6 with acute coronary syndrome. In a 90-minute ischemia and 3-hour reperfusion model, miniature pigs were randomly assigned to treatment with TXL (gavaged 1 hour prior to ischemia); TXL plus H-89 (protein kinase-A inhibitor intra- venously infused before ischemia); or TXL plus N(omega)- nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered prior to ischemia). The results of this study demonstrate that TXL treatment can decrease creatine kinase elevation, improve coronary ﬂow, and reduce infarct size. The eﬀects of TXL may be partially abolished by H-89 or completely reversed by L-NNA. In addition, TXL treat- ment can elevate the kinase activity and expression, evi- denced by expression of Thr198 phosphorated-PKA, Ser1179 phosphorated-eNOS (p-eNOS), and Ser635 p-eNOS in the ischemic myocardium. Addition of H-89 diminishes the TXL activities. Thus, pretreatment with a single low loading dose of TXL 1 hour before ischemia reduces the myocardial no-reﬂow phenomenon and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser1179 and Ser635, and this eﬀect is partially mediated by the PKA pathway [64]. Recent studies also have shown that Salvianolic acid B (Sal B) and Tanshinone IIA (Tan IIA) are two of the major components in Danshen, have cardioprotective eﬀects in an in vivo myocardial infarction model of C57 mice, have vasodilator action in an ex vivo microartery system through the endothelial nitric oxide synthase (eNOS)/nitric oxide pathway, and are involved in the regulation of the L-arginine/eNOS/NO pathways in human umbilical vein endothelial cells (HUVECs). Both Sal B and Tan IIA inhibited cardiac hypertrophy and infarction sizes and improved cardiac function at 4 weeks after induction of infarction. Furthermore, an eNOS inhibitor (L-NAME) obliterated the observed eﬀects. Sal B and Tan IIA mediated vasodilatation in mice coronaries ex vivo, the eﬀect of which was decreased with either L-NAME or PI3K inhibitor (LY294002). In addi- tion, Sal B and Tan IIA-induced vasodilatation was observ- ed ex vivo in the microvessels of eNOS−/− mice. Sal B and Tan IIA also stimulated eNOS phosphorylation in a concen- tration- and time-dependent manner in the HUVEC culture, which was diminished by LY294002. In addition, Sal B and Tan IIA were found to stimulate the phosphorylation of AMPK (Thr(172)) and Akt (Ser(473)), while compou- nd C signiﬁcantly decreased the phosphorylation of Akt (Ser(473)) mediated by both. Finally, Sal B and Tan IIA were found to induce [(3)H]-L-arginine uptake and increase the CAT-1 and CAT-2B mRNA levels in HUVEC culture [66]. It appears that select TCM herbs alone and in combination can restore NO homeostasis both through an endothelium dependent manner by activating the L-arginine pathway and through an endothelium-independent manner via the nitrate-nitrite-NO pathway that may overcome endothelial dysfunction. 7. Effects of CAM on Oxidative Stress and Preservation of NO Activity In several chronic diseases, free radicals are by-products of abnormal body metabolism and are important factors for Evidence-Based Complementary and Alternative Medicine late complications and secondary disease especially those related to NO and endothelial dysfunction [67]. There is in- creasing evidence that in certain pathologic states the increased production and/or ineﬀective scavenging of reac- tive oxygen species (ROS) may play a critical role. Medicinal plants are a source for a wide variety of natural antioxi- dants [68] and my exhibit their eﬀects via several proposed mechanisms, including inhibition of the activities of cyclo- oxygenase-2 (COX-2) and nuclear factor-Kappa B (NF-κB), inhibition of angiogenesis, and activation of Nrf2-mediated antioxidant signaling [69], all known to interface with the NO pathway. Dang Gui has been shown to hold anti-inﬂam- matory properties and antioxidant activities, especially when used concurrently with other herbs [70]. Dietz and col- leagues have reported that the major lipophilic constituent of Dang Gui, Z-ligustilide, reduces oxidative stress through upregulation of antioxidant enzymes such as NQO1, an Nrf2 pathway gene [71]. Also, A. sinensis can protect against oxidant injury through elevated glutathione synthesis whose rate limiting step is regulated by the Nrf2-regulated gene γ- GCS [72]. Of the diﬀerent components in Dan Shen, tanshi- none IIA has been identiﬁed with the most potent antiox- idant activity and cytotoxic properties by inducing apo- ptosis and diﬀerentiation in various human cancer cell lines [73]. Tanshinone IIA also displays antioxidant protection against reactive oxygen species (ROS) induced oxidative stress through stress-activated kinases JNKs and p38 MAPK and by an increase in scavenging of oxygen free radicals [74]. Drinking tea is a tradition that began in ancient China over 5000 years ago. Green tea from the leaves of Came- llia sinensis is the second most consumed beverage in the world, after water. It is a well-studied herb for its eﬀectiv- eness in chemoprevention, cancer therapy, and other beneﬁts to overall health. The main components of green tea are poly- phenols, known as catechins, which account for 30–42% of the solid weight in green tea leaves. The most abundant polyphenol in green tea is (−)-epigallocatechin-3-gallate (EGCG), which is also the most commonly studied green tea component [75]. EGCG contributes to 10–50% of the total polyphenol contents in green tea and appears to possess the strongest antioxidant activity, about 25–100 fold more potent than vitamins C and E [75]. Reducing oxidative stress and promoting endogenous antioxidant enzymatic defense systems very likely provides an additional beneﬁt of tradi- tional medicines. These antioxidants defenses will enhance endogenous NO production by keeping essential cofactors such as BH4 from becoming oxidized and also preserve and prolong NO activity once it is produced by preventing its scavenging by oxygen radicals. 8. Conclusion Taken together, the NO signaling pathway plays an important role in the therapeutic eﬀect of many CAMs used for cardio- vascular disease (Figure 2). The NO donor-like herbs may serve as an alternative source of nitrate and nitrite or other NO-donors. They contain high activities of nitrite reductase that converts the inorganic anion into NO, which, in turn,