3-4-dihydroxyphenyllactic-acid and Ischemia

To investigate the protective effect and possible mechanism of sodium Danshensu (SDSS) against pressure injury caused by ischemia/reperfusion (I/R) injury.. Sprague-Dawley rats were randomly divided into five groups of eight rats each: control group, model group, 10 mg/kg SDSS-treated group, 20 mg/kg SDSS-treated group, and 40 mg/kg SDSS-treated group. We used two round ferrite magnetic plates of 15 mm diameter and 3 mm thickness to establish stage 2 pressure injury model rats. Each rat was subjected to five cycles of ischemia and reperfusion to induce pressure injury. One cycle consisted of 2 h of ischemia and 0.5 h of reperfusion, which meant that each cycle included 2 h of pressure and 0.5 h of pressure relief. The outline of the wound was delineated by butter paper and marker pen, and histopathological changes were observed by hematoxylin and eosin staining. In addition, the number of apoptotic cells and the activity of caspase-3 were assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling and caspase-3 assay kits, respectively. The expression of apoptosis-regulatory proteins and inflammatory mediators was investigated by enzyme-linked immunosorbent assay.. Results showed that treatment with SDSS for 7 d after establishing the pressure injury model remarkably improved the healing rate of the wound. SDSS also inhibited the levels of tumor ne- crosis factor-α, myeloperoxidase, and intercellular cell adhesion molecule-1; decreased the number of apoptotic cells; increased the ratio of B-cell lymphoma-2 (Bcl-2) / Bcl-2-associated X (Bax); and regulated the expression and activity of caspase-3.. Our results suggest that SDSS exhibits a treatment efficacy for pressure injury caused by I/R injury possibly by inhibiting apoptosis and inflammatory response.

Topics: Animals; Apoptosis; Ischemia; Lactates; Pressure Ulcer; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sodium

To explore the specific molecular mechanisms of Danshensu (DSS) in the treatment of ischemia reperfusion injury (IRI).. IRI model was established with isolated rat hearts by performing global ischaemia for 30 min, and then followed by 60 min reperfusion. Also, H9C2 cells were subjected to 4-h hypoxia followed by 3-h reoxygenation. Then 10 μmol/L DSS were added in the reperfusion/reoxygenation step to intervene IRI. Cardiac function, structural change and apoptosis were respectively tested by Langendorff System, hematoxylin and eosin (HE) and terminal-deoxynucleotidyl transferase mediated nick endabeling (TUNEL) stainings. Then lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide gasification enzyme (SOD) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay (ELISA). Sirt1/FoxO1/Rab7 Signal Pathway was monitored at both protein and mRNA levels.. DSS is able to protect hearts from IRI, which may be attributable to inhibiting excessive ROS through Sirt1/FoxO1/Rab7 signaling.

Topics: Animals; Antioxidants; Disease Models, Animal; Ischemia; L-Lactate Dehydrogenase; Lactates; Myocytes, Cardiac; Nerve Tissue Proteins; Oxidative Stress; rab GTP-Binding Proteins; rab7 GTP-Binding Proteins; Rats; Reperfusion Injury; Signal Transduction; Sirtuin 1

A series of (R)-3,4-dihydroxyphenyllactic acid Danshensu (DSS) derivatives were synthesized, and their cardioprotective effects were evaluated in vitro and in vivo. Among the new derivatives, compound 14 showed significant protective effects in cultured myocardial cells and in the rat model of myocardial ischemia. The therapeutic efficacy of compound 14 was significantly higher than that of its parent compound DSS, and amlodipine, a first-line treatment for angina pain. Compound 14 potently scavenged free radicals, significantly decreased the levels of LDH and MDA, and inhibited the leakage of CK in animal model of ischemia. We had previously found that compound 14 activated PI3K/Akt/GSK-3β and Nrf2//Keap1/heme oxygenase-1 (HO-1) signaling pathways in H9c2 cells. These results suggest that compound 14 has a unique mechanism of action, that is, multifunctional. Compound 14 may be a new potential therapy for ischemic heart diseases.

Topics: Animals; Cardiotonic Agents; Cell Line, Tumor; Creatine Kinase; Disease Models, Animal; Drug Design; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heme Oxygenase-1; Ischemia; L-Lactate Dehydrogenase; Lactates; Malondialdehyde; NF-E2-Related Factor 2; Phenylpropionates; Phosphatidylinositol 3-Kinases; Protein Binding; Proto-Oncogene Proteins c-akt; Pyrazines; Rats; Signal Transduction; Stereoisomerism