Haiguang Yang

Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats.

The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.

Effect of salvianolic acid A on vascular reactivity of streptozotocin-induced diabetic rats.

AIMS The present study aims to evaluate the beneficial effect of salvianolic acid A (SAA) on the alterations in vascular reactivity of streptozotocin (STZ)-induced diabetic rats. MAIN METHODS Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Following 16 weeks of SAA treatment (1 mg/kg/day), thoracic aortic rings of rats were mounted in organ baths. Contractile responses to noradrenaline (NA) and KCl and relaxant responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed. KEY FINDINGS Loss of weight, hyperglycemia, elevated content of malondialdehyde (MDA) and decline of total antioxidant capacity (TAC) were observed in diabetic rats. SAA could reverse these metabolic and biochemical abnormalities. Compared to the control, the maximum contraction (E(max)) to NA, but not sensitivity (pD(2)), increased significantly in diabetic aortas, which was prevented by SAA treatment. However, the response of rat aortas to KCl (E(max) and pD(2)) was not altered either in diabetic group or SAA treatment compared with that of normal control group. We also observed the significant decrease in relaxation to ACh rather than SNP in diabetic group compared with controls, and SAA treatment could revert the ACh response. SIGNIFICANCE It is concluded that oral administration of SAA can significantly improve glucose metabolism and inhibit oxidative injury as well as protect against impaired vascular responsiveness in STZ-induced diabetic rats.

Effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes.

Currently there is no effective treatment for nonalcoholic fatty liver disease (NAFLD), especially hepatic fibrosis induced by type 2 diabetes. Valsartan maybe has beneficial effect on the liver disease. The aim of the present study was to investigate the effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes. An animal model of hepatic fibrosis with type 2 diabetes was developed using a high-sucrose, high-fat diet and low-dose streptozotocin. Valsartan (15 mg/kg/day, i.g.) was orally administered for four months. The livers were removed to make hematoxylin-eosin (HE) staining and Picric acid-Sirius red staining, and immunohistochemistry staining of α-smooth-muscle-actin (α-SMA), transforming growth factor β1 (TGF-β1), tumor necrosis factor (TNF-α) and monocyte chemotactic protein-1 (MCP-1). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect hepatocyte apoptosis. The liver mitochondria were isolated to measure the mitochondrial respiratory function. The results showed that valsartan significantly alleviated the lesion of hepatic steatosis and hepatic fibrosis by HE staining and Picric acid-Sirius red staining. Immunohistochemical staining suggested that the expression of α-SMA, TGF-β1, TNF-α and MCP-1 in liver tissue of diabetic rats was markedly reduced by valsartan. TUNEL staining showed that there were fewer TUNEL-positive apoptotic hepatocytes in valsartan group. In addition, valsartan restored the injured hepatic mitochondrial respiratory function. The findings demonstrated that valsartan prevented the pathological progression of hepatic fibrosis in type 2 diabetic rats, correlated with reducing α-SMA, TGF-β1, TNF-α and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential.

Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats

Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction.

Salvianolic Acid A Prevents the Pathological Progression of Hepatic Fibrosis in High-Fat Diet-Fed and Streptozotocin-Induced Diabetic Rats

Type 2 diabetes patients have an increased risk of developing hepatic fibrosis. Salvianolic acid A (SalA) has been reported to be a strong polyphenolic anti-oxidant and free radical scavenger. The aim of the present study was to evaluate the effect of SalA on the pathological progression of hepatic fibrosis in high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic rats and to clarify the underlying mechanisms. Type 2 diabetic animal model with hepatic fibrosis was developed by a high-sucrose, HFD and low-dose STZ injection (i.p.). Diabetic rats were randomly divided into SalA group (0.3 mg/kg/day) and diabetic control groups fed with a HFD. After administration for four months, SalA reversed the hyperlipidemia and reduced hepatic triglyceride (TG). Hematoxylin-Eosin (HE) and Picro acid-Sirius red staining results indicated that SalA significantly alleviated the lesions of hepatic steatosis and fibrosis, with the reduction of type I and III collagens. The expression of α-smooth-muscle-actin (α-SMA) and transforming growth factor β1 (TGF-β1) in the liver were markedly down-regulated by SalA treatment. TUNEL staining showed that SalA reduced apoptosis in hepatocytes. In addition, SalA improved hepatic mitochondrial respiratory function in diabetic rats. Taken together, these findings demonstrated that SalA could prevent the pathological progression of hepatic fibrosis in HFD-fed and STZ-induced diabetic rats. The underlying mechanisms may be involved in reducing oxidative stress, suppressing α-SMA and TGF-β1 expression, as well as exerting anti-apoptotic and mitochondria-protective effects.

Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression

Acute lung injury (ALI), characterized by pulmonary edema and inflammatory cell infiltration, is a common syndrome of acute hypoxemic respiratory failure. Methyl salicylate 2-O-β-d-lactoside (MSL), a natural derivative of salicylate extracted from Gaultheria yunnanensis (Franch.) Rehder, was reported to have potent anti-inflammatory effects on the progression of collagen or adjuvant-induced arthritis in vivo and in vitro. The aim of this study is to investigate the therapeutic effect of MSL on lipopolysaccharide (LPS)-induced acute lung injury and reveal underlying molecular mechanisms. Our results showed that MSL significantly ameliorated pulmonary edema and histological severities, and inhibited IL-6 and IL-1β production in LPS-induced ALI mice. MSL also reduced MPO activity in lung tissues and the number of inflammatory cells in BALF. Moreover, we found that MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation, as well as the expression of NLRP3 protein in lung tissues. Furthermore, MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation in Raw264.7 cells. In addition, MSL significantly inhibited nuclear translocation of NF-κB p65 in cells treated with LPS in vitro. Taken together, our results suggested that MSL exhibited a therapeutic effect on LPS-induced ALI by inhibiting TAK1/NF-κB phosphorylation and NLRP3 expression.

Activation of Nrf2 signaling by salvianolic acid C attenuates NF‑κB mediated inflammatory response both in vivo and in vitro

&NA; Neurodegenerative diseases are closely related to neuroinflammation. Drugs targeting inflammation have been proved to be effective in many animal models. Salvianolic acid C (SalC) is a compound isolated from Salvia miltiorrhiza Bunge, a plant with reported effects of inhibiting inflammation. However, the anti‐inflammation effects and biological mechanisms of SalC on LPS‐stimulated neuroinflammation remain unknown. The aim of this paper was to study its protective effects and its anti‐inflammation mechanisms. LPS was used both in vivo and in vitro to induce neuroinflammation in SD rats and microglia cells. MTT assay was carried out to detect cell viability. The levels of TNF‐&agr;, IL‐1&bgr;, IL‐6, IL‐10 and PGE2 were detected by ELISA method. The expressions of p‐AMPK, p‐NF‐&kgr;B p65, p‐I&kgr;B&agr;, Nrf2, HO‐1 and NQO1 proteins were examined by Western blot analysis. The nuclear translocation of NF‐&kgr;B p65 was studied by immunofluorescence assay. The specific Nrf2 siRNA was used to clarify the interaction between Nrf2 and NF‐&kgr;B p65. The AMPK inhibitor Compound C was used study the upstream protein of Nrf2. Results showed that LPS induced the overexpression of inflammatory cytokines and mediated the phosphorylation and nuclear translocation of NF‐&kgr;B p65 in rat brains and microglia cells. SalC reversed the inflammatory response induced by LPS and inhibited the NF‐&kgr;B activation. SalC also upregulated the expression of p‐AMPK, Nrf2, HO‐1 and NQO1. But the anti‐inflammation and NF‐&kgr;B inhibition effects of SalC were attenuated by transfection with specific Nrf2 siRNA or interference with the potent AMPK inhibitor Compound C. In conclusion, SalC inhibited LPS‐induced inflammatory response and NF‐&kgr;B activation through the activation of AMPK/Nrf2 signaling both in vivo and in vitro. Graphical abstract Figure. No caption available. HighlightsSalvianolic acid C inhibited LPS‐induced NF‐&kgr;B activation.Salvianolic acid C upregulated the levels of p‐AMPK, Nrf2, HO‐1 and NQO1 proteins.The activation of AMPK/Nrf2 attenuated NF‐&kgr;B mediated inflammatory response.