11652 J. Agric. Food Chem., Vol. 56, No. 24, 2008 increasingly likely that SA is a biopharmaceutical with a central, broadly defensive, role in animals as in plants. This simple organic chemical is, we propose, likely to become increasingly recognized as an animal bioregulator, perhaps in a class of its own. Intriguingly, as a phytohormone it may have differential, concentration-dependent, effects on programmed cell death and surrounding tissue protection (29). Some of the tissue effects of SA already described (5, 6, 25-28) raise the probability of just such a hybrid function, perhaps at a critical point in apoptosis and/or inﬂammation, in animals as in plants. If we are right that SA is not just an important phytochemical but also a key biopharmaceutical, its circulating level might well be subject to homeostatic control and not be solely inﬂuenced by dietary SA with or without benzoic acid intake. LITERATURE CITED (1) Dangl, J. Nature 1998, 394, 525–527. (2) Sneader, W. Pharm. J. 1997, 259, 614–617. (3) Needs, C. J.; Brooks, P. M. Clin. Pharmacokinet. 1985, 10, 164– 177. (4) Higg, G. A.; Salmon, J. A.; Henderson, B.; Vane, J. R. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 1417–1420. (5) Xu, X.-M.; Scansores-Garcia, L.; Chen, X.-M.; Matjevic-Aleksic, N.; Min, D.; Wu, K. K. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 5292–5297. (6) Wu, K. K. Circulation 2000, 102, 2022–2023. (7) Paterson, J. R.; Blacklock, C.; Campbell, G.; Wiles, D.; Lawrence, J. R. J. Clin. Pathol. 1998, 51, 502–505. (8) Baxter, G. J.; Lawrence, J. R.; Graham, A. B.; Wiles, D.; Paterson, J. R. Ann. Clin. Biochem. 2002, 39, 50–55. (9) Blacklock, C. J.; Lawrence, J. R.; Wiles, D.; Malcolm, E. A.; Gibson, I. H.; Kelly, C. J.; Paterson, J. R. J Clin. Pathol. 2001, 54, 553–555. (10) Lawrence, J. R.; Peter, R.; Baxter, G. J.; Robson, J.; Graham, A. B.; Paterson, J. R. J. Clin. Pathol 2003, 56, 651–653. (11) Paterson, J. R.; Srivastava, R.; Baxter, G. J.; Graham, A. B.; Lawrence, J. R. J. Agric. Food Chem. 2006, 54, 2891–2896. Paterson et al. (12) Spadafranca, A.; Bertoli, S.; Fioriollo, G.; Testolin, G.; Battezzati, A. Br. J. Nutr. 2007, 1–5. (13) El-Basyouni, S.; Chen, D.; Ibrahim, R. K.; Neish, A. C.; Towers, G. H. N. Phytochemistry 1964, 3, 485–492. (14) Yalpini, M.; Leon, J.; Lawton, M. A.; Raskin, I. Plant Physiol. 1993, 103, 315–321. (15) Zuo, Y.; Wang, C.; Zhan, J. J. Agric. Food Chem. 2002, 50, 3789– 3794. (16) Zhang, K.; Zuo, Y. J. Agric. Food Chem. 2004, 52, 222–227. (17) Armstrong, M. D.; Chao, F.-C.; Parker, V. J.; Wall, P. E. Proc. Soc. Exp. Biol. Med. 1955, 90, 675–679. (18) Young, D. S. Clin Chem 1970, 16, 681–686. (19) Swain, R.; Dutton, S. P.; Truswell, A. S. J. Am. Diet. Assoc 1985, 85, 950–960. (20) Venema, D. P.; Hollman, P. C. H.; Janssen, P. L. T. M. K. J. Agric. Food Chem. 1996, 44, 1762–1767. (21) Variyar, P. S.; Bandyopadhyay, C. J. Spices Aromatic Crops 1995, 4, 129–134. (22) Robertson, G. I.; Kermode, W. J. J. Sci. Food Agric. 1981, 833– 836. (23) Janssen, P. L. T. M. K.; Hollman, P. C. H.; Reichman, E.; et al. Am. J. Clin. Nutr. 1996, 64, 743–747. (24) Bekersky, I.; Colburn, W. A.; Fishman, L.; Kaplan, S. A. Drug Metab. Dispos. 1980, 8, 319–324. (25) Stark, L. A.; Din, F. V. M.; Zwacke, R. M.; Dunlop, M. G. FASEBJ 2001, 15, 1273–1276. (26) Borthwick, G. M.; Johnson, A. S.; Partington, M.; Burn, J.; Wilson, R.; Arthur, H. M. FASEB J. 2006, 20, 2009–2016. (27) Farthing, D.; Gehr, L.; Karnes, H. T.; Sica, D.; Gehr, T.; Larus, T.; Farthing, C.; Xi, L. Biomarkers 2007, 12 (6), 623–634. (28) Nunez, L.; Valero, R.; Senovilla, L.; Sanz-Blasco, S.; Garcia- Sancho, J.; Villalobos, C. J. Physiol. 2006, 57–73. (29) Alvarez, M. E. Plant Mol. Biol. 2000, 44, 429–442. Received for review April 25, 2008. Revised manuscript received August 7, 2008. Accepted September 9, 2008. JF800974Z