Dietary feeding of flavokawain A, a Kava chalcone, exhibits a satisfactory safety profile and its association with enhancement of phase II enzymes in mice

Toxicology Reports

Volumn 1, Issue , 2014, Pages 2-11

  Li, Xuesen ^a   Xu, Xia ^a   Ji, Tao ^a   Liu, Zhongbo ^a   Gu, Mai ^b   Hoang, Bang H ^a   Zi, Xiaolin ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Flavokawain A; Hepatotoxicity; Kava

Indexed keywords

ALANINE AMINOTRANSFERASE; ALBUMIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; CHOLESTEROL; CREATININE; DOXORUBICIN; FLAVOKAWAIN A; GLUCOSE; GLUTATHIONE TRANSFERASE; KAVA EXTRACT; LACTATE DEHYDROGENASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG;

ABSENCE OF SIDE EFFECTS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; BONE MARROW CELL; CELL COUNTING; CELL PROLIFERATION; COLONY FORMATION; CONTROLLED STUDY; CYTOTOXICITY ASSAY; DIETARY INTAKE; ENZYME ACTIVITY; HISTOPATHOLOGY; HOMEOSTASIS; HUMAN; HUMAN CELL; HYPERLIPIDEMIA; INTESTINE EPITHELIUM CELL; MALE; MOUSE; NONHUMAN; PHASE II ENZYME ACTIVITY; PROSTATE CANCER; SPLEEN; THYMUS; TUMOR GROWTH;

EID: 84922750353     PISSN: 22147500     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.toxrep.2014.02.002     Document Type: Article

References (44)

1. Ferlay J., Shin H.R., Bray F., Forman D., Mathers C., Parkin D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN. Int. J. Cancer 2008, 127:2893-2917.
2. Steiner G.G. The correlation between cancer incidence and kava consumption. Hawaii Med. J. 2000, 59:420-422.
3. Johnson T.E., Kassie F., O'Sullivan M.G., Negia M., Hanson T.E., Upadhyaya P., Ruvolo P.P., Hecht S.S., Xing C. Chemopreventive effect of kava on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo[a]pyrene-induced lung tumorigenesis in A/J mice. Cancer Prev. Res. (Phila) 2008, 1:430-438.
4. Johnson T.E., Hermanson D., Wang L., Kassie F., Upadhyaya P., O'Sullivan M.G., Hecht S.S., Lu J., Xing C. Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice. Am. J. Chin. Med. 2011, 39:727-742.
5. Li X., Liu Z., Xu X., Blair C.A., Sun Z., Xie J., Lilly M.B., Zi X. Kava components down-regulate expression of AR and AR splice variants and reduce growth in patient-derived prostate cancer xenografts in mice. PLOS ONE 2012, 7:e31213.
6. Shaik A.A., Hermanson D.L., Xing C. Identification of methysticin as a potent and non-toxic NF-kappaB inhibitor from kava, potentially responsible for kava's chemopreventive activity. Bioorg. Med. Chem. Lett. 2009, 19:5732-5736.
7. Tang Y., Simoneau A.R., Xie J., Shahandeh B., Zi X. Effects of the kava chalcone flavokawain A differ in bladder cancer cells with wild-type versus mutant p53. Cancer Prev. Res. (Phila) 2008, 1:439-451.
8. Tang Y., Li X., Liu Z., Simoneau A.R., Xie J., Zi X. Flavokawain B, a kava chalcone, induces apoptosis via up-regulation of death-receptor 5 and Bim expression in androgen receptor negative, hormonal refractory prostate cancer cell lines and reduces tumor growth. Int. J. Cancer 2010, 127:1758-1768.
9. Zi X., Simoneau A.R. Flavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice. Cancer Res. 2005, 65:3479-3486.
10. Singh Y.N. Kava: an overview. J. Ethnopharmacol. 1992, 37:13-45.
11. Kapadia G.J., Azuine M.A., Tokuda H., Hang E., Mukainaka T., Nishino H., Sridhar R. Inhibitory effect of herbal remedies on 12-O-tetradecanoylphorbol-13-acetate-promoted Epstein-Barr virus early antigen activation. Pharmacol. Res. 2002, 45:213-220.
12. Triolet J., Shaik A.A., Gallaher D.D., O'Sullivan M.G., Xing C. Reduction in colon cancer risk by consumption of kava or kava fractions in carcinogen-treated rats. Nutr. Cancer 2012, 64:838-846.
13. Clouatre D.L. Kava kava: examining new reports of toxicity. Toxicol. Lett. 2004, 150:85-96.
14. Eskander R.N., Randall L.M., Sakai T., Guo Y., Hoang B., Zi X. Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line. J. Obstet. Gynaecol. Res. 2012, 38:1086-1094.
15. Sakai T., Eskander R.N., Guo Y., Kim K.J., Mefford J., Hopkins J., Bhatia N.N., Zi X., Hoang B.H. Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines. J. Orthop. Res. 2012, 30:1045-1050.
16. Warmka J.K., Solberg E.L., Zeliadt N.A., Srinivasan B., Charlson A.T., Xing C., Wattenberg E.V. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog. Biochem. Biophys. Res. Commun. 2012, 424:488-492.
17. Lechtenberg M., Schmidt Q.B.M., Nahrstedt A. Is the alkaloid pipermethystine connected with the claimed liver toxicity of Kava products?. Pharmazie 2008, 63:71-74.
18. Teschke R., Sarris J., Lebot V. Contaminant hepatotoxins as culprits for kava hepatotoxicity - fact or fiction?. Phytother. Res. 2012, 27:472-474.
19. Zhang L., Rowe A., Braet F., Ramzan I. Macrophage depletion ameliorates kavalactone damage in the isolated perfused rat liver. J. Toxicol. Sci. 2012, 37:447-453.
20. Zhou P., Gross S., Liu J.H., Yu B.Y., Feng L.L., Nolta J., Sharma V., Piwnica-Worms D., Qiu S.X. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways. FASEB J. 2010, 24:4722-4732.
21. Dharmaratne H.R., Nanayakkara N.P., Khan I.A. Kavalactones from Piper methysticum, and their 13C NMR spectroscopic analyses. Phytochemistry 2002, 59:429-433.
22. Li N., Liu J.H., Zhang J., Yu B.Y. Comparative evaluation of cytotoxicity and antioxidative activity of 20 flavonoids. J. Agric. Food Chem. 2008, 56:3876-3883.
23. Liu Z., Xu X., Li X., et al. KAVA chalcone, flavokawain A, inhibits urothelial tumorigenesis in the UPII-SV40T transgenic mouse model. Cancer Prev. Res. (Phila) 2013, 6:1365-1375.
24. Cote C.S., Kor C., Cohen J., Auclair K. Composition and biological activity of traditional and commercial kava extracts. Biochem. Biophys. Res. Commun. 2004, 322:147-152.
25. Reagan-Shaw S., Nihal M., Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008, 22:659-666.
26. Hillier S.M., Marquis J.C., Zayas B., Wishnok J.S., Liberman R.G., Skipper P.L., Tannenbaum S.R., Essigmann J.M., Croy R.G. DNA adducts formed by a novel antitumor agent 11beta-dichloro in vitro and in vivo. Mol. Cancer Ther. 2006, 5:977-984.
27. Soleimani M., Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat. Protoc. 2009, 4:102-106.
28. Benson A.M., Hunkeler M.J., Talalay P. Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity. Proc. Natl. Acad. Sci. U. S. A. 1980, 77:5216-5220.
29. Park E.Y., Cho I.J., Kim S.G. Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-gamma and retinoid X receptor heterodimer. Cancer Res. 2004, 64:3701-3713.
30. Centers for Disease Control and Prevention Hepatic Toxicity Possibly Associated with Kava-containing Products-United States, Germany, and Switzerland 2002, 1999-2002.
31. Brown A.C., Onopa J., Holck P., Kaufusi P., Kabasawa D., Craig W.J., Dragull K., Levine A.M., Baker J.D. Traditional kava beverage consumption and liver function tests in a predominantly Tongan population in Hawaii. Clin. Toxicol. (Phila) 2007, 45:549-556.
32. Clough A.R., Bailie R.S., Currie B. Liver function test abnormalities in users of aqueous kava extracts. J. Toxicol. Clin. Toxicol. 2003, 41:821-829.
33. Clough A.R., Jacups S.P., Wang Z., Burns C.B., Bailie R.S., Cairney S.J., Collie A., Guyula T., McDonald S.P., Currie B.J. Health effects of kava use in an eastern Arnhem Land Aboriginal community. Intern. Med. J. 2003, 33:336-340.
34. DiSilvestro R.A., Zhang W., DiSilvestro D.J. Kava feeding in rats does not cause liver injury nor enhance galactosamine-induced hepatitis. Food Chem. Toxicol. 2007, 45:1293-1300.
35. Lim S.T., Dragull K., Tang C.S., Bittenbender H.C., Efird J.T., Nerurkar P.V. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats. Toxicol. Sci. 2007, 97:214-221.
36. National Toxicology Program Toxicology and carcinogenesis studies of kava kava extract (CAS No. 9000-38-8) in F344/N rats and B6C3F1 mice (Gavage Studies). Natl. Toxicol. Program Tech. Rep. Ser. 2012, 1-186.
37. Russmann S., Lauterburg B.H., Barguil Y., Choblet E., Cabalion P., Rentsch K., Wenk M. Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: protective effect against environmental carcinogens?. Clin. Pharmacol. Ther. 2005, 77:453-454.
38. Singh Y.N., Devkota A.K. Aqueous kava extracts do not affect liver function tests in rats. Planta Med. 2003, 69:496-499.
39. Sorrentino L., Capasso A., Schmidt M. Safety of ethanolic kava extract: results of a study of chronic toxicity in rats. Phytomedicine 2006, 13:542-549.
40. Teschke R. Kava hepatotoxicity-a clinical review. Ann. Hepatol. 2010, 9:251-265.
41. Maronpot R.R., Yoshizawa K., Nyska A., Harada T., Flake G., Mueller G., Singh B., Ward J.M. Hepatic enzyme induction: histopathology. Toxicol. Pathol. 2010, 38:776-795.
42. Nelson J.A., Falk R.E. The efficacy of phloridzin and phloretin on tumor cell growth. Anticancer Res. 1993, 13:2287-2292.
43. Baba M., Asano R., Takigami I., Takahashi T., Ohmura M., Okada Y., Sugimoto H., Arika T., Nishino H., Okuyama T. Studies on cancer chemoprevention by traditional folk medicines XXV, inhibitory effect of isoliquiritigenin on azoxymethane-induced murine colon aberrant crypt focus formation and carcinogenesis. Biol. Pharm. Bull. 2002, 25:247-250.
44. Hayes J.D., Pulford D.J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol. 1995, 30:445-600.