INTRODUCTION:

During the last few decades there has been an increasing interest in the study of medicinal plants and their traditional use in different parts of the world^[1]. There are hundreds of significant drugs and biologically active compounds developed from the traditional medicinal plants. Cicer is a genus of the legume family Fabaceae and the only genus found in tribe Cicereae. Its native distribution is across the Middle East and Asia. Its best known and only domesticated member is Cicer arietinum; This species includes the chickpea, also known as garbanzo bean, which is commonly used for making dal. Currently, the only domesticated species of the Cicer genus is Cicer arietinum, commonly known as the chickpea^[2]. It is extensively cultivated in India mainly in Rajasthan, Hyderabad, Patiala, East Punjab, Haryana and Madhya Pradesh^[3].

The seeds of Cicer arietinum as well as their consumption as a food, they were used traditionally as constipation, diarrhea, dyspepsia, flatulence, sunstroke, the phytochemical analysis of Cicer arietinum seeds revealed the presence of carbohydrates, proteins, amino acids, fixed oils, phytosterols, alkaloids, phenolic compounds, tannins, flavonoids, glycosides, saponins, amino acids, iron, phosphate, sulphate, and chloride. Cicer arietinum possessed antioxidant, antidiabetic, anti-inflammatory, antidiarrhoeal, anticonvulsant, hepatoprotective, antimicrobial and many other pharmacological effects. The leaves of this plant are sour, astringent, improves taste and appetite, cures bronchitis, cause flatulence^[4]. This review was designed to highlight the pharmacognostical and pharmacological effects of Cicer arietinum Linn.

PLANT PROFILE:

Synonyms:

Cicer album hort., Cicer arietinum sub sp. arietinum, Cicer edessanum Bornm., Cicer grossum Salisb., Cicer nigrum hort., Cicer physodes Rchb., Cicer rotundum Alef., Cicer sativum Schkuhr and Cicer sintenisii Bornm^[5].

Taxonomic classification:

Kingdom: Plantae;

Division: Magnoliophyta;

Class: Magnoliopsida;

Order: Fabales;

Family: Fabaceae;

Subfamily: Faboideae;

Genus: Cicer;

Species: Cicer arietinum^[6-7].

Common names:

Arabic: hummus, hommos, lablabi;

Chinese: ying zui dou;

English: Bengal gram, chickpea, garbanzo;

French: pois chiche; German: kichererbse;

India: kala chana, Bengal gram;

Italian: cece; Portuguese: grão-de-bico;

Spanish: garbanzo;

Swedish: kikärt;

Turkish: nohut^[7].

Distribution:

It was a cultivated crop grown in tropical, sub-tropical and temperate regions. It was believed that the species originated in the southern Caucasus and northern Persia, southeastern Turkey and Syria^[6-9]. However, botanical and archeological evidence showed that chickpea was first domesticated in the Middle East and was widely cultivated in India, Mediterranean area, the Middle East, and Ethiopia since antiquity. Wild species are most abundant in Turkey, Iran, Afghanistan, and Central Asia^[10]. Oman, Syria, Turkey, Yemen;

Europe:

Albania, Balearic Is, Belarus, Bulgaria, Corsica, Crete, Estonia, former Yugoslavia, France, Greece, Italy, Lithuania, Moldova, Portugal, Romania, Russia in Europe, Sardinia, Sicily, Spain, Ukraine;

Australasia;

Caribbean:

Caribbean-TRP, Dominican Republic, Haiti;

Central America:

Costa Rica, Guatemala, Mexico;

South America:

Argentina, Bolivia, Chile, Colombia and Peru^[11].

Description:

Stems are branched, erect or spreading, sometimes shrubby much branched, 0.2-1 m tall, glandular pubescent, olive, dark green or bluish green in color. Root system is robust, up to 2 m deep, but major portion up to 60 cm. Leaves imparipinnate, glandular-pubescent with 3-8 pairs of leaflets and a top leaflet (rachis ending in a leaflet); leaflets ovate to elliptic, 0.6-2.0 cm long, 0.3-1.4 cm wide; margin serrate, apex acuminate to aristate, base cuneate; stipules 2-5 toothed, stipules absent. Flowers solitary, sometimes 2 per inflorescence, axillary; peduncles 0.6-3 cm long, pedicels 0.5-1.3 cm long, bracts triangular or tripartite; calyx 7-10 mm long; corolla white, pink, purplish (fading to blue), or blue, 0.8-1.2 cm long. The staminal column is diadelphous (9-1) and the ovary is sessile, inflated and pubescent. Pod rhomboid ellipsoid, 1-2 with three seeds as a maximum, and inflated, glandular-pubescent. Seed color cream, yellow, brown, black, or green, rounded to angular, seedcoat smooth or wrinkled, or tuberculate, laterally compressed with a median groove around two-thirds of the seed, anterior beaked^[8,10,12]. Now, it was cultivated in Africa: Algeria, Egypt, Ethiopia, Kenya, Libya, Madeira, Morocco, Somalia, Sudan, Tanzania, Tunisia, Uganda, Zaire, Zimbabwe; Asia: Afghanistan, Armenia, Azerbaijan, Bhutan, China, Gruzia, India, Indonesia, Iran, Iraq, Java, Kazakhstan, Kirgizstan, Mongolia, Myanmar, Nepal, Pakistan, Russia in Asia, Sri Lanka, Taiwan, Turkmenistan, Uzbekistan; Middle East: Cyprus, East Aegean (Greek), Jordan, Lebanon,

Traditional uses:

The seeds were used traditionally as aphrodisiac, for bronchitis, catarrh, cholera, constipation, diarrhea, dyspepsia, flatulence, snakebite, sunstroke, and warts. Acids (malic and oxalic acids) are supposed to lower the blood cholesterol levels. In India these acids were harvested by spreading thin muslin over the crop during the night. In the morning the soaked cloth is wrung out, and the acids are collected and used as hypolipidemic. Seeds were also considered antibilious^[13]. Cicer arietinum which is generally consumed as a seed food is a good source of protein and traditionally used in pacifying the burning sensation in stomach, hepatomegali, stomatitis, inflammations, skin diseases and bronchitis^[14]. Chickpeas have also been widely used in traditional Uighur medicine to treat and prevent hypertension, hyperlipidemia, diabetes, itchy skin, flatulence, low libido, tumor formation and osteoporosis^[15].

Part use:

Leaves, seeds and seed pod^[10,14,15].

PHARMACOGNOSTICAL STUDIES:

Macroscopic characters of root:

The plant Cicer arietinum has a strong taproot system with 3 or 4 rows of lateral roots. The parenchymatous tissues of the root are rich in starch. All the peripheral tissues disappear at plant maturity, and are substituted by a layer of cork. The roots grow 1.5-2.0 m deep. Cicer arietinum roots bear rhizobium nodules. They are of the carotenoid type, branched with laterally flattened ramifications, sometimes forming a fanklike lobe. The outer surface is brownish in colour, rough with longitudinal wrinkles and wood part is light yellow in colour, hard and woody. Fracture is hard and short. The drug has slight characteristic taste and odour^[16].

Microscopic characters of root:

Transverse section:

A single layer of epidermis, which consists of small tangentially elongated rectangular cells with brownish, thick-outer walls and a band of cortex, which consists of 9 to 10 rows of big parenchymatous cells with intercellular spaces. The inner part of cortex contains scattered groups of lignified fibres. Stellar region shows secondary growth. The Vascular bundle comprises of xylem and phloem. The secondary phloem consists of phloem fibres and each phloem bundle is surrounded by a parenchymatous sheath containing calcium oxalate and starch grains. Medullary rays pass through both phloem and xylem. The secondary xylem was more developed and consists of vessel, tracheids, fibres and pitted parenchyma. Primary xylem was distinct on the inner side of the secondary xylem. The Medullary rays are uni-seriate or multi-seriate parenchymatous cells, narrow in the xylem region and wider in the phloem region. Medullary rays in the phloem region are non-lignified whereas lignified in the xylem region and starch grains are present in few cells. Cambium consists of 2 to 3 rows of small irregular thin-walled cells present above the secondary xylem and Pith consists of few rounds to oval thin walled parenchymatous cells^[17].

Powder characteristic of root:

The presence of cork cell, spiral vessel, reticulate vessels, bordered pits, fibres, tracheids, starch grain and crystals of calcium oxalate were observed ^[18-19].

Physicochemical parameter of Root (%w/w):

Alcohol soluble extractive 16.24, water soluble extractive 7.36, chloroform soluble extractive 3.28, petroleum ether soluble extractive 0.72, acetone soluble extractive 3.76, moisture content13.33, total ash 19.83, acid insoluble ash 13.96 and water soluble ash 14.46^[20-21].

Macroscopic evaluation of seed:

The macroscopic studies indicated important characteristics which are useful diagnostic characters. Macroscopic features of the seed powder of Cicer arietinum Linn. A sample (S1, S2) was observed. The details of result have been shown in Table 1.

Seeds:

Alcohol soluble extractive 3.7- 4.5, water soluble extractive 5.5- 6.2, total ash 6.8 6.9, acid-insoluble ash 1.8- 1.9, water-soluble ash 1.5- 1.9 and swelling index 3ml/g^[20-21].

PHYTOCHEMICAL SCREENING:

The preliminary phytochemical screening of Cicer arietinum seeds revealed the presence of carbohydrates, proteins, amino acids, fixed oils, phytosterols, alkaloids, Phenolic compounds and tannins, flavonoids, glycosides, saponins, amino acids, iron, phosphate, sulphate, and chloride^[20-24]. Chickpeas were an excellent source of carbohydrates and proteins, which constitute about 80% of the total dry seed weight. Dried chickpeas contain about 20% protein. The bulk of the seed was made up of carbohydrates (61%) and 5% fat. Crude fiber is mostly located within the seed coat. The seeds were relatively rich in lecithin, potassium, phosphorus, calcium, folate and vitamin C, and also have small quantities of vitamins A and B. 100 g of chickpeas can supply about 350 calories^[6,25-26]. Raw whole seeds contain per 100 g: 357 calories, 4.5-15.69% moisture, 14.9-24.6 g protein, 0.8-6.4 % fat, 2.1-11.7 g fiber, 2-4.8 g ash, 140-440 mg Ca, 190-382 mg P, 5.0-23, 9 mg Fe, 0-225 m g b-carotene equivalent, 0.21-1.1 mg thiamin, 0.12-0.33 mg riboflavin, and 1.3-2.9 mg niacin^[10,25]. The amino acid composition (%) of seed proteins were: 7.2 g lysine, 1.4 g methionine, 8.8 g arginine, 4.0 g glycine, 2.3 g histidine, 4.4 g isoleucine, 7.6 g leucine, 6.6 g phenylalanine, 3.3 g tyrosine, 3.5 g threonine, 4.6 g valine, 4.1 g alanine, 11.7 g aspartic acid, 16.0 g glutamic acid, 0.0 g hydroxyproline, 4.3 g proline, and 5.2 g serine^{[10, 25, 27]}.

SPECTROSCOPIC ANALYSIS:

Spectroscopic analysis was performed with the fractions f₁ of n-hexane of Dichloromethane extract of C. arietinum seed. The matrix assisted laser desorption/ionization (MALDI) mass analysis was performed for f1 fraction with Bruker 9.4T Apex-Qe FTICR instrument and the Data Analysis 3.4. Nuclear magnetic resonance (NMR) spectroscopy was carried out on VNMR 500 instrument, and sample was dissolved in d6-DMSO. MALDI mass results exhibited the following peaks: 689.21068, 637.32377, 541.17371, 527.15799, 489.31045, and 449.36009 (possible solvent impurity/stabilizer), 413.26614 and 393.29762 (possible solvent impurity/stabilizer). Normal impurities are dioctyl-adipate and dioctyl sebacate. The NMR was carried out in DMSO on a cold probe on the departments 500 MHz NMR. Due to the low solubility, the signal was collected on the cold probe overnight, equivalent to collecting data for 18 days on a standard probe. The peaks are as follows: 0.8 (~6H), 1.3 (~20H), 1.5 (~2.5H), 2.0 (~3H), 5.3 (~3H), 2.3 (~2H), 2.7 (~1.1H), and 8.5 (~1H). Chemical and spectroscopic results demonstrated that a compound with structural type shown in Figure 1 exists in the f1 fraction^[28].

THIN LAYER CHROMATOGRAPHY:

The table-2 represents the various coloured spots observed with their Rf values in respective extracts using different solvent systems and detecting agents^[29].

PHARMACOLOGICAL EFFECTS:

Antioxidant effects:

The free radicals scavenging, antioxidant properties and intestinal α-glucosidase inhibitory activity of methanol extract of two varieties of Cicer arietinum were evaluated. Compared with raw seeds increase in total polyphenol and flavonoids concentration in green gram sprouts and Kabuli Chana sprouts (KCs) were recorded. Total protein concentrations in sprouts did not differ from non-sprouted grains. 2,2'- Azinobis (3-ethyl benzthiazoline-6-sulphonic acid) cation scavenging activity was more than twice in Bengal gram sprouts of (BGs) and KCs than their raw seeds. 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide scavenging, nitro blue tetrazolium reducing and glucose-induced Hb-glycation inhibitory activity did not differ from non-sprouted raw grains. Increase in rat intestinal α-glucosidase inhibitory activity was observed in BGs and KCs. BGs significantly mitigated first 30 min starch-induced postprandial glycemic excursions and reduced 2 h postprandial glycemic load^[30].

The extent of free radical scavenging properties and antioxidant effects of crude extracts of sprouted Cicer arietinum (Chick pea/Chana/Bengal gram) seeds were evaluated. Two main varieties of Cicer arietinum seeds viz. Kabuli-Chana (cream seed-coat) and Bengal gram (brown seed-coat) were examined and compared for their free radical scavenging properties and antioxidant effects. Free radical scavenging properties were evaluated against stable 2, 2-diphenyl-1-picrylhydrazyl radical (DPPH) and hydrogen peroxide radical and the extent of antioxidant effect was assessed by lipid peroxidation induced by ferrous sulphate on the lipid present in the liver homogenate. The results showed that the two Cicer arietinum extracts were differed in their capacities to quench or inhibit DPPH, hydrogen peroxide and lipid peroxide. Brown colored Cicer arietinum sprouts showed the greatest activity against DPPH radicals, hydrogen peroxide radicals and lipid peroxide compared to the cream variety^[31]. The root of Cicer arietinum was extracted using solvents of different polarities and explored for in vitro free radical scavenging activity. Preliminary assays of three different extracts of Cicer arietinum root showed that the extracts possess electron donating ability and reduction of ferric ion to ferrous in a cell free system at pH-7.4. It has also been found from total antioxidant capacity as assessed by reduction of molybdate showed Cicer arietinum root extracts to possess (standard) ascorbic acid equivalents per milligrams of the extracts. Hydroalcoholic root extract was found more effective when compared to alcoholic and water extracts in scavenging 1, 1-diphenyl-2-picrylhydrazyl, reducing ferric ion and molybdate reduction in antioxidant capacity. Significant correlations exist between extract concentrations and percentage scavenging activity of radicals in all models^[32]. The lectin was isolated from the seeds of Cicer arietinum. The antioxidant activity of the eluted fractions containing lectin was determined. DPPH scavenging activity of isolated lectin from Cicer arietinum Linn. at concentration of 10, 100, 250,500 and 1000 (μg/ml) were 19.5 ±4.29, 34.2 ± 0.77, 42.0 ±0.35 54.3 ± 1.14 and 69.2 ± 3.67(% Inhibition)^[33]. Extract and its different fractions of mature pod wall of Cicer arietinum Linn were assessed for their antioxidant activity by in vitro methods. Antioxidant activity was studied using 1, 1- Diphenyl-2-Picrylhydrazyl (DPPH), nitric oxide scavenging activity, hydrogen peroxide scavenging activity, reducing power assay. Results showed that extracts and fractions exhibited significant DPPH, nitric oxide and hydrogen peroxide activity^[34]. Rats treated with CCl4 showed a significant decrease in superoxide dismutase, catalase, GSH, increased MDA levels. The group of rats treated with petroleum ether extract of Cicer arietinum (200mg/kg, po, once daily) showed no significance increase in catalase, GSH, SOD and no significant decrease in MDA levels. Whereas group treated with low doses of methanol and aqueous extracts (200mg/kg) showed a significant increase in the catalase, GSH, GST and a significant decrease in MDA. On the other hand, 250 and 500 mg/kg of ethanolic seeds extract of Cicer arietinum showed hepatoprotective against the paracetamol induced hepatotoxicity in rats^[35-36].

Antidiabetic effect:

It was reported that the seeds reduced postprandial plasma glucose and were useful in the treatment of diabetes^[37-38]. The antihyperglycaemic activity of petroleum ether extract of Cicer arietinum (PEECA) seeds was evaluated at three different doses i.e. 100, 200 and 400 mg/kg po in alloxan (70 mg/kg iv) induced diabetic mice. In both acute and subacute studies serum glucose level (SGL) was measured. The change in body weight was noted during subacute study. Oral glucose tolerance test (OGTT) was performed in both diabetic and non-diabetic mice previously loaded with (2.5 g/kg po) glucose. Glyburide (10 mg/kg) was used as a standard drug. The maximum reduction in SGL was observed in PEECA (400 mg/kg) group at 6h (137.17 mg/dl) in acute study and on 21st day (217.79 mg/dl) in subacute study respectively. In glyburide treated mice the maximum reduction in SGL was observed at 6h (194.97 mg/dl) and on 21st day (267.40mg/dl) respectively. PEECA (400 mg/kg) and glyburide (10 mg/kg) prevented loss of body weight in diabetic mice. OGTT showed increased glucose threshold in non-diabetic and diabetic mice. Accordingly, PEECA showed antihyperglycaemic activity comparable with glyburide^[39].

Anti-inflammatory effects:

The anti-inflammatory potency of methanolic and ethanolic extracts of Cicer arietinum seeds at different doses (250 mg/kg and 500 mg/kg body weight) were investigated against Carrageenan and histamine induced paw edema in rats. All doses of the extracts showed a significant (p<0.001) anti-inflammatory activity when compared to control groups and with standard drug (Indomethacin 10 mg/kg, orally). Both the methanolic and ethanolic extracts showed the dose dependant activity. Among these extracts, the methanolic 500 mg/kg and ethanolic 500 mg/kg extracts of Cicer arietinum showed maximum anti-inflammatory activity^[14].

Antipyretic Activity:

The antipyretic activities of the Hydroalcoholic extract, of Cicer arietinum roots and its acetone fraction and methanol fraction of the roots of this plant. The antipyretic activity of the hydroalcoholic extract and its acetone and methanol fraction was studied based on the basis of their effect on Brewer’s yeast-induced pyrexia in rats. The hydro-alcoholic extract and methanol fraction produced significant antipyretic activity (p < 0.05), while acetone fraction did not. Hydroalcoholic extract and methanol fraction of Cicer arietinum roots have antipyretic activity^[40].

Antidiarrhoeal effect:

The antidiarrhoeal activity of the hydroalcoholic extract of Cicer arietinum roots and its acetone and methanol fraction was studied based on their effect on Castor oil induced diarrhea in mice. 3 h after castor oil administration, all the mice in the control group produced copious diarrhoea. Pretreatment of mice with the hydroalcoholic extract (200 mg/kg and 400 mg/kg), acetone fraction (100 mg/kg), methanol fraction (100 mg/kg) and Loperamide (5 mg/kg) produced significant (p<0.05) antidiarrhoeal activity when compared to untreated rats. The results obtained showed that the highest reduction in diarrhoea was observed 24.63 % in hydroalcoholic extract and Loperamide (5 mg/kg) inhibited the castor oil induced diarrhoea by 75.37 %^[41].

Anticonvulsant Activity:

Dichloromethane extract was obtained from C. arietinum seeds by percolation. Acute toxicity of the extract was assessed in mice. Protective effect of the extract was examined against tonic seizures induced by maximal electroshock (MES; 50 mA, 50 Hz, 1 s) in mice, clonic seizures induced by pentylenetetrazole (PTZ; 60 mg/kg, i.p.) in mice, and electrical kindling model of complex partial seizures in rats. The extract was fractionated by n-hexane to f1 and f2 fractions. The extract and fractions underwent phytochemical analysis by thin layer chromatography. The active anticonvulsant fraction, f1, was subjected to matrix assisted laser desorption/ionization (MALDI) mass analysis. The crude extract had neither toxicity up to 7 g/kg nor protective activity in MES and kindling models. However, it significantly inhibited clonic seizures induced by PTZ. f1 fraction mimicked protective effect of the extract^[42-43].

Hemolytic activity:

Cicer arietinum L. extracted by two different extraction techniques as hemolytic agent, one of them carried out by using ultra sonication-Oven assistance extraction (UOAE)^[44-45]with ethanol as extraction solvent of choice while the other technique deals with more than one solvent with longer extraction time Phytochemical analysis of both crude extracts was performed and revealed positive result for saponins, resins, tannins and alkaloids while resins appeared only in liquid-liquid extraction (LLE)^[45-46] meanwhile results showed that flavonoids, terpenes, steroids, glycosides and polyphenols were absent for both crude extracts. Reversed high performance liquid chromatography carried out to detect presence of saponin in these crude extracts. The hemolytic activities of both Chickpea's extracts were carried out according to the procedure^[47] reported by with slight modifications. The assay involved pipetting 0, 0.25, 0.5, 0.75 and 1 ml of each extract (1.5 mg/ml) in triplicates in to clean dried test tubes. The volume was adjusted to 1 ml of distilled water. Then 2.5 ml of normal saline was added to each tube followed by the addition of freshly prepared 2% (v/v) red blood cells. The reaction mixture was incubated at 37⁰C for 1 hr. followed by centrifugation at 3,500 for 15 min. the supernatant were collected and the absorbance was recorded at 630 nm. The red blood cells treated with lysis buffer served as control and represented 100% lysis. The results of hemolytic effect on human erythrocytes showed that both crude extracts significantly potent as lytic agent compared with synthetic purchased saponin at P≤ 0.05. The highest hemolytic activity was 76.27 ± 0.18% at concentration 0.375mg/ml with UOAE technique while the opposite pattern appeared with LLE and the hemolytic activity increase to 79.40 ± 0.12%with the lowest concentration 0.094 mg/ml, statistical analysis proved that is saponins involved both of crude extracts which obtained by UOAE and LLE techniques considered as effective hemolytic agent^[48].

Hypocholesterolaemic effect:

The hypocholesterolaemic and antioxidant activities of chickpea protein were studied. All hydrolysates tested exhibited better hypocholesterolaemic activity when compared with chickpea protein isolate. The highest cholesterol micellar solubility inhibition (50%) was found after 60 min of treatment with alcalase followed by 30 min of hydrolysis with flavourzyme. To test antioxidant activity of chickpea proteins three methods were used: β-carotene bleaching method, reducing power and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging effect. Chickpea hydrolysates showed better antioxidant activity in all assays; especially reducing power and DPPH scavenging effect than chickpea protein isolate^[49].

Antimicrobial effects:

The antibacterial activities of the extracts obtained from Cicer arietinum L. varieties (seed extract, fruit skin extract and aerial part extract) were studied in vitro. Chickpea seed extracts (Cse) showed varying antibacterial activity against Gram negative strains (E. coli, P. aeruginosa, K. pneumoniae) in MIC range 16–64 μg/ ml, but were less active against gram-positive (S. aureus, B. subtilis, E. faecalis) strains with MIC of 64 μg/ ml. Statistically different MICs were observed between the extracts of the fruit skin (Cfs) and the aerial part (Cap) (p<0.05). The antibacterial activity of Chickpea fruit skin (Cfs) and Chickpea aerial parts (Cap) extracts were not statistically different (p>0.05) as they showed the same degree of inhibition against Gram-negative (E. coli and K. pneumoniae) bacteria and gram positive bacterium, (E. faecalis at the concentration of 32 μg/ml). Additionally, they were both less effective against P. aeruginosa, S. aureus, and B. subtilis at a concentration of 64 μg/ml. Of all the Chickpea extracts, Chickpea seed extract (Cse; p < 0.05). exhibited the strongest antifungal activity against C. albicans at a concentration of 8 μg/ml. Even at a concentration of 16 μg/ml, fruit skin (Cfs) and aerial part (Cap) extracts showed lower antifungal activity than the seed extract^[50]. The hydroalcoholic extract and its acetone and methanol fractions of the root of C. arietinum were studied for their antibacterial activity by disc diffusion method against different gram positive (Staphylococcus aureus and Bacillus subtilis) and gram negative (Escherchia coli) bacteria. It was observed that the hydroalcoholic extract and its acetone and methanol fraction showed significant activity against all the tested microorganisms [E. coli (NCIM - 2831), S. aureus, (NCIM - 2079) B. subtilis (NCIM - 2439)] and the hydroalcoholic extract showed the highest activity (13 mm) against S. aureus^[51]. Cicer arietinum L ferritin was successfully isolated with two subunits with molecular weights of 20.1- kDa and 29- kDa respectively. The antibacterial effect of ferritin extracted from Chick pea (Cicer arietinum L.) was evaluated against Gram negative microorganisms (Escherichia coli, Pseudomonas aeruginosa, Kliebsiella pneumonia, Proteus vulgaris), as well as Gram-positive microorganism (Staphylococcus aureus, Staphylococcus epidermis). Among all the test pathogens E. coli was found susceptible (with zone of inhibition 8 mm) to the purified ferritin extract^[52]. Several proteins, including a glucanase, a chitinase, an antifungal cyclophyllin-like protein, and three antifungal peptides designated cicerin, arietin, and cicearin were isolated from the chickpea (Cicer arietinum L)^[53]. Two antifungal peptides with novel N-terminal sequences were isolated from chickpea. Although the two chickpea peptides, cicerin and arietin, were similar in molecular weight (5-8 kDa), they differed somewhat in antifungal activity. Arietin was more potent against M. arachidicola, B. cinerea, and F. oxysporum while cicerin exhibited a higher cell-free translation-inhibiting activity than arietin^[54]. An antifungal protein, was isolated from Cicer arietinum and purified by gel filtration and tesred using agar diffusion method against human pathogenic fungi of ATCC strains and against clinical isolates of Candida krusei, Candida tropicalis and Candida parapsilosis. MIC values were varied from 1.56 to 12.5 μg/ml. Protein isolated from Cicer arietinum also inhibited the growth of fungal strains which are resistant to flukonazole^[55]. The crude water extract of Cicer arietinum showed most significant antifungal activity against Drechslera tetramera even at lower concentration of 5%. In dichloromethane fraction, the inhibitory effect was found to be proportional with the applied concentration^[56]. The antiviral activities of the extracts from the seed, fruit skin and aerial parts of ten varieties of Cicer arietinum (Chickpea) were evaluated against Herpes simplex type 1 (HSV-1) and Parainfluenza-3 (PI-3) viruses. Madin-Darby Bovine Kidney and Vero cell lines were employed for antiviral assessment of the Cicer arientinum L. extracts, in which acyclovir for HSV-1 and oseltamivir for PI-3 were tested as reference drugs. Cicer arietinum seed extracts (Aydin 92 variety) possesses significant antiviral activity against both DNA (max to min CPE inhibitory conc: 32-4 μg/ ml) and RNA (max to min CPE inhibitory conc: 32-16 μg/ ml) viruses compared to the fruit skin and aerial part extracts as well as the controls. Besides, the extracts of fruit skin (Menemen 92 variety) and aerial parts (Aydin 92 variety) showed remarkable activity against DNA viruses at 32 - 1 μg/ ml concentration^[57].

Aphrodisiac effect:

The potential aphrodisiac effect of seeds of methanolic extract of Cicer airetinum (MECA) was studied in sexually sluggish male albino rats. Sexual behavioral parameters like mount frequency (MF), intromission frequency (IF), ejaculation frequency (EF), ejaculation latency (EL), mount latency (ML) and intromission latencies (IL) were observed in male rats. The male serum cholesterol and testosterone concentrations were also estimated. Oral administration of MECA at 200 and 400 mg/kg body weight was significantly increased the MF, IF, EF and EL (P < 0.05) in comparison to control groups, while, ML and IL were significantly decreased (p<0.05). The extract also significantly (p<0.05) increased the serum cholesterol and testosterone levels. From these effects, MECA possessed significant increase in the sexual activity in male rats. The authors postulated that the augmented sexual behavior in male rats might be due to the presence of alkaloids, saponins and flavonoids in MECA^[58].

Estrogenic effects:

Aqueous, alcoholic and chloroform extract of Cicer arietinum were tested for abortifacient activity in female albino rat, it was given from day 11 to 15 of pregnancy at the dose level of 100, 200 and 400 mg/kg body weight. The aqueous extract at a dose of 400mg/kg was found to be most effective abortifacient. Similarly it was also found to increase the reproductive organ weight and possess estrogenic activity when tested in immature ovariectomised female albino rats^[59]. Isoflavones, the important chemical components of the seeds and sprouts of chickpea, have drawn attention due to their potential therapeutic use. The estrogenic activity of isoflavones extracted from chickpea Cicer arietinum L sprouts (ICS) was observed recently. MTT assay showed that ICS at the low concentration ranges (10−3 /mg/l) promoted MCF-7 cell growth, while at high concentrations, (>1 mg/l) inhibited cell proliferation, indicating that ICS worked at a diphasic mechanism. Flow cytometric analysis further calculated the proliferation rate of ICS at low concentration (1 mg/l). ERα/Luc trans-activation assay and then semi-quantitative RT-PCR analysis indicated that ICS at low concentrations induced ERα-mediated luciferase activity in MCF-7 cells and promoted the ER downstream target gene pS2 and PR trans-activation. These effects were inhibited by ICI 182,780, a special antagonist of ER, indicating that an ER-mediating pathway was involved. Alkaline phosphatase (AP) expression in Ishikawa cells showed that ICS at low concentrations stimulated AP expression. Accordingly, ICS has significant estrogenic activity in vitro. ICS may be useful as a supplement to hormone replacement therapy and in dietary supplements^[60]. Isoflavones extracted from chickpea sprouts (ICS) stimulated estrogen responsive element (ERE)-promoter activity in cells, and concurrent treatment with the nonselective estrogen receptor antagonist ICI 182,780 abolished the estrogenic activity induced by ICS^[61]. The estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) was studied in ovariectomized rats (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg/kg/day) for 5 weeks. Their uterine weight and serum levels of 17β-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. Treatments of OVX rats with ICS (50 or 100 mg/kg/day) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: (serum E2 level was significantly increased, while serum LH and FSH levels were decreased) compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive estrogen control drug E2 (0.25 mg/kg/day) produced similar, but more prominent effects^[62].

Anticancer effect:

Cytotoxic activity of C-25 protein isolated from Cicer arietinum was studied on oral cancer cells and normal cells. It reduced the cell proliferation of human oral carcinoma cells with IC50 of 37.5 μg/ml and no toxic effect was found on normal human peripheral blood mononuclear cells even at higher concentration of 600 μg/ml^[63]. Results of the cytotoxicity evaluation of isoflavones isolated from Cicer arietinum (10, 20, 40, 80, 160 and 360 μg/ml) against MCF-7 breast cancer cell line showed a dose dependent inhibition of cell growth^[64].

Anti-osteoporotic effect:

The anti-osteoporotic mechanism of Cicer arietinum extract (CAE) seeds against ovariectomized (OVX) rats was studied in that. Seventy female rats were divided into two groups. The first group (14 rats/group) represented normal rats (Sham operated) while the second group (56 rats/group) underwent bilateral ovariectomy (OVX). After one week of recovery from ovariectomy surgery, the second group was randomly subdivided into 4 subgroups (14 rats/ each subgroup). The rats administered orally; distilled water (vehicle) (1st subgroup), Cicer arietinum extract (CAE) (500 or 1000 mg/kg body weight/day) (2nd and 3rd subgroups), alendronate (6.5 mg/kg mg/kg body weight) as a positive control one time/week (4rh subgroup), daily for 10 weeks. In this study demonstrated that ovariectomy caused significant decrease in bone mineral; density (BMD) and content (BMC), Bone-specific alkaline phosphatase (BALP), calcium (Ca), phosphorus (P), parathyroid hormone (PTH) and calcitonin levels. Furthermore, ovariectomy induced significant elevation of tartrate-resistant acid phosphatase 5b (TRAP 5b) and receptor activator of nuclear factor (NF-kappa β) ligand (RANKL) concentration. Conversely, osteoprotegerin (OPG) and OPG/RANKL ratio were decreased following ovariectomy. In that work suggests that CAE has antiosteoporotic action against ovariectomy effects and its activity may results from its phytochemical and/or phytoestrogen contents^[65].

CONCLUSION:

This review discusses the pharmacognostical and pharmacological effects of Cicer arietinum as promising herbal drug because of its safety and effectiveness.

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Received on 05.06.2018 Modified on 11.07.2018

Research J. Pharm. and Tech 2018; 11(10): 4755-4763.

DOI: 10.5958/0974-360X.2018.00867.3