2 is typically referred to as CAM. TCM has its origin in ancient Taoist philosophy, which views a person as an energy system in which the body, mind, and spirit are uniﬁed into one when in harmony and are disrupted in disease. TCM practice treats the patient as a whole, not as a part, and it emphasizes a holistic approach that attempts to bring the mind, body, and spirit into harmony. TCM theory is extremely complex and originated thousands of years ago through meticulous observation of nature, the cosmos, and the human body. In TCM theory, imbalance between yin and yang is a summa- tion of all kinds of basic disease and disorders. There is a growing and sustained interest in CAM and TCM fueled by a combination of factors including recognition of the bene- ﬁts, dissatisfaction with and ineﬀectiveness of traditional Western medicines, increasing commitment to holistic care, skepticism regarding adverse side eﬀects of drugs, and in- creasing evidence for the personalized nature of various combinations of herbs for speciﬁc disorders [1]. The use of TCM is increasing in Western nations, mostly among people of Southeast Asian origin. Patients who use TCM in Western countries report that the main reason for using it is that TCM is a “more natural” and potentially safer alternative in the treatment of chronic illness than pharmaceutical drugs or surgery [1]. Of the approximately 500 herbs that are in use today, 50 or so are very commonly used alone or in combination. Rather than being prescribed individually, single herbs are combined into formulas that are designed to adapt to the speciﬁc needs of individual patients. A herbal formula can contain from 3 to 25 herbs. Each herb has one or more of the four ﬂavors/functions and one of ﬁve “temper- atures” “ ” (pronounced “chi”) (hot, warm, neutral, cool, cold). Herbal formulations work to balance the body from the inside out. Traditional herbal medicines include herbs, herbal materials, herbal preparations, and processed herbal products that contain parts of plants or other plant materials as active ingredients, which assist with strengthening the vital energies (chi), blood, and ﬂuids internally. They are typically administered as tablets, pills, elixirs, soups, liquid extracts, and teas and broadly classiﬁed as dietary supplements here in the USA. There are a number of published reports on the association of TCM and NO-related eﬀects [2, 3]. Recently, there are increased interests in the role for NO system in reg- ulation of cardiovascular function by TCM used commonly for cardiovascular disorders. Recognizing and understanding NO activity of TCM may help explain centuries of treatment eﬃcacy in a number of diseases and highlight new treatment options for conditions of NO insuﬃciency. 2. Current Global Markets for CAM A 2002 survey of US adults 18 years and older conducted by the National Center for Health Statistics (CDC) and the NCCAM indicated that 74.6% had used some form of CAM, 62.1% had done so within the preceding 12 months, 54.9% used CAM in conjunction with conventional medicine, and 14.8% sought care from a licensed or certiﬁed practitioner suggesting that most individuals who use CAM prefer to Evidence-Based Complementary and Alternative Medicine treat themselves [4]. The industry of alternative and comple- mentary medicines broadly classiﬁed as dietary supplements is expected to be $250 billion by 2016 worldwide. In 2004, a survey of nearly 1,400 US hospitals found that more than one in four oﬀered alternative and complementary therapies such as acupuncture, homeopathy, and massage therapy. Herbal treatments are the most popular form of traditional medicine or CAM and are highly lucrative in the international market- place. Annual revenues in Western Europe reached $5 billion in 2003-2004. In China, sales of products totaled $14 billi- on in 2005. Herbal medicine revenue in Brazil was $160 milli- on in 2007, according to WHO Fact Sheet no. 134, 2008. Therefore, this industry and type of health care can no longer be ignored. In order to better understand the mechanism of action and the safety proﬁle of herbal remedies, more re- search and resources are needed. Identifying physiological systems or molecular targets that may be aﬀected by TCM will help propel the ﬁeld and industry forward and create a better safety and eﬃcacy proﬁle of certain CAMs. 3. Production and Regulation of NO in the Cardiovascular System Appropriate levels of NO production are critical in tissue blood perfusion and protection of cardiovascular tissues against ischemia and infarction. NO is endogenously gener- ated from the amino acid L-arginine and molecular oxygen in reactions catalyzed by a family of enzymes called NO syn- thases (NOS). There are three mammalian NOS iso- forms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). They share 50–60% homology at the amino acid level [5]. Under physiological conditions, the dominant NOS isoform in the vasculature is eNOS, which rather than being a constitutive enzyme as was ﬁrst suggested is dynamically reg- ulated at the transcriptional, posttranscriptional, and post- translational levels [6]. Endothelial dysfunction arises from downregulation of eNOS expression and activity and uncou- pling of NOS generating free radicals [7]. We now recognize and appreciate that the endothelial production of NO declines progressively with age and can be further reduced by poor diet and lifestyle [8–10]. This becomes the basis for end- othelial dysfunction and the etiology of a number of CVD- related symptoms. Restoring endogenous production of NO or providing an exogenous source of NO would be an attrac- tive therapeutic option if this intervention could slow down the progression of endothelial dysfunction and reduce the risk of CVD. Recently, an alternative pathway for NO generation was discovered, wherein the inorganic anions nitrate and nitrite, most often considered inert end products from NO oxida- tion, can be reduced back to NO and other bioactive nitrogen oxide species. This nitrate-nitrite-nitric oxide pathway is reg- ulated diﬀerently than the classic L-arginine-nitric oxide syn- thase pathway as shown in Figure 1, and it is greatly enhanced during hypoxia and acidosis. Nitrite and nitrate have now moved to the forefront of NO biology [11] with the discovery that it represents a major storage form of NO in both blood and tissues [12]. Dietary nitrite and nitrate have been shown