Herbal Drug Toxicity

Herbs are the mines of useful drugs but due to presence of certain chemical constituents they produce the toxicity. The wonderful references and treatises on herbal cure that have been available in ancient literature. Most of the people used natural plants for diagnosis and treatment of disease as home remedies. The present review mainly focuses on some medicinal plants with their biological sources, chemical constituents, usual doses and adverse effects.

HERBAL DRUG TOXICITY-A REVIEW

 

Mishra B. Shanti 1, Dwivedi Sumeet2 and   Shashi Alok 3

1,Vinayaka Mission's College of Pharmacy, Salem (T.N.)

2, Chordia Institute of Pharmacy, Indore (M.P.)

3, I.E.S.College of Pharmacy Bhopal (M.P.)

ABSTRACT

Herbs are the mines of useful drugs but due to presence of certain chemical constituents they produce the toxicity. The wonderful references and treatises on herbal cure that have been available in ancient literature. Most of the people used natural plants for diagnosis and treatment of disease as home remedies. Later on powerful synthetic drugs come into practice, which cures the disease at faster rate than herbal drugs. As time goes the excessive use of these drugs shows unwanted toxic effects. Again it is time of natural drugs comes in practice, as a safer drugs but most of peoples unaware of the adverse effects of some medicinal plants which were used frequently as home remedies as well as herbal drugs. The present review mainly focuses on some medicinal plants with their biological sources, chemical constituents, usual doses and adverse effects.

 

For Correspondence:

Shanti B. Mishra

Vinayaka Mission's College of Pharmacy,

Salem (T.N.)

E-Mail: shanti321181yahoo.co.in, This email address is being protected from spambots. You need JavaScript enabled to view it.

 

INTRODUCTION

 

The world and Indian sub continent is enriched by a variety of flora both aromatic and medicinal, because of wide variety of climatic factors. Right from the high ranges of Himalayan track up to the sea shore of Kanyakumari numerous types of plants well recognized by the botanist and local people are actually the living treasure of this country.(Krishna Rao and Nigam, 1976). Millions of people in the world will always use herbal medicines because they believe in them and regard them as their medicine, in contrast to the allopathic (conventional western) system of medicine brought in form outside. These medicinal herbs are available locally and are prescribed by traditional practitioners of medicines who are the part of community and in whose presence the patient feels comfortable, Even in western country there is now an increased use of herbal medicines, largely because of a belief that powerful synthetic agents used in western medicines can exert more unwanted side effects and are too often used indiscriminately and irritation ally. Many members of public also have a mistake impression that medicines derived from natural plants are harmless. Although generally natural medicines induce fever side effects than conventional drug, there are plants that cause powerful side effects (Chaudhary, 1995). Among the entire world it is estimated that 35,000 to 70,000 species have been used for medicinal purpose, some 5000 of these have been studies in biomedical research. Herbal medicines continue to play an important role in primary health care. Most of the ingredients have a high therapeutic index and are unlikely to cause toxicity even if used in considerable excess, but there are a few materials with well-recognized toxicity. A common example is death from consuming wild mushrooms. Most compounds have the potential to be harmful, if consumed improperly or in excessive amounts. Some times severe poisoning because of the accumulation if the active ingredients such is the case with the herbs that contain pyrrolizidine alkaloid, which are known for their strong hepatotoxic and carcinogenic action.

In USA, women died after an ointment that contained podophyllin was used to remove a wart from vagina. Aloe may induce kidney inflammation and hemorrhoids; liquorice may cause oedema, hypertension and even cardiac arrest due to severe depletion of potassium and retention of sodium. A case of cardiac arrest due to the excessive ingestion of liquorice has been reported. Long-term use of ginseng results various side effects such as insomnia, nervousness, hypertension, and amenorrhoea. Infants and young children with immature liver enzyme may be more sensitive to the effects of a hepatically metabolized essential oil because of their relative inability to detoxify it. (Tamizhmani et al.2003)

Indian people have a tremendous passion for medicinal plants and use them for a wide range of health related applications from common cold to memory improvements and enhancement of general immunity (Mukherjee, 2005).

Herbs have created in interest among the people by its clinically proven effects like immunomodulation, adaptogenic and anti mutagenic etc. the expended use of herbal medicines has led to concerns relating to its safety, quality and effectiveness. In practice however, three groups of herbs can be identified from a safety point of view. At first a hand ful of herbs that contain near pharmaceutical concentration of poisonous constituents, which should not taken internally. Example: Belladona, Arnica and Digitalis. Second the herbs are with powerful action often causing nausea and vomiting. Example: Lobelia and Euonymus. At last there is a idiosyncratic grouping of herbs which have been alleged with some scientific support, it exhibit specific kinds of toxicity. Example: pyrrolizidine alkaloids containing comfrey, male fern, mistletoe and yohimbe. Toxicants can interrupt metabolism of carbohydrate, lipids, and proteins, alter synthesis release and storage of harmones (Edwin et al. 2005).

Some herbal alkaloids; Vincristine, Rutaecarpine, Evodamine, dehydroevodiamine, class of AQ, triterpinoids and flavonoids serve as substrates, inducers or inhibitors of CYP'S (Harle and Gaikwad, 2005).

Adverse drug reaction reports are a critical source of herbal drug safety information. Artemisia absinthium L contains an active narcotic derivative, which cause central nervous system disorders and generalized mental deterioration. Heliotropium europaeum containing pyrrolidine alkaloids, potent hepatoxins. Valerian officinalis containing valepotriates, which acts a sedative and muscle relaxants in laboratory animals. In the WHO database, there are presently11, 716 suspected herbal plants case reports. The commonly reported reaction are; pruritus, urticaria, rash, rash erythematous,nausea, vomiting, diarrhoea, fever, abdominal pain, dyspnoea.(Patvardhan, 2004)

The risk that the alkaloid Berberine in chinese coptis species elicits jaundice seems to be most substantial in infants who are deficient in glucose 6 phosphate dehydrogenase. The root of Saliva miltiorrhiza which has been used traditionally in china for the treatment of coronary disease can enhance the anticoagulant activity of warfarin, when both drugs are taken together.(Dureja et al.2005)

The world health organization (WHO) released guidelines for good agricultural and collection practices for medicinal plants an industry estimated worth more than US $60 billion. One of the major causes of adverse events is directly linked to the poor Quality of herbal medicines, including raw medicinal plant materials, and to the wrong identification of plant species. Cultivating, collecting, and classifying plants correctly are therefore of the utmost importance for the quality and safety of products. Other species or plants parts through misidentification, accidental contamination or intentional adulteration, all of which may have unsafe consequences, may contaminate medicinal plants collected in the wild (Medicinal plants, 2004).

 

 

TABLE-1: Details of Potential herbal drugs showing adverse effect (Indian Herbal Pharmacopoeia (1998),Vol.I.and  Vol. II)

 

 

S.No.

Vernacular Name

Biological Name

Family

Part used for activity

  1.  

Andrographis paniculata

Andrographis paniculata

Wall

Acanthaceae

Leaves and Stem

  1.  

Aloe vera

 

Aloe barbadensis Mill

Liliaceae

Leaves        

 

      3.

Apang

Achyranthesaspera L.

Amaranthaceae

Whole plant

      4.

Boerhavia

Boerhavia diffusa L.

Nyctaginaceae

Whole plant

      5.

Bramhi

Bacopa monnieri L.

Scrophulariaceae

Whole plant

      6.

Badi saunf

Foeniculum vulgare Mill

Umbelliferae

Fruit

      7.

Dhane

Coriandrium sativum L.

Apiaceae

Fruits

      8.

Dhatura

Datura stramonium L.

Solanaceae

Leaves

      9.

Erandi

Ricinus communis L.

Euphorbiaceae

Leaves, root seeds

     10.

Haldi

Curcuma longer L.

Zingiberaceae

Dried rhizome

     11.

Isapgol

Plantago ovata forsk

Plantaginaceae

Ripe seeds

     12.

Jangli amla

Phyllanthus amarus schum.

Euphorbiaceae

Aerial branches

     13.

Kutaki

Picrorhiza kurroa royle

Scrophulariaceae

Rhizome and roots

     14.

Kamuni

Solanum americanum L.

Solanaceae

Whole plant

     15.

Kali mirch

Piper nigrum L.

Piperaceae

Unripe fruits

     16.

Kantakari

Solanum xanthocarpum schrad & wendl

Solanaceae

Whole plant

     17.

Lavang

Syzygium aromaticum L.

Myrtaceae

Flower buds

     18.

Maka

Eclipta alba L.

Asteraceae

Whole plant

     19.

Moti-brahmi

Cantella asiatica L.

Apiaceae

Fruits

     20.

Adrak

Zingiber officinale will

Zingiberaceae

Rhizome

     21.

Pudina

Mentha piperita L.

Lamiaceae

Leaves

     22.

Papra

Podophyllum hexandrum Royle

Berberidaceae

Rhizome and roots

    23.

Revand chini

Rheum emodi wall

Polygonaceae

Rhizome

    24.

Sapergandha

Rauwolfia serpentina L.

Apocynaceae

Roots

    25.

Tulsi

Ocimum tenuiflorum L.

Lamiaceae

Leaves

    26.

Vasaka

Adhatoda zeylanica

Acanthaceae

Leaves

    27.

Yashtimadhuh

Glycyrrhiza glabra L.

Fabaceae

Roots

 

TABLE-2:  Details of potential herbal drugs with their activity.

 

 

S.

No.

Vernacular name

Chemical constituents

Biological activity

Usual Dose

      1.

Andrographis paniculata

Andrographalin, Andrograpanin,

Deoxyoxoandrographolide, oroxylin, wogonin.  

Bitter tonic, febrifuge, Hepatoprotective

1.5-3 gm of powder for anti pyretic,anti infective.25-75 gm antidiarrhoeal, 0.5-1 ml kalmegh extract as bitter

2.

Aloe vera

 

Pentocides-Barbaloin,aloin,isobarbaloin,

Betabarbaloin

Catharatic,

Purgative,

Constipation

50-200 mg powdered drug

      3.

Apang

Aglycone A,B,C,D, ecdysterone

Astringent,

Emetic

Decoction 28-56 ml

      4.

Boerhavia

Punarnavoside,lignans,

Liridodendrin,syringa resinol,

isofuroxanthone

Diuretic,

Hepatoprotective

20-30 gm decoction,2-8  ml extract as diuretic

      5.

Bramhi

Bacoside A ,Bhersaponin,betulic acid,herpestine,brahmine

Brain tonic

5-10 gm powdered drug,8-16 ml infusion.

      6.

Badi saunf

E-anethole,fenchone,

Methylchavicol,imperatonin,

miyabenol

Carminative,

spasmolytic

10-40 gm powder

5-10 ml oil

      7.

Dhane

S(+)linalool,a pinene,b pinene,

g terpinene, citronellol

Carminative

4-8 gm powder,0.1-0.3 ml oil,12-20 ml infusion

      8.

Datura

Hyoscyamine,hyoscine,

Quercetin,kaempferol,

Coumarins

Expectorent,anti spasmodic

50-100 mg dried leaf, and same infusion

      9.

Erandi

Ricinolic acid, ricine,quercetin,

N-demethylricinine

Laxative,

Lactogogue,

Anti rheumatic

Castor oil 4-16 ml as a laxative, root paste 3-6 gm, leaf paste 9-15 gm

 

                10.

Haldi

Curcuminoides,

Desmethoxycurcumin,

Ukonan A,B,C,D.

Antiinflammatory

stomachic

1-3 gm of powdered drug,3-9 gm crude drug.

     11.

Isapgol

Arabinoxylans, xylon, xylose,

Linoleic acid, oleic acid,

Oxygenated fatty acids,iridoides.

Bulk forming laxative, antidiarrhoeal.

5-15 gm of seed pre swollen with water

     12.

Jangli amla

Lignans, phyllanthin,

Hypophyllanthin,amariin,amarulone,

nyrphyllin

Anti viral

3-6 gm powder, 14-28 ml infusion

 

 

 

 

     13.

Kutaki

Picroside I, kutkoside, veronicosides,minecoside,picein,

And rosin.

Bitter tonic,

Hepatoprotective

3-4 gm for anti periodic, 0.12gm as bitter tonic

     14.

Kamuni

Solanine, solasodine, solamargine,

Tigogenin,diosgenin

Expectorent,

Antiinflammatory

Diuretic.

15-25 ml infusion,1-2 gm fruit powder,28-56 ml decoction.

     15.

Kali mirch

Piperine, pipercine, guineensine,

Sarmentine,eugenol,1,8 cineol

Anticonvulsant,

Bioavalibility enhancer

4.5-9 gm

     16.

Kantakari

Oslasodine,solamargine,solasonine,

b solamargine

Expectorent

20-30 gm drug as decoction

     17.

Lavang

Phenol eugenol,b caryophyllin,aa cardinol,fenchone,hexanal humulene,

Carminative

stomachic

Clove 100-200 mg ,clove oil 0.05-0.2 ml

     18.

Maka

Coumestan,wedelolactone,ecliptal,

Hentriacontanol,14-heptacosonal,

Hepatoprotective

3-6 gm powder ,4-12 ml infusion

     19.

Moti-brahmi

Madecassoside,asiaticoside,

Asiatic acid

Brain tonic

sedative

0.5 gm powder drug for leprosy,90-150 mg for external application

     20.

Adrak

Oleoresin, gingerols,a zingiberene,

b sesquiterpene, shoganol,gingerdiols,gingerdiones,

gingernones.

Carminative,

Antiemetic,

Antiinflammatory

1-2 gm powder as anti emetic

 

 

    

21.

 

Pudina                  

Menthol ,menthone,menthofuran,

Cineol, luteolin,apigenin,ursolic acid,a amyrin

Carminative,

spasmolytic

Dried leaf 2-3 gm,tincture 2-3 ml

     22.

Papra

Podophyllotoxins, arylterralin,

Lignan, a petatin,b peltatin

Anticancer

Podophyllum 10-40% for external applicationfor anogenital warts

    23.

Revand chini

Emodin ,chrysophanol, rhein,

physcion

Laxative

1-4 gm dried drug, 30-100 mg of hydroxyanthracene derivative preparation

    24.

Sapergandha

Reserpine, rescinnamine,yohimbine,

ajamaline

Antihypertensive

100-150 mg twice daily

    25.

Tulsi

Eugenols, b caryophylline,bornyl acetate,b elemene,neural,camphene

Stigmestrol.

Expectorant

Leaf infusion 4-12 ml , decoction 28-56 ml

 

 

 

  26.

Vasaka

Pyrralazoquinazoline,vasicine,vasicol,

Adhatonine,vasicinol

 

 

 

Bronchodilatory,

Expectorant,

Antimicrobial against gingival inflammation

 

1-2 gm as expectoprant, 1-2 ml in liquid extracts or syrup

 

 

 

    27.

Yashtimadhuh

Glycyrrhizin , Glabranin A & B,

Glycyrrhetol ,formononetin,

glabrone, herniarin

Antiinflammatory

Anti ulcer

Powder 2-4 gm,liquirice powder4-8 ml liquid extract 2-4 ml.


 

TABLE -3: Examples of adverse effect that may occur with herbal plants (Barnes et al. 1996)

 

S.No.

Potential adverse effect

Constituents/herbal ingredients

1.

Allergic, hypersensitive

Sesquiterpene lactones:arnica, chamomile and

Feverfew.

2.

Phototoxic

Furanocaumarins:angelica, celery,wild carrot

3.

Immune

Canavanine:alfalfa

4.

Cardiac

Cardiac glycosides:pleurisy root ,squill

5.

Endocrine/hypoglycemic

Alflfa,fenugreek

6.

Hyperthyroid

Iodine:focus

7.

Hormonal/mineralocorticoid

Triterpinoids:liquorice

8.

Oestrogenic anti androgen

Isoflavanoids:alfalfa, red clover saponins:

Ginseng saw palmetto

9.

Irritant /GIT

Anthraquinones:capsaicinoids, diterpenes,

Saponins, terpene rich volatile oil

10.

Renal

Aescin:Horse chestnut, terpene rich volatile oil

11.

Toxic/hepatotoxic/

carcinogenic

Pyrrolizidine alkaloids:comfrey, liferroot,

b asarone:calamus, lignans:chaparral, safrole:

sassafras

12.

Mitogenic

Proteins:mistletoe,pokeroot

13.

Cyanide poisoning

Cyanogenetic glycoside:apricots

 

 REPORTED TOXICITY OF SOME HERBS

 

  • Andrographis paniculata- gastric discomfort, vomiting and loss of appetite may be caused by large oral doses of the drug. Injection of the crude drug extract may lead to anaphylactic shock. (Chang and But, 1986)
  • Aloe-vera- 1.prolonged use may severely affect the electrolyte balance and loss of potassium may ultimately reduced the laxative action and disturb the cardiac rhythm in heart patients. Larger doses lead to accumulation of blood in pelvic region and reflux stimulation of uterine muscle and may bring about abortion or premature birth in late pregnancy. Toxic doses can also cause kidney damage. These reasons the drug is contraindicated in pregnancy, lactation kidney complication, irritable bowel condition (Bissett, 1994)
  • Apang- Apang plant possesses abortifacient and contraceptive activity and not used in pregnancy. The drug is devoid of any adverse or side effects at doses up to 8 gm/kg orally in rabbits.(Akhtar and Iqbal, 1991)
  • Bramhi- Sedation associated with the therapeutic doses of drug.
  • Badi saunf- The pure essential oil reinforces inflammation and has an irritant action on the intestinal musculature. Pure fennel oil must not be used for infants or young children due to the danger of laryngeal spasm, dyspnoea, and excitatory state (Singh et al, 1993). It is one of the plant known to provoke photo dermatitis in man.(Bissett.1994)
  • Dhane- Allergic reactions like contact dermatitis are known to be associated with the use of powdered coriander and more particularly with the oil.(Bissett.1994)
  • Datura- Careful consideration of the toxicity of the plant is required before its use. Its overdose, the mouth become dry, an intense thirst develop, the vision get blurred with prominant mydriasis and the heart rate increases. This is followed by hallucination, delirium and loss of motor coordination which may lead to coma and ultimately death by respiratory failure.(Lewis and Elvin, 1977, Evens, 1989)
  • Erandi- Long term use of castor oil must be avoided because strong purgative action can cause colic as well as dehydration with electrolyte imbalance and also reduction of absorption of nutrients. it should not taken during pregnancy as it can cause uterine contraction. (Pharmacopoeia of India, 1991)
  • Haldi-  it may cause allergic reactions to persons who are not previously exposed to the drug.21 cytotoxic effects of curcuminoides have been observed in cell culture but nothing is known about the oral toxicity of curcuminoides.(Seetharam and Pasricha,1989)
  • Isapgol-  The drug should be administered in case faecal impaction or intestinal obstruction and diabetes mellitus where insulin adjustment is difficult.(Haung, 1993)
  • Plantago preparations may affect the absorption of other drugs being taken simultaneously.(Bradley,1992)
  • Jangli amla-  Clinical trials conductedso far have not revealed any toxic effect for P.amarus.(Ansari et al.1988)
  • Kutaki-  Kutkin free extracts are not only devoid of any hepatoprotective activity but may aggravate galactosamine toxicity and therefore should be avoided in the treatment of liver disorder .(De smet et al.1993)
  • Kamuani-  Makoi higher doses of fruits powder may cause lethargy, diarrhoea and pyloric obstruction( Newall et al., 1996). Children who have eaten the berries from the plant have complained of headache, vertigeo, nausea, vomiting, and tenesmus.(Chaudhry, 1996)
  • Kalimirch- prolonged administration of the drug can results in withdrawal syndrome. The drug should not be given with alcohol.(Rao et al.,1997).
  • Kantakari-  Toxicity studies on rats  have shown that the hot water extract of the drug could be toxic at 200mg/kg dose.(Haung,1993)
  • Lavang-  Clove oil should be used with caution orally and should not be used on the skin.(Singh and Singh, 1993)
  • Maka-  alcoholic extract shows no sign of toxicity in rats and mice. the minimum lethal dose greater than 2.0gm/kg when given orally and intraperitonial in mice.(Goodman and Gillman, 1966).the drug traditionally considered safe.
  • Moti-bramhi-  contact dermatitis has been observed due to madecassol.triterpene glycoside have been identified as having oncogenic activity and asiaticoside has been implicated as possible carcinogenic where repeated application .(Laeruym and Andiversen,1972)
  • Adrak-  Excessive dose of ginger may interfere with existing cardiac, antidiabetic, anticoagulant therapy and should not be used in food during pregnancy and lactation.(Newall et al. 1996)
  • Pudina- Most of the adverse effects reported are associated with relatively high intake of menthol via confectionary, pharmaceutical and other products (stewart et al, 1987)
  • Papra- Papra podophyllin is mitotic poison and its misuse can leads to significant toxicity. Its use in pregnancy has been associated with congenital abnormalities and fetal death.(Gattuso and Kanum, 1994)
  • Revand chini-  non standard anthraquinones containing laxative preparations should not taken during the pregnancy and lactation since there pharmacological action is unpredictable. Rhubarb is also contraindicated in arthritis, intestinal obstruction and renal disorders .(Kang et al.1985)
  • Serpangandha- Rauwolfia products are contracted in patients who have previously shown hypersensitivity to rauwolfia or its alkaloids. They are also contracted in pregnancy, in mental depression, and active peptic ulcer. (Liberti and Lawrence,1992)
  • Tulsi- the herb and essential oil should not be used during pregnancy and lactation or for prolonged periods.(Bowen and Cubbin,1992)
  • Vasaka-  it has abortifacient activity and not used in pregnancy.
  • Yashtimadhuh-  the drug when used with in the recommended dosages the treatmentperiod is devoid of any adverse reaction.however,if taken in excessive amount it can cause metabolic disturbances known as pseudosteronism leading to oedema, hypertension and weight gain.(Lewis and Elwin,1977, Hikino,1985)

 

Some common examples of toxicity oxalate crystals from Halogetan glomertus. Bieb(chenopodiaceous)can damage the tubule in kidney because they are insoluble, precipitate,and collect in the kidney tubule, which then obstructs them.(Newall et al. 1996, James and butcher,1982).

The alkaloids, aconitine in aconite, affects the sodium channel on the cell membrane which can lead to increased uptake in sodium and other ions. This leads to cardiac arrhythmias and depression of respiratory system. (Lincoln and Black, 1980, Friese, 1997)

Tubocurarine, the most potent constituent in curare, denies access to neurotransmitters in nerve receptors, this result in paralysis of the muscle, including the respiratory muscle.(Chan et al.)

The psychotropic plants alkaloids; harmine and hermaline resemble serotonin and are thought to block the serotonin receptor in the brain.morphine and other opiate bind to neurotransmitter receptor in the brain. In large amount they can depress the respiratory center in the brain. Glucosinolates are compounds found commonly in plants of mustard family.some can be powerful irritant to eyes, skin and respiratory tract. (Koppaniya and Vivino,1944)

Some alkaloids disrupt nerve tissue such as coniine from poison hemlock causing nervousness; trembling, arrhythmia, bradycardia, and fatal paralysis, saponins can cause gastric upset because of its "soapy" properties, which interfere with digestion.

Impaired memory loss in human being by plants like Belladona, Datura, cardiotoxic effects by digitalis, anticholinergic symptoms by Belladona. Cyanide poisoning by seeds, bark and leaves of apricots, hypokalemia, hypertension,and cardiac problems by Liquirice,renal failure by herbs used for weight loss,hypertension ,nervousness, skin rashes, and sleeplessness by ginseng ,hepatotoxicity by turmeric, poisoning by colchicine, hypersensitivity reaction by Ephedra and severe contact dermatitis caused by garlic are few toxicities produced by herbs.(Brown and andmorra,1995)

Other factors responsible for toxicity: (WHO graphics, 1999, Tyler, 1987, Bhushan et al. 2003, Vishwanathan et al.2003, WHO Medicinal Plants, 2004, Goldman and Myserson, 1991)

i-  Substitution

ii- Heavy metal.

iii-Contamination

iv- Poor local technology

v-  Storage

vi- Product movement

CONCLUSION

The ongoing concept of natural drugs with free from toxic effects is not completely true, but they also has some potential toxic effects. People are using these medicines blindly, so it is the prime responsibility of the dispenser to give the knowledge and to aware the people about toxic effects of such medicines, which were used as, home remedies.

REFERENCES

  1. Atal C.K., (1980):  In chemistry and Pharmacology of vasicine- an oxytocic and abortifacient; Published by the Director,R.R.L., Jammu Tawi
  2. Akhtar M.S. and Iqbal J., (1991):j.Ethanopharmacology.31,49
  3. Ansari R.A., Aswal B.S., Chander R., Dhawan B.N., Garg N.K., Kapoor N.K., Kulshreshtha D.K., Mehdi H., Mehrotra B.N., Patnaik G.K. and Sharma S.K., (1988)Ind. J. Med. Res. 87,401.
  4. Bradley P.R.,(ed), (1992): British herbal compendium,BHMA,Dorset,Vol.I, 136
  5. Barnes J., Anderson L.A., and Phillipson D.J., (1996):Herbal Medicines, second ed. 15.
  6. Brown P.D. and Andmorra M.J.,(1995):J. Agric Food Chem., 43:3070-3074
  7. Bhushan B., Bhalla H.L., Manvi F.V. and Shah F., (2003):The Indian Pharmacist, 2-3
  8. Bissett N.G., (ed) (1994): Herbal drugs and Phytopharmaceuticals; Medpharm Scientific Publisher,Stuttgart, 59
  9. Bissett N.G., (ed) (1994): Herbal drugs and Phytopharmaceuticals; Medpharm Scientific Publisher,Stuttgart, 159.
  10. Bissett N.G., (ed) (1994): Herbal drugs and Phytopharmaceuticals; Medpharm Scientific Publisher,Stuttgart, 201.
  11. Bissett N.G., (ed) (1994): Herbal drugs and Phytopharmaceuticals; Medpharm Scientific Publisher,Stuttgart, 174.
  12. Bowen I.H., and Cubbin I.J., (1992): In Adverse Effects Of Herbal Drugs, Springer-Verlag,Berlin,Vol.1,171.
  13. Chaudhary R.R. (1995): Natural medicinal Products,chapter 103 in principles of pharmacology basic concepts and clinical application.chapmann and hall an international Thomson publishing company,1529
  14. Chan T.Y.,Tomlinson B.and Critchley J.A., Aust Nz J Med 23:268-271
  15. Chaudhri R.D.,(1996):Herbal Drug Industry;Eastern publishers,N.Delhi.1st ed.226
  16. Chang H.M., and But P.P.H.(eds), (1986):Pharmacology and Applications of Chinese Materia Medica;Vol 1., World scientific,918.
  17. Dureja D., kaushik D.,Kumar N., and Sardana S., (2005):Aloe Vera, The Indian Pharmacist, 9-13
  18. Dr.Mukherjee P.K.,(2005),:Promotion and development of botanical with international coordination, the pharma review,21-24
  19. De Smet P.A.G.M.,Keller K.,Hansei R. and Chandler R.F.,(1993):Adverse effects of herbal drugs,Vol.II,Springer-VerLag,Berlin,58.
  20. Dr.Patvardhan S., (2004): Monitoring of herbal medicines, 36, 31-33
  21. Evens W.C.,(1988):Trease AND Evans Pharmacognosy;13th ed. Baillere Tindall,London
  22. Edwins E.,Sheeja E.,Vabhav J. and Shewata D.,(2005):Toxicology of herbs,Pharma times, 39, (6),27-30
  23. Friese J.,(1997):Eur J Pharmacology,337:165-174
  24. Gattuso J.M. and Kanum M.A., (1994):Drug Safety,10,47.
  25. Goldman J.A., and Myserson G.,(1991):Arthritis Rheum,34:1207.
  26. Goodman and Gilmans (1966):the pharmacological basis of therapeutics 9th ed, 149.
  27. Hikino H., (1985):Recent research on on oriental medicinal plants,in wagner h., Hikino h., and fransworth N.R., (eds)Economic and medicinal plant research ;Academic press,london Vol.1,53.
  28. Haung K.C.,(1993): The phrmacology of Chinese herb.CRC press, Florida,139.
  29. Haung K.C.,(1993): The phrmacology of Chinese herb.CRC press, Florida,310.
  30. Hrle U.N. and Gaikwad N.J.(2005):Emerging challenges of herb drug interaction,39(2),71-81.
  31. Indian herbal pharmacopoeia(1998):Vol 1
  32. Indian herbal pharmacopoeia(1998):Vol 2
  33. James L.F., and Butcher J.E..,(1982):J.Anin.Sci.,35:1233-1238
  34. Krishna rao D.N., Dr.Nigam M.C., (1976):Indegenous herbs of potential value having curative priperties.Indian drugs.14(3):59-60
  35. Laeruym O.D. Andiversen O.H.(1972):cancer Res. 32, 1463.
  36. Lewis W.H., and Elvin-Lewis M.P.F., (1977) Medical Botany,John wiley &sons Newyork, 81.
  37. Lewis W.H., and Elvin-Lewis M.P.F., (1977) Medical Botany,John wiley &sons Newyork, 83.
  38. Liberti D., Lawrence Review of natural products 1(1992); Med &Aromatic plant abstract,15,602
  39. Lincoln S.D. and Black B., (1980) J Am Vet Med Assoc ,176: 717-718
  40. Medicinal Plants (2004):Guidelines to promote patients safety and plant conservation,by WHO,Vol 36
  41. Newall C.A., Anderson L.A., and Phillipson J.D., (1996), :Herbal Medicines ;a guide for healthcare professional. The pharmaceutical press,London,228
  42. Newall C.A., Anderson L.A., and Phillipson J.D., (1996), :Herbal Medicines ;a guide for healthcare professional. The pharmaceutical press,London,79
  43. Newall C.A., Anderson L.A., and Phillipson J.D., (1996), :Herbal Medicines ;a guide for healthcare professional. The pharmaceutical press,London,135
  44. Nadkarni K.M., Indian Materia Medica(1976):Popular prakashan , Bombay,Vol.1, 202.
  45. Pharmacopoeia of India: (1991).Ministry of health, Govt.of India, ed.2,631.
  46. Rao M.V., Shah K.D., and Rajani M., (1997):Phytother.Res.11,594.
  47. SeetharamK.A.,and Pasricha .S.,(1989);Indian .Dermatol.venereol.Leprol.53,325.
  48. Singh B., Saxena A.K., Chandan B.K., Agrawal G., Bhatia M.S.,  and Anand K.K., (1993):Phytotherapy Research 7, 154.
  49. Singh K.M., Singh S.P., (1993): J.Res. & Education in Indian Medicine 12,45.
  50. Stewart P.M., Wallace A.M., Valentine R., Burt D.,Shackleton C.H.L., and Edwards C.R.W., (1987):Lancet 2, 821.
  51. Tamizhmani T., Ponnasankar S., Nancy Jacob., and Suresh B., (2003):Toxicity of Herbs, Indian J. Pharm.Edu. 37,(4), 208-210
  52. Thyagarajan S.P., Subramanian S., Thirunalansundari T., Venkateswaran P.S., and Blumberg B.S., (1988) Lancet 11, (8614),764.
  53. Tyler V.E., (1987):Plant Medicine, 53:1-4
  54. Vishwanathan M.V., Unnikrishan P.M., Katsukok H.F., nad Purushottam B., (2003):Indian J. of Traditional Knowledge, 2:159-169.
  55. WHO Medicinl plants-Guidelines to promote patient safety and plant conservation, Pharma Times,2004,36:29-30.
  56. WHO Monograph on selected Medicinal Plants, Vol.1, WHO graphics,Malta,Hong Kong,1999.

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