Dissection of Mechanisms of a Chinese Medicinal Formula: Danhong Injection Therapy for Myocardial Ischemia/Reperfusion InjuryIn VivoandIn Vitro

Abstract

Traditional Chinese medicine uses a systemic treatment approach, targeting multiple etiological factors simultaneously. Danhong injection (DHI), a very popular Chinese medicine injection, is reported to be effective for many cardiovascular conditions. The primary active ingredients of DHI, and their systemic and interrelated mechanism have not been evaluated in an established myocardial ischemia/reperfusion (MI/R) model. We identified the main active constituents in DHI, including hydroxysafflor yellow A (A), salvianolic acid B (B), and danshensu (C), by HPLC fingerprint analysis and assessed their effect on MI/R rats and cardiomyocytes. These 3 compounds and DHI all decreased the levels of IL-1, TNF-α, and MDA, increased those of IL-10 and SOD activity in vivo and in vitro, and had antiapoptotic effects, as shown by flow cytometric analysis and TUNEL assay. Moreover, these compounds increased phosphorylation of Akt and ERK1/2 in cardiomyocytes. Interestingly, we found compound A exerted a more prominent anti-inflammatory effect than B and C, by decreasing NF-κB levels; compound B had more powerful antioxidative capacity than A and C, by increasing Nrf2 expression; compound C had stronger antiapoptotic ability than A and B, by lowering caspase-3 activity. Our results elucidate the mechanisms by which DHI protects against MI/R induced injury.

Danhong Injection Protects Against Hypertension-Induced Renal Injury Via Down-Regulation of Myoglobin Expression in Spontaneously Hypertensive Rats

“…Formulated based on TCM theory of “activating and promoting blood circulations to dissipate blood stasis and dredge collaterals”, DHI, a China food and drug administration approved injectable drug has been widely used in clinics with proven efficacy and safety [29] for treatment and prophylaxis of various cardio-cerebrovascular diseases, such as ischemic-reperfusion injury, atherosclerosis, and acute coronary syndrome [20, 25, 30]. Previously, we found that DHI reversed vascular remodeling and exerted an antihypertensive effect through the Kallikrein-kinin system up-regulation in SHR [27].…”

“…DHI is composed of extracts from Radix Salviae miltiorrhizae (Danshen) and Flos Carthami tinctorius (Honghua) [19] and has been used with proven efficacy and safety for treating various cardio-cerebrovascular diseases [20]. Although, DHI has many components, the main pharmacologically active components include phenolic acids, diterpenes, and flavonoids (salvianolic acid, danshensu, tanshinone, safor yellow etc.)…”

Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway

“…HSYA, one of the major active compounds of C. tinctorius L., has also been investigated for its ability to treat ischemic diseases including myocardial ischemia [33] and cerebral ischemia [25,34,35]. However, the protective effects of HSYA in these cases could not be explained solely by its antioxidant property.…”

DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia

“…Previous studies have shown that DHI exhibited diverse pharmacological effects, including protection against vascular endothelium injury [2,3] , improvements in atherosclerosis and microcirculation [4] , and neuroprotective effects [5] . It has also been suggested that DHI might have a dose-dependent protective effect on promoting angiogenesis and mesenteric microcirculation in acute hypoxia [6,7] . In addition, an experimental study indicated that DHI had a concentration-response relationship in promoting angiogenesis potentially via the increased expression of vascular endothelial growth factor (VEGF) [8] .…”