Evidence-Based Complementary and Alternative Medicine 7 L-arginine NO Regulatory herbal medicines Normoxia NOS- dependent pathway Oxidation Hypoxia NOS- independent pathway Reduction NO-donor herbal medicines NO NO2−, NO3− Figure 2: Potential mechanisms of TCM on the regulation of NO Signaling pathway TCM herbs alone and in combination can help restore NO homeostasis in the CVD and maintain “Yin-Yang” balance through reduction of Nitrate/nitrite and oxidation of L-arginine. relaxes blood vessels and prevents thrombosis. There are also some TCM which contain regulatory factors that inﬂu- ence the expression and activity of eNOS (Figure 2) and may interact with endogenous factors that modulate L- arginine/eNOS/NO signaling pathway. Modern research is providing more evidence to understand speciﬁc activity of CAMs that will hopefully provide a mechanistic understand- ing of their clinical eﬃcacy and allow for better combination of diﬀerent herbs. However, currently the use of CAM is inﬂuenced by legal restrictions, with shifts towards increasing regulation and formal recognition of CAM as means to treat or prevent disease. Further investigation and research are warranted in terms of the functional mechanisms, biosafety, and large-scale clinical trials to ﬁrmly establish the eﬃcacy of many of these approaches in the prevention and treatment of illnesses. References [1] P. Davidson, K. Hancock, D. Leung et al., “Traditional Chinese Medicine and heart disease: what does Western medicine and nursing science know about it?” European Journal of Cardio- vascular Nursing, vol. 2, no. 3, pp. 171–181, 2003. [2] C. N. Gillis, “Panax ginseng pharmacology: a nitric oxide link?” Biochemical Pharmacology, vol. 54, no. 1, pp. 1–8, 1997. [3] X. Chen, “Cardiovascular protection by ginsenosides and their nitric oxide releasing action,” Clinical and Experimental Phar- macology and Physiology, vol. 23, no. 8, pp. 728–732, 1996. [4] P. Barnes, E. Powell-Griner, K. E, McFann, and R. Nahin, CDC Advance Data Report #343. Complementary and Alternative Medicine Use Among Adults: United States, 2002. [5] D. J. Stuehr, “Structure-function aspects in the nitric oxide synthases,” Annual Review of Pharmacology and Toxicology, vol. 37, pp. 339–359, 1997. [6] R. Raﬁkov, F. V. Fonseca, S. Kumar et al., “eNOS activation and NO function: structural motifs responsible for the posttrans- lational control of endothelial nitric oxide synthase activity,” Journal of Endocrinology, vol. 210, no. 3, pp. 271–284, 2011. [7] L. J. Ignarro, C. Napoli, and J. Loscalzo, “Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: an overview,” Circulation Research, vol. 90, no. 1, pp. 21–28, 2002. [8] K. Egashira, T. Inou, Y. Hirooka et al., “Eﬀects of age on endo- thelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans,” Circulation, vol. 88, no. 1, pp. 77–81, 1993. [9] M. Gerhard, M. A. Roddy, S. J. Creager, and M. A. Creager, “Aging progressively impairs endothelium-dependent vasodi- lation in forearm resistance vessels of humans,” Hypertension, vol. 27, no. 4, pp. 849–853, 1996. [10] S. Taddei, A. Virdis, L. Ghiadoni et al., “Age-related reduction of NO availability and oxidative stress in humans,” Hyperten- sion, vol. 38, no. 2, pp. 274–279, 2001. [11] M. T. Gladwin, A. N. Schechter, D. B. Kim-Shapiro et al., “The emerging biology of the nitrite anion,” Nature Chemical Biology, vol. 1, no. 6, pp. 308–314, 2005. [12] N. S. Bryan, “Nitrite in nitric oxide biology: cause or conseq- uence?. A systems-based review,” Free Radical Biology and Medicine, vol. 41, no. 5, pp. 691–701, 2006. [13] N. S. Bryan, J. W. Calvert, J. W. Elrod, S. Gundewar, Y. J. Sang, and D. J. Lefer, “Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 48, pp. 19144–19149, 2007. [14] N. S. Bryan, J. W. Calvert, S. Gundewar, and D. J. Lefer, “Die- tary nitrite restores NO homeostasis and is cardioprotective in endothelial nitric oxide synthase-deﬁcient mice,” Free Radical Biology and Medicine, vol. 45, no. 4, pp. 468–474, 2008. [15] J. Zhan, A. Nakao, R. Sugimoto et al., “Orally administered nit- rite attenuates cardiac allograft rejection in rats,” Surgery, vol. 146, no. 2, pp. 155–165, 2009. [16] N. G. Hord, Y. Tang, and N. S. Bryan, “Food sources of nit- rates and nitrites: the physiologic context for potential health beneﬁts,” American Journal of Clinical Nutrition, vol. 90, no. 1, pp. 1–10, 2009. [17] J. O. Lundberg, M. T. Gladwin, A. Ahluwalia et al., “Nitrate and nitrite in biology, nutrition and therapeutics,” Nature Chemical Biology, vol. 5, no. 12, pp. 865–869, 2009. [18] J. O. Lundberg, E. Weitzberg, and M. T. Gladwin, “The nitrate- nitrite-nitric oxide pathway in physiology and therapeutics,” Nature Reviews Drug Discovery, vol. 7, no. 2, pp. 156–167, 2008. [19] F. J. Larsen, B. Ekblom, K. Sahlin, J. O. Lundberg, and E. Weit- zberg, “Eﬀects of dietary nitrate on blood pressure in healthy volunteers,” The New England Journal of Medicine, vol. 355, no. 26, pp. 2792–2793, 2006.