Angelica archangelica L.- A Phytochemical and Pharmacological Review
Anupam Maurya, Subash C. Verma*, Vijay Gupta, M. B. Shankar
Pharmacopoeia Commission for Indian Medicine and Homoeopathy (PCIM&H), PLIM Campus,
Ghaziabad-201002, India
*Corresponding Author E-mail: scvpharma@gmail.com
ABSTRACT:
Angelica archangelica Linn.(Garden angelica) has traditionally used in Indian system and Chinese system of medicines. In Ayurveda, it is known as Chanda and exhibits the therapeutic actions as it pacifying Vata and Kaphadosha. It is tall perennial herb mainly found in Himalayan region of India. It is only Medicinal and Aromatic Plant (MAP) with a Nordic origin. The plant is widely used in traditional and folk medicine as a remedy for nervous headaches, fever, skin rashes, wounds, rheumatism, and toothaches and epilepsy. The root of A. archangelica is internally used for gastric ulcers, anorexia, migraine, bronchitis, chronic fatigue, menstrual and obstetric complaints. It has number of biological activities like antimutagenic, antiulcerogenic, hepatoprotective, antiproliferative, antitumour, cytotoxic and anxiolytic effect. Various phytoconstiteunts were found in plant, but most abundant phytoconstituents are essential oils and furocoumarins in various part of plant. The main components of its essential oils are α-pinene, β-phellandrene, limonene, α-phellandrene, 3-carene and p-cymene and most abundant furocoumarins are archangelicin, angelicin, bergapten, imperatorin and xanthotoxin. Garden angelica has as a unique scent that is found in all parts of the plant which is used since ancient time as flavouring, confectionary and perfumes. The plant is good source of furocoumarins, which provides examples of their versatility in a range of applications in the fields of biology and pharmacology. The paper explained the evidence-based information regarding phytochemistry, pharmacological activities, traditional and medicinal uses of this plant.
KEYWORDS:Angelica archangelia, phytochemistry, essential oil, coumarins,pharmacological properties, medicinal uses.
Angelica archangelica Linn. belongs to family Apiaceae and commonly known as Garden angelica, wild celery, and Norwegian angelica. It is a perennial herb cultivated especially for culinary uses and aromatherapy.1 Synonyms includes Archangelica officinalis Hoffm. and Archangelica officnalis var. himalaica C.B. Clark (Dinesh). Angelica archangelica is an important medicinal plant widely used for long in folk medicine in Nordic countries, where it has been cultivated during the middle ages and exported to other parts ofEurope.2
It is a tall perennial herb with a thick hollow stem, bearing large bipinnate leaves, and umbels of greenish white flowers; found wild in the inner valleys of the Himalayas, namely, Kashmir, Chamba, Kullu, Pangi, Lahaul, and Kinnaur, at altitudes between 3200 and 4200 m. (India).3 The plant is widely used in traditional and folk medicine as a remedy for nervous headaches, fever, skin rashes, wounds, rheumatism, and toothaches and epilepsy.1 In Chinese system of medicine it is prescribedfor cerebral disease.4 It is essential oil containing favoring plant which possess diuretic and carminative diaphoretic properties and also internally used in digestive complaints, flatulence, cold and respiratory system.5 The root is internally used for gastric ulcers, anorexia, and migraine, bronchitis, chronic fatigue, menstrual and obstetric complaints.3 It also has wide range of biological activity like antimutagenic, antiulcerogenic, hepatoprotective, antiproliferative, antitumour, cytotoxic and anxiolytic effect.1,6-11 The constituents found in of A. archangelica are bittering agents, essential oils, flavonoids, tanning agents, resins, carbohydrates, coumarins, organic acidsand terpenes.12. The most abundant phytoconstituents found in A. archangelica are essential oils and furocoumarins. The essential oil mainly composed ofα-pinene, β-phellandrene, limonene, α-phellandrene, 3-carene and p-cymene.3Garden angelica has as a unique scent that is found in all parts of the plant. Because of the unique scent, angelica has been used since ancient times as a traditional flavouring for confectionary, liqueurs, perfumes, wines and beverage production.The most common coumarins found in plants are archangelicin, bergapten, imperatorin, isoimperatorin, isopimpinellin, osthol, ostruthol, oxypeucedanin, phellopterin, psoralen and xanthotoxin.13
Distribution and Habitat:
Angelica archangelica has a very interesting historical and cultural distribution pattern. Plant is said to have its origin from northern part of the world and has been travelling to the Central and Southern Europe to become established and widely neutralized as a domestic Plant. It is one of very few plants which spread from the north to the south. Angelica archangelica is native to Northern Europe, the Netherlands, Central Europe, eastern Central Europe, Eastern Europe, the Caucasus and West-Siberia. It grows wild in Russia, Finland, Sweden, Norway, Denmark, Greenland, the Faroe Islands, and Iceland, mostly in the northern parts of the countries. It is cultivated in France, mainly in the Marais Poitevin, a marsh region close to Niort in the department Deux-Sèvres. It also grows in certain regions in Germany like the Harz mountains, in certain regions of Romania, like the Rodna Mountains, in hilly and coastal regions of Poland and some South East Asian countries like Thailand.14, 15 In India, It is wildly distributed throughout the inner valleys of the Himalayas, namely, Kashmir, Chamba, Kullu, Pangi, Lahaul, and Kinnaur, at altitudes between 3200 and 4200 m.3
Taxonomical Classification of Angelica archangelica Linn.
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Kingdom |
Plantae |
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Phylum |
Tracheophyta |
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Class |
Magnoliopsida |
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Order |
Apiales |
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Family |
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Genus |
Angelica |
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Species |
Angelica archangelica |
Therapeutic uses in Ayurveda:
In Ayurveda, A. archangelica known as Chanda. Ayurvedic Pharmacopoeia of India (API) describes the property of roots of Angelica archangelica Linn. as it is bitter in taste and hot in potency. It exhibits the therapeutic actions as it pacifying Vata and Kapha (different bio humors as per Ayurveda), Svasahara (alleviate breathlessness), Mutrala (diuretic), Varnaprasadaka (promoting skin complexion), Svedaghna (prevent excessive perspiration), Kandughna (anti pruritic), Vishaghna (anti-poisonous), Daurgandhahara (elevating foul smell) and by virtue of these actions it can be helpful in the in Shotha (oedema), Svasa (dyspnoea/Asthma), Apasmara (epilepsy), Hikka (hiccup), Arsha (piles), Kandu (itching), Pidika (boils) and Kotha (erythema / A type of urticaria).16
Phytochemistry:
Coumarins and Others:
The most plants of the family Apiaceae are known to accumulate coumarin derivatives in their roots and seed. The most characteristic secondary metabolites of A.archangelica are essential oils and furanocoumarins.17 The furanocoumarins, or furocoumarins, are a class of organic chemical compounds produced by a variety of plants. They are biosynthesized partly through the phenylpropanoid pathwayand the mevalonate pathway, which is biosynthesized by a coupling of dimethylallyl pyrophosphate (DMAPP) and 7-hydroxycoumarin (umbelliferone). Imperatorin (1) (8-isopentenyloxypsoralen) is the major furanocoumarin of A. archangelica seeds and xanthotoxin (2) (8-methoxypsoralen) is one of themajor furanocoumarins in A. archangelica.17
Steck and Bailey (1969) isolated six furocoumarin angelicin (3), bergapten (4), imperatorin (1), isopimpinellin (5), xanthotoxin (2), oxypeucedanin (6) and five unidentified coumarins from the leaves.18Harkaret. al. (1984) reported, besides sitosterol (7), pregneol (8), Peucenin-7-methyl ether (9), osthol (10) and 18 different furocoumarins namely psoralen (11) archanegelin (12), bergaptol (13), bergapten (14), isoimperatorin (15), oxypeucedanin (16), oxypeucedanin hydrate (17), isooxypeudedanin (18), oxypeucedanin hydrate-3”-ethyl ether (19), saxalin (20) ostruthol (21), xanthaotoxol (22), xanthaotoxin (1), imperatorin (2), heraclenol (23), 8-gernanyloxy psoralen (24), allo-isoimperatorin (25) from ethyl acetate extract of the fresh roots of Angelica oflcinalis var. himuliaca (Fig.1).19 Wszelaki et. al. (2011) carried out TLC bioautography guided fractionation, isolation and identification of imperatorin (1) from the fruit's hexane extract and of heraclenol-2′-O-angelate (26) from the root's hexane extract.20
Eevaet.al. (2014) developed a reverse-phase HPLC-MS method for the separation and identification of coumarins in Angelica archangelica (L.) var. archangelica. The Turbo Method Development program was utilised to optimisethe mobile phase with two organic solvents (acetonitrile and methanol) and two aqueous solutions (1.0% formic acid and 10 mM ammonium acetate). The developed method able to separate and identified fourteen coumarins (psoralen, xanthotoxol, xanthotoxin, bergapten, isopimpinellin, imperatorin, isoimperatorin, oxypeucedanin, phellopterin, oxypeucedanin hydrate, osthrutol, umbelliferone, osthenol and osthol) in root and five coumarins (xanthotoxin, bergapten, isopimpinellin and umbelliprenin) in leaf.21
Fig. 1. Structures of some furocoumarins present in A. archangelica
Essential oil:
The yield of essential oil obtained from rhizomes and roots by steam distillation ranges 0.1-1.0 %.22It was reported that the main proportion of angelica root oil consists of monoterpene (up to 88%)22. The main components of fresh root of angelica oil areα-pinene (16.66%), limonene (13.12%), α-phellandrene (11.27%), β-phellandrene (8.92%), 3-carene (8.69%), p-cymene (5.56%), trans-β-ocimene (5.43%) and its geometric isomer, cis-β-ocimene (2.05%), myrcene (3.91%), β-pinene (1.12%) and camphene (1.09%). Sesquiterpene hydrocarbons represented (6.73%) of the oil composition mainly α-humulene (1.23%), α-copaene (1.16%), germacrene-D (1.13%), and β-bisabolene (1.13%).22Nivinskiene et.al. (2005) investigated the Chemical composition of all seeds (fruits) of A. archangelica by GC and GC-MS. The major constituent was found β-phellandrene (33.60-63.4%) followed by α-pinene (4.2-12.8%), germacrene D (3.0%), α-phellandrene (7.4%), and sabinene (3.3%).23Fraternale et.al. (2014) investigated chemical compositionofthe essential oil of Angelica archangelica L. (Apiaceae) roots from central Italy. The major components of the oil were α-pinene (21.3%), δ-3-carene (16.5%), limonene (16.4%) and α-phellandrene (8.7%).24
Pharmacological Activity:
Antitumour:
The effect of leaf extract of A. achangelica on the growth of Crl mouse breast cancer cells in-vitro and in-vivowas examined. The antiproliferative activity of the extract was measured by 3H-thymidine uptake in the Crl cells in vitro. The leaf extract was mildly antiproliferative on the Crl cells with an EC50 of 87.6 µg/ml. The antitumour activity of the extract was expressed in the mice by marked reduction in tumour growth. The leaf extract of A. archangelica demonstrate the antiproliferative activity in-vitro and antitumour activity in-vivo.10
Anti-anxiety:
The whole plant of A. achangelica subjected for successive extraction by solvents [petroleum ether (40-60° C), chloroform, ethyl acetate, methanol and decoction with water]. The all extracts were evaluated for anxiolytic effects using the elevated T-maze and forced swimming tests in rats. Oral dosing of diazepam (1 mg/kg) and extracts (50, 100 and 200 mg/kg) clearly showed an anxiolytic-like profile in the elevated T-maze test. In the forced swimming test, imipramine and all extract showed antidepressant- and anxiolytic-like effects as reflected by increased climbing time, swimming time and decreased immobility. Aqueous and methanol extracts showed the most, petroleum ether (40-60°C) and chloroform intermediate, and ethyl acetate the least anxiolytic activity (*P<0.05, **P<0.01, ***P<0.001) in both models.25
Cytotoxic Effect:
The three samples containing essential oils of fruits of A. archangelica were examined in PANC-1 human pancreas cancer cells and Crl mouse breast cancer cells in concentration ranges 10-100µg/ml, measuring the reduction of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2Htetrazolium (MTS) by mitochondrial enzymes. Two types of essential oils were found, differing mainly in the absence or presence of ‚β-phellandrene. The ED50 of the oils ranged from 48.6 µg/ml to 108.3 µg/ml for PANC-1 and 48.0 µg/ml to 91.8 µg/ml for Crl cells. The cytotoxic activity of the essential oils was independent of the quantity of their main components.11
Antiproliferative:
The tincture from the fruits of A. achangelica and its active components furanocoumarins were examined for antiproliferative effect using the human pancreas cancer cell line PANC-1 as a model. Significant dose-dependent antiproliferative activity was observed in the tincture with an EC50 value of 28.6 μg/ml as well as strong antiproliferative activity observed from the two most abundant furaocoumarins in the tincture, imperatorin and xanthotoxin with EC50 values of 2.7 μg/ml and 3.7 μg/ml, respectively. The results indicate that antiproliferative activity of the tincture is due to presence of furocoumarins.9
Hepatoprotective:
A. archangelica investigated against chronic ethanol-induced hepatotoxicity in mice which resulted in a significant elevation of the activities of serum GOT and GPT. On treatment of mice by A. archangelica (10, 25, and 50 mg/kg p.o.) after 2 weeks ameliorated the ethanol-induced hepatotoxicity effects. Hepatotoxicity was evidenced by a significant increase in hepatic lipid peroxidation manifested as the presence of malondialdehyde. It was found that A. archangelica inhibits the malondialdehyde and also inhibits the production of oxygen free radicals that cause lipid peroxidation, and hence indirectly protects the liver from oxidative stress.8
Antimutagenic:
The aqueous and alcohol extract thio-TEPA of A. archangelica L. examined against mutagenicity by micronucleus test in murine bone marrow cells. As seen during the simultaneous treatment, when the extracts were injected 2 hr before thio-TEPA treatment, it caused more profound reduction of Thio-TEPA's mutagenic activity. The observed reduction of micronuclear frequencies was as high as 77%.6
Butyrylcholinesterase Inhibitory Activity:
The inhibitory effect of hexane extracts obtained from roots and fruits of A. achangelica on acetyl cholinesterase, which prompted bioautography guided fractionation, isolation and identification of two furocoumarins imperatorin from the fruit's hexane extract and of heraclenol-2′-O-angelate from the root's hexane extract. The isolated compounds imperatorin and heraclenol-2′-O-angelate showed significant butyrylcholinesterase inhibition activity with IC50 = 14.4 ± 3.2 μM and IC50 = 7.5 ± 1.8 μM, respectively.20
Inhibition of Acetylcholinesterase:
Ethanolic extracts of Angelica archangelica showed acetylcholinesterase (AChE) inhibition with IC50 value of 2.20 mg/ml. Two furocoumarins: imperatorin and xanthotoxin from A. archangelica was evaluated for the inhibition of acetylcholinesterase. Xanthotoxin proved much more potent than imperatorin, with an IC50 value of 155 μg/ml (0.72 mm) but that for imperatorin was above 274 μg/ml (1.01 mm).17
Antimicrobial Activity:
The essential oil obtained from the roots of Angelica archangelica L. chemically investigated and tested for antimicrobial activity. The major constituents of oil were reported as α-pinene (21.3%), δ-3-carene (16.5%), limonene (16.4%) and α-phellandrene (8.7%). The essential oil showed a good antimicrobial activity against Clostridium difficile, Clostridium perfringen, Enterococcus faecalis, Eubacterium limosum, Peptostreptococcus anaerobius, and Candida albicans with minimum inhibitory concentration (MIC) values of 0.25, 0.25, 0.13, 0.25, 2.25, and 0.50% v/v, respectively.24
Antiseizure Activity:
The essential oil of the root of A. archangelica was evaluated against electrically and chemically induced seizures. The antiseizures activity of oil was compared with standard anticonvulsant agents, phenytoin and diazepam. The essential oil exhibited antiseizure effect which may be attributed due to the presence of terpenes in oil.1
CONCLUSION:
The present review collected the information regarding the phytochemistry, pharmacology and medicinal uses of A. archangelica. As per Ayurveda system of medicine, it pacifiesVata and Kapha doshaand beneficial in alleviating various skin and breathing disorders. It is used in traditional and folk medicine as a remedy for nervous headaches, fever, skin rashes, wounds, rheumatism, and toothaches, epilepsy and internally used for gastric ulcers, anorexia, and migraine, bronchitis, chronic fatigue, menstrual and obstetric complaints. The plant showed various biological activities biological activities like antimutagenic, antiulcerogenic, hepatoprotective, antiproliferative, antitumour, cytotoxic and anxiolytic effect. The literature search revealed the presence of essential oil, coumarins, acids, sugar, a bitter principle, triterpens, and flavonoids in different parts of this plant. In ancient time, essential oils present in A. archangelica used from aroma, flavouring, perfumes and beverage production. Number of furocoumarins accumulated in various part of this plant which are characteristic secondary metabolites of A. archangelica. These compounds exhibit very interesting biological effects on cell cycle, apoptosis and differentiation. Hence, the plant may be the important source for isolation of furocoumarins, which may be considered as promising drugs in the therapy of several diseases, including psoriasis, mycosis fungoides and cancer.
ACKNOWLEDGEMENTS:
Authors are thankful to Pharmacopoeia Commission for Indian Medicine and Homeopathy (PCIM&H), PLIM Campus, Ghaziabad for providing necessary facilities to write this review.
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Received on 11.07.2017 Modified on 21.08.2017
Accepted on 24.09.2017 © AJRC All right reserved
Asian J. Research Chem. 2017; 10(6):852-856.
DOI: 10.5958/0974-4150.2017.00142.0