Plant Profiler

Alfalfa (Medicago sativa)


Medicago sativa
Synonyms / Common Names / Related Terms
Al-fac-facah, arc, alfalfa weevil, buffalo herb, California clover, Chilean clover, Fabaceae (family), feuille de luzerne, isoflavone, jatt, kaba yonca, Leguminosae (family), lucerne, medicago, mielga, mu su, phytoestrogen, purple medic, purple medick, purple medicle, sai pi li ka, saranac, Spanish clover, team, weevelchek, yonja.





Mechanism of Action

Pharmacology:

  • Constituents: Vitamins A, C, E, and K, minerals, and trace elements are present in alfalfa. The amounts of each are unclear, and any benefits or toxicities due to these constituents remain unknown. Alfalfa contains coumestrol, a phytoestrogen that has been isolated from three commercially available alfalfa products4, and in vitro may have a role as a low-density lipoprotein (LDL) antioxidant16. Alfalfa saponins rather than alfalfa fiber appear to be responsible for the reduction of cholesterol absorption.17 Flavonoids have also been isolated from alfalfa.18 Manganese, found in relatively high concentrations in alfalfa, has been proposed as a possible cause of hypoglycemia in one case-report.3 Immunoreactive thyrotropin-releasing hormone-like material has been found in alfalfa in significant amounts, although its biological action is unknown.2 1,2-dimethylhydrazine, a carcinogen, binds to alfalfa when colon pH is between 10.5-12, and alfalfa has been proposed as possessing protective properties against chemically-induced colon cancer.19
  • Anti-microbial effects: Alfalfa may possess anti-microbial properties.9 G2, 2-beta-hydroxy-3-beta-O- (beta-D-glucopyranosyl)-delta 12-oleanene-23, 28-dionic acid, has been isolated from alfalfa roots and has been shown in vitro to possess a high degree of activity against Cryptococcus neoformans (MIC 2mcg/mL).10 G2 exhibits activity against a wide range of yeast strains, and appears to induce lethal ion leakage from yeast cells. 11 Medicagenic acid, hederagenin glycosides, and soyasapogenols may contribute to the antifungal actions of alfalfa, including against Aspergillus niger, Candida albicans, and Candida tropicalis.1
  • Cholesterol-lowering effects: A study in monkeys found that monkeys fed alfalfa saponins had decreased cholesterolemia without changes in high-density lipoprotein (HDL) when compared to monkeys not fed alfalfa saponins.6 It was also noted that alfalfa saponins decrease intestinal absorption and increase fecal excretion of cholesterol, a finding also reported in rats.20 Alfalfa has been shown to prevent the expected rise in cholesterol associated with intake of a high cholesterol diet in monkeys.21 Alfalfa reduces lipid levels in plasma and tissues more effectively than D-thyroxine and pyrimidine, but not as effectively as cholestyramine or diets completely void of cholesterol.22 Similar cholesterol-lowering effects have been observed in rabbits.23,24,25 Rabbits with an ileal bypass required less alfalfa to prevent hypercholesterolemia than rabbits with normal gut length24, alfalfa was an effective adjuvant to partial ileal bypass in the treatment of hypercholesterolemia in rabbits25. Following oral administration of cholesterol to rabbits, elevations in serum cholesterol were prevented when feedings included alfalfa.23 Hyperlipidemia-induced rabbits fed alfalfa were found to have lower total cholesterol, specifically triglycerides and non-esterified fatty acids, when compared to rabbits not fed alfalfa.12 A study in 72 monkeys showed that diets consisting of alfalfa and cholesterol reduced cholesterol levels and atherosclerotic plaque formation when compared with diets containing cholesterol alone.26,27
  • Hypoglycemic effects: Alfalfa has been found to significantly lower basal plasma glucose concentrations in streptozotocin diabetic mice.7 In a different study, streptozotocin diabetic mice fed alfalfa (62.5g/kg in the diet and 2.5g/L in drinking water) experienced reduced hyperglycemia when compared with normal mice.8 The hypoglycemic actions of alfalfa have been postulated to be due to the potentiation of insulin secretion and improvement of insulin action, although human data in this area is limited.
  • Immunologic effects: The alfalfa constituent L-canavanine, an amino acid, has been associated in animals and humans with the development of a lupus-like syndrome, or exacerbation of systemic lupus erythematosus (SLE).5,14,15 In vitro, alfalfa appears to act on CD8 (-) Leu8 (+) T cells to regulate antibody synthesis and proliferation.13 L-canavanine may exert an inhibitory effect on CD8 T cells15, and may also exert effects on mononuclear cells14. The mechanism of action remains unknown. An unsaponifiable substance extracted from alfalfa appeared to be beneficial in treating skin damage secondary to radiotherapy and healing gums after orthodontist operations. The substance contained cycloartenol, sitosterol, campestrol, and stigonosterol.28

Pharmacodynamics/Kinetics:

  • In a rat toxicity study, alfalfa was shown to significantly increase the activity of the hepatic enzyme, aminopyrine N-demethylase.29 It did not affect glutathione S-transferase or epoxide hydrolase activities.

References
  1. Jurzysta, M. and Waller, G. R. Antifungal and hemolytic activity of aerial parts of alfalfa (Medicago) species in relation to saponin composition. Adv Exp Med Biol 1996;404:565-574. 8957325
  2. Jackson, I. M. Abundance of immunoreactive thyrotropin-releasing hormone-like material in the alfalfa plant. Endocrinology 1981;108(1):344-346. 6780314
  3. Rubenstein AH, Levin NW, and Elliott GA. Manganese-induced hypoglycemia. Lancet 1962;1348-1351.
  4. Elakovich, S. D. and Hampton, J. M. Analysis of coumestrol, a phytoestrogen, in alfalfa tablets sold for human consumption. J Agric Food Chem  1984;32(1):173-175. 6707329
  5. Malinow, M. R., Bardana, E. J., Jr., Pirofsky, B., Craig, S., and McLaughlin, P. Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid. Science 4-23-1982;216(4544):415-417. 7071589
  6. Malinow, M. R., Connor, W. E., McLaughlin, P., Stafford, C., Lin, D. S., Livingston, A. L., Kohler, G. O., and McNulty, W. P. Cholesterol and bile acid balance in Macaca fascicularis. Effects of alfalfa saponins. J Clin Invest 1981;67(1):156-162. 7451648
  7. Swanston-Flatt, S. K., Day, C., Bailey, C. J., and Flatt, P. R. Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia 1990;33(8):462-464. 2210118
  8. Gray, A. M. and Flatt, P. R. Pancreatic and extra-pancreatic effects of the traditional anti- diabetic plant, Medicago sativa (lucerne). Br J Nutr  1997;78(2):325-334. 9301421
  9. Rosenthal, G. A. The biological effects and mode of action of L-canavanine, a structural analogue of L-arginine. Q Rev Biol 1977;52(2):155-178. 331385
  10. Polacheck, I., Zehavi, U., Naim, M., Levy, M., and Evron, R. The susceptibility of Cryptococcus neoformans to an antimycotic agent (G2) from alfalfa. Zentralbl Bakteriol Mikrobiol Hyg [A] 1986;261(4):481-486. 3532631
  11. Polacheck, I., Levy, M., Guizie, M., Zehavi, U., Naim, M., and Evron, R. Mode of action of the antimycotic agent G2 isolated from alfalfa roots. Zentralbl.Bakteriol  1991;275(4):504-512. 1755923
  12. Yanaura, S. and Sakamoto, M. [Effect of alfalfa meal on experimental hyperlipidemia]. Nippon Yakurigaku Zasshi 1975;71(5):387-393. 1238315
  13. Morimoto, I. A study on immunological effects of L-canavanine. Kobe J Med Sci  1989;35(5-6):287-298. 2635243
  14. Morimoto, I., Shiozawa, S., Tanaka, Y., and Fujita, T. L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine. Clin Immunol Immunopathol  1990;55(1):97-108. 2137742
  15. Alcocer-Varela, J., Iglesias, A., Llorente, L., and Alarcon-Segovia, D. Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa. Arthritis Rheum  1985;28(1):52-57. 3155617
  16. Hwang, J., Hodis, H. N., and Sevanian, A. Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. J Agric Food Chem  2001;49(1):308-314. 11170593
  17. Malinow, M. R., McLaughlin, P., Stafford, C., Livingston, A. L., Kohler, G. O., and Cheeke, P. R. Comparative effects of alfalfa saponins and alfalfa fiber on cholesterol absorption in rats. Am J Clin Nutr  1979;32(9):1810-1812. 474470
  18. Stochmal, A., Piacente, S., Pizza, C., De Riccardis, F., Leitz, R., and Oleszek, W. Alfalfa (Medicago sativa L.) flavonoids. 1. Apigenin and luteolin glycosides from aerial parts. J Agric Food Chem  2001;49(2):753-758. 11262024
  19. Smith-Barbaro, P., Hanson, D., and Reddy, B. S. Carcinogen binding to various types of dietary fiber. J Natl Cancer Inst  1981;67(2):495-497. 6267346
  20. Malinow, M. R., McLaughlin, P., Papworth, L., Stafford, C., Kohler, G. O., Livingston, A. L., and Cheeke, P. R. Effect of alfalfa saponins on intestinal cholesterol absorption in rats. Am J Clin Nutr  1977;30(12):2061-2067. 563169
  21. Malinow, M. R., McLaughlin, P., Kohler, G. O., and Livingston, A. L. Prevention of elevated cholesterolemia in monkeys. Steroids 1977;29(1):105-110. 402716
  22. Srinivasan, S. R., Patton, D., Radhakrishnamurthy, B., Foster, T. A., Malinow, M. R., McLaughlin, P., and Berenson, G. S. Lipid changes in atherosclerotic aortas of Macaca fascicularis after various regression regimens. Atherosclerosis 1980;37(4):591-601. 7459002
  23. Cookson, F. B. and Fedoroff, S. Quantitative relationships between administered cholesterol and alfalfa required to prevent hypercholesterolaemia in rabbits. Br J Exp Pathol  1968;49(4):348-355. V5676445
  24. Barichello, A. W. and Fedoroff, S. Effect of ileal bypass and alfalfa on hypercholesterolaemia. Br J Exp Pathol  1971;52(1):81-87. 5547660
  25. Esper, E., Barichello, A. W., Chan, E. K., Matts, J. P., and Buchwald, H. Synergistic lipid-lowering effects of alfalfa meal as an adjuvant to the partial ileal bypass operation. Surgery 1987;102(1):39-51. 3589975
  26. Malinow, M. R., McLaughlin, P., Naito, H. K., Lewis, L. A., and McNulty, W. P. Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys. Atherosclerosis 1978;30(1):27-43. 98169
  27. Malinow MR, McLaughlin P, Naito HK, and et al. Regression of atherosclerosis during cholesterol feeding in Macaca fascicularis. Am J Cardiol 1978;41:396.
  28. Mac Lean JA. Unsaponifiable substance from alfalfa for pharmaceutical and cosmetic use. Pharmaceuticals 1974;81:339.
  29. Garrett, B. J., Cheeke, P. R., Miranda, C. L., Goeger, D. E., and Buhler, D. R. Consumption of poisonous plants (Senecio jacobaea, Symphytum officinale, Pteridium aquilinum, Hypericum perforatum) by rats: chronic toxicity, mineral metabolism, and hepatic drug-metabolizing enzymes. Toxicol Lett  1982;10(2-3):183-188. 7080084




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