ABSTRACT

This review describes the genus Crotalaria focusing on its secondary metabolites and their medicinal applications. The genus Crotalaria of Fabaceae or Leguminosae family have about 600 species which are distributed in tropic and sub-tropic regions of the world. They are medicinally important due to production of various compounds. Traditional early medicines and drug discovery were based on natural products. Organisms produce some chemical compounds by their metabolic pathways that are not necessary for their growth and development and are known as secondary metabolites. This diverse group of compounds is synthesized by algae, plants, animals and fungi. These metabolites consist of variety of compounds such as phenols, coumarins, terpenoids, flavonoids, alkaloids, steroids and fatty acids. Secondary metabolites obtained from crotalaria exhibit anticancer, anti-rheumatoid arthritis, anti-allergic, antioxidant, antimicrobial, antiaging and wound healing activities along with many other medicinal applications.

INTRODUCTION

Living organisms produce chemical compounds or substances called natural products (Anulika et al., 2016). From ancient time the plant metabolites and human being have relationship. Natural sources like microorganisms and plants have ability to produce biologically active compounds against different diseases (Jabeen et al., 2014). Traditionally early medicines and drug discovery were based on natural products (Butler et al., 2005). These potential natural product derived substances have advantages and disadvantages (Debbab et al., 2010). They have been used for treatment and cure of diseases from the beginning of civilization (Scarim et al., 2017). Today many drugs are obtained from natural products derived from plants. From approximately the early 1980s, drug discovery from natural products decreased because of the advent of combination chemistry technology that led to the future source of immense numbers of novel potential and new chemical entities (NCEs)/drugs (Newman et al., 2008). Due to new registration requirements, pesticides compounds are now being replaced by natural product-based pesticides (Dayan et al., 2009). However, pharmaceutical companies have not paid due attention to these compounds (Watkins et al., 2015).

FAMILY FABACEAE

The Fabaceae or Leguminosae, commonly known as the legume, pea, or bean family, is a large and economically important family of flowering plants (Rahman and Parvin, 2015). The family includes a large number of plants, comprising about more than 600 genera with about 18,000 species (Sharma and Kumar, 2013; Melo et al., 2010; Judd et al., 2002). Fabaceae is the most diverse plant family in the world with a wide distribution; considered as the third largest family of angiosperms in species numbers after Asteraceae and Orchidaceae in the global context (Beech et al., 2017; LPWG, 2017). The family has economic importance by having food crops that provide highly nutritious sources of protein and micronutrients which can benefit health and livelihoods, particularly in the developing countries (Gomes et al., 2018).

Economic importance of family Fabaceae

The plants of this family are source of protein because their roots contain nitrogen fixing bacteria. The plants are used as food such as pulses, gram and soya bean. Some of the plants are used as source of oil such as groundnut and soya bean. Sesbania and pea plants are used as ornamental plants. Shishum and Sunn hemp are used as timber and fiber, respectively. Indigo plant gives indigo dye (Meriem et al., 2014).

Medicinal importance of family Fabaceae

There is round about 150 plants of Fabaceae family which are commonly used by medicinal herbalists. For example, Glycyrrhiza glabra is an anti-inflammatory, antiviral, antioxidant herb and also used for disorder of liver and bronchi. The wild pea is used for the treatment of skin problems like acne and wrinkles; they have terpenes and flavonoids which have anticancer and antimicrobial activities, respectively. White and red Cloves are member of Fabaceae family which are used to cure skin problems like burn, rash, sore and ulcer. Alfalfa plant of this family contains vitamins A, B, E and K. Powdered roots of Crotalaria albida are used to cure victims of snake bite, while Crotalaria pallida is used to kill intestinal worms (Parvaiz et al., 2014).

GENUS CROTALARIA

Crotalaria is known as rattlepod. The common name rattlepod or rattlebox is taken from the reality that the seeds become loose in the pod as they mature, and rattle when the pod is shaken. The genus Crotalaria is considered as one of the largest genera having 600 species which are distributed in tropic and sub-tropic regions of the world (Devendra et al., 2012). Crotalaria species are mostly herbs and shrubs with simple unifoliate or digitally foliate leaves and stamens. Anthers are dimorphic. Flowers are yellow in color (Raj et al., 2011). The plants belonging to genus Crotalaria are commonly used as green manure (Daimon, 2006). The plants are also used for ornamental purposes. Its various plants are medicinally important such as seeds of Crotalaria retusa are used as medication for fever (Umerie et al., 2010). Crotalaria juncea has anti-obesity, antitumor and anti-diarrhea properties (Lalitha et al., 2011).

Crotalaria burhia is a fibrous plant and under shrub. In Pakistan it is commonly found in Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan. In India it is found in Punjab, Rajasthan and Gujarat. In different languages it has different names such as ‘Shinio” in Rajasthan, ‘Bhata’ in Punjab, ‘Ghughato’ in Gujarat, ‘Ghagri’ in Marathi and ‘Ban Sutri’ in Bengal. Its Hindi name is ‘Khip’ (Katrria et al., 2012). Its leaves are elliptic-oblong or lanceolate. Flowers are yellow and in terminal racemes inflorescence. Seeds are sub-reniform, dark brown, compressed, shiny and smooth. Flowers and fruits are found throughout the year.

SECONDARY METABOLITES

Organisms produce chemical compounds by their metabolic pathways that are not necessary for growth and development of these organisms, called as secondary metabolites (Daniel et al., 2012). These products are intermediates of metabolism (Tiwari and Rana, 2015). Due to broad and no distinct boundaries they cannot be simply defined (Cannell, 1998). This diverse group of compounds is synthesized by algae, plants, animals and fungi (Tania et al., 2003). Some secondary metabolites isolated from plants are used as drugs, flavors, dyes, dietary supplements, phytonutrients and cosmetics (Guerriero et al., 2015). These have benzene ring having various hydroxyl groups; simple or polymerized (Velderrain et al., 2014). Now a day these have become of great interest due to their anticancer property, and their uses in treatment of heart diseases (Ibrahim et al., 2012). Phenolic acids are mostly present in potato, spinach, orange, pear, blueberry, tea, coffee beans, cherry juice and cider (Balasundram et al., 2006; Gonthier et al., 2006). These are classified into simple and complex derivatives consisting of fused aromatic rings (Kulbat, 2016). These are very effective due to their physiological effects like cardio-protective, anti-inflammatory, anti-thrombotic, anti-artherogenic, antimicrobial and antioxidant (Balalsundram et al., 2006). Various compounds, belonging to classes of secondary metabolites, isolated from genus Crotalaria are listed in table 1.

Table 1: Compounds isolated from genus Crotalaria.

Alkaloids

It is the largest group of secondary metabolites; approximately more than 6,000 compounds exhibit alkaloid like properties (Dewey and Xie, 2014). Alkaloids have significant role for toxicity against pathogens and predators (Hartmann et al., 2007). These can also detoxify stress releasing oxygen species and act as antioxidants (Matsuura and Neto, 2014; (Porto et al., 2014). These are important defense tools for organisms like amphibians (Toledo and Jared, 1995).

Terpenoids

Pine trees have volatile liquid ‘terpentine’ known as terpene that is the reason these compounds are called terpenoids (Yadav et al., 2014). Depending upon the number of basic isoprene unit, there are various classes as hemi-, mono-, sesqui-, di-, sester-, tri-, and tetra-terpenoids (carotenoids)(Heras et al., 2003). Their concentrations vary in different parts of plants like fruit, bark, root, and seed (Bhargava et al., 2013). These have been used by humans in food, development of biofuel, and in pharmaceutical and chemical industries (Tholl, 2015). These also act as defense tools in plants during stress conditions (Mazid et al., 2011; Tholl, 2006).

Coumarins

Coumarins (2H-1-benzopyran-2-one) consist of a large class of phenolic substances found in plants and are made of fused benzene and ?-pyrone rings (Aoyama et al., 1992). There are four main coumarin sub-types: the simple coumarins, furanocoumarins, pyranocoumarins and pyrone-substituted coumarins (Jain and Joshi, 2012). These are found at high levels in some essential oils, particularly cinnamon bark oil (7,000 mg L^-1), cassia leaf oil (up to 87,300 mg L^-1) and lavender oil (Lake, 1999). More than 1,300 coumarins have been identified as secondary metabolites from plants, bacteria, and fungi (Iranshahi et al., 2009). Some of these coumarin derivatives have been found useful in photochemotherapy, antitumor, anti-HIV therapy (Manfredini et al., 1997), as central nervous system (CNS)-stimulants, antibacterial, anticoagulants (Wattenberg et al., 1979; Valgas et al., 2007), antifungal, as antioxidants and dyes (Mazzone et al., 2015; Barker et al., 1971).

Steroids

The addition of different chemical groups at different positions on backbone leads to the formation of many different types of steroidal compounds including sex hormones like progesterone and testosterone, the anti-inflammatory steroids like corticosteroids, cardiac steroids like digoxin and digitoxin, animal steroids like cholesterol and steroidal glycosides (Benveniste et al., 1986). Plant steroids possess many interesting medicinal, pharmaceutical and agrochemical activities like antitumor, immunosuppressive, hepatoprotective and antibacterial (Yokota, 1997). The first steroid was isolated from shark liver oil but later on found to be present in almost all living organisms (Jovanovic et al., 2015). Cholesterol is one of the classes of steroids (Moss, 1989).

MEDICINAL IMPORTANCE OF PLANT’S SECONDARY METABOLITES

Some plants or products isolated from them have been and are still used to treat infections, health disorders or diseases (Michael, 2015). The levels and activities of a number of plant secondary metabolites are known to increase in response to increase in stress (Makkar et al., 2009). Phenolic compounds could be an important part of the plants defense system against pests and diseases including root parasitic nematodes (Mazid et al., 2011). For centuries, in India, snakeroot (Rauvolfia serpentina) is used as medicine due to its sedative consequences (Kong et al., 2003). Tulsi (Ocimum sanctum) is useed as a cure for bronchitis, vomiting and fever (Gupta et al., 2002). Kojic acid comprise antibacterial properties and employed for the cure of skin diseases and as a skin whitening agent is a part of several fungal species particularly Aspergillus oryzae (Yabuta, 1924). Augmentin is used as a broad-spectrum antibiotic (Butler, 2004). Discodermolide is a polyketide extracted from marine sponge (Discodermia dissolute), which has antitumor and immunosuppressive activities (Gunasekera et al., 1990). Medicinal importance of secondary metabolites obtained from different species of genus Crotalaria is listed in table 2.

Table 2: Medicinal importance of secondary metabolites isolated from genus Crotalaria.

CONCLUSION

The genus crotalaria, considered as one of the largest genera having about 600 species, contains a variety of compounds such as phenols, alkaloids, steroids, flavonoids and fatty acids. In the present study, 38 compounds belonging to different secondary metabolite groups isolated from 23 species of crotalaria and their medicinal importance has been reported. Most of these compounds belong to alkaloid group of secondary metabolites, the remaining belong to flavonoid, saponin and steroid groups. These are medicinally important due to having antispasmodic, antioxidant, immune modulator, antimicrobial, anticancer, anti-inflammatory, anti-nociceptive, antifungal, antiulcer, antitumor, antineoplastic, anti-hyperalgesic, anti-pyretic, anti-asthma, neuroceptive and hepatoprotective activities etc.

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