Dietary safety of cycloastragenol from Astragalus spp.: Subchronic toxicity and genotoxicity studies

Food and Chemical Toxicology

Volumn 64, Issue , 2014, Pages 322-334

  Szabo, Nancy J ^a  

^a Burdock Group   (United States)

Author keywords

Astragalus; Clastogenic; Cycloastragenol; Genotoxic; Mutagenic; Subchronic

Indexed keywords

ASTRAGALUS EXTRACT; CYCLOASTRAGENOL; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; ASTRAGALUS PLANT; BACTERIAL STRAIN; BLOOD EXAMINATION; BODY WEIGHT; CHROMOSOME ANALYSIS; CHRONIC TOXICITY; CLINICAL CHEMISTRY; CLINICAL OBSERVATION; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DIET SUPPLEMENTATION; ESCHERICHIA COLI; EYE EXAMINATION; FEMALE; FOOD INTAKE; GENOTOXICITY; HISTOPATHOLOGY; IN VITRO STUDY; IN VIVO STUDY; MALE; METABOLIC ACTIVATION; MICRONUCLEUS TEST; MUTAGENICITY; NONHUMAN; ORGAN WEIGHT; PATHOLOGY; PLANT ROOT; RAT; SALMONELLA TYPHIMURIUM; URINALYSIS;

2-AA; 2-AMINOANTHRACENE; 2-NF; 2-NITROFLUORENE; 9-AA; 9-AMINOACRIDINE; AAALAC; AMERICAN TYPE CULTURE COLLECTION; ANALYSIS OF VARIANCE; ANOVA; ASPARTATE AMINOTRANSFERASE; ASSOCIATION FOR ASSESSMENT AND ACCREDITATION OF LABORATORY ANIMAL CARE INTERNATIONAL; AST; ASTRAGALOSIDE; ASTRAGALUS; ATCC; CAG; CK; CLASTOGENIC; CPA; CREATINE PHOSPHOKINASE; CYCLOASTRAGENOL; CYCLOPHOSPHAMIDE; DIMETHYL SULFOXIDE; DMSO; EMS; ETHYLMETHANESULFONATE; FOB; FUNCTIONAL OBSERVATIONAL BATTERY; GENERALLY RECOGNIZED AS SAFE; GENOTOXIC; GLP; GOOD LABORATORY PRACTICE; GRAS; I.P.; IACUC; ICH; INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE; INTERNATIONAL CONFERENCE ON HARMONISATION; INTRAPERITONEAL; LACTATE DEHYDROGENASE; LDH; MAXIMUM TOLERATED DOSE; MCH; MEAN CORPUSCULAR HEMOGLOBIN; MEM; METHYLMETHANESULFONATE; MINIMAL ESSENTIAL MEDIUM; MMS; MTD; MUTAGENIC; NAN(3); NO-OBSERVED-ADVERSE-EFFECT LEVEL; NOAEL; OECD; ORGANISATION FOR ECONOMIC CO-OPERATION AND DEVELOPMENT; PCE; POLYCHROMATIC ERYTHROCYTES; REL. PCE; RELATIVE PCE; SODIUM AZIDE; SUBCHRONIC; TCM; TRADITIONAL CHINESE MEDICINE; WHO; WORLD HEALTH ORGANIZATION;

ANIMALS; ASTRAGALUS PLANT; CHROMOSOME ABERRATIONS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEEDING BEHAVIOR; FEMALE; MALE; MICRONUCLEUS TESTS; NO-OBSERVED-ADVERSE-EFFECT LEVEL; ORGAN SIZE; PLANT EXTRACTS; RATS; RATS, SPRAGUE-DAWLEY; SAPOGENINS; TOXICITY TESTS, SUBCHRONIC;

EID: 84890895546     PISSN: 02786915     EISSN: 18736351     Source Type: Journal    
DOI: 10.1016/j.fct.2013.11.041     Document Type: Article

References (42)

1. Anderson D.M.W. Evidence for the safety of gum tragacanth (Asiatic Astragalus spp.) and modern criteria for the evaluation of food additives. Food Addit. Contam. 1989, 6:1-12.
2. Bedir E., Çalis I., Aquino R., Piacente S., Pizza C. Cycloartane triterpene glycosides from the roots of Astragalus brachypterus and Astragalus microcephalus. J. Nat. Prod. 1998, 61:1469-1472.
3. Bedir E., Çalis I., Zerbe O., Sticher O. Cyclocephaloside I: A novel cycloartane-type glycoside from Astragalus microcephalus. J. Nat. Prod. 1998, 61:503-505.
4. Bedir E., Çalis I., Aquino R., Piacente S., Pizza C. Secondary metabolites from the roots of Astragalus trojanus. J. Nat. Prod. 1999, 62:563-568.
5. Bedir E., Çalis I., Aquino R., Piacente S., Pizza C. Trojanoside H: A cycloartane-type glycoside from the aerial parts of Astragalus trojanus. Phytochemistry 1999, 51:1017-1020.
6. Bedir E., Çalis I., Dunbar C., Sharan R., Buolamwini J.K., Khan I.A. Two novel cycloartane-type triterpene glycosides from the roots of Astragalus prusianus. Tetrahedron 2001, 57:5961-5966.
7. Bedir E., Tatli I.I., Çalis I., Khan I.A. Trojanosides I-K: New cycloartane-type glycosides from the aerial parts of Astragalus trojanus. Chem. Pharm. Bull. 2001, 49:1482-1486.
8. Castillo C., Valencia I., Reyes G., Hong E. 3-Nitropropionic acid, obtained from Astragalus species, has vasodilator and antihypertensive properties. Drug Dev. Res. 1993, 28:183-188.
9. Pharmacology and Applications of Chinese Materia Medica, vol. 2 1987, World Scientific Publishing, Singapore. H.M. Chang, P.P.H. But (Eds.).
10. de Jesus B.B., Schneeberger K., Vera E., Tejera A., Harley C.B., Blasco M.A. The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell 2011, 10:604-621.
11. Derelanko M.J. Clinical pathology. Toxicologist's Pocket Handbook 2000, 97-122. CRC Press, New York.
12. + T lymphocytes. J. Immunol. 2008, 181:7400-7406.
13. Ganzera M., Bedir E., Çalis I., Khan I.A. Separation of Astragalus saponins by reversed phase high performance liquid chromatography and evaporative light scattering detection. Chromatographia 2001, 53:131-134.
14. Gregory G. Gum. A New and Complete Dictionary of Arts and Sciences: Including the Latest Improvement and Discovery and the Present State of Every Branch of Human Knowledge 1819, vol. 2. Collins and Co., London.
15. Harley C.B., Liu W., Blasco M., Vera E., Andrews W.H., Briggs L.A., Raffaele J.M. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res. 2011, 14:45-56.
16. Harley C.B., Liu W., Flom P.L., Raffaele J.M. A natural product telomerase activator as part of a health maintenance program: metabolic and cardiovascular response. Rejuvenation Res. 2013, 16:386-395.
17. Hong C.Y., Lo Y.C., Tan F.C., Wei Y.H., Chen C.F. Astragalus membranaceus and Polygonum multiflorum protect rat heart mitochondria against lipid peroxidation. Am. J. Chin. Med. 1994, 22:63-70.
18. Kitagawa I., Wang H.K., Takagi A., Fuchida M., Miura I., Yoshikawa M. Saponin and Sapogenol. XXXIV. Chemical constituents of Astragali Radix, the root of Astragalus membranaceus Bunge. (1). Cycloastragenol, the 9,19-cyclolanostane-type aglycone of astragalosides, and the artifact aglycone astragenol. Chem. Pharm. Bull. 1983, 31:689-697.
19. Li Z.P., Cao Q. Effects of astragaloside IV on myocardial calcium transport and cardiac function in ischemic rats. Acta Pharmacol. Sin. 2002, 23:898-904.
20. Ma X.Q., Shi Q., Duan J.A., Dong T.T.X., Tsim K.W.K. Chemical analysis of Radix Astragali (Huangqi) in China: a comparison with its adulterants and seasonal variations. J. Agric. Food Chem. 2002, 50:4861-4866.
21. McKenna D.J., Jones K., Hughes K., Humphrey S. Astragalus. Botanical Medicines. The Desk Reference for Major Herbal Supplements 2002, 1-17. The Haworth Herbal Press, New York. second ed.
22. Movafeghi A., Djozan Dj., Razeghi J.A., Baheri T. Identification of volatile organic compounds in leaves, roots and gum of Astragalus compactus Lam. using solid phase microextraction followed by GC-MS analysis. Nat. Prod. Res. 2010, 24:703-709.
23. Mulambalah C.S., Siamba D.N., Vulule J.M. The molecular and medical aspects of the aging process. Res. J. Med. Sci. 2012, 6:117-123.
24. National Research Council of the National Academies, 2011. Guide for the Care and Use of Laboratory Animals. Institute of Laboratory Animal Research, Division of Earth and Life Studies. National Academy Press, Washington, DC.
25. Pettersen J.C., Morrissey R.L., Saunders D.R., Pavkov K.L., Luempert L.G., Turnier J.C., Matheson D.W., Schwartz D.R. A 2-year comparison study of Crl:CD BR and Hsd: Sprague-Dawley SD rats. Fund. Appl. Toxicol. 1996, 33:196-211.
26. Ralphs M.H., Creamer R., Baucom D., Gardner D.R., Welsh S.L., Graham J.D., Hart C., Cook D., Stegelmeier B.L. Relationship between the endophyte Embellisia spp. and the toxic alkaloid swainsonine in major locoweed species (Astragalus and Oxytropis). J. Chem. Ecol. 2008, 34:32-38.
27. Rios J.L., Waterman P.G. A review of the pharmacology and toxicology of Astragalus. Phytother. Res. 1997, 11:411-418.
28. Sevimli-Gür C., Onbaşilar I., Atilla P., Genç R., Çakar N., Deliloǧlu-Gürhan I., Bedir E. In vitro growth stimulatory and in vivo wound healing studies on cycloartane-type saponins of Astragalus genus. J. Ethnopharmacol. 2011, 134:844-850.
29. Shibata T., Sakai E., Nishi K., Anetai M. Growth and glycoside contents of Astragalus membranaceus Bunge (Leguminosae) cultivated in different soil groups. Nat. Med. 1996, 50:296-299.
30. Sors T.G., Martin C.P., Salt D.E. Characterization of selenocysteine methyltransferases from Astragalus species with contrasting selenium accumulation capacity. Plant. J. 2009, 59:110-122.
31. Verotta L., El-Sebakhy N.A. Cycloartane and oleanane saponins from Astragalus sp. Stud. Nat. Prod. Chem. 2001, 25:179-234.
32. Vogel H.J., Bonner D.M. Acetylornithinase of Escherichia coli: partial purification and some properties. J. Biol. Chem. 1956, 218:97-106.
33. Wang Q. Inotropic action of Astragalus membranaceus Bge. saponins and its possible mechanism. China J. Chin. Mater. Med. 1992, 17:557-559.
34. WHO (World Health Organization), 1999. Radix Astragali. In: WHO monographs on selected medicinal plants, vol. 1. World Health Organization, Geneva, Switzerland. pp. 50-58.
35. Xiao W.L., Motley T.J., Unachukwu U.J., Lau C.B.S., Jiang B., Hong F., Leung P.C., Wang Q.F., Livingston P.O., Cassileth B.R., Kennelly E.J. Chemical and genetic assessment of variability in commercial Radix Astragali (Astragalus spp.) by ion trap LC-MS and nuclear ribosomal DNA barcoding sequence analyses. J. Agric. Food Chem. 2011, 59:1548-1556.
36. Yang Z.G., Sun H.X., Fang W.H. Haemolytic activities and adjuvant effect of Astragalus membranaceus saponins (AMS) on the immune responses to ovalbumin in mice. Vaccine 2005, 23:5196-5203.
37. Yang W.Z., Ye M., Huang F.X., He W.N., Guoa D.A. Biocatalysis of cycloastragenol by filamentous fungi to produce unexpected triterpenes. Adv. Synth. Catal. 2012, 354:527-539.
38. Yu S.Y., Yang H.T.O., Yang J.Y., Huang X.L., Yang T., Duan J.P., Cheng J.P., Chen Y.X., Yang Y.J., Qiong P. Subchronic toxicity studies of Radix Astragali extract in rats and dogs. J. Ethnopharmacol. 2007, 110:352-355.
39. Yu Q.T., Qi L.W., Li P., Yi L., Zhao J., Bi Z. Determination of seventeen main flavonoids and saponins in the medicinal plant Huang-qi (Radix-Astragali) by HPLC-DAD-ELSD. J. Sep. Sci. 2007, 30:1292-1299.
40. Yung L.Y., Lam W.S., Ho M.K.C., Hu Y., Ip F.C.F., Pang H., Chin A.C., Harley C.B., Ip N.Y., Wong Y.H. Astragaloside IV and cycloastragenol stimulate the phosphorylation of estracellular signal-regulated protein kinase in multiple cell types. Planta Med. 2012, 78:115-121.
41. Zhang Y.D., Wang Y.L., Shen J.P., Li D.X. Effects on blood pressure and inflammation of Astragalus saponin 1, a principle isolated from Astragalus membranaceus Bge. Acta Pharm. Sin. 1984, 19:333-337. (as cited in McKenna et al., 2002).
42. Zhou R.N., Song Y.L., Ruan J.Q., Wang Y.T., Yan R. Pharmacokinetic evidence on the contribution of intestinal bacterial conversion to beneficial effects of astragaloside IV, a marker compound of Astragali Radix, in traditional oral use of the herb. Drug Metab. Pharmacokinet. 2012, 27:586-597.