Minimizing Contamination in Herbal Medicine
Herbal medicines in Asia and other countries consist of a mixture of crude or raw
herbs collected from the wild, some from cultivated fields, as well as prepared her-
bal extracts provided by other agencies. Toxic chemicals and other contaminants,
including microbes, may come from (1) environmental and agricultural conditions
where the plants have been grown or collected. (2) transport and storage condi-
tions, and (3) during manufacturing, processing, and packaging.
In order to ensure safety, it is desirable to ensure quality by removing such con-
taminants through the application of radiation processing technology [76]. In order
to increase the quality of production for domestic use and export, the quality con-
trol and assurance of raw materials from the farm as well as from forest sources
should be defined in terms of the genetic variation in the natural product content
and crop quality [77].
Herbal medicines make an enormous contribution to primary health care and
have shown great potential in modern phytomedicine against numerous ailments
and the complex diseases and ailments of the modern world. There will always be
risks when appropriate regulations do not mandate the appropriate formulation of
the remedies or when self-medication fosters abuse.
Quality is the paramount issue because it can affect both the efficacy and the
safety of the herbal medicines being used. Current product quality ranges from
very high to very low as a result of intrinsic, extrinsic, and regulatory factors. Intrin-
74 3 Herbal Medicines: Prospects and Constraints
sically, species differences, diurnal and seasonal variations can affect the qualita-
tive and quantitative accumulation of chemical constituents in the source medici-
nal plants. Extrinsically, environmental factors, field conditions, cultivation, har-
vest and post-harvest transport and storage, manufacturing practises, inadvertent
contamination and substitution, and intentional adulteration are contributing fac-
tors to the quality of herbal medicines. Plant materials that are contaminated with
microbes, microbial toxins, or environmental pollutants, or finished products that
are adulterated with toxic plants or synthetic pharmaceuticals can lead to adverse
events.
To overcome environmental, toxic, and contamination problems like pesticides,
heavy metals, microbial, toxins, control measures need to be introduced to imple-
ment necessary standard operating procedures, as are applied for foods and the
pharmaceutical industry, as well as GAPs and GSPs at source. GLPs and GMPs are
also needed to produce quality medicinal products. The quality of herbal medicines
can also be related to regulatory practises [6]. The WHO guidelines for herbal med-
icine should be strictly implemented and monitored by the concerned regulatory
agency. Most traditional medicinal herbs are used in the form of an aqueous decoc-
tion. Therefore scientific data should be generated on the development of analyti-
cal and biological procedures for use to give quality assurance and control and clin-
ical assessment of efficacy and safety of these products. There is still a need for
more scientific evaluation of Asian herbal medicines including their active constit-
uents, synergistic interactions, formulation strategies, herb–drug interactions,
standardization, pharmacological and clinical evaluation, toxicity, safety and effica-
cy evaluation and quality assurance. Furthermore, in order to ensure the use of
genuine raw materials, more priority should be given to encouraging the organic
cultivation of medicinal plants. Countries interested in promoting herbal medicine
should generously provide funds for fundamental research on above aspects.
Clearly, strategic planning for research in herbal medicine is needed. The lack of
a pharmacological basis for the efficacy and toxicity and clinical data on the major-
ity of herbal medicines is the major constraint to the integration of herbal medi-
cine into conventional medicinal practises. Adverse events, including drug–herb
interactions, must also be monitored to promote the safe integration of efficacious
medicines into conventional medical practises [78].
Acknowledgments
We are grateful to University Grant Commission, New Delhi for financial assis-
tance in the form of UGC-Major Research Project No. F.3-58/ 2002 (SR-II) on me-
dicinal plants.
Acknowledgments 75
76 3 Herbal Medicines: Prospects and Constraints
1 Murphy, J.M. Am. Org. Reg. Nurses J.
1999, 69, 173–183.
2 Chan, K. Biologist 1996, 43, 50–51.
3 Raskin, I., Ribnicky, D.M., Komarnystky,
S., Ilic, N., Poulev, A., Borisjuk, N.,
Brinker, A., Moreno, D.A., Ripoll, C.,
Yakoby, N., O’Niel, J.M., Cornwell, T.,
Pastor, I., Fridlender, B. Trends Biotechnol.
2002, 20, 1–10.
4 British Medical Association.
Complementary Medicine: New Approaches
to Good Practice. Oxford University Press,
Oxford, 1993.
5 Lewith, G., Kenyon, J., Lewis, P.
Complementary Medicine: An Integrated
Approach. Oxford University Press,
Oxford, 1996.
6 Chan, K. Chemosphere 2003, 52,
1361–1371.
7 World Health Organization. Research
Guidelines for Evaluating the Safety and
Efficacy of Herbal Medicines. Regional
Office for the Western Pacific, Manila,
1993
8 Elvin-Lewis, M.J. Ethnopharmacology
2001, 75, 141–164.
9 De Smet, P.A.G.M. Drugs 1997, 54,
801–840.
10 Lewis, W.H., Elvin-Lewis, M. Medical
Botany, Plants Affecting Man’s Health.
John Wiley Interscience, New York, 1977.
11 De Smet, P.A.G.M. Drug Safety 1995, 13,
81–93.
12 Soller, W. HerbalGram 2000, 49, 64–67.
13 Bhattaram, V.A., Graefe, U., Kohlert, C.,
veit, M., Derendorf, H. Phytomedicine
2002, 9, 1–33.
14 Business Communication Company, Inc.
Plant Derived Drugs: Products Technologies
and Applications. Study RB.121, 1998.
15 Balandrin, M. F. et al. ACS Symp. Ser.
1993, 534, 2–12.
16 U.S. Department of Health and Human
Services, Food and Drug Administration
for Drug Evaluation and Research.
Guidance for Industry Botanical Drug
Products.
http://www.Fda.gov/cder/guidance/1221
dft.htm# P131_3293.
17 Senate, U.S. Dietary Supplement Health
and Education Act. 103rd Congress, 2nd
session. 1994, pp. 103–104.
18 Greger, J.L. J. Nutr. 2001, 131,
1339S–1343S.
19 Glasser, V. Nat. Biotechnol. 1999, 17,
17–18.
20 De Smet, P.A., Bonsel, G., Van Der kyu,
A., Hakster, Y.A., Pronk, M.H., Brorens,
M.J., Lockefeer, J.H., Nuijten, M.J.
Pharmacoeconomics 2000, 18, 1–7.
21 Anonymous. The Ayurvedic Formulary of
India (Pt. 1). Ministry of Health and
Family Welfare, Government of India,
1978.
22 Kumar, S., Singh, J., Saha, N.C., Ranjan,
V. Indian Medicinal and Aromatic Plants
Facing Genetic Erosion. Central Institute of
Medicinal and Aromatic Plants (CIMAP),
Lucknow, India, 1997.
23 Singh, J., Srivastava, R.K., Singh, A.K.,
Kumar, S. J. Med. Aromatic Plant Sci.
2000, 22, 564–571.
24 Singh, J., Singh, A.K., Pravesh, R. Proc.
First NIM on Medical Aromatic Plants
2003, 50–58.
25 Ved, D.K., Anjana, M., Shankar, D. Curr.
Sci. 1998, 75, 341–344.
26 Krishna, A. Proc. First NIM on Medical
Aromatic Plants 2003, 209–214.
27 Wagner, H. Environ. Health Perspect.
1999, 107, 779–781.
28 Mauri, P., Simonetti, P., Gardana, C.,
Minoggio, M., Morazzoni, P.,
Bombardelli, E., Pietta, P. Rapid Commun.
Mass. Spectrom. 2001, 15, 929–934.
29 Biber, A. Koch, B. Planta Med. 1999, 65,
192–193.
30 Duche, J.C., Barre, J., Guinot, P.,
Duchier, J., Cournot, A., Tillement, J.P.
Int. J. Clin. Pharmacol. Res. 1989, 9,
165–168.
31 Draves, A.H., Walher, S.E. J. Chromatogr
B Biomed. Sci. Appl. 2000, 749, 57–66.
32 Kasper, S. Pharmacopsychiatry 2001, 34,
51–55.
33 Muller, W.E., Singer, A., Wonnemann,
M. Schwiz. Rundsch. Med. Prax. 2000, 89,
2111–2121.
34 Nathan, P.J. J. Psychopharmacology 2001,
15, 47–54.
35 Jacobson, J.M., Feinman, L., Liebes, L.,
Ostrow, N., Koslowski, V. Antimicrob.
Agents Chemother. 2001, 45, 517–524.
References
References 77
36 Biber, A., Fiscer, H., Romer, A.,
Chatterjee, S.S. Pharmacopsychiatery 1998,
31, 36–43.
37 Chrubaic, S. Eisenberg, E., Balan, E.,
Weinbereger, T., Luzzati, R., Condradt, C.
Am. J. Med. 2000, 109, 9–14.
38 Yoshikawa, M., Murakami, T., Yamahara,
J., Matsuda, H. Chem. Pharm. Bull.
(Tokyo) 1998, 46, 1764–1769.
39 Low, D. Schroedter, A., Schwankl, W.,
Marz, R.W. Methods Find. Clin.
Pharmacol. 2000, 22, 537–542.
40 Meyer-Bernarth, J., Kaffarnik, H.
Arzneimittelforschung 1970, 20, 147–148.
41 Venkataramanan, R., Ramachandran, V.,
Komoroski, B.J., Zhang, S., Sciff, P.L.,
Strom, S.C. Drug Metab. Dispos. 2000, 28,
1270–1273.
42 Gatti, G., Perucca, E. Int. J. Clin.
Pharmacol. Ther. 1994, 32, 614–617.
43 De Smet, P.A.G.M., Keller, K., Hansel, R.,
Chandler, R.F. Adverse Effects of Herbal
Drugs, I and II. Springer-Verlag, Berlin,
1992.
44 Bruneton, J. Pharmacognosy,
Phytochemistry, Medicinal Plants. Lavosier,
Paris, 1995.
45 Chan, K. Understanding the toxicity of
Chinese Herbal Medicinal products. In
The Way Forward for Chinese Medicines,
Chan, K., Lee, H (eds). Taylor & Francis,
London, 2002.
46 Cordell, G.A. Phytochemistry 2000, 55,
463–480.
47 Rates, S.M.K. Toxicon 2001, 39, 603–613.
48 Thomson, S.A. South African Government
Genoside and Ethnopiracy. The Gaia
Research Institute, South Africa, 2000.
49 Stewart, M. J., Steenkamp, V. South Afr.
Ethnobot. 2000, 1, 32–33.
50 Wojcikowski, K., Johnson, D.W., Gobe, G.
Nephrology 2004, 9, 313–318.
51 Goldman, P. Ann. Intern. Med. 2001, 135,
594–600.
52 Shimmer, O., Haefele, F., Kruger, A.
Mutat. Res. 1988, 206, 201–208.
53 Shimmer, O., Kruger, A., Paulini, H.,
Haefele, F. Pharmazie 1994, 49, 448–451.
54 De SaFerrira, I.C.F., Ferrago Vargas, V.M.
Phytother. Res. 1999, 13, 397–400.
55 Chauvin, P., Dillon, J.C., Moren, A. Sante
1994, 4, 263–268.
56 Drew, A.K., Myres, S.P. Med. J. Aust.
1997, 166, 538–541.
57 Saper, R.B., Kales, S.N., Paquin, J., Burns,
M.J., Eisenberg, D.M., Davis, R.B.,
Phillips, R.S. JAMA 2004, 292,
2868–2873.
58 Ernst, E., Coon, J.T. Clin. Pharmacol.
Ther. 2001, 70, 497–504.
59 Seth, P.K. Kakkar, P. Proc. First NIM on
Medicinal Aromatic Plants 2003, 29–41.
60 Ko, R.J. N. Engl. J. Med. 1998, 339, 847.
61 Marcus, D.M., Grollman, A.P. N. Engl. J.
Med. 2002, 347, 2073–2076.
62 Ernst, E. J. Intern. Med. 2002, 252, 107–113.
63 Gugh-Berman A. Lancet 2000, 355,
134–138.
64 Moore, L.B., Goodwin, B., Jones, S.A.,
Wisely, G.B., Serabjit-Singh, C.J.,
Willson, T.M., Collins, J.L., Kliewer, S.A.
Proc. Natl Acad. Sci. USA 2000, 97,
7500–7502.
65 Brinker, F. Herb Contraindications and
Herb Interactions. Electic Institute, 1997.
66 Cupp, M.J. Am. Fam. Physician 1999, 59,
1239–1245.
67 Blumenthal, M. HerbalGram 2000, 49,
52–63.
68 Schulz, V., Hansel, R., Tyler, V.E.
Rational Phytotherapy. A Physicians Guide
to Herbal Medicine, 4th edn. Springer,
Berlin, 2000.
69 Shaw, D., Leon, C., Kolev, S., Murray, V.
Drug Safety 1997, 17, 342–356.
70 Akerele, O. HerbalGram 1993, 26, 13–20.
71 Abbot, N.C., White, A.R., Ernst, E. Nature
1996, 381, 361.
72 Barnes, J. Pharm. J. 1997, 258, 76–77.
73 Akhtar, H. Essential Oils and their
Cultivation. CIMAP Publication,
Lucknow, India, 1993.
74 Akhtar, H. Medicinal Plants and their
Cultivation. CIMAP Publication,
Lucknow, India, 1993.
75 Canter, P.H., Thomas, H., Ernst, E.
Trends Biotechnol. 2003, 23, 180–185.
76 Sharma, R. J. Food. Sci. 1989, 54,
589–590.
77 Forester, S. Forest Pharmacy – Medicinal
plants in American Forest. Forest History
Society, Durham, NC, 1995.
78 Fong, H.H. Integr. Cancer Ther. 2002, 1,
287–293.
79 Chopra, R.N., Nayer, S.L., Chopra, I.C.
Glossary of Indian Medicinal Plants, 3rd
Edn. Council of Scientific and Industrial
Research, New Delhi, 7–246, 1992.
Herbal medicines in Asia and other countries consist of a mixture of crude or raw
herbs collected from the wild, some from cultivated fields, as well as prepared her-
bal extracts provided by other agencies. Toxic chemicals and other contaminants,
including microbes, may come from (1) environmental and agricultural conditions
where the plants have been grown or collected. (2) transport and storage condi-
tions, and (3) during manufacturing, processing, and packaging.
In order to ensure safety, it is desirable to ensure quality by removing such con-
taminants through the application of radiation processing technology [76]. In order
to increase the quality of production for domestic use and export, the quality con-
trol and assurance of raw materials from the farm as well as from forest sources
should be defined in terms of the genetic variation in the natural product content
and crop quality [77].
Herbal medicines make an enormous contribution to primary health care and
have shown great potential in modern phytomedicine against numerous ailments
and the complex diseases and ailments of the modern world. There will always be
risks when appropriate regulations do not mandate the appropriate formulation of
the remedies or when self-medication fosters abuse.
Quality is the paramount issue because it can affect both the efficacy and the
safety of the herbal medicines being used. Current product quality ranges from
very high to very low as a result of intrinsic, extrinsic, and regulatory factors. Intrin-
74 3 Herbal Medicines: Prospects and Constraints
sically, species differences, diurnal and seasonal variations can affect the qualita-
tive and quantitative accumulation of chemical constituents in the source medici-
nal plants. Extrinsically, environmental factors, field conditions, cultivation, har-
vest and post-harvest transport and storage, manufacturing practises, inadvertent
contamination and substitution, and intentional adulteration are contributing fac-
tors to the quality of herbal medicines. Plant materials that are contaminated with
microbes, microbial toxins, or environmental pollutants, or finished products that
are adulterated with toxic plants or synthetic pharmaceuticals can lead to adverse
events.
To overcome environmental, toxic, and contamination problems like pesticides,
heavy metals, microbial, toxins, control measures need to be introduced to imple-
ment necessary standard operating procedures, as are applied for foods and the
pharmaceutical industry, as well as GAPs and GSPs at source. GLPs and GMPs are
also needed to produce quality medicinal products. The quality of herbal medicines
can also be related to regulatory practises [6]. The WHO guidelines for herbal med-
icine should be strictly implemented and monitored by the concerned regulatory
agency. Most traditional medicinal herbs are used in the form of an aqueous decoc-
tion. Therefore scientific data should be generated on the development of analyti-
cal and biological procedures for use to give quality assurance and control and clin-
ical assessment of efficacy and safety of these products. There is still a need for
more scientific evaluation of Asian herbal medicines including their active constit-
uents, synergistic interactions, formulation strategies, herb–drug interactions,
standardization, pharmacological and clinical evaluation, toxicity, safety and effica-
cy evaluation and quality assurance. Furthermore, in order to ensure the use of
genuine raw materials, more priority should be given to encouraging the organic
cultivation of medicinal plants. Countries interested in promoting herbal medicine
should generously provide funds for fundamental research on above aspects.
Clearly, strategic planning for research in herbal medicine is needed. The lack of
a pharmacological basis for the efficacy and toxicity and clinical data on the major-
ity of herbal medicines is the major constraint to the integration of herbal medi-
cine into conventional medicinal practises. Adverse events, including drug–herb
interactions, must also be monitored to promote the safe integration of efficacious
medicines into conventional medical practises [78].
Acknowledgments
We are grateful to University Grant Commission, New Delhi for financial assis-
tance in the form of UGC-Major Research Project No. F.3-58/ 2002 (SR-II) on me-
dicinal plants.
Acknowledgments 75
76 3 Herbal Medicines: Prospects and Constraints
1 Murphy, J.M. Am. Org. Reg. Nurses J.
1999, 69, 173–183.
2 Chan, K. Biologist 1996, 43, 50–51.
3 Raskin, I., Ribnicky, D.M., Komarnystky,
S., Ilic, N., Poulev, A., Borisjuk, N.,
Brinker, A., Moreno, D.A., Ripoll, C.,
Yakoby, N., O’Niel, J.M., Cornwell, T.,
Pastor, I., Fridlender, B. Trends Biotechnol.
2002, 20, 1–10.
4 British Medical Association.
Complementary Medicine: New Approaches
to Good Practice. Oxford University Press,
Oxford, 1993.
5 Lewith, G., Kenyon, J., Lewis, P.
Complementary Medicine: An Integrated
Approach. Oxford University Press,
Oxford, 1996.
6 Chan, K. Chemosphere 2003, 52,
1361–1371.
7 World Health Organization. Research
Guidelines for Evaluating the Safety and
Efficacy of Herbal Medicines. Regional
Office for the Western Pacific, Manila,
1993
8 Elvin-Lewis, M.J. Ethnopharmacology
2001, 75, 141–164.
9 De Smet, P.A.G.M. Drugs 1997, 54,
801–840.
10 Lewis, W.H., Elvin-Lewis, M. Medical
Botany, Plants Affecting Man’s Health.
John Wiley Interscience, New York, 1977.
11 De Smet, P.A.G.M. Drug Safety 1995, 13,
81–93.
12 Soller, W. HerbalGram 2000, 49, 64–67.
13 Bhattaram, V.A., Graefe, U., Kohlert, C.,
veit, M., Derendorf, H. Phytomedicine
2002, 9, 1–33.
14 Business Communication Company, Inc.
Plant Derived Drugs: Products Technologies
and Applications. Study RB.121, 1998.
15 Balandrin, M. F. et al. ACS Symp. Ser.
1993, 534, 2–12.
16 U.S. Department of Health and Human
Services, Food and Drug Administration
for Drug Evaluation and Research.
Guidance for Industry Botanical Drug
Products.
http://www.Fda.gov/cder/guidance/1221
dft.htm# P131_3293.
17 Senate, U.S. Dietary Supplement Health
and Education Act. 103rd Congress, 2nd
session. 1994, pp. 103–104.
18 Greger, J.L. J. Nutr. 2001, 131,
1339S–1343S.
19 Glasser, V. Nat. Biotechnol. 1999, 17,
17–18.
20 De Smet, P.A., Bonsel, G., Van Der kyu,
A., Hakster, Y.A., Pronk, M.H., Brorens,
M.J., Lockefeer, J.H., Nuijten, M.J.
Pharmacoeconomics 2000, 18, 1–7.
21 Anonymous. The Ayurvedic Formulary of
India (Pt. 1). Ministry of Health and
Family Welfare, Government of India,
1978.
22 Kumar, S., Singh, J., Saha, N.C., Ranjan,
V. Indian Medicinal and Aromatic Plants
Facing Genetic Erosion. Central Institute of
Medicinal and Aromatic Plants (CIMAP),
Lucknow, India, 1997.
23 Singh, J., Srivastava, R.K., Singh, A.K.,
Kumar, S. J. Med. Aromatic Plant Sci.
2000, 22, 564–571.
24 Singh, J., Singh, A.K., Pravesh, R. Proc.
First NIM on Medical Aromatic Plants
2003, 50–58.
25 Ved, D.K., Anjana, M., Shankar, D. Curr.
Sci. 1998, 75, 341–344.
26 Krishna, A. Proc. First NIM on Medical
Aromatic Plants 2003, 209–214.
27 Wagner, H. Environ. Health Perspect.
1999, 107, 779–781.
28 Mauri, P., Simonetti, P., Gardana, C.,
Minoggio, M., Morazzoni, P.,
Bombardelli, E., Pietta, P. Rapid Commun.
Mass. Spectrom. 2001, 15, 929–934.
29 Biber, A. Koch, B. Planta Med. 1999, 65,
192–193.
30 Duche, J.C., Barre, J., Guinot, P.,
Duchier, J., Cournot, A., Tillement, J.P.
Int. J. Clin. Pharmacol. Res. 1989, 9,
165–168.
31 Draves, A.H., Walher, S.E. J. Chromatogr
B Biomed. Sci. Appl. 2000, 749, 57–66.
32 Kasper, S. Pharmacopsychiatry 2001, 34,
51–55.
33 Muller, W.E., Singer, A., Wonnemann,
M. Schwiz. Rundsch. Med. Prax. 2000, 89,
2111–2121.
34 Nathan, P.J. J. Psychopharmacology 2001,
15, 47–54.
35 Jacobson, J.M., Feinman, L., Liebes, L.,
Ostrow, N., Koslowski, V. Antimicrob.
Agents Chemother. 2001, 45, 517–524.
References
References 77
36 Biber, A., Fiscer, H., Romer, A.,
Chatterjee, S.S. Pharmacopsychiatery 1998,
31, 36–43.
37 Chrubaic, S. Eisenberg, E., Balan, E.,
Weinbereger, T., Luzzati, R., Condradt, C.
Am. J. Med. 2000, 109, 9–14.
38 Yoshikawa, M., Murakami, T., Yamahara,
J., Matsuda, H. Chem. Pharm. Bull.
(Tokyo) 1998, 46, 1764–1769.
39 Low, D. Schroedter, A., Schwankl, W.,
Marz, R.W. Methods Find. Clin.
Pharmacol. 2000, 22, 537–542.
40 Meyer-Bernarth, J., Kaffarnik, H.
Arzneimittelforschung 1970, 20, 147–148.
41 Venkataramanan, R., Ramachandran, V.,
Komoroski, B.J., Zhang, S., Sciff, P.L.,
Strom, S.C. Drug Metab. Dispos. 2000, 28,
1270–1273.
42 Gatti, G., Perucca, E. Int. J. Clin.
Pharmacol. Ther. 1994, 32, 614–617.
43 De Smet, P.A.G.M., Keller, K., Hansel, R.,
Chandler, R.F. Adverse Effects of Herbal
Drugs, I and II. Springer-Verlag, Berlin,
1992.
44 Bruneton, J. Pharmacognosy,
Phytochemistry, Medicinal Plants. Lavosier,
Paris, 1995.
45 Chan, K. Understanding the toxicity of
Chinese Herbal Medicinal products. In
The Way Forward for Chinese Medicines,
Chan, K., Lee, H (eds). Taylor & Francis,
London, 2002.
46 Cordell, G.A. Phytochemistry 2000, 55,
463–480.
47 Rates, S.M.K. Toxicon 2001, 39, 603–613.
48 Thomson, S.A. South African Government
Genoside and Ethnopiracy. The Gaia
Research Institute, South Africa, 2000.
49 Stewart, M. J., Steenkamp, V. South Afr.
Ethnobot. 2000, 1, 32–33.
50 Wojcikowski, K., Johnson, D.W., Gobe, G.
Nephrology 2004, 9, 313–318.
51 Goldman, P. Ann. Intern. Med. 2001, 135,
594–600.
52 Shimmer, O., Haefele, F., Kruger, A.
Mutat. Res. 1988, 206, 201–208.
53 Shimmer, O., Kruger, A., Paulini, H.,
Haefele, F. Pharmazie 1994, 49, 448–451.
54 De SaFerrira, I.C.F., Ferrago Vargas, V.M.
Phytother. Res. 1999, 13, 397–400.
55 Chauvin, P., Dillon, J.C., Moren, A. Sante
1994, 4, 263–268.
56 Drew, A.K., Myres, S.P. Med. J. Aust.
1997, 166, 538–541.
57 Saper, R.B., Kales, S.N., Paquin, J., Burns,
M.J., Eisenberg, D.M., Davis, R.B.,
Phillips, R.S. JAMA 2004, 292,
2868–2873.
58 Ernst, E., Coon, J.T. Clin. Pharmacol.
Ther. 2001, 70, 497–504.
59 Seth, P.K. Kakkar, P. Proc. First NIM on
Medicinal Aromatic Plants 2003, 29–41.
60 Ko, R.J. N. Engl. J. Med. 1998, 339, 847.
61 Marcus, D.M., Grollman, A.P. N. Engl. J.
Med. 2002, 347, 2073–2076.
62 Ernst, E. J. Intern. Med. 2002, 252, 107–113.
63 Gugh-Berman A. Lancet 2000, 355,
134–138.
64 Moore, L.B., Goodwin, B., Jones, S.A.,
Wisely, G.B., Serabjit-Singh, C.J.,
Willson, T.M., Collins, J.L., Kliewer, S.A.
Proc. Natl Acad. Sci. USA 2000, 97,
7500–7502.
65 Brinker, F. Herb Contraindications and
Herb Interactions. Electic Institute, 1997.
66 Cupp, M.J. Am. Fam. Physician 1999, 59,
1239–1245.
67 Blumenthal, M. HerbalGram 2000, 49,
52–63.
68 Schulz, V., Hansel, R., Tyler, V.E.
Rational Phytotherapy. A Physicians Guide
to Herbal Medicine, 4th edn. Springer,
Berlin, 2000.
69 Shaw, D., Leon, C., Kolev, S., Murray, V.
Drug Safety 1997, 17, 342–356.
70 Akerele, O. HerbalGram 1993, 26, 13–20.
71 Abbot, N.C., White, A.R., Ernst, E. Nature
1996, 381, 361.
72 Barnes, J. Pharm. J. 1997, 258, 76–77.
73 Akhtar, H. Essential Oils and their
Cultivation. CIMAP Publication,
Lucknow, India, 1993.
74 Akhtar, H. Medicinal Plants and their
Cultivation. CIMAP Publication,
Lucknow, India, 1993.
75 Canter, P.H., Thomas, H., Ernst, E.
Trends Biotechnol. 2003, 23, 180–185.
76 Sharma, R. J. Food. Sci. 1989, 54,
589–590.
77 Forester, S. Forest Pharmacy – Medicinal
plants in American Forest. Forest History
Society, Durham, NC, 1995.
78 Fong, H.H. Integr. Cancer Ther. 2002, 1,
287–293.
79 Chopra, R.N., Nayer, S.L., Chopra, I.C.
Glossary of Indian Medicinal Plants, 3rd
Edn. Council of Scientific and Industrial
Research, New Delhi, 7–246, 1992.
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