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1: J Ethnopharmacol. 2007 Mar 1;110(1):1/15. Epub 2007 Jan 4.
Asparagus racemosus/Ethnopharmacological evaluation and conservation needs.
Bopana N, Saxena S.
TERI University, Darbari Seth Block, Habitat Place, Lodhi Road, New Delhi 110003, India.
Asparagus racemosus Willd. (Asparagaceae) is an important medicinal plant of tropical and subtropical India. Its medicinal usage has been reported in the Indian and British Pharmacopoeias and in traditional systems of medicine such as Ayurveda, Unani and Siddha. Asparagus racemosus is mainly known for its phytoestrogenic properties. With an increasing realization that hormone replacement therapy with synthetic oestrogens is neither as safe nor as effective as previously envisaged, the interest in plant/derived oestrogens has increased tremendously making Asparagus racemosus particularly important. The plant has been shown to aid in the treatment of neurodegenerative disorders and in alcohol abstinence/induced withdrawal symptoms. In Ayurveda, Asparagus racemosus has been described as a rasayana herb and has been used extensively as an adaptogen to increase the non/specific resistance of organisms against a variety of stresses. Besides use in the treatment of diarrhoea and dysentery, the plant also has potent antioxidant, immunostimulant, anti/dyspepsia and antitussive effects. Due to its multiple uses, the demand for Asparagus racemosus is constantly on the rise; however, the supply is rather erratic and inadequate. Destructive harvesting, combined with habitat destruction in the form of deforestation has aggravated the problem. The plant is now considered 'endangered' in its natural habitat. Therefore, the need for conservation of this plant is crucial. This article aims to evaluate the biological activities, pharmacological applications and clinical studies of Asparagus racemosus in an attempt to provide a direction for further research. Keeping in mind the fact that it is the active principle that imparts medicinal value to a plant; consistency in quality and quantity needs to be maintained to ensure uniform drug efficacy. Also, deliberate or inadvertent adulteration needs to be dealt with at an early stage. To overcome these prevalent problems, the availability of genetically superior and uniform planting material is essential. This can be obtained by a combination of various biotechnological tools involving chemoprofiling, tissue culture and use of molecular markers. Along with the application of these methods, proper agro/techniques and adequate marketing opportunities would encourage cultivation of Asparagus racemosus and thereby contribute to its conservation. There are also several gaps in the existing literature with regard to the pharmacological actions of Asparagus racemosus. These include an incomplete understanding about the interaction/synergy between Asparagus racemosus and other plant constituents in polyherbal formulations; lack of information regarding the mode of action of the various constituents of Asparagus racemosus, etc. Consequently, we have suggested a 'systems biology' approach that includes metabolite profiling, metabolic fingerprinting, metabolite target analysis and metabonomics to enable further research.
PMID: 17240097 [PubMed / in process]
2: J Endocrinol. 2007 Jan;192(1):159/68.
Insulin secretory actions of extracts of Asparagus racemosus root in perfused pancreas, isolated islets and clonal pancreatic beta/cells.
Hannan JM, Marenah L, Ali L, Rokeya B, Flatt PR, Abdel/Wahab YH.
Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK.
Asparagus racemosus root has previously been reported to reduce blood glucose in rats and rabbits. In the present study, the effects of the ethanol extract and five partition fractions of the root of A. racemosus were evaluated on insulin secretion together with exploration of their mechanisms of action. The ethanol extract and each of the hexane, chloroform and ethyl acetate partition fractions concentration/dependently stimulated insulin secretion in isolated perfused rat pancreas, isolated rat islet cells and clonal beta/cells. The stimulatory effects of the ethanol extract, hexane, chloroform and ethyl acetate partition fractions were potentiated by glucose, 3/isobutyl/1/methyl xanthine IBMX, tolbutamide and depolarizing concentration of KCl. Inhibition of A. racemosus/induced insulin release was observed with diazoxide and verapamil. Ethanol extract and five fractions increased intracellular Ca(2+), consistent with the observed abolition of insulin secretory effects under Ca(2+) /free conditions. These findings reveal that constituents of A. racemosus root extracts have wide/ranging stimulatory effects on physiological insulinotropic pathways. Future work assessing the use of this plant as a source of active components may provide new opportunities for diabetes therapy.
PMID: 17210753 [PubMed / in process]
3: Chem Biodivers. 2004 Feb;1(2):265/79.
Two pyrrolo[1,2/a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formation.
Seger C, Mereiter K, Kaltenegger E, Pacher T, Greger H, Hofer O.
Institute of Organic Chemistry, University of Vienna, Wahringerstrasse 38, A/1090 Vienna. christoph.seger@uibk.ac.at
The alkaloids 1',2'/didehydrostemofoline (2) and 2'/hydroxystemofoline (3) from Stemona collinsae Craib (Stemonaceae) were studied by X/ray crystallography and NMR spectroscopy, and they are compared with the parent compound stemofoline (1). The X/ray analysis of the CH2Cl2 solvate of 2'/hydroxystemofoline (3) allowed the determination of the absolute configuration of this compound unequivocally, whereas optical rotation was used to infer the absolute configuration of 1',2'/didehydrostemofoline (2). Based on these results, it is shown that asparagamine A isolated from Asparagus racemosus Willd. (Asparagaceae) is identical to 1',2'/didehydrostemofoline obtained from S. collinsae Craib, and that the reported plant source of asparagamine A was most likely a Stemona species. In the context of the current investigations, a novel concept on the biosynthesis of Stemona alkaloids has been worked out and is presented here.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 17191845 [PubMed / indexed for MEDLINE]
4: J Herb Pharmacother. 2006;6(1):13/20.
Antisecretory and antiulcer activity of Asparagus racemosus Willd. against indomethacin plus phyloric ligation/induced gastric ulcer in rats.
Bhatnagar M, Sisodia SS.
Department of Zoology, University College of Science, MLS University, Udaipur/313001, India. mbhatnagar@yahoo.com
OBJECTIVE: To study the antisecretory and antiulcer activity of Asparagus racemosus Willd. (methanolic extract) and its action against indomethacin (a non/steroidal anti/inflammatory drug) plus pyloric ligation (PL)/induced gastric ulcers in rats. METHOD: Indomethacin plus PL/induced gastric ulceration model was used in the study. RESULTS: Treatment with Asparagus racemosus (Shatavari) crude extract (100 mg/kg/day orally) for fifteen days significantly reduced ulcer index when compared with control group. The reduction in gastric lesions was comparable to a standard antiulcer drug Ranitidine (30 mg/kg/ day orally). Crude extract also significantly reduced volume of gastric secretion, free acidity and total acidity. A significant increase in total carbohydrate (TC) and TC/total protein (TP) ratio of gastric juice was also observed. No significant change in the total protein was noted. CONCLUSION: Asparagus racemosus was found to be an effective antiulcerogenic agent, whose activity can well be compared with that of ranitidine hydrochloride. The results of this study suggest that Asparagus racemosus causes an inhibitory effect on release of gastric hydrochloric acid and protects gastric mucosal damage.
Publication Types: Comparative Study
PMID: 17135157 [PubMed / indexed for MEDLINE]
5: Indian J Exp Biol. 2006 Jul;44(7):570/3.
Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine.
Goel RK, Prabha T, Kumar MM, Dorababu M, Prakash, Singh G.
Department of Anatomy, Institute of Medical Sciences, Banaras Hindu Univerisity, Varanasi 221 005, India. rkgoel_bhu@yahoo.co.in
Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 16872047 [PubMed / indexed for MEDLINE]
6: Phytochemistry. 2006 Jul;67(13):1316/21. Epub 2006 Jun 8.
Steroidal saponins from the fruits of Asparagus racemosus.
Mandal D, Banerjee S, Mondal NB, Chakravarty AK, Sahu NP.
Steroid and Terpenoid Chemistry Department, Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Jadavpur, Kolkata 700 032, West Bengal, India.
Three steroidal saponins, racemosides A (1), B (2) and C (3), were isolated from the methanolic extract of the fruits of Asparagus racemosus, and characterized as (25S)/5beta/spirostan/3beta/ol/3/O/{beta/D/ glucopyranosyl (1//>6)/[alpha/L/rhamnopyranosyl (1//>6)/beta/D/glucopyranosyl (1//>4)]/beta/D/glucopyranoside}, (25S)/5beta/spirostan/3beta/ol/3/O/alpha/L/rhamnopyranosyl (1//>6)/beta/D/glucopyranosyl (1//>6)/beta/D/glucopyranoside and (25S)/5beta/spirostan/3beta/ol/3/O/{alpha/L/rhamnopyranosyl/(1//>6)/[alpha/L/rha mnopyranosyl (1//>4)]/beta/D/glucopyranoside}, respectively, by spectrometric analysis and some chemical strategies.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 16759676 [PubMed / indexed for MEDLINE]
7: Ann N Y Acad Sci. 2005 Nov;1056:261/78.
Antiulcer and Antioxidant Activity of Asparagus racemosus WILLD and Withania somnifera DUNAL in Rats.
Bhatnagar M, Sisodia SS, Bhatnagar R.
Department of Zoology, University College of Science, Mohan Lal Sukhadia University, Udaipur/313001, India. mbhatnagar@yahoo.com.
Comparative study of the antiulcer and antisecretory activity of Asparagus racemosus Willd (Shatawari) and Withania somnifera Dunal (Ashwagandha) root extract with a standard drug, ranitidine, in various models of gastric ulcer in rats is presented. Ulcer was induced by the indomethacin (NSAID) and swim (restraint) stress treatment. Results demonstrated that A. racemosus as well as W. somnifera methanolic extract (100 mg/kg BW/day p.o.) given orally for 15 days significantly reduced the ulcer index, volume of gastric secretion, free acidity, and total acidity. A significant increase in the total carbohydrate and total carbohydrate/protein ratio was also observed. Study also indicated an increase in antioxidant defense, that is, enzymes superoxide dismutase, catalase, and ascorbic acid, increased significantly, whereas a significant decrease in lipid peroxidation was observed. A. racemosus was more effective in reducing gastric ulcer in indomethacin/treated gastric ulcerative rats, whereas W. somnifera was effective in stress/induced gastric ulcer. Results obtained for both herbal drugs were comparable to those of the standard drug ranitidine.
PMID: 16387694 [PubMed / in process]
8: Methods Find Exp Clin Pharmacol. 2005 Nov;27(9):633/8.
Antilithiatic effect of Asparagus racemosus Willd on ethylene glycol/induced lithiasis in male albino Wistar rats.
Christina AJ, Ashok K, Packialakshmi M, Tobin GC, Preethi J, Murugesh N.
Department of Pharmacology, K.M. College of Pharmacy, Tamil Nadu, India. kmcp@sancharnet.in
The ethanolic extract of Asparagus racemosus Willd. was evaluated for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days. The ionic chemistry of urine was altered by ethylene glycol, which elevated the urinary concentration of crucial ions viz. calcium, oxalate, and phosphate, thereby contributing to renal stone formation. The ethanolic extract, however, significantly (p < 0.05) reduced the elevated level of these ions in urine. Also, it elevated the urinary concentration of magnesium, which is considered as one of the inhibitors of crystallization. The high serum creatinine level observed in ethylene glycol/treated rats was also reduced, following treatment with the extract. The histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment.
PMID: 16357948 [PubMed / indexed for MEDLINE]
9: Phytother Res. 2005 Aug;19(8):721/4.
Effect of Asparagus racemosus rhizome (Shatavari) on mammary gland and genital organs of pregnant rat.
Pandey SK, Sahay A, Pandey RS, Tripathi YB.
Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. pandeyskbhu@rediffmail.com
Asparagus racemosus (AR) Willd (family Liliaceae) is commonly known as Shatavari. The alcoholic extract of its rhizome was administered orally to adult pregnant female albino rats at a dose of 30 mg/100 g body weight, daily for 15 days (days 1/15 of gestation). The macroscopic findings revealed a prominence of the mammary glands, a dilated vaginal opening and a transversely situated uterine horn in the treated group of animals. The weight of the uterine horns of the treated group was found to be significantly higher (p < 0.001) but the length was shorter (p > 0.01). Microscopic examination of the treated group showed proliferation in the lumen of the duct of mammary gland. It was obliterated due to hypertrophy of ductal and glandular cells. Hyperplasia of the glandular and muscular tissue and hypertrophy of the glandular cells were observed in the genital organs. The parenchyma of the genital organs showed abundant glycogen granules with dilated blood vessels and thickening of the epithelial lining. The oviduct in the treated group showed hypertrophied muscular wall, whereas the ovary revealed no effect of the drug. The results suggest an oestrogenic effect of Shatavari on the female mammary gland and genital organs. Copyright (c) 2005 John Wiley & Sons, Ltd.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 16177978 [PubMed / indexed for MEDLINE]
10: J Pharm Pharm Sci. 2005 Feb 25;8(1):39/46.
Anti/diarrhoeal potential of Asparagus racemosus wild root extracts in laboratory animals.
Venkatesan N, Thiyagarajan V, Narayanan S, Arul A, Raja S, Vijaya Kumar SG, Rajarajan T, Perianayagam JB.
K.P. College of Pharmacy, Thiruvannamalai, India.
PURPOSE: Asparagus racemosus Wild root has been used traditionally in Ayurveda for the treatment of diarrhoea and dysentery. However, the claims of Ayurveda need to be validated by a suitable experimental model. Therefore, the present study was undertaken to evaluate the effect of ethanol and aqueous extracts of Asparagus racemosus for its antidiarrhoeal potential against several experimental models of diarrhoea in Albino Wistar rats. METHODS: The antidiarrhoeal activity of ethanol and aqueous extracts of Asparagus racemosus root was evaluated using castor oil/induced diarrhoea model in rats. Further, we evaluated the effect of ethanol and aqueous extracts on gastrointestinal tract motility after charcoal meal administration and PGE2 induced intestinal fluid accumulation (enteropooling). Loperamide was used as positive control. RESULTS: The plant extracts showed significant (P < 0.05) inhibitor activity against castor oil induced diarrhoea and PGE2 induced enteropooling in rats when tested at 200 mg/kg. Both extracts also showed significant (P < 0.001) reduction in gastrointestinal motility in charcoal meal test in rats. CONCLUSION: The results point out the possible anti/diarrhoeal effect of the plant extracts and substantiate the use of this herbal remedy as a non/specific treatment for diarrhoea in folk medicine.
Publication Types: Comparative Study
PMID: 15946596 [PubMed / indexed for MEDLINE]
11: Phytother Res. 2004 Sep;18(9):771/3.
Identification of antioxidant compound from Asparagus racemosus.
Wiboonpun N, Phuwapraisirisan P, Tip/pyang S.
Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
Roots of Asparagus racemosus were found to possess antioxidant property. DPPH autography/directed separation resulted in the identification of a new antioxidant compound named racemofuran (3) along with two known compounds asparagamine A (1) and racemosol (2). The structure of 3 was fully characterized by spectroscopic data (UV, MS, 1H NMR, 13C NMR, and 2D NMR). Racemofuran revealed antioxidant property against DPPH with IC50 value of 130 microM. Copyright (c) 2004 John Wiley & Sons, Ltd.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 15478181 [PubMed / indexed for MEDLINE]
12: J Ethnopharmacol. 2004 Apr;91(2/3):251/5.
Immunoadjuvant potential of Asparagus racemosus aqueous extract in experimental system.
Gautam M, Diwanay S, Gairola S, Shinde Y, Patki P, Patwardhan B.
Interdisciplinary School of Health Sciences, University of Pune, Pune, Maharastra 411007, India. gautam_monty@hotmail.com
The immunoadjuvant potential of Asparagus racemosus (Willd.) Family (Liliaceae) aqueous root extract was evaluated in experimental animals immunized with diphtheria, tetanus, pertussis (DTP) vaccine. Immunostimulation was evaluated using serological and hematological parameters. Oral administration of test material at 100 mg/kg per day dose for 15 days resulted significant increase (P = 0.0052) in antibody titers to Bordtella pertussis as compared to untreated (control) animals. Immunized animals (treated and untreated) were challenged with B. pertussis 18323 strain and the animals were observed for 14 days. Results indicate that the treated animals did show significant increase in antibody titers as compared to untreated animals after challenge (P = 0.002). Immunoprotection against intra/cerebral challenge of live B. pertussis cells was evaluated based on degree of sickness, paralysis and subsequent death. Reduced mortality accompanied with overall improved health status was observed in treated animals after intra/cerebral challenge of B. pertussis indicating development of protective immune response. Present study indicates applications of test material as potential immunoadjuvant that also offers direct therapeutic benefits resulting in less morbidity and mortality.
PMID: 15120447 [PubMed / indexed for MEDLINE]
13: J Neural Transm. 2004 Jan;111(1):1/12. Epub 2003 Dec 3.
Experimental excitotoxicity provokes oxidative damage in mice brain and attenuation by extract of Asparagus racemosus.
Parihar MS, Hemnani T.
Biochemistry Division, Faculty of Life Science, School of Studies in Zoology, Vikram University, Ujjain, M.P., India. mdsparihar@yahoo.com
Excitotoxicity and oxidative stress are the major mechanisms of neuronal cell death in neurodegenerative disorders that occurs in both Alzheimer's and Parkinson's diseases. Reactive oxygen species (ROS) that are generated extracellularly and intracellularly by various mechanisms are among the major risk factors that initiate and promote neurodegeneration.Therefore, it is important to find the compound which retard or reverse the neuronal injury. We designed this study to investigate the potential of extract of Asparagus racemosus (AR) against kainic acid (KA)/induced hippocampal and striatal neuronal damage. The dose of AR extract given to experimental animals was based on the evaluation of its total antioxidant activity. Extract of AR displayed potent reductant of Fe(3+). The excitotoxic lesion in brain was produced by intra/hippocampal and intra/striatal injections of kainic acid (KA; 0.25 microg in a volume of 0.5 microl) to ketamine and xylazine (200 and 2 mg/kg b.w. respectively) anesthetized mice. The results showed impairment of hippocampus and striatal regions of brain after KA injection marked by an increase in lipid peroxidation and protein carbonyl content and decline in glutathione peroxidase (GPx) activity and reduced glutathione (GSH) content. The AR extract supplemented mice displayed an improvement in GPx activity and GSH content and reduction in membranal lipid peroxidation and protein carbonyl. We show that the minimizing effect of AR extract on oxidative damage in addition to the elevation of GPx activity and GSH content could eventually result in protective effect on the KA/induced excitotoxicity.
Publication Types: Comparative Study Research Support, Non/U.S. Gov't
PMID: 14714211 [PubMed / indexed for MEDLINE]
14: J Ethnopharmacol. 2004 Jan;90(1):49/55.
Immunoprotection by botanical drugs in cancer chemotherapy.
Diwanay S, Chitre D, Patwardhan B.
Department of Microbiology, Abasaheb Garware College, Pune, India.
Most of the synthetic chemotherapeutic agents available today are immunosuppressants, cytotoxic, and exert variety of side effects that are particularly evident in cancer chemotherapy. Botanical based immunomodulators are often employed as supportive or adjuvant therapy to overcome the undesired effects of cytotoxic chemotherapeutic agents and to restore normal health. Total extract, polar and non/polar extracts, and their formulations, prepared from medicinal plants mentioned in Ayurveda, namely, Withania somnifera (Linn Dunal) (Solanaceae), Tinospora cordifolia (Miers) (Menispermaceae), and Asparagus racemosus (Willd.) (Liliaceae), exhibited various immunopharmacological activities in cyclophosphamide (CP)/treated mouse ascitic sarcoma. Treatment of ascitic sarcoma/bearing mice with a formulation of total extracts of Withania somnifera and Tinospora cordifolia (80:20) and alkaloid/free polar fraction of Withania somnifera resulted in protection towards CP/induced myelo/ and immunoprotection as evident by significant increase in white cell counts and hemagglutinating and hemolytic antibody titers. Treatment with these candidate drugs will be important in development of supportive treatment with cancer chemotherapy.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 14698508 [PubMed / indexed for MEDLINE]
15: Indian J Med Sci. 2003 Sep;57(9):408/14.
Asparagus racemosus//an update.
Goyal RK, Singh J, Lal H.
Pt. B. D. Sharma Post Graduate Institute of Medical Science, Rohtak, Haryana.
Asparagus racemosus (Shatavari) is recommended in Ayurvedic texts for prevention and treatment of gastric ulcers, dyspepsia and as a galactogogue. A. racemosus has also been used successfully by some Ayurvedic practitioners for nervous disorders, inflammation, liver diseases and certain infectious diseases. However, no scientific proof justifying aforementioned uses of root extract of A. racemosus is available so far. Recently few reports are available demonstrating beneficial effects of alcoholic and water extracts of the root of A. racemosus in some clinical conditions and experimentally induced diseases, e.g. galactogogue effect, antihepatotoxic and immunomodulatory activities. The present article includes the detailed exploration of pharmacological properties of the root extract of A. racemosus reported so far.
Publication Types: Review
PMID: 14515032 [PubMed / indexed for MEDLINE]
16: Indian J Exp Biol. 2002 Oct;40(10):1173/7.
Antiulcerogenic activity of Satavari mandur//an Ayurvedic herbo/mineral preparation.
Datta GK, Sairam K, Priyambada S, Debnath PK, Goel RK.
Department of Kayachikitsa, J B Roy State Ayurvedic Medical College and Hospital, Calcutta 700 004, India.
Satavari mandur (SM) is a herbo/mineral preparation containing Asparagus racemosus, which finds mention in ancient Indian texts for treatment of gastric ulcers. The ulcer protective effect of SM, 125/500 mg/kg given orally, twice daily for three, five and seven days, was studied on cold restraint stress/induced gastric ulcer in rats. The effective regimen was found to be 250 mg/kg given for five days and hence was used for further experiments. SM showed significant protection against acute gastric ulcers induced by pyloric ligation but was ineffective against aspirin/ and ethanol/induced ulcers. Further, gastric juice studies showed that, SM significantly increased the mucosal defensive factors like mucus secretion, but had little or no effect on offensive factors like acid and pepsin secretion.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 12693700 [PubMed / indexed for MEDLINE]
17: Indian J Exp Biol. 2002 Oct;40(10):1161/3.
Effect of poly herbal formulation, EuMil, on neurochemical perturbations induced by chronic stress.
Bhattacharya A, Muruganandam AV, Kumar V, Bhattacharya SK.
Neuropharmacology Laboratory, Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.
EuMil, a polyherbal formulation consisting of standardised extracts of Withania somnifera (L) Dunal, Ocimum sanctum L, Asparagus racemosus Wilid and Emblica officinalis Gaertn., is used as an anti/stress agent to attenuate the various aspects of stress related disorders. In the present study, the neurochemical mechanisms underlying the anti/stress activity of EuMil were evaluated by measuring the rat brain monoamine neurotransmitter levels and tribulin activity. Chronic electroshock stress (14 days) significantly decreased the nor/adrenaline (NA) and dopamine (DA) levels in frontal Cortex, pons/medulla, hypothalamus, hippocampus and striatal, hypothalamal region, respectively, and increased the 5/hydroxytryptamine (5HT) level in frontal cortex, pons medulla, hypothalamus and hippocampus. Chronic stress, also increased the rat brain tribulin activity. EuMil (100 mg/kg, p.o., 14 days) treatment normalized the perturbed regional NA, DA, 5HT concentrations, induced by chronic stress. EuMil also significantly attenuated the stress/induced increase in the rat brain tribulin activity. The amelioration of chronic stress/induced neurochemical perturbations by EuMil explains the neurochemical mechanisms underlying the observed putative anti/stress activity of the product.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 12693697 [PubMed / indexed for MEDLINE]
18: Indian J Exp Biol. 2002 Oct;40(10):1151/60.
Effect of poly herbal formulation, EuMil, on chronic stress/induced homeostatic perturbations in rats.
Muruganandam AV, Kumar V, Bhattacharya SK.
R & D Centre, Indian Herbs Ltd., Saharanpur 247 001, India. ihsre@vsnl.com
EuMil, is a herbal formulation comprising the standardised extracts of Withania somnifera (L) Dunal, Ocimum sanctum L, Asparagus racemosus Willd and Emblica officinalis Gaertn., all of which are classified in Ayurveda as rasayanas to promote physical and mental health, improve defense mechanisms of the body and enhance longevity. These attributes are similar to the modern concept of adaptogenic agents, which are, known to afford protection to the human physiological system against diverse stressors. The present study was undertaken to investigate the adaptogenic and antistress activity of EuMil against chronic unpredictable, but mild, footshock stress/induced perturbations in behaviour (depression), glucose metabolism, suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in CF strain albino rats. Panex ginseng (PG) was used for comparison. Gastric ulceration, plasma corticosterone levels, serum lipid, hepatic and renal functions were used as the stress indices. These effects were attenuated by EuMil (dose 100 mg/kg, p.o.) and PG (100 mg/kg. p.o.), administered once daily over a period of 14 days, the period of stress induction period. Further, chronic stress also induced glucose intolerance, suppressed male sexual behaviour, induced behavioural despair and cognitive dysfunction and immunosuppression. All these chronic stress/induced perturbations were attenuated, in a dose dependent manner by EuMil and PG. Thus, the results indicate that EuMil has significant adaptogenic and anti/stress, activity, qualitatively comparable to PG, against a variety of behavioural, biochemical and physiological perturbations, induced by unpredictable stress, which has been proposed to be a better indicator of clinical stress than acute stress. The likely contribution of the individual constituents of EuMil in the observed adaptogenic action of the polyherbal formulation, has been discussed.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 12693696 [PubMed / indexed for MEDLINE]
19: J Ethnopharmacol. 2003 May;86(1):1/10.
Gastroduodenal ulcer protective activity of Asparagus racemosus: an experimental, biochemical and histological study.
Sairam K, Priyambada S, Aryya NC, Goel RK.
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Asparagus racemosus is an Ayurvedic rasayana, which finds mention in ancient Indian texts for treatment of gastric ulcers. The ulcer protective effect of methanolic extract of fresh roots of A. racemosus (ARM), 25/100 mg/kg given orally, twice daily for 5 days, was studied on different gastroduodenal ulcer models. ARM 50 mg/kg, twice daily, orally (total saponins 0.9%) showed significant protection against acute gastric ulcers induced by cold restraint stress (CRS), pyloric ligation, aspirin plus pyloric ligation, and duodenal ulcers induced by cysteamine. ARM in the above dose also significantly healed chronic gastric ulcers induced by acetic acid after 10 days treatment. However, ARM was ineffective against aspirin/ and ethanol/induced gastric ulcers. Further, gastric juice and mucosal studies showed that ARM significantly increased the mucosal defensive factors like mucus secretion, cellular mucus, life span of cells and also possessed significant anti/oxidant effect, but had little or no effect on offensive factors like acid and pepsin.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 12686434 [PubMed / indexed for MEDLINE]
20: Fitoterapia. 2001 Mar;72(3):307/9.
A new isoflavone from the roots of Asparagus racemosus.
Saxena VK, Chourasia S.
Natural Products Laboratory, Department of Chemistry, Dr Harisingh Gour University, /470003 (M.P.), Sagar, India.
The isolation and spectral data of a new isoflavone, 8/methoxy/5,6,4'/trihydroxyisoflavone 7/O/beta/D/glucopyranoside (1), from the roots of Asparagus racemosus are reported.
PMID: 11295314 [PubMed / indexed for MEDLINE]
21: Indian J Exp Biol. 2000 Feb;38(2):119/28.
Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas.
Bhattacharya SK, Bhattacharya A, Chakrabarti A.
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.
Siotone (ST) is a herbal formulation comprising of Withania somnifera, Ocimum sanctum, Asparagus racemosus, Tribulus terristris and shilajit, all of which are classified in Ayurveda as rasayanas which are reputed to promote physical and mental health, improve defence mechanisms of the body and enhance longevity. These attributes are similar to the modern concept of adaptogenic agents, which are, known to afford protection of the human physiological system against diverse stressors. The present study was undertaken to investigate the adaptogenic activity of ST against chronic unpredictable, but mild, footshock stress induced perturbations in behaviour (depression), glucose metabolism, suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in CF strain albino rats. Gastric ulceration, adrenal gland and spleen weights, ascorbic acid and corticosterone concentrations of adrenal cortex, and plasma corticosterone levels, were used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. Additionally, rat brain levels of tribulin, an endogenous endocoid postulated to be involved in stress, were also assessed in terms of endogenous monoamine oxidase (MAO) A and MAOB inhibitory activity. Chronic unpredictable footshock induced marked gastric ulceration, significant increase in adrenal gland weight and plasma corticosterone levels, with concomitant decreases in spleen weight, and concentrations of adrenal gland ascorbic acid and corticosterone. These effects were attenuated by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.), administered once daily over a period of 14 days, the period of stress induction. Chronic stress also induced glucose intolerance, suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests), and immunosuppression (leucocyte migration inhibition and sheep RBC challenged increase in paw oedema in sensitized rats). All these chronic stress/induced perturbations were attenuated, dose/dependently by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.). Chronic stress/induced increase in rat brain tribulin activity was also reversed by these doses of ST and by PG. The results indicate that ST has significant adaptogenic activity, qualitatively comparable to PG, against a variety of behavioural, biochemical and physiological perturbations induced by unpredictable stress, which has been proposed to be a better indicator of clinical stress than acute stress parameters. The likely contribution of the individual constituents of ST in the observed adaptogenic action of the polyherbal formulation, have been discussed.
Publication Types: Research Support, Non/U.S. Gov't
PMID: 11218827 [PubMed / indexed for MEDLINE]
22: Fitoterapia. 2000 Dec;71(6):686/9.
Antitussive effect of Asparagus racemosus root against sulfur dioxide/induced cough in mice.
Mandal SC, Kumar C K A, Mohana Lakshmi S, Sinha S, Murugesan T, Saha BP, Pal M.
Division of Pharmacognosy, Department of Pharmaceutical Technology, Faculty of Engineering and Technology, Jadavpur University, Calcutta/700 032, India. madhabi@giasc101.vsnl.net.in
The methanol extract of Asparagus racemosus root (200 and 400 mg/kg, p.o.) showed significant antitussive activity on sulfur dioxide/induced cough in mice, the cough inhibition (40.0 and 58.5%, respectively) being comparable to that of 10/20 mg/kg of codeine phosphate (36.0 and 55.4%, respectively).
PMID: 11077176 [PubMed / indexed for MEDLINE]
23: J Ethnopharmacol. 2000 Aug;71(3):425/35.
Antioxidant properties of Asparagus racemosus against damage induced by gamma/radiation in rat liver mitochondria.
Kamat JP, Boloor KK, Devasagayam TP, Venkatachalam SR.
Cell Biology Division, Bhabha Atomic Research Centre, 400 085, Mumbai, India.
The possible antioxidant effects of crude extract and a purified aqueous fraction of Asparagus racemosus against membrane damage induced by the free radicals generated during gamma/radiation were examined in rat liver mitochondria. gamma/Radiation, in the dose range of 75/900 Gy, induced lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH). Using an effective dose of 450 Gy, antioxidant effects of A. racemosus extract were studied against oxidative damage in terms of protection against lipid peroxidation, protein oxidation, depletion of protein thiols and the levels of the antioxidant enzyme, superoxide dismutase. An active fraction consisting of polysaccharides (termed as P3) was effective even at a low concentration of 10 microg/ml. Both the crude extract as well as the P3 fraction significantly inhibited lipid peroxidation and protein oxidation. The antioxidant effect of P3 fraction was more pronounced against lipid peroxidation, as assessed by TBARS formation, while that of the crude extract was more effective in inhibiting protein oxidation. Both the crude extract and P3 fraction also partly protects against radiation/induced loss of protein thiols and inactivation of superoxide dismutase. The inhibitory effects of these active principles, at the concentration of 10 microg/ml, are comparable to that of the established antioxidants glutathione and ascorbic acid. Hence our results indicate that extracts from A. racemosus have potent antioxidant properties in vitro in mitochondrial membranes of rat liver.
PMID: 10940579 [PubMed / indexed for MEDLINE]
24: Phytother Res. 2000 Mar;14(2):118/9.
Evaluation of antibacterial activity of Asparagus racemosus willd. root.
Mandal SC, Nandy A, Pal M, Saha BP.
Division of Pharmacognosy, Department of Pharmaceutical Technology, Faculty of Engineering and Technology, Jadavpur University, Calcutta / 700 032, India. abhi@juphys.ernet.in
Different concentrations (50, 100, 150 microg/mL) of the methanol extract of the roots of Asparagus racemosus Willd. showed considerable in vitro antibacterial efficacy against Escherichia coli, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Pseudomonas putida, Bacillus subtilis and Staphylococcus aureus. The effects produced by the methanol extract were compared with chloramphenicol. Copyright 2000 John Wiley & Sons, Ltd.
PMID: 10685109 [PubMed / indexed for MEDLINE]
25: Environ Health Perspect. 1999 Oct;107(10):783/9.
Ancient/modern concordance in Ayurvedic plants: some examples.
Dev S.
University of Delhi, B.R.A. Centre for Biomedical Research, Delhi, India. ssda@ndf.vsnl.net.in
Ayurveda is the ancient (before 2500 b.c.) Indian system of health care and longevity. It involves a holistic view of man, his health, and illness. Ayurvedic treatment of a disease consists of salubrious use of drugs, diets, and certain practices. Medicinal preparations are invariably complex mixtures, based mostly on plant products. Around 1,250 plants are currently used in various Ayurvedic preparations. Many Indian medicinal plants have come under scientific scrutiny since the middle of the nineteenth century, although in a sporadic fashion. The first significant contribution from Ayurvedic materia medica came with the isolation of the hypertensive alkaloid from the sarpagandha plant (Rouwolfia serpentina), valued in Ayurveda for the treatment of hypertension, insomnia, and insanity. This was the first important ancient/modern concordance in Ayurvedic plants. With the gradual coming of age of chemistry and biology, disciplines central to the study of biologic activities of natural products, many Ayurvedic plants have been reinvestigated. Our work on Commiphora wightti gum/resin, valued in Ayurveda for correcting lipid disorders, has been described in some detail; based on these investigations, a modern antihyperlipoproteinemic drug is on the market in India and some other countries. There has also been concordance for a few other Ayurvedic crude drugs such as Asparagus racemosus, Cedrus deodara, and Psoralea corylifolia.
PMID: 10504143 [PubMed / indexed for MEDLINE]
26: Phytother Res. 1999 Jun;13(4):275/91.
Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.
Rege NN, Thatte UM, Dahanukar SA.
Ayurveda Research Centre, Department of Pharmacology and Therapeutics, Seth GS Medical College, Parel, Mumbai, India. kemarc@bom3.vsnl.net.in
Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.
Publication Types: Review
PMID: 10404532 [PubMed / indexed for MEDLINE]
27: J Ethnopharmacol. 1997 Sep;58(1):15/20.
Effect of some Indian herbs on macrophage functions in ochratoxin A treated mice.
Dhuley JN.
Department of Pharmacology and Toxicology, Research Centre, Hindustan Antibiotics Limited, Pimpri, India.
The effect of Indian herbs namely, Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa on the functions of macrophages obtained from mice treated with the carcinogen ochratoxin A (OTA) was investigated. The chemotactic activity of murine macrophages was significantly decreased by 17 weeks of treatment with OTA compared with controls. Production of interleukin/1 (IL/1) and tumor necrosis factor (TNF) was also markedly reduced. Treatment with Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa significantly inhibited OTA/induced suppression of chemotactic activity and production of IL/1 and TNF/alpha by macropahges. Moreover, we found that Withania somnifera treated macrophage chemotaxis and that Asparagus racemosus induced excess production of TNF/alpha when compared with controls.
Publication Types: Comparative Study
PMID: 9324000 [PubMed / indexed for MEDLINE]
28: Indian Pediatr. 1996 Aug;33(8):675/7.
Randomized controlled trial of Asparagus racemosus (Shatavari) as a lactogogue in lactational inadequacy.
Sharma S, Ramji S, Kumari S, Bapna JS.
Department of Pharmacology, Maulana Azad Medical College, New Delhi.
Publication Types: Clinical Trial Randomized Controlled Trial
PMID: 8979551 [PubMed / indexed for MEDLINE]
29: Pharmacol Res. 1993 Dec;28(4):333/40.
Phytochemical screening and molluscicidal potency of some Zairean medicinal plants.
Chifundera K, Baluku B, Mashimango B.
Laboratory of Medicinal Plants and Herpetology, Centre de Recherche en Sciences Naturelles, Bukuvu, Kivu, Zaire.
A total number of 48 plants used in the Zairean pharmacopoeia were tested against molluscan intermediate hosts of schistosomiasis and fascioliasis. Aqueous and ethanolic extracts from five plants: Maesa lanceolata, Chenopodium ugandae, Asparagus racemosus, Phyllanthus nummulariifolius and Crinum zeylanicum, exhibited high mortality rate (100%) against Biomphalaria pfeifferi and Lymnaea natalensis. Their LC50 was respectively 0.1, 5, 5, 10 and 50 mg ml/1 for B. pfeifferi and 0.5, 5, 1, 10 and 10 mg ml/1 for L. natalensis. The activities are attributed to the presence of terpenoids, steroids and saponins in the plant extracts. Except for the extracts from Ch. ugandae however, the plants have shown toxic effect on fishes and aquatic insects.
PMID: 8140033 [PubMed / indexed for MEDLINE]
30: J Postgrad Med. 1993 Jan/Mar;39(1):22/5.
Quantitation of microbicidal activity of mononuclear phagocytes: an in vitro technique.
Rege NN, Dahanukar SA.
Dept of Pharmacology, Seth GS Medical College and KEM Hospital, Parel, Bombay, Maharashtra.
An in vitro assay technique was set up to determine the phagocytic and microbicidal activity of a monocyte/macrophage cell line using Candida species as test organisms. The norms were determined for the activity of peritoneal macrophages of rats (24.69 +// 2.6% phagocytosis and 35.4 +// 5.22% ICK) and human (27.89 +// 3.63% phagocytosis and 50.91 +// 6.3% ICK). The assay technique was used to test the degree of activation of macrophages induced by metronidazole, Tinospora cordifolia and Asparaqus racemousus and to compare their effects with a standard immunomodulator muramyl/dipeptide. All the three test agents increased the phagocytic and killing capacity of macrophages in a dose dependent manner upto a certain dose, beyond which either these activities were found to have plateaued or decreased. The optimal doses for MDP, Metronidazole, Asparagus racemosus and Tinospora cordifolia were found to be 100 micrograms, 300 mg/kg, 200 mg/kg and 100 mg/kg respectively. Patients with cirrhosis were screened for defects in monocyte function. The depressed monocyte function (20.58 +// 5% phago and 41.24 +// 12.19% ICK; P < 0.05) was observed indicating a compromised host defense. The utility of this candidicidal assay in experimental and clinical studies is discussed.
PMID: 8295140 [PubMed / indexed for MEDLINE]
31: J Postgrad Med. 1990 Apr;36(2):91/4.
Effect of Asparagus racemosus (Shatavari) on gastric emptying time in normal healthy volunteers.
Dalvi SS, Nadkarni PM, Gupta KC.
Department of Pharmacology, Seth G. S. Medical College, Bombay, Maharashtra.
Asparagus racemosus (Shatavari) is used in Ayurveda for dyspepsia (amlapitta) and as a galactogogue. It was hence compared with a modern drug, metoclopramide, which is used in dyspepsia to reduce gastric emptying time. Gastric emptying half/ time (GE t1/2) was studied in 8 healthy male volunteers using a cross/over design. The basal GE t1/2 in volunteers was 159.9 +// 45.9 min (mean +// SD) which was reduced to 101 +// 40.8 min by Shatavari (p less than 0.001) and to 85.3 +// 21.9 by metoclopramide (p less than 0.001). Metoclopramide and Shatavari did not differ significantly in their effects.
Publication Types: Clinical Trial Comparative Study Research Support, Non/U.S. Gov't
PMID: 2097375 [PubMed / indexed for MEDLINE]
32: J Postgrad Med. 1989 Oct;35(4):199/203.
Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus.
Rege NN, Nazareth HM, Isaac A, Karandikar SM, Dahanukar SA.
The hypothesis that macrophages appear to play a pivotal role in the development of intraperitoneal adhesions and that modulation of macrophage activity, therefore, is likely to provide a tool for prevention of adhesions, was tested in the present study. Effect of Asparagus racemosus, an indigenous agent with immunostimulant properties, was evaluated in an animal model of intraperitoneal adhesions induced by caecal rubbing. Animals were sacrificed 15 days following surgery. The peritoneal macrophages were collected to assess their activity. At the same time, peritoneal cavity was examined for the presence of adhesions, which were graded. A significant decrease was observed in the adhesion scores attained by animals receiving Asparagus racemosus. This was associated with significant increase in the activity of macrophages (70.1 +// 2.52), compared to that in surgical controls (53.77 +// 10.8). These findings support our hypothesis and provide a novel approach for the prevention and management of post/operative adhesions.
PMID: 2641519 [PubMed / indexed for MEDLINE]
33: Methods Find Exp Clin Pharmacol. 1988 Oct;10(10):639/44.
Comparative study of immunomodulating activity of Indian medicinal plants, lithium carbonate and glucan.
Thatte UM, Dahanukar SA.
Department of Pharmacology, Seth G.S. Medical College, Bombay, India.
The protective effects of Asparagus racemosus (AR) and Tinospora cordifolia (TC) against myelosuppression induced by single doses of cyclophosphamide (CP) have been previously reported. Presented here are the results of a comparative study between AR, TC, glucan and lithium carbonate against the myelosuppressive effects of single and multiple doses of cyclophosphamide in mice. Cyclophosphamide was administered as a single dose 200 mg/kg subcutaneously to one group of mice, while a second group received 3 doses of 30 mg/kg intraperitoneally. Both groups received AR, TC and lithium orally for 15 days before CP. Glucan was administered intravenously in 3 doses, before cyclophosphamide in the first group and together with cyclophosphamide in the second group. In both groups peripheral and differential WBC counts were done before and after drug treatment and serially after cyclophosphamide injection. All four drugs produced leucocytosis with neutrophilia. When compared to control group, all 4 drugs prevented, to varying degrees, leucopenia produced by cyclophosphamide. We conclude, therefore, that both indigenous plants, AR and TC, are potent immunostimulants, with effects comparable to lithium and glucan. They need further evaluation in patients receiving cytotoxic drugs.
Publication Types: Comparative Study Research Support, Non/U.S. Gov't
PMID: 3236938 [PubMed / indexed for MEDLINE]
34: Int J Cancer. 1981 Nov 15;28(5):607/10.
Inhibitory action of Asparagus racemosus on DMBA/induced mammary carcinogenesis in rats.
Rao AR.
PMID: 6796529 [PubMed / indexed for MEDLINE]
35: Planta Med. 1969 Oct;17(4):393/5.
Amylase and lipase activities in the root of Asparagus racemosus.
Dange PS, Kanitkar UK, Pendse GS.
PMID: 5380197 [PubMed / indexed for MEDLINE]
36: Indian Vet J. 1969 Aug;46(8):718/21.
Asparagus racemosus willd//form bordi, as a galactogogue, in buffaloes.
Patel AB, Kanitkar UK.
PMID: 5389557 [PubMed / indexed for MEDLINE]
37: Arch Int Pharmacodyn Ther. 1969 May;179(1):121/9.
Antioxytocic action of saponin isolated from Asparagus racemosus Willd (Shatavari) on uterine muscle.
Gaitonde BB, Jetmalani MH.
Publication Types: In Vitro
PMID: 5348388 [PubMed / indexed for MEDLINE]
38: Indian J Exp Biol. 1968 Jan;6(1):55/7.
Effects of alcoholic extracts of Asparagus racemosus on mammary glands of rats.
Sabnis PB, Gaitonde BB, Jetmalani M.
PMID: 5666039 [PubMed / indexed for MEDLINE]
39: Indian Med J. 1967 Jul;61(7):165.
Galactogogue effect of Asparagus racemosus. Preliminary communication.
Joglekar GV, Ahuja RH, Balwani JH.
PMID: 5624301 [PubMed / indexed for MEDLINE]
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