An Overview on Chemical Constituents and ...

Review Article

An Overview on Chemical Constituents and Pharmacological Effects of Citrus Aurantium Species SYED TAZIB RAHAMAN 1 , PRAVEEN VASIREDDY 2 Gitam Institute of Pharmacy, Gitam University, Visakhapatnam, Andhra Pradesh - 284050. Email id : [email protected], [email protected], (M) – 7702149861 Received: 30.08.17, Revised: 15.09.17, Accepted: 20.11.17 ABSTRACT Nature has provided almost each and every valuable resource which all the living organism are in need of. There have been many medicinal plants which have been possessing various medicinal and pharmacological properties which can cure several diseases which effect living organisms most importantly humans. One of those vital plants are Citrus aurantium species. With this review we would able to identify different chemicals such as Linalool, Bergamot, Farnesol, D-Limonene in higher concentrations and a-thujene, apinene, Camphene, Sabinene, b-pinene, b-Myrcene, pCymene, Ocimene (E), Linalool oxide (Trans), Linalool oxide (Cis), Terpinen-4-ol, Terpineol, Nerol (Or) Cis-Geraniol, Neral, Geranial, Neryl acetate, Geranyl acetate, Nerolidol, Farnesal, Eicosane, Tetracosane, Pentacosane in lower concentrations which in total constitute the volatile oil isolated from this plant and we would also discuss about several pharmacological effects possessed by this plant such as Analgesic, Anti- cancer, Anti- diabetic, Anti Bacterial, Anti oxidant, Anxiolytic, Hypoglycemic and Hypolipidemic properties which makes Citrus aurantium the most Valuable medicinal plant for Medical and Allied Health Sciences. Keywords: Citrus aurantium; Pharmacological properties; Anti diabetic; Anti oxidant; Antibacterial INTRODUCTION Recent study states that the main proto alkaloid namely p-synephrine present in Citrus aurantium alone or in combination with caffeine would do not produce any adverse effects on cardiovascular activity whereas it is identified that it increase the resting metabolic rate and it may also lead to moderate weight loss when take for a longer period of time.In this review article firstly we would identify various chemicals present in volatile oil of Citrus aurantium and then we would discuss several Pharmacological properties.Citrus aurantium which is commonly known as Bitter orange belongs to Rutaceae family. This plant consist of proto alkaloids such as p-synephrine and Octopamine which act as active components. The p-synephrine content in the dried fruit of this plant is reported to be 3-6%[1].This plant is generally found in secluded and wooded parts like Florida and the Bahamas. This plant has been widely used as Herbal medicine, stimulant and Appetite suppressant [3]. The extract of this plant is used as Dietary supplement which helps in Weight loss. This may have dangerous drug interactions with drugs like statins. The fruits and leaves give lather and thus can be used in preparation of soaps. The hard white or light yellow wood of this plant can be used for woodworking purposes. Bitter orange oil or Volatile of this plant is extracted from the peel of this plant. This volatile oil

shows Anti fungal action which helps in preventing fungal infections such as Ringworm and athlete’s foot [3]. This oil is also used in treatment Gastrointestinal (GIT) disorders. The flowers of this plant are also used to remove impurities from the skin and to prevent hair loss. Thus by this we can understand that each and every part of C.aurantium is very much helpful in many ways for living organisms. Chemical Constituents Chemical composition of Volatile Oil isolated from Citrus aurantium According to a study done by Salim Makhoul et al;[8] the chemicals of volatile oil are isolated from Lebanese Citrus aurantium using Gas chromatography coupled with Mass Spectroscopic Method. After collection of the plant species is done, firstly volatile oil is isolated by Hydrodistillation using Clevenger type apparatus. The volatile oil isolated was then stored in dark glass vessels at 40C until the further process is initiated. During Gas chromatographic and Mass spectroscopic method the separation was performed in a silica capillary column which was coated with 0.25μm film Rtx-5MS. The injector and the detector temperatures was respectively 250 and 280 °C. The oven temperature was held at 40 °C for 4 min initially and programmed from 40 to 80 °C at

International Journal of Pharmaceutical Research | Apr-June 2018 | Vol 10 | Issue 2|15

Tazib et al / An Overview on Chemical constituents and Pharmacological effects of Citrus aurantium species 6 °C min-1 then to 150 °C at 6 °C min-1 and finally are responsible for the odour and flavor of citrus to 280 at 16°C.min-1. The chemical composition of and they are also used for many medicinal the oil was identified by comparing their spectra applications. Linalool is used as a natural with those of a NIST library and was then insecticidal which shows similarity in activity to Dconfirmed by comparing their retention indices with limonene and it also exhibits antifungal properties. data published in various literatures. The results of Limonene which is commonly a Terpene is generally the performed chromatography showed that used as a flavoring agent in foods and drinks. There volatile oil consists of 26 chemical components out several chemical components which are isolated of which Linalool was said to be available in higher from volatile oil of this plant which are present in concentrations i.e 29.99% which is followed by lower concentrations. Bergamot (14.94%), Farnesol (9.86%) and Dlimonene (8.42%). The above identified chemicals All the chemical components which are present in Volatile Oil of Lebanese C. aurantium are given below: Name of Chemical constituent α-Thujene

Table 1. Chemical constituents of C.aurantium Chemical Structure

Retention Index 927[8]

α-Pinene

933[8]

Camphene

953[8]

Sabinene

972[8]

β-Pinene

978[8]

16| International Journal of Pharmaceutical Research | Apr-June 2018 | Vol 10 | Issue 2

Tazib et al / An Overview on Chemical constituents and Pharmacological effects of Citrus aurantium species Myrcene

991[8]

p-Cymene

1025[8],[9]

Limonene

1030[8],[9]

Ocimene (E)

1046[8],[10]

Linalool oxide (Trans)

1080[8]

Linalool oxide (Cis)

1095[8]

Linalool

1101[8]

Terpinen-4-ol

1180[8]

Terpineol

1198[8]


Tazib et al / An Overview on Chemical constituents and Pharmacological effects of Citrus aurantium species Nerol

1229[8]

Neral

1238[8]

Linalyl acetate

1250[8]

Geranial

1268[8]

Neryl acetate

1361[8]

Geranyl acetate

1380[8]

Nerolidol

1562[8]

Farnesol

1716[8]

Farnesal

1737[8]

Eicosane

2000[8]

Tetracosane

2400[8]

Pentacosane

2500[8]


Alkaloids present in C. aurantium There are several alkaloids present in this plant which is very much useful for several pharmaceutical applications. p-synephrine is considered to be a proto alkaloid which is a derivative of phenylethanolamine with the hydroxy group in the paraposition onthe benzene ring of the molecule. This alkaloid is structurally similar to ephedrine which is a phenylpropanolamine derivative [2] and does not contain hydroxyl group in para position. Ephedrine and m-synephrine exhibits cardiovascular effects. Citrus aurantium is a proto alkaloid psynephrine useful for the producing desirable products. Bitter orange extracts are isolated individually or in combined form with any other plant ingredients which do not produce any severe effects such as increase in blood pressure and count of the blood cells. This plant increases the chemical reactions in the body and one of the main component in it’s composition is p-synephrine bitter orange extract which is obtained from the not fully grown fruits of seville orange. Scientific research done till date has failed to differentiate

between p-synephrine which has hydroxyl group in para positon of benzene ring with that of synthetic p-synephrine which is having hydroxyl group on meta position as it exhibits cardiovascular effect but not from the component of bitter orange. The safety and desirable product problems are the matters of concern with respect to this plant because of structural similarity between psynephrine and ephedrine. The products obtained from this plant are mostly containing plant product extract along with caffeine. The concentration of synephrine in the juice of orange is reported to be 57mcg/ml[2]. Bloomer et;al [11,12] reported on the effects of two or more than two-component products which do not contain both p-synephrine and bitter orange extract but contains only methylsynephrine Hcl and yohimbine .Different types of studies showing lipolytic activity of p-synephrine stated about it binding to β-3 adrenergic receptors . p-synephrine also plays a major role in stimulation of β-3 adrenergic receptors which causes the modulation. p-synephrine do not show severe effects on blood vessels.

Pharmacological effects of C. Aurantium are discussed briefly below: Analgesic effect The volatile oil isolated from this plant consists of several chemical constituents which belong to monoterpenes, sesquiterpenes and other chemical groups. The study performed by Damião Pergentino de Sousa et, al;[4] proved to be essential in knowing that several of those chemical constituents are useful in relieving pain and thus shows analgesic effects. The compounds which showed analgesic properties were identified by observing the effects shown in specific animal models for evaluation of the anti-nociceptive

activity. The results showed that around 43 chemical constituents showed analgesic properties out of which 62.8% were Monoterpenes (βMyrcene, α-Pinene, β-Pinene,(+)-Limonene, 1,8Cineole etc.) 18.6% Sesquiterpenes (Zerumbone, Caryophyllene oxide, Agarospirol, Jinkoheremol, αSantalol, β-Santalol etc. ) and other constituents represented 18.6%( Phenylpropanoids). Thus this showed that C.aurantium had a great source analgesic drugs which can be used to relieve pain. Many people in this world are commonly effected by pain at varied parts of the body. There is a lot of clinical research going on in decreasing the amount of pain with respect to the mode of administration


Tazib et al / An Overview on Chemical constituents and Pharmacological effects of Citrus aurantium species of drug and part of the body which is paining. Most of the drugs which are obtained from plants which help in reducing pain are generally tested on rats and mice. The drugs obtained from these plants have biologically effecting oils which are obtained by extraction from plant parts such as leaves ,flowers and stem. Chemical components of oils are terpenoids . There are different types of terpenoids which contain essential oils which are further differentiated based on their number of isoprene units. Monoterpenoid contains 90%of oils and terpenoids exhbhit different properties such as relieving spasm of smooth muscle ,reducing of anxiety ,blocking of detention by painful injuries and anti convolusant activity. Basing on the analgesic activity many experiments have been conducted on isolation of the essential oils for varied applications in the pharmaceutical and cosmetic industries. danggui a Chinese plant showed larger concentrations of essential oils. Anti diabetic action In the study performed by Joan Campbell-Tofte et al; [7]An active fraction is extracted from the fruit of C.aurantium by filtering the boiling tea and concentrating the supernatant. This active fraction is useful in treatment for elevated glucose levels in blood i.e diabetes. Thus citrus is found to have anti diabetic action. This fraction is also used in treatment of hyperphagia, abnormal lipid mobilization, abnormal fatty acid profile from the eye of the subject[7], ulcers and a glucosuria. Anti microbial effects In the study done by Sarah Almeida Coelho Oliveira et,al;[5] evaluation of essential oils of Citrus aurantium is performed using multi species formed by Candida albicans, Enterococcus faecalis and Escherichia coli. Candida albacans is the major yeast which is a causative agent for diseases related to cavity of the mouth and it is considered to be the most harmful bacteria Enterococcus feacalis is the most common living bacteria used for the treatment of oral cavity. Citrus fruits contains nutrients which is helpful for enriching nutrient intake of humans. They also contain mostly flavonoids which is rarely found in most of the medicinal plants. Microorganisms combine and attach with each other and adhere to surface which forms a film known as Biofilm which acts as a protective sheath from antigens. Citrus limonum contains pencillin and methicillin which are potent drugs of E.coli which also contains essential olis. The biofilms are firstly made to grow in acrylic disks immersed in broth, inoculated with microbial suspension (106 cells/mL) and incubated at 37°C /

48 h. Then the biofilms are exposed for 5 min to the solutions like 0.2% chlorhexidine (CHX) and 1% sodium hypochlorite (NaOCl) and essential oils of C. aurantium and C. limonum. The results of this experiment showed that essential oil of C.aurantium and Sodium hypochlorite promoted inhibition of all Microorganisms. Thus this study proved the Anti microbial action of this plant. Anti oxidant property In the study performed by Adeline Dorcas. F et,al; [6] discussed about the evaluation of Citrus peel powder by DPPH assay which was further followed by FRAP Assay which determined the scavenging activity of this plant’s peel powder in five different extracts (aqueous, acetone, ethanol, petroleum ether and chloroform).The results showed that the peel powder in Acetone showed greater scavenging activity which was followed by ethanol, aqueous, and chloroform at 30 minutes. The antioxidant activity of peel powder of this plant using ethanol extract by FRAP Assay was 2.010mM Fe/g indicating high antioxidant activity. This hence proved the presence of Anti oxidant activity in C.aurantium. Conclusion In this review article we could understand the vital importance of Citrus aurantium in medical and pharmaceutical field. There have been several Chemical constituents such as Terpenes, Proto alkaloids which are very much essential in treatment of several diseases and in producing various pharmacological actions. Thus there is an alarming need for us to utilize the resources what this plant is providing in an effective manner. We have found that C.aurantium shows Analgesic, Anti diabetic, Anti oxidant and Anti microbial actions which is very much beneficial in various fields. Acknowledgement The author is thankful to GITAM University, Visakhapatnam, Andhra Pradesh, India, for providing financial support and facilities to carry out this review. Financial support and sponsorship This study was supported by GITAM University, Visakhapatnam, Andhra Pradesh, India. Conflicts of interest There are no conflicts of interest. References 1. Sheng Jia, Xiaoyong Zhao ; Hypoglycemic and hypolipidemic effects of neohesperidin derived from Citrus aurantium L. in diabetic KK-A y mice DOI: 10.1039/c4fo00993b of· Source: PubMed. 2. Sidney J.Stohs ; A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine .


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