Pharmacological and Toxicological Study of Herbal Medicines

1.2.3 Pharmacological and Toxicological Study of Herbal Medicines

Similar to modern pharmaceutical study, pharmacological study of herbal medicines include pharmacodynamic (PD) and pharmacokinetic (PK) aspects. Broadly, toxicology is also part of the pharmacology.

PD study of traditional herbal medicines is not always easy. Up to now, only the most popularly used herbs, a very small fraction of the total number used, have been well known with respect to pharmacological effects on animals. One reason is that herbs might treat diseases in a way different from known modern drugs. Black cohosh is one example. This herb has long been used in North America for menopause symptoms in women, but in vivo animal study indicated that its extract did not exhibit effects in ovariectomized Sprague–Dawley rats. Further study showed that instead of directly binding to estrogen receptors, extract of black cohosh was reported acting as a mixed competitive ligand and partial agonist of the serotonin and opiate receptor,6,7 which indicates that this herb might treat menopause symp- toms through regulation of the central nervous system.

Chinese scientists have done numerous pharmacological studies on Chinese herbs. Therapeutic mechanisms of the most commonly used Chinese herbs have been known by systematic PD studies.8–10 However, there is another challenge in the pharmacological study of Chinese herbs; that is, in the vast majority of cases, the practitioners prescribe formulas that consist of several (sometimes over 20) herbal ingredients for the treatment. This makes the study difficult not only due to the complex analysis of chemical composition for quality control of the test samples, which is important to keep good reproducibility of the results, but also because of the complex theories of TCM behind the combination of different herbs, which will be mentioned in Chapter 10.

Many people mistakenly believe that herbal products are safe. Although most herbal medicines are relatively safe in comparison with modern drugs, results from toxicological studies show that this is not always true. To a large extent, the safety of herbs depends on dosage and period of administration. It is necessary to mention that purification of some herbal extracts may increase their toxicity. This is because, while the active components are concentrated, the concentration of toxic compounds may also be increased. Sometimes, the active components are toxic. In this case, while the therapeutic effect is enhanced, the toxicity is also increased. Examples include ephedra extract and herbal extracts from the Aristolochia family. Studies of aristolochic acid found in several herbs in Aristolochia family have shown its significant carcinogenic and mutagenic effects and poisoning of the kidney.11–13 In TCM, pro- cessing of raw herbal materials with different methods, such as extended heating with steaming or boiling to decompose the chemical bonds of toxic ester or glycoside compounds in herbs, has been long applied to reduce the toxicity of Chinese herbs. Examples include aconitine in radix Aconiti and sennosides in rhubarb.

PK study of herbal medicines is so far mainly applied to herbs with known active compounds. The concentrations of these active index compounds in the blood, urine, and other body liquids or tissues after a certain period of administration are measured and compared by means of UV, MS, GC-MS, HPLC-MS, and other analytical methods to analyze the distribution of the compounds and change of concentrations with time. To herbs with unclear composition or whose concentration could not be monitored with analytical methods, their efficacies are measured and time-efficacy curves are drawn. In addition, PK–PD models are also applied to the study of herbal PK.

This book covers the PD and toxicology studies of herbal medicines, but not the PK. The reason is that the methods of sample collection for PK study of herbal medi- cine are the same as those for modern drugs. The analytical methods for absorbed and metabolized known compounds in herbs can refer to the qualitative and quantitative analysis of herbal medicines in Chapter 9. Keep in mind that the complex chemical composition of herbal preparations always makes the analysis relatively difficult.

In comparison with so many PD study reports of herbal medicines, only a few systematic PK studies for herbal preparations have been reported; one example is the PK of alkamides in Echinacea purpurea.14 Progress of the PK study is covered in recent review articles.15–17

Soure: Traditional Herbal Medicine Research Methods, Edited by Willow J.H. Liu Copyright © 2011 John Wiley & Sons, Inc.

REFERENCES

6. Burdette, J.E., et al. (2003) Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. Journal of Agricultural and Food Chemistry 51(19):5661–5670.

7. Rhyu, M.R., et al. (2006) Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu opiate receptor. Journal of Agricultural and Food Chemistry 54(26):9852–9857.

8. Shen, Y.J. and Chen, C.X. (2008) Traditional Chinese Pharmacology (5th ed.), Shanghai, Shanghai Science and Technology Publisher.

9. Chen, Q. (2006) Pharmacological Research Methodology of Chinese Medicine (2nd ed.), Beijing, People’s Health Publishing House.

10. State Administration of Traditional Chinese Medicine (1999) Zhong Hua Ben Cao. Shanghai, Shanghai Science and Technology Publisher.

11. Arlt, V.M., et al. (2002) Aristolochic acid as a probable human cancer hazard in herbal remedies: a review. Mutagenesis 17(4):265–277.

12. Debelle, F.D., et al. (2008) Aristolochic acid nephropathy: a worldwide problem. Kidney International 74(2):158–169.

13. Schmeiser, H.H., et al. (2009) Chemical and molecular basis of the carcinogenicity of Aristolochia plants. Current Opinion in Drug Discovery & Development 12(1):141–148.

14. Woelkart, K., et al. (2008) Pharmacokinetics of the main alkamides after administration of three different Echinacea purpurea preparations in humans. Planta Medica 74(6):651–656.

15. Bhattaram, V.A., et al. (2002) Pharmacokinetics and bioavailability of herbal medicinal products. Phytomedicine Suppl. 3:1–33.

16. Zhang, L., et al. (2005) Advances in clinical pharmacokinetics of herbal medicines. Journal of US–China Medical Science 2(6):59–72.

17. Clement, Y.N. (2009) Factors affecting the pharmacokinetics of herbal preparations and their impact on the outcome of clinical trials. Focus Alternative Complementary Therapies 14(2):87–91.