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Alhagi : A Plant Genus Rich in Bioactives for Pharmaceuticals

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REVIEW Alhagi: A Plant Genus Rich in Bioactives for Pharmaceuticals Gulzar Muhammad, 1 Muhammad Ajaz Hussain, 1 * Farooq Anwar, 1,2 Muhammad Ashraf 3 and Anwarul-Hassan Gilani 4,5 * 1 Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan 2 Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdulaziz University, PO Box 173, Al-Kharj 11942, Saudi Arabia 3 University College of Agriculture, University of Sargodha, Sargodha 40100, Pakistan 4 Natural Products Research Unit, Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi 74800, Pakistan 5 Department of Pharmacy, College of Health Sciences, Mekelle University, PO Box 1871, Mekelle, Ethiopia Alhagi, a plant genus from family Fabaceae, is widely distributed in many countries of Asia, Australia and Europe. Commonly known as camel thorn, Alhagi has many species famous for feed and folk medicinal uses. Different species of Alhagi such as Alhagi pseudalhagi, A. graecorum, A. sparsifolia, A. kirgisorum, A. maurorum, A. camelorum and A. persarum have been explored for their antioxidant potential and nutritive value along with various medicinal properties. A wide array of pharmacologically active secondary metabolites such as flavonoids, alkaloids (alhacidin and alhacin), steroids, pseudalhagin A, phospholipids and polysaccharides have been reported from different parts of Alhagi species. A broad range of biological activities such as antioxidant, cardiovascular, anti- ulcer, hepatoprotective, antispasmodic, antidiarrheal, antinociceptive, antipyretic, anti-inflammatory, anti-rheumatic, antibacterial and antifungal have been ascribed to different parts of Alhagi. In addition, Alhagi plants are also valued as a rich source of digestible protein and important minerals. This review focuses on the medicinal applications and detailed profile of high-value bioactive phytochemicals along with pharmacological attributes and therapeutic potential of these multi-purpose plants. Copyright © 2014 John Wiley & Sons, Ltd. Keywords: Alhagi; medicinal uses; phytochemistry; bioactives; natural pharmaceuticals; nutraceuticals. INTRODUCTION Currently, much scientific research is being focused on understanding the basis for the continuing progress of plant-based bioactive chemicals offering various health benefits (Lattanzio et al., 2009; Banerjee et al., 2011; Russell and Duthie, 2011). Plants are not only valued as an important source for human food and animal feed, they are also esteemed as natural remedies to cure many health disorders. Traditionally, plants have a long history of folk medicinal uses that can be supported be- cause they contain a wide array of bioactives commonly classed as secondary metabolites such as phenolics possessing multiple medicinal properties and health benefits (Gilani, 1998; Anwar et al., 2007; Lattanzio et al., 2009; Banerjee et al., 2011; Russell and Duthie, 2011; Zaini et al., 2011; Ghanbari et al., 2012). Nowadays, there is revival of interest in the use of plants as a source of food and medicine. According to a recent WHO report (2011), about 80% of the world population, especially in the developing world, relies on traditional medicines for curing different health dis- orders and diseases. The use of phytomedicines for health benefits is evident in almost all systems of medi- cines (Chinese, Greco-Arab, Ayurveda etc.). A large number of reports can be easily deciphered from literature, which presents medicinal and pharmaco- logical attributes of traditional phytomedicine (WHO, 2002; Hasani-Ranjbar et al., 2008; Gilani and Atta-ur- Rahman, 2005). The genus Alhagi (Camel thorn) is a famous herb because of its multi-purpose uses. Almost all species of Alhagi are known for potential medicinal applications (Zou et al., 2012; Laghari et al., 2012a, 2012b; Gholamhoseinian and Razmi, 2012). The folk medicinal uses of Alhagi date back to centuries. Traditionally, Alhagi plants are used to treat numerous diseases such as gastroenteritis (Varshney and Singh, 2008), ulcers (Amani et al., 2006), fever (Khan, 2009; Marwat et al., 2008), inflammations and angina pain (Seredin and Sokolov, 1978), headache and toothache (Zou et al., 2012), diarrhea (Uphof, 1959; Atta and Mouneir, 2004), rheumatoid arthritis (Boulos, 1983), liver disorders (Shaker et al., 2010; Al-Douri and Al-Essa, 2010), kidney stone and urinary tract infections (Badshah and Hussain, 2011), hypertension (Kouchmeshky et al., 2012) and cancer (Zou et al., 2012). A number of biological and pharmaceutical attributes such as antibacterial (Neamah, 2012), cardiac depressant (Khushbaktova et al., 1992), anti-ulcer (Amani et al., 2006), spasmolytic (Marashdah and Al-Hazimi, 2010), an- tioxidant (Muhammad et al., 2011), cholegogue, diuretic, anti-lithiatic and antifungal (Laghari et al., 2012b) have * Correspondence to: Anwarul-Hassan Gilani, Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi- 74800, Pakistan; Muhammad Ajaz Hussain, Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan. E-mail: [email protected] (Anwarul-Hassan Gilani); majaz172@yahoo. com (Muhammad Ajaz Hussain) PHYTOTHERAPY RESEARCH Phytother. Res. (2014) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ptr.5222 Copyright © 2014 John Wiley & Sons, Ltd. Received 20 November 2013 Revised 12 July 2014 Accepted 21 August 2014
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* Correspand Biome74800, PakUniversityE-mail: anwcom (Muha

PHYTOTHERAPY RESEARCHPhytother. Res. (2014)Published online in Wiley Online Library(wileyonlinelibrary.com) DOI: 10.1002/ptr.5222

Copyright

REVIEW

Alhagi: A Plant Genus Rich in Bioactives forPharmaceuticals

Gulzar Muhammad,1 Muhammad Ajaz Hussain,1* Farooq Anwar,1,2 Muhammad Ashraf3and Anwarul-Hassan Gilani4,5*1Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan2Department of Pharmaceutical Chemistry, College of Pharmacy, Salman binAbdulazizUniversity, POBox 173,Al-Kharj 11942, SaudiArabia3University College of Agriculture, University of Sargodha, Sargodha 40100, Pakistan4Natural Products Research Unit, Department of Biological and Biomedical Sciences, Aga Khan University Medical College, Karachi74800, Pakistan5Department of Pharmacy, College of Health Sciences, Mekelle University, PO Box 1871, Mekelle, Ethiopia

Alhagi, a plant genus from family Fabaceae, is widely distributed in many countries of Asia, Australia and Europe.Commonly known as camel thorn, Alhagi has many species famous for feed and folk medicinal uses. Differentspecies of Alhagi such as Alhagi pseudalhagi, A. graecorum, A. sparsifolia, A. kirgisorum, A. maurorum,A. camelorum and A. persarum have been explored for their antioxidant potential and nutritive value along withvarious medicinal properties. A wide array of pharmacologically active secondary metabolites such as flavonoids,alkaloids (alhacidin and alhacin), steroids, pseudalhagin A, phospholipids and polysaccharides have been reportedfrom different parts ofAlhagi species. A broad range of biological activities such as antioxidant, cardiovascular, anti-ulcer, hepatoprotective, antispasmodic, antidiarrheal, antinociceptive, antipyretic, anti-inflammatory, anti-rheumatic,antibacterial and antifungal have been ascribed to different parts ofAlhagi. In addition,Alhagi plants are also valuedas a rich source of digestible protein and important minerals. This review focuses on the medicinal applications anddetailed profile of high-value bioactive phytochemicals alongwith pharmacological attributes and therapeutic potentialof these multi-purpose plants. Copyright © 2014 John Wiley & Sons, Ltd.

Keywords: Alhagi; medicinal uses; phytochemistry; bioactives; natural pharmaceuticals; nutraceuticals.

INTRODUCTION

Currently, much scientific research is being focused onunderstanding the basis for the continuing progress ofplant-based bioactive chemicals offering various healthbenefits (Lattanzio et al., 2009; Banerjee et al., 2011;Russell and Duthie, 2011). Plants are not only valuedas an important source for human food and animal feed,they are also esteemed as natural remedies to cure manyhealth disorders. Traditionally, plants have a longhistory of folk medicinal uses that can be supported be-cause they contain a wide array of bioactives commonlyclassed as secondary metabolites such as phenolicspossessing multiple medicinal properties and healthbenefits (Gilani, 1998; Anwar et al., 2007; Lattanzioet al., 2009; Banerjee et al., 2011; Russell and Duthie,2011; Zaini et al., 2011; Ghanbari et al., 2012).Nowadays, there is revival of interest in the use of

plants as a source of food and medicine. According toa recent WHO report (2011), about 80% of the worldpopulation, especially in the developing world, relieson traditional medicines for curing different health dis-orders and diseases. The use of phytomedicines for

ondence to: Anwarul-Hassan Gilani, Department of Biologicaldical Sciences, Aga Khan University Medical College, Karachi-istan; Muhammad Ajaz Hussain, Department of Chemistry,of Sargodha, Sargodha 40100, [email protected] (Anwarul-Hassan Gilani); [email protected] Ajaz Hussain)

© 2014 John Wiley & Sons, Ltd.

health benefits is evident in almost all systems of medi-cines (Chinese, Greco-Arab, Ayurveda etc.). A largenumber of reports can be easily deciphered fromliterature, which presents medicinal and pharmaco-logical attributes of traditional phytomedicine (WHO,2002; Hasani-Ranjbar et al., 2008; Gilani and Atta-ur-Rahman, 2005).

The genus Alhagi (Camel thorn) is a famous herbbecause of its multi-purpose uses. Almost all species ofAlhagi are known for potential medicinal applications(Zou et al., 2012; Laghari et al., 2012a, 2012b;Gholamhoseinian and Razmi, 2012). The folk medicinaluses of Alhagi date back to centuries. Traditionally,Alhagi plants are used to treat numerous diseases suchas gastroenteritis (Varshney and Singh, 2008), ulcers(Amani et al., 2006), fever (Khan, 2009; Marwat et al.,2008), inflammations and angina pain (Seredin andSokolov, 1978), headache and toothache (Zou et al.,2012), diarrhea (Uphof, 1959; Atta and Mouneir,2004), rheumatoid arthritis (Boulos, 1983), liver disorders(Shaker et al., 2010; Al-Douri and Al-Essa, 2010), kidneystone and urinary tract infections (Badshah and Hussain,2011), hypertension (Kouchmeshky et al., 2012) andcancer (Zou et al., 2012).

A number of biological and pharmaceutical attributessuch as antibacterial (Neamah, 2012), cardiac depressant(Khushbaktova et al., 1992), anti-ulcer (Amani et al.,2006), spasmolytic (Marashdah andAl-Hazimi, 2010), an-tioxidant (Muhammad et al., 2011), cholegogue, diuretic,anti-lithiatic and antifungal (Laghari et al., 2012b) have

Received 20 November 2013Revised 12 July 2014

Accepted 21 August 2014

G. MUHAMMAD ET AL.

been ascribed to different parts of Alhagi plants. As acosmo-nutraceutical ingredient, the uses of Alhagi in cos-metics have also been reported recently for treatment ofhyperpigmentation skin disorders (Gholamhoseinianand Razmi, 2012). Alhagi is of particular interest as aningredient of functional foods because of the presenceof high amounts of digestible protein along with a vari-ety of other bioactives and essential minerals (Towhidiand Zhandi, 2007). Alhagi as a fodder crop is widelyfound growing in saline dry lands of Central Asia,Northwestern China and North Africa, wherein itprovided the most common feedstuff for ruminants(Piri et al., 2012; Ghosal et al., 1974; Liu and Adilla,1991; Towhidi, 2007).So far, no comprehensive review is reported on de-

tailed profile of phytochemicals and biological activitiesas well as folk medicinal uses of Alhagi. Its broad spec-trum of biological attributes supported by the presenceof a multitude of bioactive compounds, wide uses as folkmedicine and a plethora of proven pharmacologicalapplications motivated us to write the present reviewthat comprehensively focuses on the description ofmedicinal uses, bioactive phytochemicals and pharma-cological attributes of this high valued genus, so as toexplore the potential utilization of its different speciesas ingredients of pharmaceutics and nutraceuticals.

DISTRIBUTION, TAXONOMYAND GROWTH

The genus Alhagi (commonly known as Camel thorn,Caspian manna or Persian manna) belongs to familyFabaceae and has been placed under sub-familyPapilionaceae (Ali, 1977). Alhagi genus comprises dif-ferent species such as A. pseudalhagi M. Mieb. Desv.,A. graecorum Boiss., A. sparsifolia Shap., A. kirgisorumSchrenk, A. maurorum Medik., A. camelorum Fisch., A.persarum Boiss., A. canescens Regel, A. alhagi Huth.and A. nepalensis D. Don & Shap. (Khan, 2009;Badshah and Hussain, 2011; Burasheva et al., 1975;Hassanein and Mazen, 2001; Islambekov et al., 1982;Kurban et al., 1999; Mikaili et al., 2012; Xue et al., 2012).Alhagi shrubs are widely distributed in Central Asia,

North America, Europe, Mediterranean, Orient, NorthAfrica, South Africa and Northwestern China (Ghosalet al., 1974; Liu and Adilla, 1991; Ali, 1977; Smailovet al., 1990). Alhagi plants commonly occur in dry landsassociated with low rainfall and in areas with highsalinity and alkalinity (Kawase and Kanno, 1983). Sensi-tivity of Fabaceae plants (e.g., Alhagi plants) to salinityis remarkable (Bernstein and Pearson, 1956). Espe-cially, tolerance of A. pseudalhagi (a halophytic plant)to salinity is considerable (Kurban et al., 1999; Kurbanet al., 1998).Alhagi plants are about 1–2m high noxious green

shrubs with simple leaves, thorny branches anddeepest/extensive root system of about 15m long. Theseplants grow rapidly by clonal vegetation reproductionfrom vigorous rhizomes. Leaves are alternate, sparse,thick, leathery and 7–20mm long. Flowers are short-stalked pea-like, 2–6 in number, 8–9mm long and withmagenta to pink petals, and appear alternately along eachthorn branchlet axis. Pods are reddish brown, 1–3 cm longand with 5–8 greenish brown seeds (Ali, 1977).

Copyright © 2014 John Wiley & Sons, Ltd.

MEDICINAL APPLICATIONS

Various parts of plants like roots, bark, leaves andflowers are used commonly to treat pain, respiratorydisorders, wounds, pyrexia, stomach disorders andsexual diseases (Rahmatullah et al., 2010a, 2010b). Theestablished folk medicinal uses and biological benefitsas well as pharmaceutical properties of several plantscan be attributed to the presence of a wide array of bio-actives and secondary metabolites with multiple biolog-ical activities (Gilani and Atta-ur, 2005; Balick and Cox,1996). Among other plants, Alhagi genus is a rich sourceof a wide variety of medicinal compounds with provenpharmacological applications.

Almost all species of Alhagi have long been recog-nized in the Unani and Ayurvedic systems of medicines.The medicinal potential and pharmacological activitiesof different species of Alhagi are listed in Table 1. Al-most all parts of Alhagi plant are prescribed to treat sev-eral diseases in the native medicine system of severalcivilizations. Extracts of flowers, roots, stem and leaves,and oil and seeds of Alhagi plant are biologically activeand are used to treat several diseases (Varshney andSingh, 2008; Amani et al., 2006; Al-Douri and Al-Essa,2010; Badshah and Hussain, 2011; Kouchmeshky et al.,2012; Marashdah and Farraj, 2010; Zain et al., 2012;Amiri et al., 2010). Folk medicinal uses of Alhagi speciesin Unani and Ayurvedic systems of medicines are wellrecognized over the centuries. They are famous andwidely used to treat ulcers of gastrointestinal tracts andhemorrhoids in South Asian countries (Khaiitbaevet al., 1993). Several other gut diseases are being treatedwith extracts of Alhagi (Varshney and Singh, 2008).

A. pseudalhagi is one of the old and common reme-dies in folk medicine that is considered effective in gas-tric and duodenal ulcers of stomach and hemorrhoids(Khaiitbaev et al., 1993). Recent reports have shownthat among genus Alhagi, A. pseudalhagi is one of themost widely used medicinal plants for the treatment ofvarious diseases in different rural and remote areas ofdistrict Etah in UP, India (Varshney and Singh, 2008).

Decoctions of A. pseudalhagi have been used in thetraditional medicine systems as cholegogue and astrin-gent for treatment of colitis, gastritis and stomach ulcers(Khaiitbaev et al., 1993), as well as in hemorrhoids andwound dressing (Altmysheva, 1976), dysentery, naso-pharynx diseases, angina and extremity eczema (Seredinand Sokolov, 1978). Decoction of leaves ofA. pseudalhagiis used as an antipyretic agent, while that prepared fromaerial parts is used to treat intestinal infections(Rakhimov and Dzhumamuratova, 1993). Tincture pre-pared from the runners of A. pseudalhagi shows diuretic,litholytic, hypoazotemic, antioxidant and cholegogueactivities (Sidibi, 2003).

A. maurorum is another species used in folk medicinesince long as a laxative, diaphoretic, expectorant anddiuretic (Uphof, 1959; Marashdah and Farraj, 2010).Its flowers are used to treat piles, migraine and warts.Oil from the leaves is used in the treatment of rheuma-tism (Brown, 1995). Locally, the aqueous extracts of itsseeds are used to relax the ureter and remove kidneystones (Marashdah and Farraj, 2010). Powdered rootsof A. maurorum are also used to remove kidney stonespartly because of its diuretic property (Badshah andHussain, 2011).

Phytother. Res. (2014)

Table 1. Common medicinal uses of different species of genus Alhagi

Species Medicinal uses References

A. pseudalhagi Antibacterial, antiurolithic, anti-ulcer, cholegogue and astringentfor cholitis, gastritis, dysentery, nasopharynx diseases,antianginal, antipyretic, antioxidant, diuretic, hypoazotemic anduseful in hemorrhoids andeczema

Khushbaktova et al., 1992; Muhammad et al., 2011;Khaiitbaev et al., 1993; Altmysheva, 1976; Cirouset al., 2010

A. maurorum Blood purifier, expectorant, litholytic, cardiac depressant,spasmolytic, ureter relaxant, antibacterial, anti-inflammatory,analgesic, anti-ulcer, antioxidant, hepatoprotective,antinociceptive, antidiarrheal, laxative, diaphoretic, anti-migraineand anti-rheumatic

Amani et al., 2006; Marwat et al., 2008; Atta andMouneir, 2004; Shaker et al., 2010; Badshah andHussain, 2011; Neamah, 2012; Marashdah and Farraj,2010 Brown, 1995; Bonjar, 2004; Alqasoumi et al.,2008; Atta and Abo, 2004; Shafaeifar et al., 2012

A. sparsifolia Cholegogue, diuretic, sudorifics, useful in dysentery, stomachdisorders, cold, headache, toothache and cancer

Malik et al., 1997; Zou et al., 2012

A. graecorum Laxative, vermifuge, bilharzias anduseful in rheumatism, liver disorders,urinary tract infection, gastrointestinal discomfort and hemorrhoids

Amani et al., 2006; Al-Douri and Al-Essa, 2010;Zain et al., 2012; Harvey, 1999

A. camelorum Antifungal, antipyretic, anthelmintic, diuretic, laxative,expectorant, diaphoretic, useful in piles, hyperpigmentationdisorders, impaction in cattle, indigestion and dysentery,abdominal troubles and hyperpigmentation disorders

Laghari et al., 2012b; Gholamhoseinian andRazmi, 2012; Khan, 2009; Marwat et al., 2008;Mishra, 2009; Vardhana, 2008

A. persarum Diuretic, antidiarrheal, antiurolithic, antihypertensive and usefulin urinary tract infections

Kouchmeshky et al., 2012; Mikaili et al., 2012; Amiriet al., 2010

ALHAGI: A PLANT GENUS RICH IN BIOACTIVES FOR PHARMACEUTICALS

The exudation of leaves and branches of A. maurorumis used once a day to purify blood and as expectorant(Badshah andHussain, 2011). Dry plants ofA. graecorumare in use as laxative and vermifuge for bilharzias andrheumatic pains (Boulos, 1983). A. graecorum is usedfor rheumatic pains, liver disorders, urinary tract infectionand various types of gastrointestinal discomforts. Almostall parts of the plant are also in use to treat hemorrhoidsas reported in several studies (Amani et al., 2006;Al-Douri and Al-Essa, 2010; Zain et al., 2012; Harvey,1999). Aerial parts of A. persarum with antidiarrhealand diuretic effects are used as a folk medicine. It has alsostone-releasing effects from kidney as proved by a recentstudy (Amiri et al., 2010). Infusion of leaves of A.persarum is used to control renal stones and urinary tractinfections (Mikaili et al., 2012). Hemorrhoids and bloodydiarrhea can be treated by decoction of Alhagi roots(Rakhimov and Dzhumamuratova, 1993).Decoctions of A. sparsifolia are used as cholegogue,

diuretics and sudorifics in the treatment of dysenteryand diseases of stomach (Malik et al., 1997). It is also usedto relieve physical stress and to treat cold, headache,toothache and cancer (Zou et al., 2012). Decoctions ofA. camelorum are used in impaction in cattle’s indigestionand dysentery, abdominal troubles, de-worming and fever(Khan, 2009; Marwat et al., 2008; Mishra, 2009). Flowersof A. camelorum are used for the treatment of piles. Theplant is considered as laxative, diuretic and expectorant,and its infusion is diaphoretic (Vardhana, 2008). Afore-mentioned literature reports support the uses of thismulti-purpose genus as a source of bioactives for the devel-opment of phytomedicines to improve health of mankind.

PHYTOCHEMISTRY

Nature has blessed the world with rich flora of medici-nally and/or economically important plants. Many ofsuch plants have been in use as ingredients of food andfolk medicine since the history of mankind because they

Copyright © 2014 John Wiley & Sons, Ltd.

contain a variety of high-value nutrients, therapeuticagents and pharmacologically active phytochemicals(Joshi et al., 2011; Siahsar et al., 2011; Kamba andHassan, 2011). Alhagi is rich in biologically active phyto-chemicals such as phenolics, flavonoids, alkaloids andpolysaccharides along with different essential minerals,proteins and lipids. Fig. 1 summarizes some importantphytochemicals identified in different species of Alhagi.Among the isolatedphytochemicals, kaempferol, rhamnetin,ombuine, isorhamnetin, tamarixetin, kaempferol-3-O-β-D-(6-O-p-coumaroyl)-glucoside, isoquercitrin, D-3-O-methylinositol, 1-O-β-methyl-glucoside, isoswertianolin,isorhamnetin-3-O-β-D-rutinoside, stigmasterol and tyra-mine have been identified from polar extracts of aerialparts of A. pseudalhagi (Xiuwei et al., 1996).

A number of secondary metabolites have been isolatedfrom aerial parts of A. pseudalhagi and identified asisorhamnetin-3-O-β-D-glucopyranoside, isorhamnetin-3-O-β-D-rutinoside, quercetin, rutin, ononin, 1-hexacosanol,1-heptacosanol, octacosanol, 1-triacontanol, triacontanoicacidmethyl ester, 5-hydroxymaltol, saccharose, alhagidin,β-D-glucopyranoside, delphinidin-3-monoglucoside, cyanidin-3,5-diglucoside and delphinidin-3,5-diglucoside (Novruzovet al., 2009; Guijie et al., 2010; Sultan et al., 2011). Typically,the species A. pseudalhagi has great medicinal andnutraceutical potential due to possessing a variety ofbiologically active catechins. Epigeal parts of A.pseudalhagi contain catechins and proanthocyanidins,that is, (+)-catechin, (±)-gallocatechin, (�)-epigallocate-chin and leucodelphinidin (Islambekov et al., 1982).

Alhagi plants have been reported to be a rich source ofnovel and structurally diverse and biologically active com-pounds. Two such diverse macromolecular phytochemi-cals proanthocyanidin glucosides (158.0 g/6.0 kg), that is,alhacin [12] and alhacidin [13], and isoflavonolignin, thatis, pseudalhagin A [14], have been isolated from aerialparts of A. pseudalhagi (Alimova et al., 2010), and theirstructures are shown in Fig. 2. Recently, a new flavonolglycoside, alhaoside (3′,4′-di-O-methylquercetin-3-O-α-L-rhamnopyranosyl-(1→ 6)-β-D-glucopyranosyl-7-O-α-L-rhamnopyranosyl-(1→6)-β-D-galactopyranoside), has been

Phytother. Res. (2014)

Figure 1. Structure of selected phytochemicals from Alhagi:β-sitosterol [1], stigmasterol [2], rutin [3], isorhamnetin-3-rutinoside[4], gallocatechin [5], epigallocatechin [6], isorhamnetin [7], tamarixetin[8], proanthocyanidins [9], tyramine [10] and octacosanol [11].

Figure 2. Structures of selected proanthocyanidins from aerial partsof A. pseudalhagi: alhacin [12], alhacidin [13] and isoflavonolignin,that is, pseudalhagin A [14].

Figure 3. Structure of 5,6,7,8,2′,3′,5′,6′-octamethoxyflavan-3-en-4′-ol [15] isolated from roots of A. maurorum.

G. MUHAMMAD ET AL.

isolated from the aerial parts of A. pseudalhagi (Alimovaet al., 2013). Pseudalhagin A has shown remarkablequinine reductase-inducing activity in hepa lclc 7 cells(Li et al., 2010). Alhagi graecorum is also a rich sourceof powerful antioxidant flavonoid glycosides and severalalkaloids. Aerial parts of A. graecorum containtamarixetin 3-O-dirhamnoside and isorhamnetin 3-O-glucosyl neohesperidoside (El-Sayed et al., 1993).

Copyright © 2014 John Wiley & Sons, Ltd.

Epigeal parts ofA. kirgisorum have shown the presenceof polyphenols isorhamnetin-3-O-β-D-glucopyranoside,isorhamnetin-3-O-α-L-galactopyranoside, isorhamnetin-3-O-(O-β-D-glucofurnosyl-(1→ 2))-β-D-glucopyranosideand isorhamnetin-3-[6-β-D-glucopyranosyl-β-D-glucofuranoside]-7-α-L-rhamnofuranoside (Burasheva et al., 1975; Burashevaet al., 1977).

Alhagi maurorum is another species famous for itspotent urease inhibitory activity. Being a rich source ofdifferent minerals, oils and fats, it is of high food value.In a recent work, a urease inhibitory flavanenol (Fig. 3)named as 5,6,7,8,2′,3′,5′,6′-octamethoxyflavan-3-en-4′-ol [15] was isolated from ethyl acetate fraction of theroots of A. maurorum (Laghari et al., 2010).

Ahmad et al. (2009) isolated numerous secondary me-tabolites from themethanolic extract (400 g) of aerial partsofA.maurorum, which included β-sitoserol (22mg), trans-cinnamic acid (20mg), p-coumaric acid (26mg), 4-hydroxybenzoic acid (18mg), 3′-O-methylorobol (17mg),methyl β-D-glucopyranoside (18mg), β-sitosterol-3-O-β-D-glucopyranoside (29mg) and quercetin-3-O-β-D-glucopyranoside (16mg) (Ahmad et al., 2009). Lateron, Ahmad et al. (2010) also reported the occurrenceof antioxidant compounds namely isorhamnetin-3-O-[-α-L-rhamnopyranosyl-(1→3)]-β-D-glucopyranoside, 3′-O-methylorobol and quercetin 3-O-β-D-glucopyranoside fromA. maurorum (Ahmad et al., 2010).

Alhagi persarum has also appeared a highly valuablespecies because of its antioxidant potential being rich ina variety of flavonoids distributed in its aerial parts. Theseinclude quercetin, isorhamnetin, quercetin-3-O-α-L-rhamnopyranoside, quercetin-3-O-α-L-arabofuranoside,isorhamnetin-3-O-β-D-glucopyranoside, isorhamnetin-3-O-α-L-arabopyranoside and 5,3′,4′-trimethoxyflavone-3-O-β-D-galactopyranoside-(2→1)-α-L-rhamnopyranoside-7-O-α-L-rhamnopyranoside (Eskalieva and Burasheva,2002).

Polysaccharides have also been found in seeds and epi-geal parts ofA. persarum. Product of hydrolysis has shownthe presence of glucose, rhamnose, galactose, mannose,xylose and arabinose (Rakhimov and Dzhumamuratova,1993). Several known β-phenylethylamine and importanttetrahydroisoquinoline alkaloids including β-phenethylamine,3,4-dihydroxy-β-phenethyltrimethylammonium hydroxide,hordenine,N-methyl-β-phenethylamine,N-methylmescalineand salsolidine have been found in the stem of A.pseudalhagi. In the same study, it was found that the rootscontained essentially the same compounds as the stembut in different quantities. The phylogenetic significanceof the occurrence of the eight alkaloids in a single plantspecies was appraised in the light of parallelism and com-plexities involved (Ghosal and Srivastava, 1973). The bio-logical activities of plant extracts were attributed to theiralkaloidal constituents (Ghosal and Srivastava, 1973).

Somenovel alkaloids, alhagifolineA [16], pyrrolezanthine[17] and pyrrolezanthine-6-methyl ether [18], have been

Phytother. Res. (2014)

Figure 4. Structures of selected alkaloids from A. sparsifolia: alhagifoline A [16], pyrrolezanthine [17] and pyrrolezanthine-6-methyl ether [18].

Figure 5. Structures of a selected novel oleanane type triterpeneglycoside [19] isolated from roots of A. maurorum.

ALHAGI: A PLANT GENUS RICH IN BIOACTIVES FOR PHARMACEUTICALS

found in the aerial parts ofA. sparsifolia (Fig. 4). Structur-ally, diverse alkaloids were characterized by 2D NMRand high resolution mass spectroscopic techniques (Zouet al., 2012). Like A. pseudalhagi, A. sparsifolia alsoshowed the occurrence of catechins and anthocyanidinsin its epigeal parts (Malik et al., 1997).Seeds of A. maurorum contained 22–25% vegetable

oil comprising saturated and unsaturated fatty acids(Weber et al., 2007). However, in a recent study, essen-tial oils were isolated and identified in the leaves andstems of A. maurorum. Essential oils (volatile fractions)contained terpenoids 26.8% and 18.7%; ketones 4.4%and 5.2%; acid derivatives 1.5% and 1.8%; and hydro-carbons 19.3% and 50.6% in the leaves and stems, re-spectively. A higher concentration of drimenol (23.2%)followed by 9-octylheptadecane (9.3%) along with2-nonadecanone (4.4%), 4-hexyl-2,5-dihydro-2,5-dioxo-3-furanacetic acid (5.2%) and pentacosane (4.3%) hasbeen reported. Stem of A. maurorum is rich in essentialoils (Samejo et al., 2012) having neophytadiene (39.3%)as the major component along with many othersincluding trans-β-ionone (5.4%), 6,10,14-trimethyl-2-pentadecanone (5.2%), actinidiolide (4.9%) andnonacosane (4.3%). Additionally, it has been noted thatA. maurorum leaves and stems contained tetracosane,drimenol, eicosane, octadecane, squalene and docosaneas the volatile components of essential oil (Samejo et al.,2012). In another study, Amani et al. 2006 isolated six fla-vonoid glycosides from ethanol extract of A. maurorum.Structures of the chemical compounds in the extract wereconfirmed as kaempferol, chrysoeriol, isorhamnetin,chrysoeriol-7-O-xylosoid, kaempferol-3-galactorhamnosideand isorhamnetin 3-O-β-D-apio-furanosyl (1–2) β-D-galactopyranoside by using different spectroscopic tech-niques (Amani et al., 2006).Antiproliferative/anticancer activity of plant material

depends on the presence of different secondary metabo-lites from which terpenoidal glycosides are an importantclass (Dinda et al., 2010). Besides lipidic components(Islambekov et al., 1982), A. maurorum is also a richsource of a variety of terpenenoids, especially triterpeneglycosides. Recently, Hamid et al. 2012 reported the isola-tion of three novel oleanane type triterpene glycosides[19] (Fig. 5), along with four known terpenoids from theroots of A. maurorum (Hamid et al., 2012). A recent arti-cle has shown the presence of bioactive terpenoid lupeol(0.11 g), as the principal component in the root bark(100 g) of A. maurorum (Laghari et al., 2011). Because ofthe presence of awide array of terpene glycosides, extractsof A. maurorum could be explored as a potential candi-date to isolate novel antiproliferative agents.Qualitative analysis of lipids in A. pseudalhagi and A.

persarum (both from Tashkent, Uzbekistan) has shown thatA. pseudalhagi has 1.1% while A. persarum has 1.5% ofphospholipids present in seeds as identified by the Thin layerchromatography (TLC)method, by qualitative reactions andwith the help of markers (Isamukhamedov et al., 1993).

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Nevertheless, six phospholipids were identified in A.persarum, while seven in A. pseudalhagi. Total degreeof unsaturation in the lipids of A. persarum was foundto be higher than that in A. pseudalhagi.

Composition of monosaccharides in polysaccharides ofAlhagi honey has shown the presence of glucose, galac-tose, mannose, rhamnose, arabinose, glucuronic acidand galacturonic acid as investigated by high performancecapillary electrophoresis and UV/Vis detection after acidhydrolysis of polysaccharides (Li-jun et al., 2012).

ISOLATION STRATEGIES OF BIOACTIVECOMPONENTS FROM ALHAGI PLANTS

Isolation of flavonoids

Different procedures have been devised for the isolationof flavonoids. For example, air-dried aerial parts of A.persarum were extracted with ethyl acetate and separatedover polyamide column. By using this strategy, a widevariety of flavonoids such as quercetin, isorhamnetin,quercetin-3-O-α-L-rhamnopyranoside, quercetin-3-O-α-L-arabofuranoside, isorhamnetin-3-O-β-D-glucopyranoside,isorhamnetin-3-O-α-L-arabopyranoside and 5,3′,4′-trimethoxyflavone-3-O-β-D-galactopyranoside-(2→ 1)-α-L-rhamnopyranoside-7-O-α-L-rhamnopyranoside wereisolated from the extracts and structurally characterizedin detail (Eskalieva and Burasheva, 2002). For totalflavonol isolation from A. pseudalhagi, powderedplant material was boiled on a water bath with 48%ethanol. The extract was diluted with 48% ethanol againand then boiled with 10% HCl solution for 3 h tohydrolyze the flavonoids into possible flavonol aglycones.The mixture after cooling was shaken with ethyl acetate,and organic layers were separated. Ethyl acetate was thenevaporated to bear flavonols containing extract. Theresidue was added to 95% ethanol and absorbance readfor calculating flavonol aglycones content (Khaiitbaevet al., 1993).

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G. MUHAMMAD ET AL.

In some recent studies, the most common extractionscheme has been opted for the extraction of flavonoidsfrom the aerial parts of A. pseudalhagi. Air-dried aerialparts were extracted with aqueous-ethanol (30:70). Theconcentrated extract was diluted with water and workedup with n-butyl alcohol, petroleum ether and ethylacetate (EtOAc). The EtOAc and butanol (n-BuOH)extracts were separated using the column chromatogra-phy and then identified by advanced chromatographicand spectroscopic techniques (Novruzov et al., 2009;Sultan et al., 2011; Alimova et al., 2010). The given stud-ies reported the isolation of several known and newflavonoids, for example, flavonols, anthocyanins andproanthocyanidin glucosides.In another study, powdered plant material of A.

maurorum was soaked in methanol, and then methanolextract was concentrated. It was then divided into chlo-roform, n-hexane, n-butanol, ethyl acetate and aqueousfractions. The chloroform extract of the aerial parts ofA. maurorum has shown the presence of several second-ary metabolites along with different flavonoids (Ahmadet al., 2009).

Isolation of alkaloids

The aerial parts of A. sparsifolia were extracted withethanol (50%), concentrated and fractionated into pe-troleum ether, CH2Cl2 and n-BuOH. The n-BuOH ex-tract was dissolved in water. Ethanol and n-BuOHfractions were then separated by the column chromatog-raphy over silica gel where new alkaloids were isolatedand identified as alhagifoline A, pyrrolezanthine andpyrrolezanthine-6-methyl ether (Zou et al., 2012). Insome other studies (Sultan et al., 2011; El-Sayed et al.,1993; Ghosal and Srivastava, 1973), the similar extrac-tion method for the quantification of alkaloids from dif-ferent species of Alhagi has been used.

Isolation of proanthocyanidins

Alimova et al. (2010) recently reported a solvent extrac-tion method for the isolation of proanthocyanidins fromthe aerial and underground parts of A. pseudalhagi. Theplant material was ground and extracted with 80% eth-anol. The ethanol was distilled off, and the remainingthick extract was diluted with water; subsequently,partitioning of the extract was carried out into ether,ethyl acetate and n-butyl alcohol. The n-BuOH extractwas eluted through a column packed with microcrystal-line cellulose with solvents of different polarity. Struc-turally diverse and novel proanthocyanidin glucosideswere isolated, purified and identified, which includealhacin and alhacidin.

Isolation of polysaccharides and lipophilic and pectinsubstances

In a study, seeds and epigeal parts of A. persarum weresubjected to polar, non-polar and alkaline extractions(Rakhimov and Dzhumamuratova, 1993). Lipophilic sub-stances were separated by using n-hexane and chloro-form, and then the extract was fractioned into watersoluble polysaccharides with water, pectic substances with

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a mixture of oxalic acid and ammonium acetate, andhemicelluloses with alkali. After precipitation with etha-nol, these three fractions were hydrolyzedwith 2N sulfuricacid, and monosaccharide composition was determinedby paper chromatography and gas liquid chromatography.

PHARMACOLOGICAL ATTRIBUTES

A number of pharmacological and biological activitieshave been ascribed to different parts of Alhagi plants.The scientific basis for such diverse biological function-alities of Alhagi plants can be attributed to the presenceof a wide array of bioactives and high-value components(Table 2).

Cardiovascular

Cardiovascular diseases are the major cause of mor-bidity and mortality while growing with rapid pace(American Heart Association, 2004; Mackay andMensah, 2004), and the research on natural productshas contributed immensely in this field (Gilani, 1998).Interestingly, the plant species of Alhagi have significantpotential to treat heart diseases (Rahmatullah et al.,2010a, 2010b). Plant-derived flavonoids are reported toreduce the incidence of ischemic heart disease (Yaoet al., 2004). It is evident from the literature that thegenus Alhagi is a very famous plant introduced sincelong in folk medicine to treat cardiovascular diseases.The pronounced effects noted for Alhagi are its myocar-dial depression. For instance, A. pseudalhagi, due toproanthocyanidin secondary metabolites, is also a plantof choice to treat patients with myocardial infarction(Khushbaktova et al., 1992).

Powdered extract (2% aqueous) of A. maurorumroots acted as a myocardial depressant in rats(Khushbaktova et al., 1992). Proanthocyanidin isolatedfrom A. pseudalhagi injected (5–10mg/kg) intrave-nously to rats and rabbits did not affect general hemody-namics and cardiac contractility of the organisms. Butwhen given to animals with myocardial infarction, it re-duced creatinine phosphate level and lipid peroxidationboth in serum and myocardium (Khushbaktova et al.,1992). In Unani medicine, dried gum has been used asan antihypertensive and diuretic agent. Interestingly,the antihypertensive and diuretic potential of A.persarum has been scientifically proved by a recentstudy (Kouchmeshky et al., 2012).

Antibacterial and antifungal. Although antibiotics areused commonly to control bacterial and fungal infec-tions, there are safety concerns due to their side effectsassociated with their long-term uses, and they areknown to suppress natural immunity of the body(Ahmad et al., 1998). Another growing concern is thatmicrobes usually develop resistance against syntheticantibiotics; hence, there is a need to explore new bioac-tive components from plants (Essawi and Srour, 2000)or use plant in their natural form with the hope to pro-vide safer and broader coverage in different microbialinfections.

Escherichia coli is a facultative bacterium, which re-sides in the intestine of animals and human beings

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Table 2. Bioactive phytochemicals identified in Alhagi plants

Species Plant parts Components separated References

A. pseudalhagi Alhagi honey Polysaccharides Li-jun et al., 2012Aerial parts Alkaloids, steroids and flavonoids Sultan et al., 2011Aerial parts Flavonoids Novruzov et al., 2009Epigeal parts Catechins and proanthocyanidins Islambekov et al., 1982Aerial parts and roots Alhacin and alhacidin Alimova et al., 2010Aerial parts Fourteen flavonoids Xiuwei et al., 1996Aerial parts and roots Eight alkaloids Ghosal and Srivastava, 1973Aerial parts Pseudalhagin A Li et al., 2010Aerial parts Twelve different compounds Guijie et al., 2010

A. graecorum Whole plant Two new flavonoids El-Sayed et al., 1993A. sparsifolia Aerial parts Three alkaloids Zou et al., 2012

Epigeal parts Catechins and proanthocyanidins Malik et al., 1997Aerial parts Seven new flavonoids Eskalieva and Burasheva, 2002

A. persarum Seeds and epigeal parts Polysaccharide Rakhimov and Dzhumamuratova, 1993Epigeal parts Three polyphenols Burasheva et al., 1977Epigeal parts Flavonoid Burasheva et al., 1975

A. kirgisorum Aerial parts Eight new compounds Ahmad et al., 2009A. maurorum Roots New flavanenol Laghari et al., 2012b

Root bark Lupeol Laghari et al., 2011Whole plant Cu, Al, Mn and Zn Hashem and Alfarhan, 1993Seeds Oils, saturated and unsaturated fatty acids Weber et al., 2007

ALHAGI: A PLANT GENUS RICH IN BIOACTIVES FOR PHARMACEUTICALS

(Bonten et al., 1990; Conway and Macfarlane, 1995).But disease-causing strains of this bacterium can causeurinary infections and other related disorders (Falagasand Gorbach, 1995). It has been recently reported insome studies that methanolic extract of A. maurorumstem showed remarkable anti-E. coli activity at20mg/L as studied using the agar well diffusion assay.In this study, minimum inhibitory concentration wasfound to be 3.75mg/mL, and zone of inhibition was9mm for E. coli (PTCC No. 1330) strain (Neamah,2012; Bonjar, 2004).Fungi produce toxic chemicals called mycotoxins,

which destroy food. The fungus-contaminated food cancause cancer, liver disorders, mutations and genotoxicity,and decrease the immunity of body (Marin et al., 1999).A number of studies have been reported wherein plantmaterials have been applied to avoid and treat fungaldiseases (Khan et al., 2003; Okigbo and Ogbonnaya,2006; Shariff et al., 2006; Ergene et al., 2006). Recently,Laghari et al. (2012b) have reported the isolation of anew ursine-type triterpine namely norursenol frommethanolic extract of roots of A. camelorum that showedgreat antifungal activity against Aspergillus niger andSaccharomyces cerevisiae (Laghari et al., 2012b).Norursenol (5mg) was dissolved in 20mL methanoland water and applied againstA. niger and S. cerevisiaeusing well diffusion plate method and streak-platemethod. Methanolic solution (0.6mL) inhibited thegrowth of both fungal species, but aqueous solution(0.2, 0.3 and 0.6mL) showed inhibition only againstA. niger (Laghari et al., 2012b).

Anti-ulcer

The gastric ulcer is caused bymany factors like increase inacid and pepsin secretions, damaged bicarbonate neutral-ization, reduced resistance of mucus and injuries on themucus layer (Kent-Lloyd and Debas, 1994). Ulcer is

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treated by controlling acid or pepsin secretion, bile, orby increasing defense of mucus. In patients with ulcers,gastrointestinal mucus is also infected by Helicobacterpylori (Tepperman and Jacobson, 1994), and eradicationof H. pylori requires co-administration of multiple drugsincluding antibiotics (Blaser, 1998; Megraud, 1997). Inter-estingly, Alhagi is one of the several plants, whichpossesses anti-ulcer activity and has long history as anti-ulcer folk medicine. Ethanolic extracts of aerial parts ofA. maurorum have shown to possess strong anti-ulcerogenic activity in albino mice that could be attrib-uted to the presence of flavonoid glycosides. Totalethanolic extract (300 and 400mg/kg) and two isolatedflavonoid glycosides, chrysoeriol-7-O-xyloside andkaempferol-3-galactorhamnoside (100mg/kg each), were66.31%, 69.57%, 75.49% and 77.93% effective againstulcer, respectively. The anti-ulcer activity of the saidextracts was significantly higher than ranitidine (anti-ulcer drug) with curative ratio of 2.43% only (Amaniet al., 2006). Another study also revealed that ethanolicextract of A. maurorum and ranitidine (100mg/kg each)showed great potential against ulcer in rat model inducedafter ingestion of aspirin (200mg/kg) twice a day for10days. This controlled study has shown that both A.maurorum and ranitidine protected the liver enzymes,oxidation status, fucosidase tumor marker and risk lipidratio (Shaker et al., 2010).

Antioxidant and hepatoprotective activities

Many disorders like AIDS, cancer, arthritis, central ner-vous system impairment, gastritis and hepatitis arecaused by free radicals (Lai and Kim, 2010; Hazraet al., 2008; Kalim et al., 2010) produced by oxidativestress. Currently, the use of natural antioxidants as alter-native to synthetic antioxidants is contemplated to beadvantageous because of their positive effects on health

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G. MUHAMMAD ET AL.

(Kumpulainen and Salonen, 1999; Cook and Samman,1996; Barlow, 1990).Alhagi plants are a rich source of natural antioxidants

especially flavonoids. In a recent study, antioxidantactivity of the aqueous extract of A. maurorum wasappraised by estimating the level of malondialdehydeusing thiobarbituric acid assay (Beuge and Aust, 1978).Total antioxidant activity of the extracts was examinedby comparing with acetylsalicylic acid as the positivecontrol. Both doses (250 and 500 μg) showed good anti-oxidant activity with inhibition of 82.88% and 86.70%,respectively. The extract (500μg) markedly reducedthe level of malondialdehyde from 1.03 ± 0.05 to0.49 ± 0.07, indicating a strong antioxidant potential(Neamah, 2012). Similarly, extracts of A. pseudalhagiwere found to be a rich source of antioxidants, and theypossessed antimicrobial activity as well. Antioxidantactivity of the extracts from A. pseudalhagi was evalu-ated by measuring 2,2′-azino-bis-(3-ethylbenzothiazo-line-6-sulpohonic acid) radical cation scavenging, 2,2-diphenyl-1-picrylhydrazil (DPPH) scavenging, totalphenolic contents and total antioxidant activity (ferricthiocyanate method). Trolox equivalent antioxidantactivity was found in the range of 0.888–5.525mM ofdifferent fractions of aerial parts of A. pseudalhagi.Total phenolic and total flavonoid contents of differentfractions ranged from 10.657 to 21.759mg/L of gallicacid equivalents and 1.815–10.911mg/L of quercetinequivalents, respectively (Muhammad et al., 2011).Free phenolic acids of methanolic extract of the

flowers and leaves of A. maurorum were analyzed byHigh-Performance Liquid Chromatography- Diode-ArrayDetection (HPLC-DAD) and Liquid chromatography-Mass spectrometry (LC-MS)-atmospheric pressure chemi-cal ionization. Another study has shown that the extractsof leaves (20μg/mL) have greater free radical scavengingactivity (83.5%) than flowers extracts (72.3%) as deter-mined byDPPH free radical scavenging, while quercetinstandard has less antioxidant potential (63.41%) thanleaves and flowers (Laghari et al., 2012a).Liver is an important organ of body, where key

metabolic activities are carried out. Malfunction of livercauses several diseases, while modern medicine haslimited success to control hepatic abnormalities(Valiathan, 1998). Many diseases including liver disor-ders are caused by free radicals and reactive oxygenspecies (Burdon, 1994). Liver diseases are mostlytreated by herbal products (Gilani and Janbaz, 1995;Gilani et al., 2005; Thabrew and Hughes, 1996; Yaeeshet al., 2006; 2010). The market of related herbal formu-lation in Germany is estimated to be of 180 milliondollars. This market increased three times between1992 and 1996 (Breevort, 1996). Liver damage isfollowed by increase in serum glutamate oxaloacetatetransaminase (SGOT), serum glutamate pyruvate trans-aminase (SGPT), alkaline phosphatase (ALP) and totalbilirubin. Interestingly, Alhagi species have potential totreat liver diseases. For example, the ethanolic extractof aerial parts of A. maurorum when studied in CCl4-induced hepatotoxicity in rats at a dose of 500mg/kg, itdecreased SGOT, SGPT and total bilirubin by 10.1%,9.7% and 16.8%, respectively. There was no changein ALP. Reference standard silymarin (10mg/kg)decreased SGOT, SGPT, ALP and total bilirubinby 66.5%, 65.02%, 50.6% and 69.6%, respectively.These results showed hepatoprotective activity of

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ethanolic extract from aerial parts of A. maurorum(Alqasoumi et al., 2008).

Antinociceptive, anti-inflammatory and antipyretic ac-tivities. Several diseases can be diagnosed by sensationof pain. Herbal drugs are used worldwide to relieve pain(Almeida et al., 2001). Because of the side effects of syn-thetic analgesic drugs, there is still a need to developnew drugs from plants (Elisabetsky et al., 1995). Themethanolic extract of A. maurorum, when tested for itspossible antinociceptive effect in rats using acetic acid-induced writhing and tail-flick test, showed promisingresults with high potency. Both the extract (400mg/kg)and the standard drug dipyrone (50mg/kg) protectedacetic acid-induced writhing by 81.8% and 80.5%,respectively. While, in tail-flick test, methanolic extractof A. maurorum exhibited a prominent increase(5.00 ± 1.58) in latency as compared with standarddipyrone (5.10 ± 1.57) (Atta and Abo, 2004).

Non-steroidal anti-inflammatory drugs (NSAIDs) areused nowadays to treat inflammation and to relievepain, but these drugs have serious side effects causinggastric ulcer (Fries, 1991). The development of new se-lective COX-2 inhibitors is highly expensive and beyondthe reach of common man, yet not free from side effects(Emery et al., 1999). On the other hand, medicinalplants can be used to develop economical and safer rem-edies (Ikram, 1983; Gilani and Atta-ur, 2005). The aque-ous extract of green parts of A. maurorum exhibitedstrong anti-inflammatory and analgesic activities in rats.Formalin-induced rat paw edema was reduced by the A.maurorum extract. Percentage inhibition of three doses125, 250 and 500μg are 37.2%, 47.67% and 64.65%,respectively, which is less than the reference drugdiclofenac sodium (78.13%) after 4 h of formalin injec-tion (Neamah, 2012). Similarly, powdered extract (2%aqueous) from the roots of A. maurorum appeared asan effective antipyretic agent when tested using a rat’smodel. It decreased rectal temperature in dose-dependent and time-dependent manners. Temperaturedecrease was found to be 2.2, 2.4 and 3.2 °C for 250,500 and 1000mg/kg of body weight of rats after 30min(Marashdah and Farraj, 2010). Moreover, ananti-inflammatory tripterpenoid lupeol (Nguemfo et al.,2009; Nikiéma et al., 2001; Sudhahar et al., 2006) was iso-lated by Laghari et al. (2011) from n-hexane fraction ofmethanolic extract of root bark ofA. maurorum by elutingit with 20% EtOAc (Laghari et al., 2011). As there is clearevidence that the Alhagi plants possess a combination ofanalgesic, antipyretic and anti-inflammatory activities,potential thus exists for the development of some safernatural anti-inflammatory and pain killers from this species.

Skin hyperpigmentation disorder treatment

Melasma and post-inflammatory melanoderma like skindiseases are usually caused by enhanced production andaccumulation of melanins (Urabe et al., 1998; Cullen,1998). Hyperpigmentation can be the result of increasednumber of melanocytes or activity of melanogenic en-zymes (Ortonne and Norlund, 1998). Hyperpigmenta-tion can be treated by depigmenting agents that mustbe quick in action and effective, and have no sideeffects. Depigmentation can be achieved by controllingthe activity and transcription of tyrosinase, regulating

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ALHAGI: A PLANT GENUS RICH IN BIOACTIVES FOR PHARMACEUTICALS

the uptake and distribution of melanosomes in recipientkeratinocytes and melanin and melanosome degradation(Briganti et al., 2003). Plant extracts have potential toact as potent, safer, non-toxic and anti-mutagenicdepigmenting agents (Zhu and Gao, 2008). An importantcosmetic use of Alhagi has been recently reported. It hasbeen noted that methanolic extract of aerial parts of A.camelorum, in particular, can be successfully used in skincare to treat hyperpigmentation disorders. When evalu-ated, the extract inhibited the activity of tyrosinaseenzyme effectively, and percentage inhibition was foundto be 63 (Gholamhoseinian and Razmi, 2012).

Antidiarrheal

Methanolic extract of A. maurorum showed significantantidiarrheal effects against castor oil-induced diarrheain rabbits. It had strong effect on motility of isolated rab-bit’s duodenum mediated possibly because of blockingof calcium channels (Atta and Mouneir, 2004). The un-derground parts ofA. maurorum have shown spasmolyticactivity in pigs (Marashdah and Al-Hazimi, 2010), thuspartially explaining its antidiarrheal activity observed inthe in vivo studies.Tannins, flavonoids, unsaturated sterols, terpenoids,

lactones, carbohydrates and proteins were found in theextract of aerial parts of A. maurorum by phytochemicalscreening that may contribute to antidiarrheal activity ofthis species, particularly tannins and flavonoids areconsidered useful in diarrhea. Rats were given castoroil (1mL) after 1 h of administration with methanolicextract (400mg/kg) of A. maurorum. The extract pro-duced antidiarrheal effect after 4 h as compared withthe standard drug diphenoxylate that inhibited diarrheaafter 3 h (Atta and Mouneir, 2004).

Antiurolithic

Stone formation occurs repeatedly in the patients suffer-ing from stone disease (Tiselius et al., 2001). Stones aremostly calcium oxalate or magnesium ammonium phos-phate type (Otnes, 1983). There are 5–10% chances ofstone formation in life. Several in vitro and in vivo stud-ies on medicinal plants used in traditional antiurolithictherapy have proven that these remedies are effective(Bashir et al., 2010; Khan et al., 2011; 2012). In India, agroup of plants, that, pashanabheda, is used for removalof stone (Narayanaswami and Ali, 1967).Treatment of urolithiasis with distillate of A.

pseudalhagi has been examined in many patients. Renalcolic patients were divided into two groups. One wastreated with A. pseudalhagi distillate and the second withthiazide, tamsulosin and analgesics. Stone expulsion was66% in patients treated with A. pseudalhagi distillateand 40% in victims administeredwith thiazide, tamsulosinand analgesics. The results showed that A. pseudalhagihad a significant effect on the rate of stone expulsionand decreased the time for passage of urinary stones(Narayanaswami and Ali, 1967; Cirous et al., 2010).Hydrophilic extract of A. maurorum was experimentedto study glycol-induced renal stones in rats with urinesamples collected regularly. After 30days, the rats weresacrificed and their kidneys evaluated for the presenceof calcium oxalate crystals. The study confirmed that

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the hydrophilic extract of A. maurorum is effective inpreventing urinary calcium oxalate stones in rats(Shafaeifar et al., 2012).

Genotoxicity. Genotoxic agents can change replicationof DNA and transmission of genes. Genotoxicitydestroys DNA and causes mutations. Comet assay is asensitive and rapid test to study genotoxicity (Buschiniet al., 2001). Literature search revealed that some herbalproducts can cause mutation and have genotoxic and cy-totoxic effects in in vivo and in vitro tests (Higashimotoet al., 1993; Schimmer et al., 1994; De Sa Ferreira andVargas, 1999). The aqueous extract of A. pseudalhagiwhen studied by the Comet assay technique using fluo-rescence microscopy tail length to assess the effect onDNA, the plant extract was found safe at the studieddose of 5μg/mL (Etebari et al., 2012).

CONCLUSION AND FUTURE PROSPECTS

Alhagi plants are widely used as folk medicines to treat alarge number of diseases of which a few are the following:gastroenteritis, diarrhea, ulcers, liver disorders, fever,hypertension, angina pain, headache and toothache,inflammations, rheumatoid arthritis, renal stone andurinary tract infections. Pharmacological attributes ofAlhagi plants have shown that almost all species are bio-logically active. Because of the presence of a wide arrayof physiologically active phytochemicals, Alhagi speciesoffer remarkable antibacterial, cardio-tonic, anti-ulcer,spasmolytic, antidiarrheal, antioxidant, cholegogic,antiurolithic, urease inhibitory, diuretic and antifungalactivities. This in fact prompts the need to isolate andpurify functional bioactives and high-value componentsfrom various species of Alhagi for use as natural pharma-ceuticals. Besides, further efforts can be focused for betterunderstanding of the activity-directed medicinal effectsof these plants via clinical trials, using some animal andhuman models.

Because of the presence of a variety of potential anti-oxidant compounds such as flavonoids, the use ofAlhagispecies in cosmetics has also been reported recently totreat hyperpigmentation skin disorders. Therefore,upscaling of propagation and commercialization ofthese plants for utilization as source of natural antioxi-dants for cosmo-nutraceuticals and therapeutic medi-cine can be explored. These plants are a good sourcefor functional foods because of the presence of digest-ible proteins and a wide range of minerals and essentialoils. However, a more focused attention is needed forthe standardization and validation of medicinal uses ofAlhagi plants as a potential source of bioactivepharmaceuticals.

Alhagi plant has been shown to possess a combinationof antipyretic, analgesic and anti-inflammatory activi-ties, similar to that of NSAIDs. NSAIDs are well knownto cause serious side effects such as gastric ulcers, whenused beyond a few days. Interestingly, Alhagi plant hasbeen shown to be beneficial in ulcer; hence, the plantoffers safer remedy while sharing all therapeuticproperties of NSAIDs. The plant has been traditionallyused to treat hypertension and ischemic heart disease,but there is still a need to conduct further scientific-basedstudies including antidyslipidemic, antihypertensive and

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G. MUHAMMAD ET AL.

vasodilator activities, providing evidence for its effective-ness in cardiovascular disorders.Interestingly, Alhagi plant has been used traditionally

to treat constipation and diarrhea, two opposite diseasestates of gutmotility disorder, in linewith some other pop-ular natural remedies, such as psyllium husk and Ginger,which are dually affective in constipation and diarrhea(Mahmood et al., 2011; Ghayur and Gilani, 2005). Whilethere is a preliminary report (Atta and Mouneir, 2004),showing its antidiarrheal effect without clear mode of ac-tion, there is no report on its effectiveness in constipation.A comprehensive study showing dual effectiveness of theplant would add to its therapeutic potential in gut motilitydisorders (Gilani et al., 2007).Anticancer activity of plant material can be related to

the presence of terpenoidal glycosides as reported byDinda et al. (2010). For example, roots of A. maurorumare a rich source of terpenenoids especially noveloleanane type triterpenoidal glycosides; therefore,different parts of these species can be evaluated for

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detailed antiproliferative activity as well as to isolateanticancer agents.

Regarding the lipid profile, like that of other plants ofFabaceae, Alhagi plants appeared to be a rich source oflipids and essential oils. Up till now, qualitative distribu-tion of lipids has been explored only in A. pseudalhagiand A. persarum (both from Tashkent Uzbekistan). Nev-ertheless, a great thrust can be felt in the rest of the speciesof the genus Alhagi so as to explore their potential lipidprofiles. A great deal is yet to be studied for the potentialdepots of essential oils in Alhagi plants. With respect toisolation of essential oils, only one species A. maurorumhas yet been explored. A lot of work is urged to explorethe other Alhagi species (A. canescens, A. alhagi andA. nepalensis) for their secondary metabolite potential.

Conflict of Interest

The authors have declared that there is no conflict of interest.

REFERENCES

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