Metabonomic Strategy for the Evaluation of Chinese Medicine Salvia miltiorrhiza and Dalbergia odorifera Interfering with Myocardial Ischemia/Reperfusion Injury in Rats

Abstract

Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis. Metabonomics technology was further performed to evaluate the endogenous metabolites profiling systematically. According to the results of pattern recognition analysis, a clear separation of MI/R injury in the Model group and Sham group was achieved and SM-DOO pretreatment group was located much closer to the Sham group than the Model group, which was consistent with results of biochemistry and histopathological assay. Moreover, potential biomarkers were identified to elucidate the drug mechanism of SM-DOO, which may be related with pathways of energy metabolism, especially tricarboxylic acid (TCA) cycle (citric acid) and β-oxidation of fatty acids (3-hydroxybutyric, palmitoleic acid, heptadecanoic acid, and arachidonic acid). In addition, the protein expressions of p-AMPK and p-ACC in the SM-DOO group were significantly elevated, while the levels of carnitine palmitoyl-CoA transferase-1 (CPT-1), p-PDK, and p-PDC were dramatically reduced by SM-DOO. In conclusion, SM-DOO pretreatment could ameliorate MI/R injury by intervening with energy metabolism, especially TCA cycle and β-oxidation of fatty acids. This work showed that the metabonomics method combinate with conventional pharmacological methods is a promising tool in the efficacy and mechanism research of traditional Chinese medicines.

APPL1 ameliorates myocardial ischemia‑reperfusion injury by regulating the AMPK signaling pathway

“…This process can be modulated by AMPK (31). The AMPK/ACC signaling pathway is markedly altered in myocardial I/R as reported by previous studies (32,33). The present study provided evidence of this in H9c2 cells exposed to H/R conditions, which was in agreement with the aforementioned studies.…”

Hydroxysafflor Yellow A Protects Against Myocardial Ischemia/Reperfusion Injury via Suppressing NLRP3 Inflammasome and Activating Autophagy

“…Therefore, DTZ was selected as the positive control in the present study. The dosage for HSYA and DTZ was chosen based on previous pharmacodynamics studies ( Mu et al, 2017 ; Yu L. et al, 2018 ; Yu et al, 2020 ). HSYA and DTZ were dissolved in 0.9% sodium chloride and stored at 4°C.…”

Salvia miltiorrhiza and the Volatile of Dalbergia odorifera Attenuate Chronic Myocardial Ischemia Injury in a Pig Model: A Metabonomic Approach for the Mechanism Study

“…The combination of SM and DO can effectively treat cardiovascular diseases, such as GuanXin II prescription, QiShe-nYiQi drop pill, Guanxin Danshen formula, and Xiangdan injection [9][10][11][12]. Previously, we reported that SM-the volatile oil of DO (SM-DOO)-exhibited a significant effect in myocardial ischemia/reperfusion (MI/R) injury rats in both traditional pharmacological methods and metabonomic methods [13,14]. On this basis of these data, traditional pharmacological methods (myocardial injury markers, myocardial oxygen consumption, ventricular function, and myocardial tissue damage) were used to evaluate the therapeutic effect of SM-DOO on chronic myocardial ischemia in pigs [15].…”