Abstract: Caper (Capparis spinosa L.), a drought tolerant plant belonging to genus Capparis of the family Capparidaceae is mainly distributed in arid and semi-arid regions of the tropical and subtropical world. The plant, as a potential source of valuable nutrients such as vitamins (especially vitamin C), digestible protein, reducing sugars and essential minerals is valued for human food. The fruit of this plant, being a rich source of high-value components, is usually pickled and added to salads, sauces and jams. The plant has been used traditionally to prevent and/or treat a number of health disorders such as diabetes, hepatitis, obesity and kidney problems. Besides uses as an ingredient for food and feed, the contents of bioactive phytochemicals such as terpenoids, alkaloids, glucosinolates, tocopherols, polyprenols, isothiocyanates, carotenoids and phenolics, have allowed to envisage potential applications of C. spinosa as a health promoter plant. A broad range of pharmacological activities such as antioxidant, cardiovascular, antimicrobial, anti-inflammatory, hepatoprotective, antipyretic, diuretic and hypoglycemic have been ascribed to different parts of C . spinosa. This comprehensive review describes the detailed profile of high-value nutrients and bioactives along with pharmacological and phyto-medicinal attributes of this multipurpose food plant with the aim to exploring its potential uses as ingredients for functional foods and nutraceutical/pharmaceutical industry.
INTRODUCTION
Plants have been valued as a rich source of medicinal and nutraceutical agents for centuries. In the new era, even though, around 25% of the modern drugs have been isolated from plant sources (WHO., 2013; Xu et al., 2015). Currently, there is a revival of interest in the use of herbal medicines world over particularly in the form of dietary supplements (Al Qura'n, 2008; Olsen and Larsen, 2003; Gilani and Atta-ur-Rahman, 2005). Diets rich in biologically-active phytochemicals not only provide nutrients, but are also known to reduce the risk of different diseases such as cancer, inflammation, cardiovascular and neurodegenerative diseases (Banerjee et al., 2011; Ahmed and Gilani, 2014; Kim et al., 2014).
Among valuable flora, wild plants have gained much attention because of their functional food and potential health benefits (Mcdougall and Stewart, 2005; Ndhlala et al., 2006; Stewart et al., 2007). According to an estimate, among 95000 wild plants, 7500 are used in phyto-medicines and 3900 are harvested to fulfill nutritional needs (Mishra et al., 2007). An important plant genus namely Capparis contains 250 species (Cronquist, 1981; Heywood, 1993; Mabberley, 1997; Hamed et al., 2007). Most plants belonging to genus Capparis are wild species and are distributed in arid and semi-arid dry lands of tropical and sub-tropical regions of the world (Hansen, 1991; Jiang et al., 2007). Several members of the Capparis genus have been recognized for their food and medicinal uses owing to their high nutritional value and strong antioxidant properties attributable to the presence of essential minerals, vitamins and high contents of phenolics and flavonoids (Yadav et al., 1997; Sharma et al., 2009; Duman et al., 2013). The potential folk medicinal and pharmaceutical uses of different caper species have been reviewed recently by our research group (Gull et al., 2015). Interestingly, different parts of caper species have been proposed to be effective as antihypertensive, anti-inflammatory, anti-asthmatic, anti-hyperlipidemic and antimicrobial agents (Mali et al., 2004; Purohit and Vyas, 2005, 2006; Eldeen and Staden, 2008; Chahlia, 2009; Castro et al., 2014a, b; Duman et al., 2013; Gull et al., 2015).
Among the Capparis species, Capparis spinosa L. is especially important due to its impressive nutritional and medicinal attributes (Cronquist, 1981; Heywood, 1993; Hamed et al., 2007; Gull et al., 2015). This plant is well known for the edible flower buds and the fruit (caper berries), both of which are frequently consumed as pickled. The fruit from this species is used to garnish pizza and also added to salads, sauces and jams (Panico et al., 2005; Musallam et al., 2011).
A number of folk medicinal and therapeutic properties have also been ascribed to different parts of C. spinosa which include the treatment of diabetes, high blood pressure and liver, spleen and kidney disorders (Baytop, 1984; Handa et al., 1986; Yaniv et al., 1987; Ziyyat et al., 1997; Calis et al., 1999; Azaizeh et al., 2003; Hussain et al., 2007; Taifour et al., 2011). Interestingly, the bark and fruit aqueous extracts from this species have been reported to act as diuretic, poultice, expectorant and astringent as well as they possess anti-inflammatory and antifungal activities (Al-Said et al., 1988; Ali-Shtayeh and Abu Ghdeib, 1999; Baytop, 1999; Calis et al., 1999; Eddouks et al., 2005; Hussain et al., 2007). The reported medicinal health functions and nutritional attributes of C. spinosa can be mainly attributed to the occurrence of alkaloids, glucosides, reducing sugars, essential fatty acids, organic acids, vitamin C, terpenoids, flavonoids and resins in the fruit and leaves of this species (Rastogi and Mehrotra, 1995; Joshi et al., 2011).
There is no comprehensive review available in the literature particularly focusing on the detailed medicinal uses, bioactive constituents, nutritional and pharmacological attributes of C. spinosa. Its wide spectrum of biological applications and folk medicinal uses inspired the authors to compile a comprehensive review, which covers the detailed profile of high-value nutrients and phytochemicals/bioactives as well as traditional medicinal and biological attributes of C. spinosa with the objective to explore potential applications of this multipurpose tree for the functional food and nutraceutical/pharmaceutical industry.
Taxonomy/distribution: Capparis spinosa, the caper bush, also known as flinders rose, is an economically vital plant among 250 species of genus Capparis of the family Capparidaceae (Fici, 2001). It is dicotyledonous perennial, 20-30 cm long creeping shrub, wildly distributed in semi-arid or arid areas of Southeast Asia, South-Western and Central Asia, Himalayas, Mediterranean, the Pacific Islands, East Africa, Madagascar and Australia (Rhizopoulou, 1990; Bakshi et al., 1999; Psaras and Sofroniou, 1999; Fici, 2001; Levizou et al., 2004). Capparis spinosa is widespread in drylands, deserts and rocky areas of India and Pakistan. It usually grows on bare rocks, cracks, crevices and sand dunes (Bakshi et al., 1999; Psaras and Sofroniou, 1999).
The plant has showy white or pinkish white, hermaphrodite, auxiliary and solitary (about 8 cm) flowers attached on the peduncle. Two spines (slightly curved at the end) are usually present at the base of ovate, round, fleshy, alternate or rarely opposite leaves. Fruit are oval shaped, approximately 3 cm long, greenish in color with red pulp. Seeds are small in size, numerous, 1-3 cm broad, kidney-shaped and grayish brown (Sher and Alyemeni, 2010; Al-Soqeer, 2011)
Growth and flowering of this shrub starts from mid-April to end of September showing that it can tolerate high temperature (above 40°C) and low water availability. Interestingly, C. spinosa can grow well in nutrient deficient soils and saline areas under harsh environment and is relatively resistant to fire (Pugnaire and Esteban, 1991; Sakcali et al., 2008).
During the last few decades, the caper bush has been introduced as a specialized culture in some european countries. A high commercial value of caper plant led to a significant increase in both the area under cultivation and production yield of this typical species by the late 1980s. Capers are now commercially valuable plants cultivated in several parts of the world including Greece, Turkey, Italy, France, Spain and Morocco. These countries are big exporters while UK and USA are big importers (Musallam et al., 2011; Sozzi, 2001; Panico et al., 2005; Infantino et al., 2008).
Proximate composition: Capparis spinosa is a potential source of some basic dietary components for human nutrition. For example, the fruit of this species is reported to contain moisture (79%), ash (1.6%), protein (5.8%), fat (1.6%), crude fiber (5.4%) and important minerals such as calcium (871 ppm), magnesium (636 ppm), potassium (542 ppm), sodium (226 ppm), iron (13 ppm) and phosphorous (21 ppm) (Rodrigo et al., 1992). But the concentration of these nutrients is affected with regard to the nature of cultivar, time of cultivation/harvest and size of the fruit. Poly-unsaturated fatty acids contribute 50% of total fatty acids of the fruit lipids of this species (Rodrigo et al., 1992).
A monomeric protein with molecular mass 38 kDa showing some resemblance to imidazole glycerol phosphate synthase was separated from the seeds of C. spinosa using different chromatographic techniques. This protein was reported to repress the multiplication of hepatoma HepG2 cells, colon cancer HT 29 cells and breast cancer MCF-7 cells. It also exhibited the inhibition of HIV-I reverse transcriptase (Lam and Ng, 2009). Another dimeric protein, lectin having molecular mass 62 kDa has also been isolated from the seeds of C. spinosa and further purified by various chromatographic techniques. Inhibition of HIV-1 reverse transcriptase was reported by this protein (Lam et al., 2009). Similarly, proliferation of hepatoma HepG2 and breast cancer MCF-7 cells was inhibited by lectin (Lam et al., 2009).
The raw fruit of C. spinosa contains high contents of moisture, crude oil, fibers, sodium, potassium and phosphorous, which make this fruit more appropriate for pickling at un-ripened stage (Ozcan and Aydin, 2004). Different sized buds of C. spinosa have been investigated for their chemical composition in raw and pickled forms. Small buds are more preferred for processing than larger ones because of their high contents of flavonoids, lipids, protein and minerals (Na, K, Ca and Mg) (Giuffrida et al., 2002).
Traditional food/culinary uses: The flower buds (capers) and the fruit (caper berries) of C. spinosa due to having high nutritional status have been traditionally consumed as a seasoning or garnish. Capers are a common ingredient in mediterranean cuisine, especially, italian, cypriot and maltese. Moreover, in ancient Greece the caper had been used as a carminative (Megaloudi, 2005). The fruit is used to garnish pizza and also added to salads, sauces and jams (Panico et al., 2005; Musallam et al., 2011).
Both the caper buds and the fruit are often pickled in salt or in a salt and vinegar solution resulting in development of a pungent flavor resembling mustard oil (glucocapparin). During this, an enzymatic reaction leads to the formation of rutin and the presence of this flavonoid compound can be seen as crystallized white spots on the surfaces of caper buds. Capers are considered as a unique ingredient in Italian cuisine, especially in sicilian and southern italian cooking. These are usually utilized in salads, pasta sauces and meat dishes (Panico et al., 2005). On commercial basis capers are graded and sold based upon their size, with the smallest size being the most marketable. The pickled fruit can be served as a Greek mezze and snack in Menorca. Dried caper leaves are also used as a substitute for an enzyme, rennet, which is mostly employed during preparation of high-quality cheese (Panico et al., 2005; Musallam et al., 2011). In the current perspectives of malnutrition, especially in under-developed and developing countries, C. spinosa can be explored as a nutritious plant to serve rural communities.
Medicinal applications: According to WHO, herbal medicines are used to maintain health by more than 80% people of the world particularly in Africa and Asia along with some Western countries (Al Qura'n, 2008; Olsen and Larsen, 2003; Gilani and Atta-ur-Rahman, 2005). Besides treating ailments, phyto-medicines are widely used in cosmetics and as functional foods (Gilani and Atta-ur-Rahman, 2005; Rahmatullah et al., 2010).
Among other plant species of the genus Capparis, (C. spinosa) is recognized as a rich source of a wide array of medicinal compounds with proven pharmacological actions. Almost all species of Capparis have long been used in the Unani (Greco-Arab) and Ayurvedic systems of medicines. However, C. spinosa is of particular importance due to the presence of several classes of medicinally important alkaloids along with potential antioxidant compounds (Bonina et al., 2002; Panico et al., 2005). The presence of a wide variety of nutrients including; lipids, protein, minerals and tocopherols in C. spinosa is well documented. Different parts of this plant have been reported to be used for the treatment of female infertility, infections, inflammations, allergies, heart, kidney and liver disorders. Examples of medicinal applications and pharmacological attributes of C. spinosa are listed in Table 1. The extracts from flowers, roots, stem, leaves and seeds of C. spinosa plant are biologically active and are used to treat several disorders (Yaniv et al., 1987; Ziyyat et al., 1997; Calis et al., 1999; Hussain et al., 2007). Important folk medicinal applications of different parts of C. spinosa are discussed below:
Fruits: Metabolic disorders including diabetes and cardiovascular complications are on the rise at the global level and it is not uncommon that diabetes is usually associated with hypertension (Jali et al., 2009). Both of these disorders are simultaneously treated by taking orally dried fruits of C. spinosa (Sher and Alyemeni, 2010). Fruits of C. spinosa are perhaps mostly used in folk medicines. The fruits have a number of traditional medicinal applications including; diuretic, expectorant and astringent activities (Gupta and Ali, 1997; Al-Said et al., 1988; Fici, 2001) and treatment of tuberculosis, atherosclerosis, hepatitis and kidney diseases (Bond, 1990). The fruit (dry powder) also acts as a tonic and used to expel worms from intestine and gas from stomach (Baytop, 1984; Hussain et al., 2007). Capers have demonstrated powerful antioxidant and anti-cancer properties (Inocencio et al., 2000). The hydrolysis products of indol-3-ylmethyl glucosinolates and potent flavonoids (rutin and quercetin) as well as selenium in capers have been linked with its antioxidant and anti-carcinogenic effects (Winter, 1978; Rosa et al., 1996; Inocencio et al., 2000).
Roots and root bark: The root-bark of C. spinosa has versatile medicinal applications and acts as analgesic, diuretic, expectorant, anthelmintic, antihaemorrhoidal, aperient, depurative, deobstruent, emmenagogue, vasoconstrictive and tonic (Chiej, 1984). The paste from the root bark of C. spinosa plant is reported to be used as a tonic to treat skin diseases (Sher and Alyemeni, 2010). The root bark of this species has been used as a remedy for cold, liver, spleen and kidney disorders and constipation. Moreover, in Greece, herbal tea made from caper young shoots and root is considered to be beneficial against rheumatism (Baytop, 1984; Hussain et al., 2007). Aghel et al. (2007) reported that gout, anemia and dropsy can also be treated by taking water-decoction of root bark of C. spinosa.
Flowers and leaves: The steam of boiling leaves of C. spinosa has been inhaled since a long time by females to improve fertility (Bailey and Dannin, 1981). The flowers of C. spinosa are used to treat gout and arthritis (Ageel et al., 1986; Fu et al., 2008). The flowers are also used to lower blood pressure and for diuretic and tonic applications (Baytop, 1984; Calis et al., 1999).
| Table 1: | Medicinal uses and pharmacological attributes of different parts of C. spinosa |
Moreover, aqueous extract from the aerial parts of C. spinosa is reported to inhibit the growth of fungus (Ali-Shtayeh and Abu Ghdeib, 1999) and is also used for the treatment of liver disorders (Handa et al., 1986), diabetes (Yaniv et al., 1987; Ziyyat et al., 1997) and high blood pressure (Calis et al., 1999). A decoction of leaves and buds of C. spinosa is considered to be useful against common cold and headache (Bailey and Dannin, 1981; Sher and Alyemeni, 2010).
Whole plant: The whole plant of C. spinosa is used as antifungal agent and for its antioxidant, anti-inflammatory and odynolytic properties (Yang et al., 2008). The plant is also used in folk medicine to treat hepatitis, diabetes, urolithiasis, rheumatism and arthritis. The whole plant extracts can be employed as memory enhancer and anticoagulant as well (Yang et al., 2008) in India and Morocco, people use C. spinosa as an antibacterial (Singh et al., 2002), anti-proliferative (Nakano et al., 1998) and anti-ulcerogenic (Khayyal et al., 2001) agent. Multiple medicinal uses ascribed to different parts of C. spinosa support the potential utilization of this species for the development of nutraceuticals and safer phyto-medicines to improve health status of the consumers (Singh et al., 2002; Yang et al., 2008).
Pharmacological attributes: Caper has been well studied for its multiple biological activities supported by the presence of a wide array of bioactive such as alkaloids, steroids, terpenoids, flavonoids and tocopherols (Aghel et al., 2007; Ali et al., 2007; Zhou et al., 2011; Bhoyar et al., 2011). The details on individual pharmacological activities of C. spinosa are discussed below:
Anti-diabetic activity: Diabetes is one of the major health problems in the world and particularly in Middle-East and South-Asia (Jali et al., 2009; Harlev et al., 2013; Muhammad et al., 2015). The treatment of diabetes requires a life-long use of multiple drugs resulting in multiple side-effects in addition to the high cost of medication. Currently, due to revival of interest in optimal nutrition, there is much focus on the use of plant based functional foods and nutraceuticals as alternative therapies for health improvement and disease control (Shahidi, 2009).
Herbal remedies have been extensively used for the treatment of diabetes (Bhuvaneswari and Krishnakumari, 2012). For example, the aqueous extract of fruit of C. spinosa was found to decrease glucose to normal level in the blood of rats with diabetes induced by streptozotocin. Glucose level did not decrease in the control (normal) rats indicating that glucose lowering pathway may not depend upon secretion of insulin (Eddouks et al., 2004). In another study, the aqueous extract of C. spinosa was found to be effective against diabetes in obese rats (Lemhadri et al., 2007).
Anti-inflammatory activity: Non-steroidal anti-inflammatory drugs (NSAIDs), although effective in reducing pain, are associated with increased risk of gastric ulcer. Similarly, the expensive and selective COX-2 inhibitors are still not free from side effects (Fries, 1991; Emery et al., 1999). However, safer and cheaper drugs can be developed from medicinal plants (Gilani and Atta-ur-Rahman, 2005; Ikram, 1983; Gautam and Jachak, 2009). The alcoholic extracts of C. spinosa showed strong anti-inflammatory activity inhibiting paw edema in rats (Al-Said et al., 1988). This anti-inflammatory activity of the alcoholic extracts was linked to the presence of polyprenols like cappaprenol-12, cappaprenol-13 and cappaprenol-14 containing 12, 13 and 14 isoprenoid units, respectively. Other researchers reported that aqueous and chloroform extracts of C. spinosa also showed a remarkable anti-inflammatory activity against carrageenan-induced paw edema in rats (Ageel et al., 1986; Zhou et al., 2010).
In a recent study, secreted placental alkaline phosphatase (SEAP) reporter assay was used to measure the anti-inflammatory effect of biflavonoids, isoginkgetin and ginkgetin separated from fruit of C. spinosa based on nuclear factor-kappa B (NF-κB) activation. Studies revealed that ginkgetin was more potent than isoginkgetin with IC50 value of 7.5 μM indicating it a good NF-κB inhibitor (Zhou et al., 2011). Furthermore, the fruit of C. spinosa was extracted in aqueous-ethanol to study its anti-arthritic effect in rats. The extract showed anti-arthritic and anti-inflammatory activities. Bioactive phytochemicals isolated from the active fraction of the tested extract were identified as stachydrine, p-hydroxy benzoic acid, 5 (hydroxymethyl) furfural, bis(5-formylfurfural) ether, daucosterol, uracil and α-D-fructofuranosides methyl (Feng et al., 2011). Based on these reports it appears that C. spinosa plant is a good source for isolation of natural anti-inflammatory agents.
Antioxidant activity: Synthetic antioxidants, although effectively used in the food industry, have been reported to have some side effects. Therefore, there is a need to replace synthetic antioxidants by plant-based safer natural antioxidants (Anwar et al., 2015). Antioxidants present in medicinal plants capture and neutralize reactive oxygen species and free radicals and thus protect body from cancer, cardiovascular and degenerative disorders (Kalim et al., 2010; Saeed et al., 2014).
Likewise, C. spinosa contains different natural antioxidants including; phenols, rutin, carotenoids and tocopherols in significant quantities, which are helpful in scavenging free radicals and imparting medicinal benefits (Prakash et al., 2007; Mozaffarieh et al., 2003). Antioxidant activity of the methanolic extract of C. spinosa leaves has been assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and Ferric Reducing Antioxidant Power (FRAP) assays. The extract showed very good antioxidant capacity with average IC50 values 73.0 and 34.0 μg mL–1 in DPPH and ABTS assays, respectively. Total antioxidant content assessed by using FRAP assay ranged from 83.43-87.14% at 0.1 mg mL–1 concentration. While phenolic content of extract was determined to be 21.42-27.62 mg GAE g–1 dry weight (Bhoyar et al., 2011).
In another investigation, the infusions of C. spinosa were prepared by boiling the plant stalks and flower tops with water for 30 min and evaluated for their antioxidant activity before and after in vitro digestion. The samples were found to have good antioxidant potential as assessed by DPPH free radical scavenging, β-carotene bleaching and copper-induced oxidation of human LDL assays. A number of antioxidant compounds including; cinnamoylquinic acid derivatives along with rutin, kaempferol 3-O-rutinoside and isorhamnetin 3-O-rutinside were confirmed in the infusion by HPLC/UV-Vis-DAD/ESI-MS (Siracusa et al., 2011).
In another in vivo study, hot water extract of C. spinosa was found to show a strong antioxidant activity against lead mediated lipid peroxidation in model rats (Al-Soqeer, 2011). Antioxidant activity of methanolic extract of buds of C. spinosa, carried out using tests like ascorbate/Fe2+-mediated lipid peroxidation, DPPH and autoxidation of Fe2+ ion in the presence of bathophenanthroline disulfonate, confirmed that this activity was due to phenolic contents. In the same study, participation of glucosinolates in antioxidant activity was excluded by removing these compounds from methanolic extract and performed the assays again. The HPLC analysis of the hydrolyzed sample confirmed that the buds contained 0.39% of a potent flavonoid, rutin (Germano et al., 2002).
Bonina et al. (2002) investigated that methanolic extract of flowering buds of C. spinosa has strong in vitro and in vivo antioxidant activity followed by DPPH assay, peroxidation induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride of mixed dipalmitoyl phosphatidyl choline/linoleic acid unilamellar vesicles (LUVs) (LP-LUV test) and UV-induced peroxidation of phosphatidyl choline multi lamellar vesicles (UV-IP test). Characterization of the extract by chromatographic and spectroscopic techniques revealed the presence of quercetin derivatives, kaempferol, ferulic acid, cinnamic acid, caffeic acid and p-cumaric acid. The presence of these phenolic compounds was strongly linked to the antioxidant properties of C. spinosa.
According to Tesoriere et al. (2007), the flower buds of C. spinosa also exhibited a strong antioxidant potential, which was measured by different assays. Total phenolic contents of flower buds were estimated to be 4.19 mg of gallic acid equivalents, while total antioxidant potential using [2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] diammonium salt (ABTS) cation radical decolorization assay was 25.8 μmol of Trolox equivalents. Meanwhile, hydrophilic extract of flower buds of C. spinosa inhibited lipid oxidation in red meat up to level of 70-280 μM GAE (Tesoriere et al., 2007). Skin sclerosis, initiated by reactive oxygen species, was treated by applying ethanolic extract of C. spinosa fruits. The tested ethanolic extract caused a significant reduction in the generation of reactive species like O2-, H2O2, etc. Interestingly, a decrease in expression of P-ERK1/2 and Ha-Ras, as well as apoptosis was also recorded in the same experiments (Cao et al., 2010).
In another study, hydro-distilled essential oils isolated from flower buds and leaves of C. spinosa were evaluated for antioxidant attributes by applying DPPH scavenging, thiobarbituric acid and β-carotene bleaching assays and copper induced oxidation of human low-density lipoprotein. Essential oils showed low free radical scavenging activity in DPPH assay but high antioxidant activity in β-carotene bleaching and thiobarbituric acid assays (Kulisic-Bilusic et al., 2010). Capparis spinosa hence can be explored as potential plant for isolation of natural antioxidants to be uses in food systems to prevent degenerative diseases.
Cardiovascular activity: The major cause of mortality in the world is cardiovascular diseases. The prevalence of cardiovascular diseases is increasing at a rapid rate and can be minimized by exercise and optimal nutrition (Stampfer et al., 2000; Weisburger, 2000; Hu and Willet, 2002; AHA., 2004; Ding and Mozaffarian, 2006). Medicinal plants can contribute to the prevention and control of such civilization diseases. The aqueous extract of C. spinosa, when given to hypertensive rats at a dose of 150 mg kg–1 for 20 days, decreased systolic blood pressure considerably along with increase in potassium, sodium and chloride concentrations in urine without affecting plasma angiotensin converting enzyme and renin activities, indicating that the blood pressure lowering effect of the plant was possibly due to its diuretic activity (Ali et al., 2007).
Hepatoprotective activity: Viral and drug-induced hepatitis is one of the major health issues in developing countries such as Pakistan and India. Unfortunately, the hepatitis treatment is very expensive and beyond the reach of a large population in these countries in addition to its miserable side-effects. On the other hand, phytomedicines are traditionally used by the locals to treat liver disorders (Gilani and Atta-ur-Rahman, 2005; Yaeesh et al., 2010; Muhammad et al., 2015). One of such popular herbal formulations is Liv-52, which contains 65 mg of C. spinosa. It is widely used for different types of hepatitis (Kolhapure and Mitra, 2004; Bardhan et al., 1985). When C. spinosa was studied for its possible hepatoprotective effect in rats, the results were encouraging (Gadgoli and Mishra, 1999). In an earlier study, the aqueous extract of aerial parts of C. spinosa showed a notable hepatoprotective effect in carbon tetrachloride (CCl4) and paracetamol induced hepatitis in rats (Gadgoli and Mishra, 1999). Likewise, ethanolic extract of root bark of C. spinosa was evaluated for its hepatoprotective activity in rats and was found to protect liver from injury caused by CCl4 and lowered the alanine transaminase and aspartate transaminase levels in the blood (Aghel et al., 2007). Petroleum ether, ethanol and ethyl acetate extracts of bark of C. spinosa roots were evaluated for their hepatoprotective activity in rats where hepatitis was induced by CCl4. All the tested extracts reduced serum transaminases, petroleum ether extract being the most effective indicating that C. spinosa has a significant potential to treat hepatitis (Shirwaikar et al., 1996). In another study, thioacetamide induced liver damage was cured by C. spinosa extract (Yusufoglu et al., 2014).
Antimicrobial activity: Due to long term use of synthetic drugs, antimicrobial resistance is a growing concern, therefore, development of new safer antibiotics is highly required (Alves et al., 2012). Plants containing bioactives such as flavonoids, terpenoids, alkaloids and tannins are reported to possess antimicrobial activity (Bouzada et al., 2009; Sher, 2009).
The antimicrobial activity of aqueous, ethanol and butanol extracts of C. spinosa was assessed in different studies. The results have shown that aqueous and ethanol extracts had low while butanol extract had high antimicrobial activity when tested against Gram negative and Gram positive bacteria including; E. coli, P. aeruginosa, S. typhimurium, B. cerreus and S. aureus and fungi such as; C. albicans, F. oxysporum and A. flavus. The results were comparable to standard antimicrobials such as chloramphenicol, tetracycline and nalidixic acid (Mahasneh, 2002). In another study, the aqueous extract of C. spinosa showed a significant antifungal activity against M. canis and T. violaceum (Ali-Shtayeh and Abu Ghdeib, 1999). These studies support the potential uses of C. spinosa plant for the isolation of natural antimicrobial agents to treat infectious diseases.
Antiviral and anti-tumor activity: There is a limited number of anti-viral drugs available, while resistance of virus against currently available antiviral drugs is on the rise (De Clercq, 1993). Thus, there is a high demand for searching new plant-based antiviral drugs (McCutcheon et al., 1995).
The species C. spinosa, is reported to be a potential source of natural anti-viral and anti-tumor agents due to containing a wide array of bioactives. In this regard, methanolic extract of buds of C. spinosa inhibited the multiplication of HSV-2 in human peripheral blood mononuclear cells. The extract also prevented the extracellular virus release and improved immunity against HSV-2 infection by regulating the expression of proinflammatory cytokines140. Moreover, proteins isolated from the seeds of C. spinosa repressed the multiplication of hepatoma HepG2 cells, colon cancer HT29 cells and breast cancer MCF-7 cells. It also exhibited the inhibition of HIV-1 reverse transcriptase (Lam and Ng, 2009; Lam et al., 2009). The aqueous extract of flower buds of C. spinosa was used to study genotoxic and anti-mutagenic effects induced by ethyl methane sulphonate on root tip meristem of Allium cepa L. Meristem cells were treated with ethyl methane sulphonate for 2 h before the application of different concentrations of the aqueous extract. Subsequently, meristem cells from A. cepa were stained with aceto-orcein after squashing. The results showed a remarked reduction in mitotic index and chromosomal aberrations (Sultan and Celik, 2009).
Cholesterol lowering and anti-obesity: One of the major causes of cardiovascular diseases is the high cholesterol and triglycerides levels in plasma (Castelli, 1988; Moreyra et al., 2005). Similarly, obesity which leads to metabolic syndrome is a growing concern in many countries (Popkin, 2001; Grundy, 2004). Unfortunately, pharmaceutical medicine has limited therapeutic success and offers only symptomatic relief with life-long use of multiple medicines. Such medication is not only expensive but also causes multiple side-effects. Hence, life-style modifications and herbal remedies are contemplated as an alternative option.
Dietary fibers and plant materials can minimize LDL-cholesterol and reduce the chances of cardiovascular diseases (Anderson et al., 1999). An important plant in this regard is C. spinosa. Aqueous extract of C. spinosa was administered to rats orally, which significantly reduced blood cholesterol level. The extract also decreased lipids level in the rats suffering from diabetes (Eddouks et al., 2005). In another study (Lemhadri et al., 2007), it was demonstrated that the aqueous extract of C. spinosa could be used to reduce obesity, though further investigation is required to confirm the results.
Phytochemicals: It is well understood that the biological activities of plants and their formulations are due to the presence of a wide variety of phytochemicals such as alkaloids, steroids, terpenoids, polyphenols and tocopherols among others (Joshi et al., 2011). Capparis spinosa is rich in a wide variety of biologically active compounds including natural antioxidants (phenolic acids, flavonoids, tocopherols), alkaloids, polyprenols, glucosinolates and reducing sugars along with several essential minerals, proteins and lipids. Fruit of C. spinosa has been well studied for its phytochemical constituents and found to contain alkaloids (0.74%), glucosides (0.083%), fats (3.75%), ascorbic acid (13.5%), reducing sugars (32.9%), resins (23.75%) and organic acids (14.1%) (Rastogi and Mehrotra, 1995). The potential biological activities and medicinal functions of different parts of C. spinosa can be attributed to the presence of different bioactives. Figure 1 presents the chemical structures of selected high-value bioactive phytochemicals identified in different parts of C. spinosa.
Flavonoids: Several important flavonoids have been identified in C. spinosa including rutin (quercetin 3-rutinoside), quercetin 3-glucoside-7-rhamnoside, quercetin 7-rutinoside, kaempferol-3-glucoside, kaempferol-3 rutinoside and kaempferol-3-rhamnorutinoside (Winter, 1978). Rutin is a versatile and potential antioxidant flavonoid that has several biological applications with no toxicity. It has been reported to decrease blood pressure, permeability of vessels and risk of arteriosclerosis along with its hypolipidemic and hepatoprotective activities (Pathak et al., 1991; Lima et al., 1999; Janbaz et al., 2002). Interestingly, C. spinosa is a rich source of rutin. In this regard, Ramezani et al. (2008) conducted a detailed study for the quantification of rutin from leaves, flowers and fruits of C. spinosa. From the extract (50% ethanol), rutin was separated by Thin Layer Chromatography (TLC), identified by UV light (254 nm) and further authenticated and quantified by the HPLC/UV method. The amount of rutin in leaves, fruit and flowers of C. spinosa was determined to be 61.09, 6.03 and 43.72 mg 100 g–1 of dried powder, respectively (Ramezani et al., 2008).
Previously, it was reported that methanolic extract of aerial parts of C. spinosa contained a novel flavonoid, quercetin 3-O-[6 ‘’- α-l-rhamnosyl-6’‘-β-d-glucosyl]-β-D-glucoside along with some known flavonoids such as rutin, quercetin 3-O-glucoside, quercetin 3-O-glucoside-7-O-rhamnoside, kaempferol-3-rutinoside and kaempferol-3-rhamnorutinoside (Rodrigo et al., 1992; Sharaf et al., 2000). Sharaf et al. (1997) also reported that leaves and stems of C. spinosa (extracted with 70% ethanol) contained quercetin-3-rutinoside, quercetin-7-rutinoside, kaempferol-3-rutinoside and quercetin 3- glucoside-7-rhamnoside. In another study, powdered fruit of C. spinosa was extracted with water. Ethanol eluted fractions contained eight new along with five known compounds out of which apigenin, kaempferol and the vetiaflavone were noted to be flavonoids (Zhou et al., 2010).
In a recent study, structurally diverse bioflavonoids (isoginkgetin, ginkgetin and sakuranetin) were isolated for the first time from the fruit of C. spinosa and their structures were confirmed by spectroscopic techniques (Zhou et al., 2011). In another study, HPLC coupled with a diode-array detector was used to evaluate quercetin 3-rutinoside, kaempferol 3-rutinoside and kaempferol 3-rhamnosyl-rutinoside and aglycones (quercetin and kaempferol) in brined flower buds of C. spinosa. According to the analysis the brined buds only contained quercetin and kaempferol. Meanwhile, total flavonoids and aglycones in flower buds available in market were estimated to be 5.18 and 3.86 mg g–1 of fresh caper, respectively (Inocencio et al., 2000). It can be inferred that C. spinosa is a potential plant to be explored as a viable source for extraction of antioxidant flavonoids for food and therapeutic uses.
Alkaloids: It is worth mentioning that C. spinosa is a rich source of different classes of alkaloids which include spermidine, indole and pyrrole alkaloids along with indol-aldehyde and indol-nitrile type derivatives. Several new alkaloids and their glycosides have also been identified in C. spinosa. For example, three new spermidine alkaloids including capparispine, capparispine 26-O-β-D-glucoside and cadabicine 26-O-β-D-glucoside hydrochloride were separated from the roots of C. spinosa and their structures were confirmed by NMR spectroscopy (Fu et al., 2008). Figure 2 shows two novel spermidine alkaloids identified in the roots of C. spinosa.
Furthermore, three novel alkaloids, capparisine A, capparisine B and capparisine C and two known alkaloids, 2-(5-hydroxymethyl-2-formylpyrrol-1-yl) propionic acid lactone and N-(3 -maleimidy1)-5-hydroxymethyl-2-pyrrole formaldehyde were isolated from the fruit of C. spinosa (Fig. 3). The isolated alkaloids were purified by the column chromatography, solvent separation and preparative TLC and their structures were confirmed by the spectroscopic and X-ray crystallographic techniques (Yang et al., 2010).
Mature fruit of C. spinosa was also shown to contain two glucose containing 1H-indole-3-acetonitrile compounds, 1H-indole-3-acetonitrile 4-O-β-glucopyranoside and 1H-indole-3-acetonitrile 4-O-β-(6-O-β-glucopyranosyl)-glucopyranoside, as confirmed by advanced spectroscopic techniques (Calis et al., 1999).
| Fig. 1: | Some important secondary metabolites of C. spinosa: 3-Methyl-2-butenyl-β-glucoside (1), β-Sitosterylglucoside-6'-octadecanoate (2), Stachydrine (3), Flazen (4), Quercetin 3-O-[6 "-α-l-rhamnosyl-6"-β-d-glucosyl]-β-d-glucoside (5), Cappariloside A (6), Cappariloside B (7), Capparine A (8), (+)-(6S,9S)-9-O-β-D-gluc opyranosyloxy-6-hydroxy-3-oxo-α-ionol (corchoionoside C, (6S,9S)-roseoside) (9), Spionoside A (10), Spionoside B(11) and Capparine B (12) |
| Fig. 2: | Capparispine (13) and Capparispine 26-O-β-d-glucoside (14) |
| Fig. 3: | Capparisine A (15), Capparisine B (16), Capparisine C (17), 2-(5-hydroxymethyl-2-formylpyrrol-1-yl) propionic acid lactone (18) and N-(3 -maleimidy1)-5-hydroxymethyl-2-pyrrole formaldehyde (19) |
According to a recent report, powdered fruit of C. spinosa (extracted with 70% ethanol and diluted with water and sulphuric acid) was found to have an important alkaloid cappariloside A along with hypoxanthine, uracil and adenosine (Fu et al., 2007). Other alkaloid compounds in the fruit of C. spinosa include flazin, guanosine, capparine A, capparine B, 1H-indole-3-carboxaldehyde and 4-hydroxy-1H-indole-3-carboxaldehyde (Zhou et al., 2010).
Essential oils and terpenoids: Essential oils, hydro-distilled products isolated from different parts of plants, are gaining much recognition as potential ingredients of functional foods, pharmaceuticals and cosmo-nutraceuticals due to their multiple medicinal and biological activities (Hussain et al., 2008, 2013). In particular, essential oils are popular for their antimicrobial, insecticidal, antiviral, antioxidant and food flavoring and preservative properties (Hussain et al., 2008, 2013; Karpouhtsis et al., 1998; Rusenova and Parvanov, 2009).
Capparis spinosa is rich in essential oil as reported by several studies. The flower buds and leaves of C. spinosa were used to extract essential oil by hydro-distillation in a clevenger-type apparatus. The GC-MS analysis of the essential oil revealed the presence of isothiocyanate (92.06%), sec-butyl isothiocyanate (0.25%), butyl isothiocyanate (0.38%), benzeneacetaldehyde (0.23%), benzeneacetonitrile (0.4%), E-β-ionone (0.5%), methyl methylsalicilate (0.17%), benzyl isothiocyanate (0.74%) and 3-hexenyl benzoate (0.27%) (Kulisic-Bilusic et al., 2010). Previously, it has been reported that C. spinosa essential oil contained 145 compounds when analyzed by HS-SPME/GC-MS. Among those, aldehydes (22.2%) and ketones (8.42%) are most abundant classes followed by sulphur compounds (8.42%). The plant also contained five sesquiterpenes and ten monoterpenes (Romeo et al., 2007). From Jordanian C. spinosa, γ-sitosterylglucoside-6'-octadecanoate and 3-methyl-2-butenyl-γ-glucoside were also isolated164. Moreover, isothiocyanates, n-alkanes, terpenoids, a phenyl propanoid, an aldehyde and a fatty acid were isolated from the leaf oil of C. spinosa. The fruit and root oils also contained methyl, isopropyl and sec-butyl isothiocyanates (Afsharypuor et al., 1998).
In another study, extraction of essential oil via steam-distillation was carried out from dried fruit of C. spinosa. Out of 53 essential oil compounds identified by capillary GC-MS method, the main twelve compounds were found to be (Z,Z)-9,12-octadecadienoic acid (26.40%), hexadecanoic acid (15.35%), octadec-9-enoic acid (11.41%), 1,2-benzene dicarboxylic acid-bis(2-methylpropyl) ester (5.77%), di-(2-ethylhexyl) phthalate (4.41%), 2-methoxy-phenol (2.94%), tetradecanoic acid (2.67%), dodecanoic acid (2.47%), (Z,Z)-9,12-octadecadienoic acid-methyl ester (2.03%), Z-11-Hexadecenoic acid (1.86%), 1-(1H-pyrrol-2-yl)-ethanone(1.04%) and hexadecanoic acid-methyl ester (1.02%). These twelve compounds accounted for 77.37% of total separated compounds of the essential oil (Bai et al., 2007). Presence of a considerable amount of essential oil rich in diverse classes of chemical constituents, advocates that this species can be commercially exploited for essential oil production and its utilization in pharmaceutical, food and cosmo-nutraceutical industry leading to value-addition.
Lipid components: Plant lipids, being a potential source of essential fatty acids and natural antioxidant tocols and phytosterols, are another important class of bioactives with multiple functionalities (Anwar et al., 2008). The seeds of C. spinosa fruit have oil content varying between 27.3-37.6 g 100 g–1. The fruit seed oil contains fatty acids (linoleic acid 24.6-50.5%, oleic acid 10%, vaccenic acid 30%), tocopherols (γ-tocopherol 124.3-1944.9 mg 100 g–1, δ-tocopherol 2.7-269.5 mg 100 g–1 and α-tocopherol 0.6-13.8 mg 100 g–1), total sterols (4.96-10.0 g kg–1) and glucosinolates (42.6-88.9 μmol g–1). Among the oil sterols, β-sitosterol (60%) is most abundant followed by campesterol (16%) and stigmasterol (10%) (Matthaus and Ozcan, 2005).
Tlili et al. (2009a) investigated the composition of fatty acids, tocopherols and carotenoids in the fruit seed oil of Tunisian caper (C. spinosa). According to the results, the seed oil contents of C. spinosa fruits ranged from 23.25-33.64% dry weight basis. The seed oil contained appreciable amount of tocopherols (ca. 628 mg 100 g–1) and carotenoids (ca. 457 μg 100 g–1). The occurrence of fatty acids such as oleic acid (45.82%), linoleic acid (25.37%), palmitic acid (15.93%), palmitoleic acid (4.55%) and stearic acid (4.06%) alongwith γ-tocopherol (ca. 92%), α-tocopherol (ca. 4%), δ-tocopherol (ca. 2%) and β-carotene (ca.375 μg 100 g–1) was established in the tested seed oil (Tlili et al., 2009a).
Tlili et al. (2011), reported the contents of protein, lipid, aliphatic and triterpenic alcohols in the caper (C. spinosa) seeds. The amount of total protein and lipids was noted to be 27 and 33%, respectively. Aliphatic alcohols including hexadecanol, octadecanol and tetracosanol were determined as high as 45 mg kg–1 of total lipophilic substances. The amount of triterpenic alcohols such as citrostadienol, β-amyrin, gramisterol, cycloartanol and 2,4 methylcycloartenol was estimated to be 396.82 mg kg–1 with octadecanol (28 mg kg–1) and citrostadienol (170 mg kg–1) as the major compound.
In a similar study by Yili et al. (2006), extraction of lipids from the roots of C. spinosa was carried out using a mixture of chloroform and methanol (1:1 v/v) and the yield found to be 0.54% of total raw material. The analysis of the extracted lipids, after elution through a column using chloroform, showed the presence of neutral lipids, hydrocarbons, esters of sterols and high-molecular-weight fatty acids, triacylglycerides, free fatty acids, free sterols and aliphatic alcohols. Monogalactosyldiglycerides, sterolglycosides, cerebrosides, esters of sterolglycosides and digalactosylglycerides were found to be the main classes of glycolipids when separated from a column using acetone as a mobile phase, whereas methanol fraction mainly contained phosphatidylinosites, phosphatidylcholines and phosphatidylethanolamines (Yili et al., 2006). The lipids extracted from the epigeal parts of C. spinosa were found to contain hydrocarbons (5.4%), sterol and triterpenol components (18.6%), triacylglycerols (28.7%), free fatty acids (32.5%) and triterpenols (2.1%) as the neutral lipids while N-acyl- phosphatidylethanolamines (14.6%), N-acyl-lyso-phosphatidylethanolamines (6.7%), phosphatidylglycerols (26.1%), phosphatidylcholine (16.5%), phosphatidylethanolamines (20.4%), phosphatidylinositols (12.8%) and phosphatidic acid (2.8%) were identified as phospholipids. Glycolipids, esters of sterol glycosides (12.8%), sterol glycosides (25.7%), monogalactosyldiglycerides (18.2%), digalactosyldiglycerides (42.4%) and sulfoglucolipids (0.9%) were also identified among others (Talibaev and Glushenkova, 1995).
In a recent study by Yuldasheva et al. (2008) powdered seeds of C. spinosa were extracted with hydrocarbons for free lipids and with chloroform-methanol for bound lipids using Soxhlet apparatus. Bound lipids were further isolated into neutral lipids, phospholipids and glycolipids by separation with column packed with silica gel. Monogalactosyl diacylglycerides (MGDGs), digalactosyl diacylglycerides (DGDG), sterolglycosides and their esters were identified as glycolipids while phosphatidylinositols, phosphatidylethanolamines and phosphatidylcholines were confirmed as phospholipids. Fatty acid composition by alkaline hydrolysis was also established.
Glucosinolates, polysaccharides and sugars: Glucosinolates are glucose derivatives, containing nitrogen and sulphur. These compounds are recognized as a natural pesticide (i.e., biopesticides) (Bridges et al., 2002) and cancer inhibitors (Hayes et al., 2008). Glusinolates are widely distributed in the plants of family Capparidaceae, Brassicaceae and Caricaceae (Rodman et al., 1996). Capparis spinosa L. plant has also been investigated as a potential candidate for isolation of glucosinolates. Matthaus and Ozcan (2002) reported total contents of glucosinolates in shoots and large flowers buds of C. spinosa amounting to levels as high as 6.55 μmol g–1. Among glucosinolates, glucocapperin was found to be the most abundant compound with contribution of 90%. The study concluded that glucosinolates composition may vary with the size of buds (Matthaus and Ozcan, 2002). In another report, indole glucosinolates such as glucobrassicin, neoglucobrassicin and 4-methoxy-glucobrassicin were isolated from roots of C. spinosa and identified by HPLC and mass spectrometry (Schraudolf, 1989). Glucosinolates are reported to act as stimulant and appetizer for the digestive process. Other important biological effects exhibited by these compounds include cytotoxic, antibiotic, anti-cancer activities (Montaut and Bleeker, 2013).
Another important group of compounds namely hydrophilic polysaccharides, hemicelluloses and pectin compounds have also been extracted/isolated with water, base and oxalic acid/ammonium oxalate, respectively from the roots of C. spinosa and analyzed. The important monosaccharides detected in the roots of C. spinosa were xylose, arabinose and galactose (Yili et al., 2006).
Phytosterols: Phytosterols, which are derived from vegetable sources, especially, the vegetable oils, are linked with decreasing blood cholesterol level and thus mitigating the risk of heart diseases (Ortega et al., 2006). Phytosterols also possess anti-inflammatory, anti-tumor, antibacterial and anti-ulcerative properties (Beveridge et al., 2002). Capparis spinosa is also a good source of phytosterols. Petroleum ether-extract (oil) from the seeds of C. spinosa has notably high amount of total phytosterols (2240.4 mg kg–1 of extract). Among these, most abundant phytosterol was β-sitosterol (57.53%) followed by campesterol (17.05%), stigmasterol (11.85%) and 5-avenasterol (6%). Brassicasterol, cholesterol and campestanol were also identified in smaller amounts (Tlili et al., 2010a).
Carotenoids, tocopherols and phenolics: Carotenoids are antioxidants that protect cells from oxidative damage, which results in degenerative diseases such as cancer, aging and inflammation (Mayne, 1996; Sies and Stahl, 1995). Leaves, buds and flowers of C. spinosa contain an appreciable amount of total carotenoids, 3452.5±1639.4, 1002±518.5 and 342.7±187.9 μg g–1, respectively. Among carotenoids, lutein and violaxanthin had the highest and lowest contents, respectively. The amount of α-tocopherol was found to be 20.19±10 mg 100 g–1, 49.12±17.48 and 28.68±9.13 mg 100 g–1 in the leaves, buds and flowers, respectively. There was no γ-tocopherol detected in the leaves but a considerable amount of -tocopherol was present in the buds (48.13±15.08 mg 100 g–1) and leaves (27.8±16.01 mg 100 g–1), respectively (Tlili et al., 2009b).
In another study, the analysis of flower buds of C. spinosa demonstrated that they did not contain α-tocopherol but γ-tocopherol and vitamin C were present in small amounts (Tesoriere et al., 2007). Tlili et al. (2010a) evaluated the antioxidant capacity of methanol extracts of leaves and flower buds of C. spinosa by analyzing different bioactives. A high amount of phenolic compounds ca. 3,643 and 2,621 mg 100 g–1 fresh weight along with carotenoids ca. 4 and 18 mg 100 g–1 was detected in the leaves and flower buds of C. spinosa, respectively supporting that the plant could be explored as a potential source of different types of natural antioxidants.
Other components: Some studies demonstrated the occurrence of miscellaneous types of phytochemicals in C. spinosa. For example, GC-MS analysis of the fruit of C. spinosa showed the presence of sulphides, isothiocyanates and elemental sulphur (S8). Response of caper to dithiocarbamate test was shown to be positive (Brevard et al., 1992). The mature fruit of C. spinosa showed the presence of two new glycosides, which were isolated and identified as (6S)-hydroxy-3-oxo-á-ionol glucosides (Calis et al., 2002). Al-Said et al. (1988) reported the presence of polyprenols (anti-inflammatory agents) such as cappaprenol-12, cappaprenol-13 and cappaprenol-14, containing 12, 13 and 14 isoprenoid units, respectively, in alcoholic extract of C. spinosa.
According to a recent report, it was also found that 8.6 g of C. spinosa fruit contained considerable amount of rutin (13.76 mg) and isothiocyanates (42.14 μmol). Linoleic acid (18:2 ω 6), γ-linolenic acid (18:3 ω 6), rutin and kaempferol-3-rutinoside were also discovered from buds of C. spinosa (Giuffrida et al., 2002). Various bioactive components separated and identified from C. spinosa are listed in Table 2.
| Table 2: | Bioactivities separated and identified from different parts of C. spinosa |
Conclusion and future prospects: Capparis spinosa (C. spinosa) is mostly popular as a folk remedy for the treatment of hepatitis, tuberculosis, kidney problems, stomach disorders, diabetes and high blood pressure. The plant is also recognized for its anti-inflammatory, antioxidant, cardiovascular, hepatoprotective, antimicrobial, antiviral, hypolipidemic and hypoglycemic activities. Hence, it would be meaningful to isolate and characterize related bioactives from different parts of this species. Further efforts are also needed for the appraisal of clinical and pharmacological applications of novel bio actives in this species using some in-vitro and in vivo studies.
Various studies have confirmed that C. spinosa is a rich source of antioxidants, such as flavonoids and contains rutin and querecitin in considerably high amounts. Therefore, this wildly grown species, which is quite salt and drought tolerant, can be cultivated in saline arid and dry lands as a commercial source of natural antioxidants and preservatives for the functional food and nutraceutical industry. Different anti-inflammatory agents including cappaprenol-13, isoginkgetin and ginkgetin have been separated from different parts of C. spinosa to treat arthritis. This supports the future prospects of this species for the discovery of natural drugs. Fruit extract showed anti-hyperglycemic effect in rats; hence, screening of new anti-diabetic compounds in this plant will be helpful in the development of new drugs to treat diabetes. Similarly, the established anti-ulcer attributes of this species provoke the need to isolate and purify the anti-ulcer components and develop natural drug for the treatment of ulcerative disorders.
The plant possesses very good anti-tumor and antimicrobial activities; the related bioactive compounds still need to be isolated in purified form for drug development. Moreover, there is need to isolate potential anti-viral components from this species. The plant seeds also contain a protein that inhibits the multiplication of hepatoma HepG2 cells, colon cancer HT29 cells and breast cancer MCF-7 cells. Other parts of this plant should also be investigated for the isolation of functional bio-peptides and elucidation of their mechanism of biological actions.