Sharma M et.al. / JPBMS, 2011, 6 (12)

Available online at www.jpbms.info ISSN NO- 2230 - 7885 Review Article

JPBMS

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL SCIENCES

Ethnopharmacological importance of racemosus : A review

*Manorma Sharma 1, Archana Sharma 1 , Ashwani Kumar 2 1Department of Botany, Vedic PG Girls College, University of Rajasthan Jaipur 302004, . 2Department of Botany, University of Rajasthan, Jaipur 302004 , India.

Abstract Tuberous are the vital source of medicinal drugs. Among these Asparagus racemosus is an important herb which is well known for its pharmacological applications. A lot of medicinally importance attributes have been assigned to this herb. It has been used by tribes located in distinct area of India from primeval time. Key component of this herb is saponins. Recent developments in transgenic research have opened up the possibility of the metabolic engineering of biosynthetic pathways to produce these high-value secondary metabolites. The present review is a pragmatic approach to accrue the findings on this very important herb.

Keywords :- Asparagus racemosus , Saponins, Ethnopharmacology, Disease.

Introduction: Use of plants as a source of medicine has been inherited Ayurveda describes Asparagus racemosus as rasayana and and is an important component of the health care system in galactogogue, which is used to treat various diseases such India. India is one of the 12 mega biodiversity centers as ulcer, dyspepsia and debility. It contains adventitious having 45,000 plants species, its diversity is unmatched root system with tuberous roots. These tuberous roots due to the 16 different agro climatic zones, 10 vegetative after proper processing and drying are used as ayurveda zones and 15 biotic provinces. “The world Health medicine, with the name of Shatavari. Its leaves are Organization" estimates that up to 80 % of people still rely reduced to form cladodes. Branches contain spines on mainly on traditional remedies such as herbs to cure their them. In Indian medicine it is well known as an disease. The World Health Organization (The World Health antispasmodic, aphrodisiac, demulcent, diuretic, Report, 2003) has estimated that 80% of the population of galactogogue and refrigerant. It is also used in the developing countries being unable to afford treatment of diarrhea, rheumatism, diabetes and brain pharmaceutical drugs relies on traditional medicines complaints (Chadha 2003). During previous investigations (Bopana and Saxena 2007). In the Indian system of influence of fertilizers on growth (Vijay and Kumar, 2005) medicine, most practitioners formulate and dispense their and biochemical composition ( Vijay, Kumar and Bhoite, own recipes (Sharma et al., 2005). The age-old tribal 2009) and in vitro propagation of Asparagus racemosus ( knowledge of plants is an important aspect of ethno Kumar and Vijay , 2008) was studied. botanical research. The tribal tracts are the storehouse of information and knowledge on the multiple uses of plants Chemical constituent (Singh, et al., 2002). Potential plants for Ayurvedic A lot of chemical analysis has been carried out on the roots medicines have been reported by Kumar (2008). of Asparagus racemosus . The major reported constituent These plants are not only used for common diseases but include steroidal saponins, shatavarin I (3-O-{[a-L- also for fetal diseases. Among these plants Asparagus rhamnopyranosyl(1!2)][b-D-glucopyranosyl(1!4)]-b-D- racemosus is an important medicinal which has been glucopyranosyl}-26-O-(b-D-glucopyranosyl)-(25S)-5b- used world wide. The Asparagus genus () has furostan-3b,22a,26-triol), shatavarin II (no reported over 300 species, which are widely distributed in structure), shatavarin IV (3-O-{[a-L- temperate and tropical regions. Asparagus racemosus rhamnopyranosyl(1!2)][b-D-glucopyranosyl(1!4)]-b-D- Willd. or "Satavar" is a creeper of the plant genus glucopyranosyl}-( 25S)-5b-spirostan-3b-ol) and glycoside- Asparagus. Its medicinal properties are reported in AR-4(incomplete structure elucidation) with the two major traditional systems of medicine such as Ayurveda, Siddha ones being named shatavarins I and IV (Hayes et al ., 2006). and Unani (Sharma 1970). Shatawarin I is the major glycoside with 3 glucose and rhamnose moieties attached to sarsasapogenin, whereas *Corresponding Author shatavarin-IV contains Alkaloids, proteins, starch and Manorma Sharma., Department of Botany, Vedic tannin. Isoflavones including 8-methoxy-5,6,4'- PG Girls College, University of Rajasthan trihydroxyisoflavone 7-O- beta-D-glucopyranoside. Jaipur 302004,India. Asparagamine, a polycyclic alkaloid. Racemosol, a cyclic

1 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 06, Issue 06 Sharma M et.al. / JPBMS, 2011, 6 (12) hydrocarbon(9,10-dihydrophenanthrene).Polysaccharides, mucilage is present in the roots.

phytum borivilianum Sant. F., Curculigo orchioides Gaertn, Dactylorhiza hatagirea (D. Don) Soo and Orchis latifolia Linn. (200 mg/Kg body weight) } is formulated by Thakur et al., (Thakur et al., 2008) treat heat induced testicular damage in mice. Administration of this recipe results in significant amelioration of sexual behavior and the mount, intromission and ejaculatory latencies were significantly reduced (Thakur et al., 2009).

Cognitive disorders: Neurological and psychiatric disorders together account for more chronic suffering than all other disorders combined (Cowan and Kandel 2001). In Alzheimer’s and Parkinson’s diseases, ex -cito toxicity and oxidative stress are the major mechanisms of neuronal cell death. Toxicity profile of Asparagus racemosus Therefore, to combat neurodegenerative disorders, there is The LD50 is >1g/kg. No toxic effects or mortality were a need for a compound that can retard or reverse this observed with doses ranging from 50mg/kg to 1g/kg for neuronal damage. four weeks. Acute and subacute (15-30 days In ongoing AD clinical trials, scientists are looking at many administration) toxicity studies did not detect any changes possible interventions, such as cardiovascular treatments, in vital organ function tests (Rege, et al ., 1999). antioxidants, immunization therapy.

Pharmacological applications of Asparagus Ethanopharmacological approach racemosus Asparagus racemosus Willd . is a well-known nervine tonic Aphrodisiac : in the Ayurvedic system of medicine. Parihar and hamnani An aphrodisiac is a substance that is used in the belief that (2004) investigated neuroprotective properties of extracts it increases sexual desire. The name comes from Aphrodite , of Asparagus racemosus Willd , Convolvulus pleuricauas and the Greek goddess of sensuality and love. Phytoestrogens Withania somnifera against free radicals induced damage are defined as any plant compound structurally and/or in different brain regions in experimental animals. functionally similar to ovarian and placental oestrogens Strategies to rescue or protect injured neurons usually and their active metabolites (Whitten and Patisaul 2001) involve promoting neuronal growth and functions or .Phytoestrogens affect the regulation of ovarian cycles and interfering with neurotoxic processes. ‘Mentat’, an herbal oestrous in female mammals and the promotion of growth, psychotropic preparation containing Asparagus racemosus differentiation and physiological functions of the female Willd has been found to be effective in the treatment of genital tract, pituitary, breast and several other organs and alcohol abstinence induced withdrawal symptoms such as tissues in both sexes. The interest in plant-derived tremors, convulsions, hallucinations and anxiety in ethanol oestrogens or ‘phytoestrogens’ has increased due to the administered rats (Kulkarni and Verma 1993) due to its realization that hormone replacement therapy is neither as anticonvulsant and anxiogenic action. safe nor as effective as previously envisaged (Cornwell et al., 2004) . Galactogague: A galactagogue is a substance that promotes lactation in Ethanopharmacological approach humans and other animals. It may be synthetic, plant- The herbs have been traditionally used as Vajikaran derived, or endogenous. Generally hormone replacement Rasayana herbs because of their putative positive influence therapy is used to increase lactation but it is neither safe on sexual performance in humans. Detectable level of nor cheap (Singh and Goyal, 2004). Phytoecdysteroids in Asparagus racemosus Willd. seeds were reveled by Dinan et al., (Dinan et al., 2001) who did Ethanopharmacological approach his research on 16 Asparagus species. Aphrodisiac Asparagus racemosus Willd . root are one of the chief source property of this herb was investigated by Pandey et al., of galactagogue. It has been shown to promote growth as (Pandey et al., 2005) The macroscopic findings revealed a well as increase in weight of mammary lobulo-alycolar prominence of the mammary glands, a dilated vaginal tissue and milk yield in weaning rats by systemic opening and a transversely situated uterine horn, administration of the alcoholic extract (Sabin et al., 1968). proliferation in the lumen of the duct of mammary gland in The extract increased the weight of mammary glands in the treated group of animals. The parenchyma of the post partum and estrogen-primed rats. A. racemosus along genital organs showed abundant glycogen granules with with some other herbal substances in the form of a dilated blood vessels and thickening of the epithelial lining. commercial preparation is reported to enhance milk The oviduct in the treated group showed hypertrophied output in women complaining of scanty breast milk, on 5th muscular wall, whereas the ovary revealed no effect of the day after delivery (Sholapurkar 1986). Patel and Kaniker drug. The results suggest an estrogenic effect of Shatavari (Kaniker,1969) have also shown galactogogue effect of on the female mammary gland and genital organs. Herbal roots of Asparagus racemosus in buffaloes. A mixture preparation of Asparagus racemosus Willd. {lyophilized 'Lactare', containing Asparagus racemosus Willd . its major aqueous extracts of Asparagus racemosus Willd, Chloro- component, has been reported to cause significant rise in

2 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 06, Issue 06 Sharma M et.al. / JPBMS, 2011, 6 (12) serum prolactin levels (Ghosh et al., 1987). The alcoholic g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 extract of Asparagus racemosus has been shown to increase adjuvant activity. In Administration of Asparagus the prolactin levels in female rats (Sabin et al., 1968). racemosus, Sida cordifolia in combination with Levamisole Randomized controlled trial of Asparagus racemosus was the more effective in producing immunomodulatory (Shatavari) as a lactogogue in lactational inadequacy was effect in immunosuppressed (by Cyclophosphamide) birds also studied by Sharma et al.,( Sharma et al., 1996). (Tekade 2008).

Immunoadjuvant and immunomodulater activity: Anti -tussive activity: Adjuvants are nonspecific substance acting to enhance the Anti-tussive means those drugs which are capable of immune response to an antigen with which it is relieving or suppressing coughing. The plants have been administered. Adjuvants are mostly pharmacological used as anti-tussives agents due to their anti-inflammatory, agents of drug or biological origin used to modify the antibiotic, antiviral, demulcents, expectorant and mucolytic antigenicity of immunization components, i.e., to stimulate properties, related with their ability to elaborate active or depress the immune response or to inhibit or enhance principles such as aldehydes, alcohols, alkaloids, essential specific subclasses of immunocytes. Adjuvants augment, or oils, glycosides, flavonoids, gums, ketones, lactones, modulate the immune response at either the cellular or mucilages, oleoresins, pectin, phenols, tannins and humoral level. terpenoids (Waizel-Bucay and Waizel-Haiat 2009). Like immunoadjuvant which increase or decrease immune response by binding to specific protein, immunomodulater Ethanopharmacological approach bind at allosteric site of enzyme and modulate immune The plants have been used as antitussives agents due to response, thus immunomodulater may be defined as a their anti-inflammatory, antibiotic, antiviral, demulcents, substance, biology or synthetic, which can stimulate, expectorant and mucolytic properties, related with their suppress or modulate any of the components of the ability to elaborate active principles such as aldehydes, immune system including both innate and adaptive arms of alcohols, alkaloids, essential oils, glycosides, flavonoids, the immune response (Agrawal and Singh 1999). Therefore gums, ketones, lactones, mucilages, oleoresins, pectin, scientist attempts to extend the reported phenols, tannins and terpenoids. Asteraceae (Compositae), immunopotentiating activity of botanical Lamiaceae (Labiatae), Boraginaceae, Rosaceae and immunomodulators for their possible applications in Brassicaceae (Cruciferae), was the principal immunotherapeutics and immunochemical industry. families reported, perhaps their secondary metabolites as i.e. sesquiterpenes and essential oils (Waizel-Bucay and Ethanopharmacological approach Waizel-Haiat 2009). The , leaves, and aerial parts The immunoadjuvant potential of Asparagus racemosus are most frequently used. The mainly common form of Willd. aqueous root extract was evaluated by Gautam et al., preparation is as decoction or infusion (tea) and the (2009) in experimental animals immunized with administration type is usually oral. The methanol extract of diphtheria, tetanus, pertussis (DTP) vaccine. Asparagus racemosus root showed significant antitussive Immunostimulation was evaluated using serological and activity on sulfur dioxide induced cough in mice (Mandal et hematological parameters. Oral administration of al., 2000). decoction of powdered root of A. racemosus has been reported to produce leucocytosis and predominant Adaptogenic activity: neutrophilia along with enhanced phagocytic activity of the The term adaptogen is used by herbalists to refer to a macrophages and polymorphs (Goyal, Singh et al., 2003). natural herb product that is proposed to increase the Asparagus racemosus Willd . was found to be significantly body's resistance to stress, trauma, anxiety and fatigue. In reduced the mortality of experimental animals while the past, they have been called rejuvenating herbs, qi survival rate was comparable to that of the group treated tonics, rasayanas, or restoratives. All adaptogens contain with a combination of metronidazole and gentamicin antioxidants, but antioxidants are not necessarily (Thatte et al., 1987). adaptogens and that is not proposed to be their primary In immune system helper T cells (Th) are most important mode of action (Winston 2007). Mechanisms of action for part of cell mediated immunity (Th1) and humoral adaptogenic activity seem to fall into 3 categories: those immunity (Th2) and these cells are produced only in that act to regulate the stress response via the neuro- childhood and after a certain age when its number start to endocrine HPA axis, those that act as antioxidants and decrease it create problems. Alcoholic extract has been those that either inhibit or enhance CNS activity. Anti- found to enhance both humoral and cell mediated inflammatory and enzyme inhibition or stimulation was immunity of albino mice injected with sheep red blood also reported albeit rarely. cells as particulate antigen (Muruganadan, 2000).Therefore Modulation of Th1/Th2 immunity is Ethanopharmacological approach emerging as one of biological targets for such Adaptogenic drugs are those which are useful to counteract immunostimulants (Romagnani, 2000).Gautam et al.,, stressful factors by promoting non-specific resistance of (2009) have studied possible immunoregulatory effects of the body (Brekhman and Dardimov 1969). Adaptogens are Asparagus racemosus Willd . ethanolic (ARE) extract on presumed to increase the resistance of the body to stress murine Th1/Th2 immunity using sheep red blood cells as by modulating stress mediators such as corticosteroids, antigenic stimulus. Treatment with ARE resulted in catecholamines, and nitric oxide (Rege et al., 1999).The significant increase of CD3+ and CD4/CD8+ percentages stress indices for evaluation were gastric ulceration, suggesting its effect on T cell activation. ARE treated adrenal gland and spleen weights, ascorbic acid and animals showed significant up-regulation of Th1 (IL-2, IFN- corticosterone concentrations of adrenal cortex & plasma

3 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 06, Issue 06 Sharma M et.al. / JPBMS, 2011, 6 (12) corticosterone levels (Bopana and Saxena 2007). The used traditionally in Ayurveda for the treatment of prevention and management of stress disorders poses a diarrhoea and dysentery. Nanal et al., (1974) found major clinical challenge. Benzodiazepines (BDZs) appear to Satavari to be extremely effective in the treatment of Atisar be effective only against acute stress and not chronic (diarrhoea), Pravahika (dysentery) and Pittaj shool stress. Also, the prolonged use of BDZs exasperates (gastritis) as described in Ayurvedic texts such as Sushruta physical dependence on it and increases the tolerance Samhita and Sharangdhar Samhita . Ethanol and aqueous thereby limiting the utility of the medication. Under such extracts of Asparagus racemosus Willd. roots exhibited circumstances, plant derived agents could induce an significant anti-diarrhoeal activity against castor oil increase in non-specific resistance. Rege et al ., (1999) induced diarrhoea in rats demonstrating an activity similar administered orally the aqueous, standardized extract of to loperamide(Venkatesan et al., 2005). The plant extracts Asparagus racemosus to experimental animals, following showed significant inhibitor activity against castor oil which they were exposed to a variety of biological, physical induced diarrhoea and PGE 2 induced enteropooling in rats. and chemical stresses. Antiulcerogenic action of an Both extracts also showed significant reduction in ayurvedic herbo-mineral formulation ‘Satavari mandur’ gastrointestinal motility in charcoal meal test in rats (SM) was investigated for its efficacy in the treatment of (Venkatesan et al., 2005). It has been reported that coldrestraint stress-induced gastric ulcer in rats (Datta and asparagus decreases gastric emptying time (Dalvi et al., Goel 2002). Bhattacharya et al., (Bhattacharya 1990). Other studies have shown that the methanolic 2004)undertook a study to investigate the adaptogenic extracts of asparagus root reduced intestinal propulsive activity of ‘Siotone’ (a herbal formulation consisting of movement, castor oil-induced diarrhoea and intestinal Withania somnifera, Ocimum sanctum, Asparagus fluid accumulation (Nwafor et al., 2000). racemosus Willd. , Tríbulus terristris and shilajit) against chronic unpredictable, but mild, foot shock stress induced Anti ulceric activity: perturbations in behaviour (depression), glucose Ulcers are sores on the lining of digestive tract (Peptic metabolism, suppressed male sexual behaviour, ulcer), oral cavity (Oral ulcer and Aphthous ulcer), cornea immunosuppression and cognitive dysfunction in albino (Corneal ulcer), valves of the veins (Venous ulcer) and rats. genital area (Genital ulcer). Most ulcers are caused by an infection. The infection is caused by a bacterium called Anti-diarrhea activity: Helicobacter pylori . The usual treatment for peptic ulcers is Diarrhea is increased fluidity, frequency or volume of endoscopic therapy to control active bleeding, drug bowel movements. It may be acute or chronic. A study with therapy to suppress stomach acid (for example, proton- partial results released in October 2009 suggests diarrhea pump inhibitor [PPI] and H2 blockers) and protecting the is now estimated to cause 3 times more deaths than injured area so it can heal. Non-steroidal anti-inflammatory previously thought, at 1.1 million annually for people aged drugs such as ibuprofen (iso-butyl-propanoic-phenolic 5 and over, up from 300,000 assumed in a 2002 study acid), Misoprostol (synthetic prostaglandin E 1 (PGE 1) (Bhatnagar et al., 2010). According to UNICEF, diarrhea analogue) and Ketoprofen ((RS) 2-(3-benzoylphenyl)- kills some 1.5 million children under the age of 5 annually. propionic acid) used widely for treatment of ulcers. But Mainly diarrhea is of 6 types Secretary, Osmotic, Exudatic, long term use of anti-inflammatory drug can cause various Motility, Inflammatory, and Dysentery. Principal causes of serious side effects like constipation, diarrhea, sores in the diarrhea are bacteria, virus, parasites and food intolerance. mouth, headache, dizziness, nervousness, drowsiness etc At present Loperamide and Bismuth subsalicylate are used (Sung et al., 2010). Therefore new researches have been as antidiarrheal drug. Loperamide works by slowing down aimed to evaluate drug composition without side effects. the speed of fluids moving through intestines (bowels). Bismuth subsalicylate works by balancing the way fluid Ethanopharmacological approach moves through intestines. It also reduces inflammation and In Ayurveda, Asparagus racemosus Willd . has also been keeps certain bacteria and viruses that cause diarrhea from mentioned for the treatment of ulcerative disorders of growing in the stomach and intestines. Probiotics, stomach and Parinama Sula, a clinical entity akin to the particularly Bifidobacterium infantis , Sacchromyces duodenal ulcer diseases (Goyal et al., 2003). Singh et boulardii , Lactobacillus plantarum and combination al .,(1986) showed that Shatavari promptly and persistently probiotics, are also used to control bowel movements. relieve the pain and burning sensation as well as other dyspeptic symptoms due to duodenal ulcer. The juice of Ethanopharmacological approach fresh root of Asparagus racemosus Willd. has been shown Diarrhea symptoms vary from mild to fatal. As today to have definite curative effect in patients of duodenal loperamide and bismuth subsalicylate have been used ulcers (Kishore et al., 1980). Nanal et al., (1974) studied the widely but both drugs can cause some side effects like effect of Asparagus racemosus Willd . on Amlapitta abdominal pain, constipation, dizziness, nausea, blackened (hyperacidity), Grahani (ulcerative colitis), Parinam shool stools, ringing sound in ear (called tinnitus). Therefore (septic ulcer) and Vataj shool (spastic colon) and observed there is a need arise to discover such type of drug which an amelioration of symptoms. Mangal et al., (2006) had have wide action spectrum and cure diseases without side done his study on human and found that Asparagus effects. It have studied that saponins extract from racemosus Willd . treatment increase lifespan of gastric Geranium incanum leaves (Amabeoku 2009), Cylico discus mucosal epithelium cells as well as secretion and viscosity bark(Kouticheu et al.,2006)and Paullina pinnata of gastric mucus. Antiulcerogenic action of an ayurvedic leavescontain anti diarrhea activity. Since the Asparagus herbo-mineral formulation ‘Satavari mandur’ (SM) was racemosus Willd. root extract is composed of saponins, investigated for its efficacy in the treatment of alkaloids, flavonoids, sterols and terpenes its root has been coldrestraint stress-induced gastric ulcer in rats (Datta and

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Goel 2002). In another study by Sairam et al.,( 2003), the bupropion (Rush et al., 2006) and Venlafaxine. But regular methanolic extract of fresh roots of Asparagus racemosus use of these drugs may cause some serious side effects like showed significant protection against acute gastric ulcers Seizures, confusion, hallucinating (seeing things or hearing induced by cold restraint stress, acetic acid, pylorus voices that do not exist), irrational fears, fever, rash or ligation, aspirin plus pylorus ligation and cysteamine blisters, itching etc. induced duodenal ulcers. In this study it was concluded that the healing of gastric ulcers could be attributed to the Ethanopharmacological approach effect of the Asparagus racemosus Willd. extract on the Ayurvedic rasayanas are those drugs, which prevent mucosal defensive factors rather than the offensive ones. ageing, increase longevity, impartimmunity, improve Also, the increase in the gastric emptying time aggravates mental functions and add vigor and vitality to the body duodenal ulcers and the ability of Asparagus racemosus (Sharma, 1970). Anti stress drugs such as Benzodiazepines Willd . to limit this gastric emptying time may also be the (BDZs) appear to be effective only against acute stress and reason for the duodenal anti-ulcer activity. Bhatnagar et al ., not chronic stress. Also, the prolonged use of BDZs (2005) evaluated the anti-ulcer effect of Asparagus exasperates physical dependence on it and increases the racemosus Willd . on indomethacin induced ulcers in rats. tolerance thereby limiting the utility of the medication. They found a significant reduction in the ulcer index, free Under such circumstances, plant derived agents could acidity, and volume of gastric secretion and total acidity induce an increase in non-specific resistance (Bopana and which was comparable to the standard drug Ranitidine. In Saxena 2007). Singh et al .,(2009) administered orally the addition they observed an increase in the antioxidant methanol, standardized extract of Asparagus racemosus defense. Previously, extracts from Asparagus racemosus roots to rats, following which they were exposed to a Willd . have been shown to exert potent antioxidant effects variety of biological, physical and chemical stresses. The in vitro against membrane damage induced by free radicals results show that methanolic extract of Asparagus produced by gamma radiation in rat liver mitochondria racemosus decreases immobility in forced swimming test (Kamat et al., 2000). Both the crude extract as well as the and increases avoidance response in learned helpless purified aqueous fraction was found to inhibit lipid indicating antidepressant activity. Same result previously peroxidation and protein oxidation significantly which was received by Rege et al., (1999). Using a model of cisplatin comparable to that of the established antioxidants induced alterations in gastrointestinal motility; the ability glutathione and ascorbic acid though the mechanisms of this extract to exert a normalizing effect, irrespective of responsible for the anti-oxidant properties are still unclear. direction of pathological change was tested. Asparagus racemosus has been found to be effective in EuMil, is a herbal formulation comprising the standardised dyspepsia, being associated with anti-ulcerogenic activity extracts of Withania somnifera (L) Dunal, Ocimum sanctum (De et al., 1997). Asparagus racemosus Willd. along with L, Asparagus racemosus Willd and Emblica officinalis Terminalia chebula reported to protect gastric mucosa Gaertn., the results indicate that EuMil has significant against pentagastrin and carbachol induced ulcers, by adaptogenic and anti-stress, activity, against a variety of significantly reducing both severity of ulceration and ulcer behavioral, biochemical and physiological perturbations, index (Dahanukar et al., 1983). The antisecretory and induced by unpredictable stress, which has been proposed antiulcer activity of Asparagus racemosus Willd. to be a better indicator of clinical stress than acute stress (methanolic extract) and its action against indomethacin (a (Muruganandam, 2002). non-steroidal anti-inflammatory drug) plus pyloric ligation (PL)-induced gastric ulcers in rats have studied. The Anticancer: results of this study suggest that Asparagus racemosus ancer is of two types benign and malignant. Any agent Willd . causes an inhibitory effect on release of gastric which may chemically modify DNA known as carcinogen. hydrochloric acid and protects gastric mucosal damage. Most of the medicine used today are immunosuppressant, cytotoxic, and exert variety of side effects that are Anti depressant: particularly evident in cancer chemotherapy. The Depression is a common chronic recurrent syndrome, deleterious effects of ionizing radiation in biological often refractive to drug treatment affecting quality of life systems are mainly mediated through the generation of and overall productivity (Singh et al., 2009). reactive oxygen species (ROS) in cells as a result of water Most antidepressant medications increase the levels of one radiolysis (Kamat et al., 2000). ROS/RNS are free radicals or more of the monoamines (the neurotransmitters) which posses’ carcinogen activity (Cerutti, 1994) release serotonin, norepinephrine and dopamine in the synaptic by radiation treatment. Among them, particularly, the cleft. Reduction in brain serotonin (Drevets 2001; highly damaging hydroxyl radical (•OH) can cause injury Anguelova and Turecki 2003) has been reported to be one by reacting with bio-molecules (Breen and Murphy 1995) . of the most important etiological factors for genesis of Hydroxyl radical attack upon DNA generates a whole series depression and the most widely used antidepressants of modified purine and pyrimidine bases many of which namely selective serotonin reuptake inhibitors (SSRIs such are known to be mutagenic. Therefore, there is a constant as sertraline, escitalopram, fluoxetine, paroxetine, and need for the development of effective, non-toxic, radical citalopram) act by inhibiting serotonin reuptake into the scavengers that can protect humans against free-radical presynaptic cell, increasing the level of serotonin available genetic damage induced by radiation and other agents. to bind to the postsynaptic receptor (Schreiber et al., 1995). Further noradrenergic and dopaminergic systems Ethanopharmacological approach are reported to be involved and act in tandem with the Rasayana are the medicine useful in strethening the serotonergic system (Millan et al., 2000; Koch et al., 2002). immune system (Patwardhan et al., 1990) . Beside SSRIs ‘atypical’ antidepressants have been used like Immunomodulation is a procedure, which can alter the

5 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 06, Issue 06 Sharma M et.al. / JPBMS, 2011, 6 (12) immune system of an organism by interfering with its cause side effects like fever, blisters, yellowing of the skin function, which primarily implies stimulation of non- or eyes, excessive tiredness, unusual bleeding or bruising, specific system (Neelam et al., 2001). Immunosupression lack of energy, nausea, loss of appetite, pain in the upper right part of the stomach, flu-like symptoms etc. implies mainly to reduce resistance against infections, stress and may occur on account of environmental or Ethanopharmacological approach chemotherapeutic factors. Asparagus racemosus is well Antilithiatic effect of Asparagus racemosus Willd on known for its immunomodulater activity (Gautam et al., ethylene glycol-induced lithiasis in male albino Wister rats 2009), phytoestrogenic properties and use as a hormone was studied by Christina et al., (2005). Oral administration modulator (Mayo 1998). Treatment with Asparagus of Asparagus racemosus ethanolic extract racemosus Willd . Tinospora cordifolia , Withania somnifera , reduce oxalate, calcium and phosphate ions in urin which and Picrorhiza kurrooa significantly inhibited ochratoxin A- are the main cause of renal stone formation (Chitme et induced suppression of chemotactic activity and al .,2010). An in vitro assay technique was set up to production of inflammatory cytokines interleukin (IL)-1 determine the phagocytic and microbicidal activity of a and tumor necrosis factor (TNF)-alpha by macrophages monocyte-macrophage cell line using Candida species as (Dhuley 1998). Moreover, Asparagus racemosus Willd . test organisms. The optimal doses for MDP, Metronidazole, induced excess production of TNF-α when compared with Asparagus racemosus and Tinospora cordifolia were found controls. The crude saponins obtained from asparagus to be 100 micrograms, 300 mg/kg, 200 mg/kg and 100 shoots were found to have antitumor activity. It inhibited mg/kg respectively. Patients with cirrhosis were screened the growth of human leukemia HL-60 cells in culture and for defects in monocyte function. The depressed monocyte macromolecular synthesis in a dose and time-dependent function (20.58 +/- 5% phago and 41.24 +/- 12.19% ICK; P manner (Shao and Huang 1996). Total extract, polar and < 0.05) was observed indicating a compromised host non-polar extracts, and their formulations, prepared from defense. The utility of this candidicidal assay in medicinal plants mentioned in Ayurveda, namely, Withania experimental and clinical studies was discussed by Rege somnifera (Linn Dunal) (Solanaceae), Tinospora cordifolia and Dahanukar(1993). The aqueous extract of the root was (Miers) (Menispermaceae), and Asparagus racemosus lethal or inhibitory, in vitro studies to hatching (Willd.) (Liliaceae) exhibited various of Meloidogyne javanica and M. arenaria. A 1% solution of immunopharmacological activities in cyclophosphamide the active material contained in the nematicide, Nemaphos (CP)-treated mouse ascitic sarcoma (Diwanay 2004). Rao O-O-diethyl-O-2-pyrazinyl phosphothionate suppressed (1982), studied inhibitory action of DMBA induced hatching in dilutions up to 10000 times and was mammary carcinogenesis. Agrawal et al., (2008) proved comparable to the activity of 1 ml undiluted plant extract that the aqueous extract of the roots of Asparagus 10 g/100 ml (Swarup and Sharma 1967). Sairam et al ., racemosus has the potential to act as an effective 2003 have reported antiulcerogenic activity of methanolic formulation to prevent hepatocarcinogenesis induced by extract of fresh roots of AR in the cold restraint stress treatment with diethylnitrosamine. Anti-cancer activity of (CRS), pyloric ligation, aspirin plus pyloric ligation induced asparagus extract was also proved by Seena et al., (1993). gastric ulcer models and cysteamine induced duodenal There are several studies that indicate a lower rate of ulcer model. AR was found to be effective in the CRU, AL, breast cancer in populations with a high exposure to and cysteamine induced ulcer models, but was ineffective phytoestrogens (Beral, 2003) which is found in PL and ASP models. Effectiveness of Asparagus predominantly in asparagus However; contradictory racemosus ethanol extract compare to the methanol and studies also exist regarding this evaluation. Studies found distill water extract of the same plant was reveled by no association between phytoestrogens and breast cancer S.Alok et al .,2008. It was found that the ethanolic extract of (Weinstein et al., 1993). Asparagus racemosus Willd. had an inhibitory potential on lithiasis induced by oral administration of 0.75% ethylene Antilithiatic effect: glycolated water to adult male albino Wistar rats for 28 Kidney stones are one of the most painful and common days. The ethanolic extract, significantly reduced the disorders of the urinary tract. Depending on where they elevated level of calculogenic ions in urine and it elevated are located, kidney stones are known as urinary calculi, the urinary concentration of magnesium,which is urinary tract stone disease, renal calculi, nephrolithiasis, considered as one of the inhibitors of crystallization ureterolithiasis and urolithiasis. Kidney stones are small, (S.Alok et a l., 2008). solid crystals that develop when salts or minerals in urine Parasitism is a type of symbiotic relationship become solid inside the kidneys or uterus. Kidney stones between organisms of different species where one can be due to underlying metabolic conditions, such organism, the parasite, benefits at the expense of the host. as renal tubular cidosis (Moe 2006), Dent's disease (Lloyd In general, parasites are much smaller than their hosts, et al., 1996), hyperparathyroidis and medullary sponge show a high degree of specialization for their mode of life, kidney (Ginalski et al., 1991). There are two drugs have and reproduce more quickly and in greater numbers than been used Ketorolac (Toradol), an injectable their hosts. Parasites reduce host fitness in many ways, antiinflammatory drug and Tamsulosin may be used to ranging from general or specialized pathology (such as help facilitate the passage of stones into the bladder. castration), impairment of secondary sex characteristics, to Tamsulosin may cause side effects like Sleepiness, difficulty the modification of host behavior. Actions against parasite falling asleep or staying asleep, weakness, back pain, depend on type of parasite and mode of infection. Drugs diarrhea, runny or stuffy nose, pain or pressure in the face, are design according to these parasites to cure diseases. sore throat, cough, fever, chills, or other signs of infection, Some of the antiparasitic drugs are DL-Propranolol, blurred vision and difficulty ejaculating. Ketorolac may Nitrobenzamides, Diclazuril/Clazuril, Febrifugine,

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Halofuginone, Halogenated Hydrocarbons, Hetolin, Mycobacterium 607; and antifungal actions against four Cyclosporin A, Quinuronium sulfate (= Acaprine), fungi viz., Microsporum gypseum, Trichophyton Amicarbalide, Paraherquamide, Benzimidazoles mentagrophytes, Candida albicans and Helminthosporium (Albendazole, Mebendazole, Triclabendazole) sativum (Bhawasar et al., 1965). The methanol fraction of Nifutimox.etc. These drugs are isolated from plants as well the leaves using the disc diffusion test at a concentration of as from microorganism. And former source is cheapest 4000 and 5000 ppm was found to inhibit Proteus among all, thus from ancient time people have been used vulgaris while it was devoid of any activity plants as antiparasitic agent. against Escherichia coli, Klebsiella aerogenes and Pseudomonas aerogenes (Perumal et al., Ethanopharmacological approach 1998). The fresh juice of the plant showed antibacterial Anticandidal activity of Asparagus racemosus Willd. against activity against Staphylococcus (Bhawasar et al., 1965). The six species of candida ( Candida albicans, Candida tropicalis, extract of the plant showed moderate toxicity Candida krusei, Candida guillermondii, Candida parapsilosis against Rhizoctonia solaniI (Renu. 1983). and Candida stellatoida) had evaluated by Uma et al., (2009). Asparagus racemosus extract showed high degree Antidiebetic activity: of inhibition against candida in compare to any other Diabetes is a metabolic disorder . It is a condition in which a antibiotics. Antibacterial activity of Asparagus racemosus person has a high blood sugar (glucose) level as a result of was studied against Escherichia coli, Shigella dysenteriae, the body either not producing enough insulin, or because Shigella sonnei, Shigella flexneri, Vibrio cholerae, Salmonella body cells do not properly respond to the insulin that is typhi, Salmonella typhimurium, Pseudomonas putida, produced. Where in human body does not produce or Bacillus subtilis and Staphylococcus aureus by Mandal et al., properly uses insulin, a hormone that is required to (2000). Asparagus racemosus extract activity against convert sugar, starches, and other food into energy. There leishmania and plasmodium has also been demonstrated. are three types of drugs have been used for the treatment (Kigondu et al., 2009). of diabetes are Sulfonylureas (such as Glipizide, and The alcoholic extract of the root was found to possess in Glyburide), Biguanides (such as metformin), vitro antibacterial activity against Staphylcoccus Thiazolidinediones (such as Starlix® and Prandin®), Alpha aureus and Escherichia coli . However, the aqueous extract glucosidase inhibitors (such as Precose®). Metformin was found to be inactive (George et al., 1947) . The hexane, improves hyperglycemia primarily through its suppression aqueous and alcoholic extracts of the root at concentration of hepatic glucose production (Kirpichnikov et al., 2002). of 200 mg /ml were devoid of any in vitro antibacterial Metformin decreases hepatic gluconeogenesis by activity against Bacillus subtilis, Escherichia coli, Proteus interfering with respiratory oxidation in mitochondria. It vulgaris, Salmonella typhimurium, Pseudomonas suppresses gluconeogenesis from several substrates, aeruginosa and Staphylococcus aureus using the agar well including lactate, pyruvate, glycerol, and amino acids. In diffusion test (Ahmad et al., 1998). The juice of the root addition, metformin increases intramitochondrial levels of showed fungitoxicity against three plant fungi viz., calcium (Ca ++ ), a modulator of mitochondrial respiration. In Helminthosporium sativum (60. 7%) Colletotrichum insulin-sensitive tissues (such as skeletal muscle), falcatum (58.2 ) and Fusarium oxysporum (60.7%) (Singh metformin facilitates glucose transport by increasing and Shanna, 1978). tyrosine kinase activity in insulin receptors and enhancing The root bark showed marked antibacterial, against eight glucose transporter (GLUT) trafficking to the cell bacteria viz., Micrococcus pyogenes var. aureus, Bacillus membrane. Metformin inhibits fatty acid (FA) production subtilis, Diplococcus pneumoniae, Streptococcus pyogenes, and oxidation, thereby reducing fatty acid–induced insulin Escherichia coli, Salmonella typhosa, Vibrio resistance and hepatic glucose production comma and Shigella dysenteriae ; antitubercular against two mycobacteria Mycobacterium phlei and Figure 2: Mechanism of metformin (Kirpichnikov et al., 2002)

Some people have developed a life-threatening condition other hand Glipizide mechanism of action is produced by called lactic acidosis while taking metformin. Symptoms of blocking potassium channels in the beta cells of the islets of lactic acidosis are weakness, increasing sleepiness, slow langerhans. By partially blocking the potassium channels, it heart rate, cold feeling, muscle pain, shortness of breath, will increase the time the cell spends in the calcium release stomach pain, feeling light-headed, and fainting. On the stage of cell signaling leading to an increase in calcium. The increase in calcium will initiate insomnia, paresthesia, anxiety, depression,nausea, more insulin release from each beta cell. But some side dyspepsia, constipation and vomiting, rhinitis, pruritus, effects are also associated with this drug are Pain,

7 Journal of Pharmaceutical and Biomedical Sciences (JPBMS), Vol. 06, Issue 06 Sharma M et.al. / JPBMS, 2011, 6 (12) polyuria etc.therefore scientists are looking forward Ethanopharmacological approach production of cheap drugs with lesser side effects. Ayurvedic treatment of aplastic anemia is basically directed at treating the immune dysfunction and improving Ethanopharmacological approach normal bone marrow production. Immuno-modulatory Diabetes mellitus (DM) is a major cause of disability and herbal medicines like Ashwagandha ( Withania somnifera ), hospitalization that presents a significant burden on Shatavari ( Asparagus racemosus ), Bala ( Sida cordifolia ), societies worldwide (Booth et al., 2006). The recent Nagbala ( Sida humilis ), Yashtimadhuk ( Glycerrhiza glabra ), explosion in the area of herbal medicine has lead to a Guduchi ( Tinospora cordifolia ) and Punarnava ( Boerhaavia resurgence of nutritional, clinical and scientific interest in diffusa ) are used. Asparagus is high in folic acid, which is the potential of plant treatments for diabetes across the essential for the production of new red blood cells and may world (Swanston-Flatt et al., 1991; Gray and Flatt 1997). therefore be helpful in preventing anemia. It is a rich More than 100 medicinal plants are mentioned in the source of folate and vitamin K. folate helps to get rid of the Indian system of medicines including folk medicines for the problem of anemia. Vitamin K is found to play a role in management of diabetes, which are effective either regulating the process of blood coagulation. Shatavari separately or in combinations (Kar et al., 2003). Asparagus churna with milk or shatavarisidhdha racemosus is consistently used by the tribal communities ghrut (medicated ghee ) is recommended for women for the treatment of diabetes (Rana et al., 1996; Rana et al., suffering from anemia especially due to the loss of blood 1999) as well as in modern medicine. As describe above through periods. Hence, asparagus is a vital drug to cure metformin drug for diabetes increase Ca++ level in anemia . mitochondria, same mechanism was evaluated by Hannan et al ., (2007). Hannan et al ., (2007) revealed that Antioxytocic: constituents of A. racemosus root extracts have wide- The alcoholic extract of the root exhibited antioxytocic ranging stimulatory effects on physiological insulinotropic activity. The saponin-glycoside A4, mp 191-95° C in doses pathways. They found that ethanol extract and each of the of 20-50 µg/ml produced a specific and competitive block hexane, chloroform and ethyl acetate partition fractions of the pitocin syntocinon -induced contraction of rat, concentration-dependently stimulated insulin secretion in guinea pig and rabbit uteri in vitro as well as in situ. The isolated perfused rat pancreas, isolated rat islet cells and saponin also blocked the spontaneous uterine motility. It clonal beta-cells. And it also increased intracellular Ca (2+), was also found that the hypotensive action of syntocinon in consistent with the observed abolition of insulin secretory cat was unaffected by previous administration of saponin effects under Ca (2+) -free conditions. The dried ethanolic A4 (Jetmalani and Gaitonde 1969). extract 250 mg per kg body weight and the inorganic parts Conclusion 90 mg pure ash/kg body weight of the root revealed From the above description (concluded in Table 1), it may hypoglycaemic activity in a single dose effect on the oral be concluded that Asparagus racemosus Willd. could be a glucose tolerance test GTT in fasting albino rats (Kar et al., useful natural herb which posses no side effects compare 1999). to allopathic drugs and can be used to cure many fatal dieses like cancer, gonorrhea, piles, diabetes etc. There are Anti anemic: many unraveled applications of this herb remain A condition in which there is a reduction in the number of uninvestigated in relatively newer areas of its function. circulating red blood cells per cubic millimeter, the amount Hence, phytochemicals and minerals of these plants will of hemoglobin per 100 milliliters, or the volume of packed enable to exploit its therapeutic use. The drug is without red cells per 100 milliliters of blood. It exists when having any serious toxicity or side effects known till date hemoglobin content is less than that required to provide and thus can be safely used in humans for acute and the oxygen demands of the body. Anemia is not a disease; it chronic treatment regime. is a symptom of various diseases. Anemia is classified on In order to have a excellent medicine it is very necessary to the basis of mean corpuscular volume and by etiological coordinate the quality of raw materials, in process (causes) factors. Anemia may result from excessive blood materials and the final products, it has become essential to loss, excessive blood cell destruction, or decreased blood develop reliable, specific and sensitive quality control cell formation. Due to excessive blood cell destruction: methods using a combination of classical and modern treatment of specific hemolytic disorder. Due to decreased instrumental method of analysis. In vitro induction of blood cell formation: replacement therapy to combat the stress response is in progress to increase secondary specific deficiency (iron, vitamin B12, folic acid, ascorbic metabolites in this plant using various abiotic and biotic acid). elicitors. This would help in conservation of this species and provide pharmaceutical component in less time and cheap cost. Table 1: Therapeutic use of Asparagus racemosus,proposed mechanism of action. Therapeutic use of S.No . Proposed mechanism of action References Asparagus racemosus 1. Aphrodisiac Plant compound structurally and/or functionally Thakur et al. , 2009; (Pandey, Sahay et a l., similar to ovarian and placental oestrogens. 2005); Dinan et al ., 2001(Dinan,Savchenko et al., 2001; Dinan L 2001) 2. Alzheimer’s disease • Antioxidative mechanism Parihar and hamnani (2004) • Regulate neurotransmitters • Neuritis regeneration

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3. Galactogague Activate adenohypophysis (anterior pituitary Sharma et al ., 1996 gland) to produce prolactin Ghosh et al .,1987 Patel and Kaniker 1969 Sabin et al ., 1968 4. Immunoadjuvant and • Modify the antigenicity of immunization Gautam et al .,2009 immunomodulater components. Tekade et al ., 2008 activity • Activate T cells Singh and Goyal, 2004 • Up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL- Gautam et al ., 2004 4) cytokines. Romagnani, 2000 Thatte et al .,1987 5. Antitussive activiy Anti -inflammatory property Waizel and Waizel, 2009 Mandal et al ., 2000

6. Adaptogenic activity Modulate stress mediators (corticosteroids, Bopana and Saxena 2007 catecholamines, and nitric oxide) Bhattacharya et al., 2004 Datta et al., 2002 Panossian et al .,1999 7. Anti -diarrhea activity • Balancing the way fluid moves through intestines Venkatesan et al ., 2005 • Anti bacterial and anti viral activity Nwafor et al ., 2000 • Reduce inflammation Dalvi et al ., 1990 Nanal et al ., 1974 8. Antiulceric activity Inhibit lipid peroxidation and protein oxidation. Singh et al .,2009 Antioxidant activity Mangal et al ., 2005 Bhatnagar et al ., 2005 Goyal and singh,2003 Sairam et al., 2003 Datta et al ., 2002 Bhatnagar et al ., 2005 Kamat et al ., 2000

9. Anti depressant • Serotonin reuptake inhibitors Bopana and Saxena, 2007 • Antioxident activity Muruganandam et al., 2003 • Increase GABA level in the brain Sharma, 2001 Rege et al ., (1999

10. Anticancer activity • Immunomodulater activity Gautam et al .,2009 • Enhance production of inflammatory cytokines Agrawal et al ., 2008 interleukin (IL)-1 and tumor necrosis factor Diwanay et al ., 2004 (TNF)-alpha by macrophages Neelam et al ., 2001 • Inhibited the growth of human leukemia HL- Dhuley, 1997 60 cells Shao et al., 1996 Beral 1993 11. Antilithiatic effect Asparagus racemosus ethanolic e xtract reduce Chitme et al .,2010 oxalate, calcium and phosphate ions in urin which S.Alok et al .,2008 are the main cause of renal stone formation. Christina et al ., 2005 Sairam et al .,2003 Rege and Dahanukar1993 Swarup and Sharma, 1967

12. Antiparasitic activity Inhibition of parasite through antiparasitic agents Uma et al ., 200 9 which break parasite resistance system. Kigondu et al., 2009 Biochemical of this plant act by two ways: Mandal et al .,2000 • Destruction of metabolic pathways of parasite. Perumal Samy et al ., 1998] • Disturb physical resistance system of parasite. Singh and Sharma, 1978 Bhatnagar et al ., 1961 George et al ., 1947

13. Antidiebetic activity Hypoglycaemic activity Hannan et al ., 2007 Increased intracellular Ca (2+) Booth et al ., 2006 Balami,N.P., 2004 Kar et al, 2003 Rana et al. , 1999 Gray & Flatt 1997 14. Anti anemic Vitamin K coagulate blood Dr.Satish Kulkarni,2009 Folic acid produce new blood cells

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