Plant Profiler

Ephedra (Ephedra sinica)


Synonyms / Common Names / Related Terms
6-hydroxykynurenic acid, amp II, amsania, brigham tea, budshur, cao ma huang (Chinese), cathine, chewa, Chinese ephedra, Chinese joint fir, D-pseudoephedrine, desert herb, desert tea, dextro-rotatory, EPH 833, Ephedra altissima, Ephedra americana, Ephedra anti-syphilitica, Ephedra distachya, Ephedra distachya, Ephedra equisetina, Ephedra fasciculata, Ephedra geradiana, Ephedra helvetica, Ephedra intermedia, Ephedra major, Ephedra nevadensis, Ephedra shennungiana, Ephedra sinica, Ephedra trifurca, Ephedra viridis, Ephedra vulgaris, Ephedraceae (family), ephedrae herba, ephedrine, ephedrine alkaloids, epitonin, European ephedra, Gnetales, herba ephedrae, horsetail, hum, huma, Indian joint fir, intermediate ephedra, isoephedrine, joint fir, khama, L-ephedrine, levorotatory ephedrine, mahoàng, máhuáng, "Mao" (Chinese), mao-kon, mahuuanggen, methylephedrine, methylpseudoephedrine, Mexican tea, môc tac ma hoàng, Mongolian ephedra, Mormon tea, mu-tsei-ma-huang, muzei mu huang, natural ecstasy, norephedrine, norpseudoephedrine, phok, popotillo, pseudoepehdrine, quinoline, san-ma-huang, sea grape, shrubby, soma, song tuê ma hoàng, squaw tea, synephrine, tannins, teamster's tea, trun aa hoàng, tsao-ma-huang, tutgantha, yellow astringent, yellow horse, zhong ma huang.
Note: There are approximately 40 species of ephedra.


Mechanism of Action
Pharmacology:
  • Constituents: Ephedra contains the alkaloids ephedrine, pseudoephedrine (isoephedrine), norpseudoephedrine (cathine), norephedrine, methylephedrine, methylpseudoephedrine8, tannins9, and other constituents, including quinoline and 6-hydroxykynurenic acid10. The stem contains approximately 0.5-2.5% alkaloids, with ephedrine accounting for 30- 90% of the total alkaloid content. The variation in content depends upon the species harvested and the part of the plant used. For example, the woody stems are low in alkaloids and the fruits and roots have practically none, while the softer stems contain up to 2.5% active alkaloids. Ephedra sinica generally contains substantially greater concentrations of alkaloids than Ephedra intermedia.4,11 The North American species, Ephedra nevadensis (Mormon tea, Mexican tea, squaw tea, or desert tea), is apparently devoid of alkaloids altogether. Different extraction methods also yield different quantities of active compounds.12 In Ephedra sinica, pseudoephedrine is typically found as dextro-rotatory (D-pseudoephedrine) and ephedrine is typically levo-rotatory (L-ephedrine), while synthetically manufactured ephedrine is usually a racemic mixture.13
  • Alkaloids: Ephedrine and pseudoephedrine are found in the leaves and stems of ephedra and are structurally related to amphetamines. They increase the availability and action of the endogenous neurotransmitters norepinephrine and epinephrine and stimulate catecholamine receptors in the brain, heart, and blood vessels both directly and indirectly. Both ephedrine and pseudoephedrine elicit central nervous system stimulation, bronchodilation, hypertension, and chronotropic/inotropic effects.7 The synthetic form of pseudoephedrine is widely used in non-prescription decongestants. Pseudoephedrine is a more potent diuretic than ephedrine. Ephedrine stimulates thermogenesis in adipocytes in vitro and in animal studies, an effect that appears to be enhanced by chronic administration.14 In mice, rats, and monkeys, ephedrine has been associated with significant weight loss, possibly by enhancing thermogenesis or anorexia.15,16,17,18,19,20 These effects have been enhanced by combining ephedrine with aspirin and/or methylxanthines (caffeine or theophylline).21,22,23,24,25 Jonderko et al. reported that ephedrine inhibits gastric emptying, which may result in a feeling of satiety and thereby aid in weight loss.6
  • Tannins: Tannins present in ephedra possess astringent effects and have historically been used in topical preparations to reduce oozing and weeping of skin lesions. Ephedra's tannins have been proposed to possess some renal protective properties, based on experimental models of kidney failure in rats.26
  • Anti-inflammatory effects: Ephedra's stems have demonstrated anti-inflammatory activity in a mouse paw model of carageenan-induced inflammation.27 Ephedra extracts have been found to inhibit complement activity in vitro.28 Anti-inflammatory and anti-arthritic effects of water distillates of Ephedra sinica Stapf have also been studied in herb-acupuncture to assess the inflammatory responses in arthritic rats.1
  • Antitussive effects: Based on animal study, the Kampo formula eppikahangeto (which contains several ingredients, including ephedra) is thought to decrease the number of coughs dose-dependently.29 Furthermore, ephedrae herba extract alone reduced the number of coughs, but the extract of eppikahangeto without ephedrae herba did not.
  • Cardiovascular effects: Based on human evidence, TrimSpa® (which contains ephedra) does not appear to alter QT (QTc) interval duration and systolic blood pressure when taken short term (7 days).5 However, because the QTc interval dramatically changed in one subject taking TrimSpa®, a large study is needed to determine if the effect is an artifact or if the subject represents a subset of people for whom the drug may pose a risk.
  • Genetic effects: Based on laboratory study, ephedra may decrease tyrosinase activity and melanin content in a dose-dependent manner. 2 Ephedra may also decrease microphthalmia-associated transcription factor (MITF) and tyrosinase gene expression. Kim et al. suggest that ephedra may also alter the expression of about 100 other genes.

Pharmacodynamics/Kinetics:
  • The ephedra plant has been identified as an excellent source of ephedrine and pseudoephedrine, both of which can be chemically reduced to form the widely abused illicit drug methamphetamine. Ephedra contains several additional alkaloids that undergo analogous reductions to form amphetamine and N,N-dimethylamphetamine (also drugs of abuse).30
  • Ephedrine is well absorbed after oral administration, with a reported half-life of 3-6 hours. Following oral administration, 88% is excreted in the urine within 24 hours and 97% is excreted within 48 hours. Ephedrine and pseudoephedrine are excreted more rapidly with urinary acidifiers (such as ammonium chloride) and more slowly with urinary alkalinizers (such as disodium bicarbonate).
  • Per anecdotal reports, the onset of bronchodilatory effects with oral ephedrine occurs within 15-60 minutes, with a duration of 2-4 hours. Oral ephedrine causes pressor and cardiac effects for approximately four hours. Intramuscular or subcutaneous administration of ephedrine results in cardiac effects lasting for approximately one hour.
  • The natural and synthetic forms of ephedrine have similar absorption and pharmacokinetics in adults, but the available natural products contain considerably different concentrations of active alkaloids.3 Pharmacokinetics has not been extensively studied in children.

References
  1. Yeom, M. J., Lee, H. C., Kim, G. H., Lee, H. J., Shim, I., Oh, S. K., Kang, S. K., and Hahm, D. H. Anti-arthritic effects of Ephedra sinica STAPF herb-acupuncture: inhibition of lipopolysaccharide-induced inflammation and adjuvant-induced polyarthritis. J Pharmacol Sci 2006;100(1):41-50. 16404132
  2. Kim, H. J., Cho, Y. D., Leem, K. H., Lee, D. N., Kim, E. H., Kim, M. G., Kim, D. K., Shin, T. Y., Boo, Y., Lee, J. H., and Kim, H. K. Effects of ephedrae herba on melanogenesis and gene expression profiles using cDNA microarray in B16 melanocytes. Phytother Res 2006;20(9):748-754. 16807878
  3. Gurley, B. J., Wang, P., and Gardner, S. F. Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica (Ma-huang) as determined by high performance liquid chromatography. J Pharm Sci 1998;87(12):1547-1553. 10189265
  4. Liu YM and Sheu SJ. Determination of Ephedrine alkaloids by capillary electrophoresis. J Chromatog 1992;600:370-372.
  5. Caron, M. F., Dore, D. D., Min, B., Kluger, J., Boguk, I., and White, C. M. Electrocardiographic and blood pressure effects of the ephedra-containing TrimSpa thermogenic herbal compound in healthy volunteers. Pharmacotherapy 2006;26(9):1241-1246. 16945045
  6. Jonderko, K. and Kucio, C. Effect of anti-obesity drugs promoting energy expenditure, yohimbine and ephedrine, on gastric emptying in obese patients. Aliment Pharmacol Ther 1991;5(4):413-418. 1777550
  7. Kalix, P. The pharmacology of psychoactive alkaloids from ephedra and catha. J Ethnopharmacol 1991;32(1-3):201-208. 1881158
  8. Cui, J. F., Niu, C. Q., and Zhang, J. S. [Determination of six Ephedra alkaloids in Chinese Ephedra (Ma Huang) by gas chromatography]. Yao Xue Xue Bao 1991;26(11):852-857. 1823980
  9. Friedrich, H. and Wiedemeyer, H. [Quantitative determination of the tannin-precursors and the tannins in Ephedra helvetica (author's transl)]. Planta Med 1976;30(3):223-231. 1005523
  10. Caveney S and Starratt A. Glutamatergic signals in Ephedra. Nature 1994;372:509.
  11. Liu YM, Sheu SJ, Chiou SH, and et al. A comparative study on commercial samples of Ephedrae herba. Planta Med 1993;59:376-378.
  12. Zhang, Z., Sun, X., Wang, L., Liu, H., and Lu, Q. [Comparison of two extraction methods for maxingshigan decoction]. Chin J Integ Trad West Med 1997;22(7):413-5, 447. 11038900
  13. Gurley, B. J., Gardner, S. F., White, L. M., and Wang, P. L. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit 1998;20(4):439-445. 9712471
  14. Astrup, A., Madsen, J., Holst, J. J., and Christensen, N. J. The effect of chronic ephedrine treatment on substrate utilization, the sympathoadrenal activity, and energy expenditure during glucose-induced thermogenesis in man. Metabolism 1986;35(3):260-265. 3512957
  15. Arch, J. R., Ainsworth, A. T., and Cawthorne, M. A. Thermogenic and anorectic effects of ephedrine and congeners in mice and rats. Life Sci 5-24-1982;30(21):1817-1826. 7098772
  16. Dulloo, A. G. and Miller, D. S. Thermogenic drugs for the treatment of obesity: sympathetic stimulants in animal models. Br J Nutr 1984;52(2):179-196. 6477859
  17. Dulloo, A. G., Seydoux, J., and Girardier, L. Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition? Metabolism 1992;41(11):1233-1241. 1435297
  18. Ramsey, J. J., Colman, R. J., Swick, A. G., and Kemnitz, J. W. Energy expenditure, body composition, and glucose metabolism in lean and obese rhesus monkeys treated with ephedrine and caffeine. Am J Clin Nutr 1998;68(1):42-51. 9665095
  19. Yen, T. T., McKee, M. M., and Bemis, K. G. Ephedrine reduces weight of viable yellow obese mice (Avy/a). Life Sci 1-12-1981;28(2):119-128. 7253810
  20. Zarrindast, M. R., Hosseini-Nia, T., and Farnoodi, F. Anorectic effect of ephedrine. Gen Pharmacol 1987;18(5):559-561. 3653677
  21. Astrup, A. and Toubro, S. Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man. Int J Obes Relat Metab Disord 1993;17 Suppl 1:S41-S43. 8384179
  22. Dulloo, A. G. and Miller, D. S. Aspirin as a promoter of ephedrine-induced thermogenesis: potential use in the treatment of obesity. Am J Clin Nutr 1987;45(3):564-569. 3825983
  23. Dulloo, A. G. and Miller, D. S. The thermogenic properties of ephedrine/methylxanthine mixtures: animal studies. Am J Clin Nutr 1986;43(3):388-394. 3953478
  24. Dulloo, A. G. and Miller, D. S. Reversal of obesity in the genetically obese fa/fa Zucker rat with an ephedrine/methylxanthines thermogenic mixture. J Nutr 1987;117(2):383-389. 3559753
  25. Dulloo, A. G. Ephedrine, xanthines and prostaglandin-inhibitors: actions and interactions in the stimulation of thermogenesis. Int J Obes Relat Metab Disord 1993;17 Suppl 1:S35-S40. 8384178
  26. Wang, G. Z. and Hikokichi, O. [Experimental study in treating chronic renal failure with dry extract and tannins of herba ephedra]. Chinsese Journal of Integrated Traditional and Western Medicine 1994;14(8):485-488. 7841758
  27. Hikino, H., Konno, C., Takata, H., and Tamada, M. Antiinflammatory principle of Ephedra Herbs. Chem Pharm Bull (Tokyo) 1980;28(10):2900-2904. 7448938
  28. Ling, M., Piddlesden, S. J., and Morgan, B. P. A component of the medicinal herb ephedra blocks activation in the classical and alternative pathways of complement. Clin Exp Immunol 1995;102(3):582-588. 8536376
  29. Minamizawa, K., Goto, H., Shimada, Y., Terasawa, K., and Haji, A. Effects of eppikahangeto, a Kampo formula, and Ephedrae herba against citric acid-induced laryngeal cough in guinea pigs. J Pharmacol Sci 2006;101(2):118-125. 16778362
  30. Barker, W. D. and Antia, U. A study of the use of Ephedra in the manufacture of methamphetamine. Forensic Sci Int 3-2-2007;166(2-3):102-109. 16707238




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