Evidence-Based Complementary and Alternative Medicine 5 Table 1: The measurements of nitrite, nitrate, nitroso, nitrite reductase activity in several TCM herbs commonly used for CAD. Chinese name English name DanShen Danahen Root Latin name Radix Salviae Miltiorrhizae Indication CAD Snakegourd Fruit Fructus Trichosanthis CHAypDe,ralicpuidteemMiIa, GuaLou Longstamen Onion Bulbus Allii Macrostemi CAD, acute MI, XieBai Bulb Hyperlipidemia SanChi Sanchi Radix Notoginseng CAD RuXiang Frankincense Resina Olibani Hypertension ChiShao Red Peony Root Radix Paeonia Rubra CAD HongSheng Ginseng Radix Ginseng Heart failure, CAD Increase other herb’s BingPiang Borneol Borneolum Syntheticum function for CAD or brain disease Increase other herb’s TianRanBingPiang Borneol Cinnamomum function for CAD or brain disease Nitrite Nitrate Nitroso (ng/g) (mg/g) (nmoL/g) NO production (pmol/mg) 330 260 150 210 980 120 300 120 160 12000 278 530 2069 61 37 243 2.99 2.39 120 120 842 73 3210 450 76 6 0 7 46 134 13 72 255 360 45 875 for the inability of the endothelium to convert L-arginine to NO in coronary heart disease. This concept has recently been tested through the development of a rationally designed dietary supplement with natural products selected for their NO activity based on their nitrite, nitrate content, and an oxygen independent nitrite reductase. In a double-blinded placebo-controlled study in patients over the age of 40 with at least 3 cardiovascular risk factors, this type of technology was found to signiﬁcantly restore plasma levels of nitrite and nitrate, reduce triglycerides by 27%, and modestly reduce blood pressure and C-reactive protein thereby modifying the cardiovascular risk proﬁle of patients after only 30 days [56]. Recent clinical studies have provided new evidence on Danshen, a commonly used herbal medicine for CVD in China, which may have a similar eﬃcacy to the known NO donor nitroglycerin [57–59]. The extract of Salviae Miltior- rhiae, or Danshen in Chinese, contains large amounts of nitrate [32]. The demonstration of beneﬁcial eﬀects of this herb on ischemic diseases oﬀers an alternative avenue for the management of angina pectoris, myocardial infarction, or stroke [60, 61]. Danshen-related Chinese herbal medicines have been widely used for treatment of coronary heart dis- ease in the East, and a clinical trial is on the way in the United States. Danshen is a routine herbal medication for acute angina pectoris. In addition, it may be eﬀective for dyslipi- demia, blood hyperviscosity syndrome, peripheral angiopa- thy (superﬁcial thrombophlebitis, venous thrombosis, aller- gic arteriolitis), diabetes mellitus, and cirrhosis and is also used for altitude sickness. Experimental studies have shown that Danshen dilates coronary arteries, increases coronary blood ﬂow, and scavenges free radicals in ischemic diseases, reducing cellular damage from ischemia and improving heart functions, remarkably similar to known eﬀects of NO and nitrite [59]. However, the nitrate/nitrite reductase activity in Danshen is relatively low. Often, Danshen is mixed with other herbal products. One of which is an extract of cinna- mon or borneol. Borneol is consumed excessively in China and Southeast Asian countries, particularly in a combined formula for preventing cardiovascular disease. Borneol exerts a concentration-dependent inhibitory eﬀect on venous thrombosis [62]. The antithrombotic activity of borneol con- tributes to its action in combined formula for preventing car- diovascular diseases. Our recent studies have shown that although the natural form of borneol itself contains very little nitrite and nitrate, it displays a potent nitrite reductase activity [32] that when used in combination with nitrite and nitrate-rich DanShen provides the system for generating NO. Another herbal medicine made from the root of Radix ginseng may also have synergistic eﬀects with Danshen. Ginseng contains modest amounts of nitrate but has stronger reductase activity [32]. Therefore, this may explain the mech- anism behind the theory of synergy of speciﬁc combination of herbs. 6. Effects of TCM on L-Arginine/eNOS/NO Signaling Pathway Some TCM may regulate NO production by exerting reg- ulatory eﬀects on the L-arginine/eNOS/NO signaling path- way. Puerarin is a major active ingredient extracted from the traditional Chinese medicine Ge-gen (Radix Puerariae, RP). It has long been used to treat cardiovascular diseases in- cluding coronary artery diseases (CAD), arrhythmia, and hypertension. Recent studies have shown that puerarin increases serum nitrite concentrations in rats with myocar- dial ischemia through the induction of protein expression and activation of eNOS and through Akt/PKB phosphoryla- tion [63]. Tongxinluo (TXL), a mixture of traditional Chi- nese medicines, can attenuate the no-reﬂow and ischemia- reperfusion injury in an infarct animal model [64, 65]. TXL is composed of Radix ginseng, Buthus martensii, Hirudo, Eu- polyphaga seu steleophaga, Scolopendra subspinipes, Perios- tracum cicadae, Radix paeoniae rubra, Semen ziziphi spinosae, Lignum dalbergiae odoriferae, Lignum santali albi, and Borne- olum syntheticum. Owing to its eﬃcacy and minimal adverse eﬀects, TXL has been widely used in China to treat patients