Three clinical trials on this disease were performed. Two of them provided evidence that cassia cinnamon reduced 10.3%–29% blood glucose and it did not play any role in lowering glycosylated hemoglobin (HbA1c). Third trial did not show any result. LDL cholesterol, total cholesterol and triglycerides are also lowered in one trial. But no effect was observed in other two trials. These evidences showed that cinnamon species was not effective in treating H. pylori infection. Chronic salmonellosis and oral candidiasis related to HIV patients can be cured to some extent by Cinnamon zeylanicum. As very little efficacy effects were shown by cinnamon in treatment of these diseases⁴⁵.

Jayathilakan et al. evaluated the antioxidant potential of natural Cinnamon zeylanicum. Many antioxidants like TBHQ and BHA are also synthesized and their antioxidant potential were also evaluated based on some parameters. It was concluded that 82-91% antioxidant activity was shown by TBHQ and MRPs. During refrigerated storage, lower non-haem iron and hexanal values were calculated which indicated that these antioxidants may be suitable for controlling warmed over flavor. Different parameters were used to perform analysis of Non-linear correlation regression. For beef and pork exponential fit equations were obtained whereas in sheep polynomial relationship was obtained and correlation coefficient for non-haem and WOF was 0.90 and 0.97 respectively. It was observed that MRPs showed maximum antioxidant potential than cloves which showed greater than ascorbic acid. While in these, cinnamon showed less antioxidant potential. Among synthetic antioxidants TBHQ showed higher antioxidant potential than BHA which showed higher than PG⁴⁶.

Tulini et al. produced solid lipid microparticles by spray chilling method loaded with proanthocyanidins rich cinnamon extract (Cinnamon zeylanicum), with significant antioxidant potential and reduced bitterness. As proanthocyanidins belongs to the class of flavonoids, have the potential to prevent from damage and severe complications that are caused by diabetes. But the unpleasant taste and stability of these compounds are not favorable for daily intake. So, spray chilling method was used for the incorporation of these compounds into microparticles of solid lipids. This method has remarkable taste masking property and no organic solvent required for this method. Vegetable fat was used as a carrier with melting point (48°C). Physical as well as chemical properties, its structure, stability of proanthocyanidins and sensory properties were some parameters for the characterization of these microparticles. Size distribution of these microparticles was in the range of 60-130 µm and these proanthocyanidins rich active compounds were highly stable. For 90 days they can be remained stabilized at different temperatures. Moreover, it will also help in making better taste of proanthocyanidins by reducing the bitter taste. Other polyphenols from cinnamon extract can also be applied in functional foods to increase their antioxidant potential especially directed for diabetic patients⁸.

Tulini et al. determined that extract of Cinnamon zeylanicum encapsulated by α-tocopherol into the gastrointestinal tract was rich with proanthocyanidins. Its stability and antioxidant activity were also determined by spray chilling method. Proanthocyanidins rich Cinnamon extract which was encapsulated by α-tocopherol incorporated into solid lipid microparticles and their characterization was done with different techniques. The shape of microparticles was spherical having an average diameter of 80 µm and these were highly stable up to 90 days at different temperatures. SLMs protect proanthocyanidins from the low pH in stomach by releasing them into gastrointestinal fluids via diffusion process. These SLMs exhibited high radical scavenging activity against both reactive oxygen and nitrogen species. Functional foods with higher antioxidant activity can be developed by help of these microparticles⁹.

Jayaprakasha et al. reported the chemical composition, biogenesis, and biological activities of Cinnamon zeylanicum. Essential oils from different parts of cinnamon tree i.e. leaves, roots, root bark, stem bark, fruit and flowers were extracted by using SCF, hydro and steam distillation methods. GC and GCMS were used to determine the Chemical constituents of essential oils. By using these methods more than 80 chemical constituents were identified. The major constituents in essential oils extracted from leaves, barks of roots and stems were eugenol, camphor and cinnamaldehyde respectively. Trans-cinnamyl acetate is the main compound in flowers, fruits and fruit stalks. Other compounds were present in minor quantity. Bark and fruits of cinnamon also contained proanthocyanidins. These compounds have double bisﬂavan-3-ol units in molecule. These compounds are applicable in food and pharmaceutical industries. Different pharmacological activities of these essential oils include antioxidant, antimicrobial, and antidiabetic activities⁴⁷.

Sariozkan et al. reported the protective effect of essential oils extracted from the bark of cinnamon. Different types of tests were performed on rats to check effects of antioxidant potentials of cinnamon. Long term consumption of cinnamon bark proved to be protective for cells and tissues of rats. It also provided efficacy curative effects to male reproductive organs. As a result, quality and quantity of sperm cells increased⁴⁸.

CONCLUSION:

This review presented the antioxidant activity of Cinnamon zeylanicum and its various chemical constituents such as eugenol, cinnamaldehyde, camphor, cinnamal acetate, flavonoid and phenolic compounds that are present in different parts of the plant i.e. bark, leaves, roots, root bark, buds, fruit and flowers are responsible for its antioxidant potential. Due to its antioxidant potential it can be used to treat serious diseases like type 2 diabetes, infertility and neurological disorders. It can also be used in preparation and preservation of food and have applications in pharmaceutical industries. Their nanoparticles are also synthesizing now a days which are showing outstanding antioxidant activities. It is suggested that further studies should concentrate on synergistic effect of Cinnamon zeylanicum with other spices.

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Received on 30.07.2020 Modified on 20.10.2020

Asian Journal of Pharmaceutical Research. 2021; 11(2):106-116.

DOI: 10.52711/2231-5691.2021.00021