Apium graveolens L.: A Phytochemical and Pharmacological Review
Makarova E.I.1, Bokov D.O.1,2*, Sergunova E.V.1, Chevidaev V.V. 1, Kakhramanova S.D. 1,3, Bessonov V.V. 2, Friesen N.V. 1,4, Luferov A.N. 1
¹Sechenov First Moscow State Medical University, 8 Trubetskaya St., Bldg. 2,
Moscow, 119991, Russian Federation.
2Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr.,
Moscow, 109240, Russian Federation.
3Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products”,
8/2 Petrovsky Boulevard, Moscow, 127051, Russian Federation.
4Botanical Garden of the University of Osnabrueck, Albrechtstr. 29, Osnabrueck, 490776 Germany.
*Corresponding Author E-mail: fmmsu@mail.ru
ABSTRACT:
Phytochemical composition data of various parts of celery (Apium graveolens L.) and pharmacological activity thereof are analyzed herein. Flavonoids, organic acids, hydroxycinnamic acids, ether oil terpenoids, tannins, vitamins and microelements are A. graveolens biologically active substances (BAS). Rich composition of BAS causes multiple both biological and pharmacological effects of herbal raw materials extracts mainly due to antioxidant activity. Furthermore, the extracts have neuroprotective, anti-inflammatory, hypolipidemic, antihypertensive and antibacterial effects. A. graveolens possesses wide spectrum of pharmacological activities and is a nontoxic plant; A. graveolens-based medicines will have high margin of safety. The results obtained provide opportunities for making herbal pharmaceutical celery-based substances and introduction thereof into the academic medicine.
KEYWORDS: Celery, Apium graveolens, Extracts, Phytochemical Composition, Biologically Active Substances.
INTRODUCTION:
Celery (Apium graveolens L.) is a high-value vegetable crop and due to unique phytochemical composition thereof, has critical nutritional, therapeutic and prophylactic values.1,2 Rich and diverse composition of BAS both in the top and underground of A. graveolens is to be thoroughly studied; and these studies are to be made for application thereof as a medicinal plant raw materials and herbal pharmaceutical substances.3
Botanical description
The genus belongs to the Apiaceae L. family, Apioideae subfamily, Apieae tribe.4,5
This systematic position is also supported by molecular genetic testing data based on the study of chloroplast DNA and nuclear ribosomal DNA.6,7 The Apium genus is found to take an isolated position in autonomous clade within the Apieae tribe8 and is monophyletic, and some species attributed thereto are to be included to separate Helosciadium genus; with the species thereof being very similar to Apium species by structure of vegetative organs, e.g.: Helosciadium repens (Jacq.) W.D.J. Koch.9,10 According to various sources the genus includes from 1 (A. graveolens)11 to 1712 and 31 species.13
Intraspecific classification of A. graveolens includes 4 varieties:
1) Var. Graveolens is a wild variety with a tap-root, fibrous or mixed system (both tap-root, lateral and secondary roots are preserved), with no root crop being formed. The 5-12 leaves of the rosette are deviated from the stem aside or upwards. Celery stalks are thin, slightly ribbed and either with or without the barely visible cavity within. Some populations of wild A. graveolens var. graveolens are known to be able to genetic changes. In this connection, e.g. in Germany, certain measures to conserve this variety and make the genetic bank to be used in further selection are proposed.14
The other three varieties are mostly found and run wild sometimes. Main diagnostic signs thereof according to L.I. Levandovskaya (1971) are given by us indicating these taxa authorship.15
2) Var. dulce (Mill.) Poir. 1804, in: Lam. Encycl. 5: 194. – Stalked variety with a fibrous root system, with the root crop having no progress. The rosette of leaves is semi-spreading consisting of 15-20 leaves. Leafstalks are thin, strongly ribbed and more or less flattened, with no cavity within.
3) Var. rapaceum (Mill.) Poir. 1804, in: Lam. Encycl. 5: 195. – Root crop variety with a tap-root system. The root crops are either ball- or egg-shaped. The rosette of leaves is semi-spreading or erected consisting of 15-40 leaves. Leafstalks are thin and hollow.
4) Var. secalinum Alef. 1866, Landw. Fl.: 151. – Leaf variety with a fibrous root system. The rosette of leaves of most varieties is spreading (leaves are close to the substrate) or directed upwards. The number of leaves is varying from 40 to 70, sometimes to 200. Leafstalks are long, thin and hollow.
A. graveolens is a biennial herb, monocarpic, hemicryptophyte, mesophyte (Fig.1).
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Figure 1: The appearance of medicinal plant raw material: 1– flowering plant; 2 – roots; 3 –herb; 4 – fruits.
A. graveolens leaves are forming rosettes with long, basal leafstalks covering each other.16
The sequence of leaves formation is called Apium-type. First, a simple leaf is being formed at the root rosette leaves growing, then in the process of organogenesis large odd-pinnate leaves are formed, while inflorescence shoot leaves, on the contrary, are modified from complex to simple ones.17 The root crop is of grey-white color, either flat-rounded or rounded with a great number of roots. The pith thereof containing numerous vascular bundles is quite loose, with the voids being often found therein.18 Flowers are small, with broad, frequently arranged petals of white or cream color. The inflorescence is a compound umbel consisting of 10-18 simple umbellets. The umbellets have no involucels. Fruits are dark brown rounded cremocarps (schizocarp), up to 2 mm in diameter that break up into two hemicarps (mericarps) at maturity. Each pair of hemicarps is attached to a single pedicel, the one side thereof is flat while the other one is convex (back). There are three ribs on the back and one longitudinal rib on each side. The A. graveolens seeds, unlike curly parsley seeds (Petroselinum crispum (Mill.) Fuss), do not have an elongated spout. Fiber vascular bundles are in the ribs. The essential oil-bearing channels are in the mericarp, with the number thereof being varied from 10 to 14. The channels are smooth with no branches.19 The seeds are of grey or brown color. The color of the furrows is always darker than the longitudinal ribs. Blooming of A. graveolens occurs in June-July; with fruit ripening in August.20
A. graveolens is native to Mediterranean area (center) of cultivar origin21, where this species is not cultivated only, but also grows in the wild of the countries of Southern Europe, Asia Minor, the Middle East and North Africa. The generic variety of var. graveolens, as well as cultivated varieties and numerous species thereof are found in the countries of Western, Southern and Eastern Europe, in Siberia and the Far East of Russia, China, Japan, Malaysia, Indonesia, Myanma, Bhutan, Nepal, India, Sri-Lanka, Pakistan, Kazakhstan, Kirghizia, Tajikistan, Uzbekistan, Turkmenistan, Afghanistan, Iran, Iraq, Oman, Saudi Arabia, Yemen, UAE, Bahrain, Egypt, Lebanon, Syria, Jordan, Israel, Cyprus, Greece, Africa, North America, South America, Australia, Oceania. 22,23 They grow in damp meadows and wetlands: soil, clay, sand, saline substrate, including the shores of seas and salt lakes, usually among thinned grassland and shrubs, and are also widely cultivated in agricultural fields, vegetable gardens, orchards11,14,15, and sometimes they grow wild.24
Biologically active compounds:
Due to its unique biochemical composition A. graveolens has an important nutritional and therapeutic value. The A. graveolens leaves contain a large amount of essential oils (up to 300 mg%), a lot of vitamin C (up to 130 mg%), carotene (up to 10 mg%), B vitamins (up to 100 mg%), vitamin U (up to 38 mg%), nicotinic acid (up to 42 mg%), mineral salts (especially K and Na). The raw mass of the root crop contains (%): dry matter – 12.2-16.1; sugars – 2.3-3.4; proteins – 1.1-2.7; ash – 1.4; fiber – 1.3-1.6; essential oils – 0.05-0.06, as well as (mg%): vitamin C – up to 10.0-13.5; phosphorus salts – 50-110 and calcium salts – 65-74. 25
About 20 compounds including oplopandiol, isofraxidine, lunularin and some other compounds that were first obtained from the Apium genus were isolated and purified from all parts of A. graveolens using column chromatography and spectral analysis.26 Furthermore, over ten known flavonoids, three new triterpenoids, choline, furocoumarins and organic acids, in particular ascorbic acid, were found in the composition; with the structure of new compounds being confirmed by analysis of spectroscopic data.27
In general, the plant contains 15% of fatty oil with such fatty acids as petroselenic (64.3%), oleic (8.1%), linoleic (18%), linolenic (0.6%) and palmitic.28 The composition of the essential oil components containing about 28 substances, i.e. about 73% of the total amount of the lipophilic fraction in the plant was identified in A. graveolens leaves by gas chromatography and mass spectroscopy (GC-MS).29 The A. graveolens seeds contain about 2% of essential oil, with limonene and selenene making about 60% and 20%, respectively. However, many important components are 3-n-butyl-4-5-dihydrophthalide (sedanenolide), 3-n-butylphthalide, sedanolide and sedanonic anhydride, occurring in very low amounts (1-3%).28
The A. graveolens roots contain essential oil, aspagarin, mucus, mannitol, citrine, K, Ca, P, Na, Cu, Mn, and Zn salts.30 When analyzing dichloromethane extraction, falcarinol, falkarindiol, panaxiol and previously unknown polyacetylene 8-O-methylfalkarindiol were isolated. The structure of the new compound was established using one- and two-dimensional (1D and 2D) NMR, mass spectrometry and specific data of optical rotation.31
Under such a diverse phytochemical composition, it should be taken into account that the selection of BAS group, with the quantitative content thereof being indicated as a parameter for standardization of a certain herbal medicine type, should consider the level of accumulation in certain part of the plant and certain pharmacological activity. Identification of raw sources for phenolic compounds, namely flavonoids and hydroxycinnamic acids, characterized by multi-vector pharmacological activity is very important.32 Positive results of qualitative reactions indicate the presence of flavonoids in the raw material under study.33
Current regulatory documents (RD) requirements to standardization of medicinal plant raw materials and herbal medicines require the use of accurate, express and current methods of analysis, including high performance liquid chromatography (HPLC), to be most often used when studying BAS composition of medicinal plant raw materials in the Pharmacopoeias of different countries. According to research results of Lugansk Medical University scientists A. graveolens is accumulating flavonoids and hydroxycinnamic acids. The analysis was made by high performance liquid chromatography method; extraction of BAS from crushed raw materials was made by 90% ethanol with further filtration thereof. Chromatographic separation of phenolic compounds was made using a column packed with octadecylsilyl sorbent. The eluents were: A – an aqueous solution of 0.1% phosphoric acid, 0.2% of tetrahydrofuran and 0.018% of triethylamine and B – methanol. Compounds were identified by comparing the retention times of the main peak and the external standard. Alcohol solutions of standard samples of phenolic compounds are used as standards. Therefore, apigenin-7-O-apioside was found to be the major flavonoid in A. graveolens herb. Hydroxycinnamic acids in A.graveolens herb were defined by UV spectrophotometry; with 20% ethanol being used as a reference solution. The content of hydroxycinnamic acids is almost three times higher than that of flavonoids. For the purposes of standardization, the following standards are recommended to be used: the content of flavonoids and hydroxycinnamic acids in the A. graveolens herb is not less than 1% and 3%, respectively.32
Gas chromatographic analysis of hydrolates enabled to identify the main components of essential oil in composition thereof; β-selenene and 3-butylphthalide were found in the A.graveolens roots, while the seeds contain (+) limonene, β-selenene, carvone, and carveyl acetate.34 The content of ascorbic acid in fresh homogenates of different parts of A. graveolens varieties was determined by redox titration, with 2,6-dichlorophenol sodium indophenolate being used as a titrant. The ratio of ascorbic acid content in leaves / roots / petioles for A. graveolens is 8:1:1 (in leaves about 250mg/100g).35 The extraction of tocopherols from A. graveolens leaves was carried out 6 times by mobile maceration method, with hexane being used as an extractant. Saponification is to be done to define tocopherols in the plant extract. According to studies A. graveolens leaves are found to contain 0.36 to 6.02 mg of α-tocopherol / 100g of wet weight.36
Toxicity and pharmacological activity:
The acute toxicity of the decoction and herb infusion from A. graveolens was defined by the Karber's method. The animal survival rates and the general pattern of intoxication are used to evaluate the results. The experiments were carried out on white outbred mature male and female rats. The decoction and infusion of A. graveolens herb were administered in doses calculated taking into account body weight and the maximum allowable amount of fluid to be administered once intragastrically to these animals. The results obtained indicate that the introduction of a decoction from the A. graveolens herb at a dose of 42000 mg/kg did not result in mice death; therefore, it may be concluded that LD50> 42000 mg/kg. When the infusion of A. graveolens herb was administered at a dose of 41000 mg/kg, no mice death was also observed. Therefore, for A. graveolens infusion LD50>41000mg/kg. Thus, according to K.K. Sidorov's toxicity classification the decoction and infusion of A. graveolens herb belong to class VI toxicity, i.e. are relatively harmless to humans.33
All parts of the plant have strong antioxidant properties due to high content of such phenolic compounds as flavonoids and hydroxycinnamic acids.37 The essential oil from A. graveolens leaves was analyzed to reduce the activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and according to the results it may be used as a natural antioxidant thereby suppressing the unwanted oxidation.29 3-n-butylphthalide (NBP) was found in the composition of extract, sap and essential oil, demonstrating significant neuroprotective effects. According to extensive research NBP enables better recovering from ischemic stroke providing multipurpose, both prophylactic and therapeutic effects through multiple mechanisms.37-39 It stimulates angiogenesis, has antioxidant, anti-inflammatory, antiapoptotic, and antithrombotic effects.40,41 This compound also facilitates the treatment of the Alzheimer's disease by improving cognitive function and memory by restoring synaptic communication.42,43
The extract, sap and essential oil of A. graveolens were indicated to contain, apart from active antioxidants, substances capable of inhibiting monoamine oxidase of A type (MAO-A), acetylcholinesterase and GABA transferase, and to increase the content of monoamines, acetylcholine and GABA in the central nervous system of laboratory animals. Furthermore, the extract was reducing the peroxidation of brain lipids and increasing the activity of the antioxidant system of glutathione peroxidase and the percentage of inhibition of the oxide anion. Therefore, consumption of A. graveolens extract improves cognitive functions and antidepressant activity, as well as modulates endogenous antioxidant and neurotransmitter systems in the brain, thereby resulting in increase in neuronal density. These data demonstrate the important role of A. graveolens extract in preventing age-related cognitive decline associated with depression.44
Extracts from A. graveolens seeds (hexane, methanol, and water-ethanol ones) have an antihypertensive effect. In animal studies, all extracts were reducing blood pressure and increasing heart rate in hypertensive rats, but had no effect in normal blood pressure rats. This mechanism of action enables using A. graveolens for treating chronic hypertension.44 Therewith all extracts resulted in dose-dependent vasodilating and antihypertensive effect.45,46 The combination thereof with captopril drug may be effective for the treatment of hypertension, since A. graveolens is changing the pharmacokinetics of this drug, causing an increase in its concentration in blood plasma, improving the efficiency thereof.47 The A. graveolens herb and seeds have a marked analgesic and anti-inflammatory effect, due to apiin – the diglycoside of flavone apigenin. This compound causes repression of nitric oxide synthase, being an inflammatory mediator.48-50 In addition to analgesic and anti-inflammatory effect thereof, the seed extracts were shown to protect and/or reduce stomach irritation caused by NSAIDs and also act synergistically therewith them to reduce inflammation.51
A. graveolens lipophilic extracts may be useful in the clinical treatment of fungal diseases, as the essential oil thereof has antifungal activity, being detrimental to fungi of Candida, Trichophyton, Microsporum and Aspergillus genus.52,53 Antibacterial activity is expressed in the growth inhibition of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.51 The “compound with anti-Helicobacter activity” isolated from the alcoholic extract of seeds, according to NMR and MS data, of a dimeric phthalide structure, has a strong bactericidal effect against H. pylori, exhibiting a strong anti-adhesive activity.54,55 The methanol extract also showed 100% mortality for nematodes and mosquito larvae.56
Antiulcer, antisecretory and cytoprotective properties of A. graveolens are known. Thus, in the course of the study experimentally induced gastric lesions were reduced in all rats previously treated by aqueous and alcoholic extracts.57 A study by Iranian doctors have showed that the intake of A. graveolens and Trachyspermum copticom tea is more effective than omeprazole in the treatment of functional dyspepsia.57 Alcoholic extracts of A. graveolens seeds may be effective in combating hyperglycemia and hyperlipidemia. They reduce glucose, triglyceride, and cholesterol levels, while insulin and high-density lipoprotein (HDL) levels are increased.58, 59 TLC analysis showed the availability of 3-n-butylphthalide, a unique A. graveolens compound with a hypolipidemic effect.60 The seeds and leaves of A. graveolens have strong hepatoprotective properties, with alcohol extracts therefrom revealing higher hepatoprotective activity than silymarin drug, and the ability to protect hepatocytes from the damaging effects of paracetamol and thioacetamide.61-64
One of the topical areas of modern pharmacy is the study of medicinal plant materials, including those that are food products in order to obtain medicinal herbal preparations based on them. It should be noted that a special place in the study of medicinal plant raw materials is occupied by questions regarding the possibility of integrated use of the raw material base of a plant in terms of a rational solution to the issue of integrated processing and increasing economic efficiency, determining safety indicators (content of heavy metals, microbiological purity, etc.).65-75 Consequently, further detailed study of the qualitative and quantitative composition of biologically active substances, indicators of the quality of A. graveolens raw materials seems to be an urgent research area.76-81
CONCLUSION:
Both the botanical and chemical characteristics of Apium graveolens, being a source of valuable medicinal raw materials and food products, are presented. An overview of the pharmacological action of biologically active compounds thereof is given. Analysis of the chemical composition of vegetative organs, flowers and fruits enabled to identify flavonoids, organic acids, hydroxycinnamic acids, essential oil terpenoids, tannins, vitamins and microelements. The biologically active compounds-rich composition provides the pharmacological effect of plant raw materials. The extracts reveal neuroprotective, anti-inflammatory, hypolipidemic, antihypertensive and antibacterial effects, being safe for human health and affecting no adverse affect on the metabolic processes of the body. The results obtained give opportunities for the development of herbal pharmaceutical substance based on this plant and introduction thereof into medical practice.
CONFLICTS OF INTEREST:
None.
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Received on 20.02.2021 Modified on 10.06.2021
Accepted on 04.08.2021 © RJPT All right reserved
Research J. Pharm.and Tech 2022; 15(2):927-934.
DOI: 10.52711/0974-360X.2022.00155