salvianolic-acid-a and Body-Weight

Heart failure with preserved ejection fraction (HFpEF) is a morbid, fatal, and common syndrome for which lack of evidence-based therapies. Salvianolic acid A (SAA), a major active ingredient of Salvia miltiorrhiza Burge, has shown potential to protect against cardiovascular diseases. This study aims to elucidate whether SAA possessed therapeutic activity against HFpEF and explore the potential mechanism. HFpEF mouse model was established infusing a combination of high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) for 14 weeks. After 10 weeks of feeding, HFpEF mice were given SAA (2.5, 5, 10 mg/kg) via oral gavage for four weeks. Body weight, blood pressure, blood lipids, glucose tolerance, exercise performance, cardiac systolic/diastolic function, cardiac pathophysiological changes, and inflammatory factors were assessed. Experimental results showed that SAA reduced HFpEF risk factors, such as body weight gain, glucose intolerance, lipid disorders, and increased exercise tolerance in HFpEF mice. Moreover, SAA not only relieved myocardial hypertrophy and fibrosis by reducing interventricular septal wall thickness, left ventricular posterior wall thickness, left ventricular mass, heart index, cardiomyocyte cross-sectional area and cardiac collagen content, but also improved cardiac diastolic function via reducing E/E' ratio. Finally, SAA inhibited TLR2/TLR4-mediated Myd88 activation and its downstream molecules TRAF6 and IRAK4, which decreases the release of proinflammatory cytokines and mediators through NF-κB and p38 MAPK pathways. In conclusion, SAA could attenuate cardiac inflammation and cardiac disfunction by TLR/Myd88/TRAF/NF-κB and p38MAPK/CREB signaling pathways in HFpEF mice, which provides evidence for SAA as a potential drug for treatment of HFpEF in clinic.

Topics: Animals; Body Weight; Heart Failure; Mice; Myeloid Differentiation Factor 88; Myocytes, Cardiac; NF-kappa B; Signal Transduction; Stroke Volume

Salvianolic acid A (SalA) is one of the main efficacious, water-soluble constituents of Salvia miltiorrhiza Bunge. This study investigated the protective effects of SalA on peripheral nerve in diabetic rats. Administration of SalA (0.3, 1 and 3 mg/kg, ig) was started from the 5th week after strepotozotocin (STZ60 mg/kg) intraperitoneal injection and continued for 8 weeks. Paw withdrawal mechanical threshold (PWMT) and motor nerve conduction velocity (MNCV) were used to assess peripheral nerve function. The western blot methods were employed to test the expression levels of serine-threonine liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), silent information regulator protein3 (sirtuin 3/Sirt3) and neuronal nitric oxide synthase (nNOS) in sciatic nerve. Results showed that SalA administration could increase PWMT and MNCV in diabetic rats; reduce the deterioration of sciatic nerve pathology; increase AMPK phosphorylation level, up-regulate PGC-1α, Sirt3 and nNOS expression, but had no influence on LKB1. These results suggest that SalA has protective effects against diabetic neuropathy. The beneficial effects of SalA on peripheral nerve function in diabetic rats might be attributed to improvements in glucose metabolism through regulation of the AMPK-PGC1α-Sirt3 axis.

Topics: AMP-Activated Protein Kinase Kinases; Animals; Blood Glucose; Body Weight; Caffeic Acids; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Glycation End Products, Advanced; Lactates; Malondialdehyde; Nitric Oxide Synthase Type I; Peripheral Nerves; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Protein Kinases; Protein Serine-Threonine Kinases; Rats; RNA-Binding Proteins; Salvia miltiorrhiza; Sciatic Nerve; Sirtuin 3; Streptozocin; Superoxide Dismutase; Transcription Factors

Salvianolic acid A (SalA) is the main efficacious, water-soluble constituent of Salvia miltiorrhiza Bunge. This study evaluated the effects of SalA on plantar microcirculation and peripheral nerve dysfunction in streptozotocin (STZ )-induced type 2 diabetic rats. The rats were given a high-fat and high-sucrose diet for a month followed by intraperitoneal injection of STZ (30 mg/kg). Oral administration of SalA (1 and 3mg/kg, respectively) was performed daily for 10 weeks after modeling. Diabetic rats were given a high-fat diet, while age-matched healthy rats were given a standard chow. Plantar microcirculation was measured by Laser Doppler flowmetry, and peripheral nerve function was measured with regard to pain withdrawal latency and motor nerve conduction velocity. The results show that the plantar blood perfusion and vasodilation reactivities decreased significantly, and latency of pain withdrawal and motor nerve conduction velocity rose in diabetic rats compared with the normal control group. SalA increased peripheral blood perfusion and vascular activities; improved peripheral nerve function; and decreased AGEs levels, vascular eNOS expression, and blood glucose, lipid, vWF and malondialdehyde levels in diabetic rats. The beneficial effects of SalA on plantar microcirculation and peripheral nerve function in diabetic rats might be attributed to improvements in lipid and glucose metabolism in diabetic rats, the inhibition of AGEs formation and the development of oxidative stress-related nervous and vascular damage. Based on these findings, we proposed that therapeutic use of SalA to prevent the development of diabetic foot problems.

Topics: Animals; Aorta; Blood Glucose; Body Weight; Caffeic Acids; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Foot; Foot; Glycation End Products, Advanced; Hyperemia; Lactates; Lipid Metabolism; Male; Malondialdehyde; Microcirculation; Motor Activity; Nitric Oxide Synthase Type III; Pain; Peripheral Nerves; Rats; Rats, Sprague-Dawley; Reaction Time; Survival Rate; von Willebrand Factor

Although doxorubicin is an effective antitumor agent, the serious cardiotoxicity mediated by the production of reactive oxygen species has remained a considerable clinical problem. In China, salvianolic acids has been widely used for cardioprotection. To test whether salvianolic acids holds the potential to be protective against cardiotoxicity of doxorubicin, we created an acute cardiac injury mice model. Therapeutic treatment with salvianolic acids (40 mg/kg for 3 connective days) significantly reduced doxorubicin-induced (15 mg/kg) toxicity, including elevation of body weight and heart weight/tibia length ratio, decrease of creatine kinase, improvement of electrocardiography and heart vacuolation. Furthermore, the antioxidative effects of salvianolic acids were verified by oxygen radicals absorbance capacities assay in vitro and malondialdehyde detection in vivo, suggesting one possible mechanism of salvianolic acids on cardioprotection through blocking oxidative stress.

Topics: Animals; Antibiotics, Antineoplastic; Benzofurans; Body Weight; Caffeic Acids; Cardiotonic Agents; Creatine Kinase; Doxorubicin; Electrocardiography; Heart Diseases; Lactates; Male; Malondialdehyde; Mice; Myocardium; Oxidative Stress; Reactive Oxygen Species; Tissue Fixation