scholarly journals Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhen Yang ◽  
Yanli Chen ◽  
Zhaoyuan Yan ◽  
Tian Tian Xu ◽  
Xiangyao Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Palmitic Acid ◽  
Target Genes ◽  
Morphological Changes ◽  
Salvia Miltiorrhiza ◽  
Myocardial Damage ◽  
H9c2 Cells ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Underlying Mechanisms

The occurrence of lipotoxicity during obesity-associated cardiomyopathy is detrimental to health. Salvianolic acid A (SAA), a natural polyphenol extract of Salvia miltiorrhiza Bunge (Danshen in China), is known to be cardioprotective. However, its clinical benefits against obesity-associated cardiomyocyte injuries are unclear. This study aimed at evaluating the protective effects of SAA against lipotoxicity-induced myocardial injury and its underlying mechanisms in high fat diet (HFD)-fed mice and in palmitate-treated cardiomyocyte cells (H9c2). Our analysis of aspartate aminotransferase and creatine kinase isoenzyme-MB (CM-KB) levels revealed that SAA significantly reversed HFD-induced myocardium morphological changes and improved myocardial damage. Salvianolic acid A pretreatment ameliorated palmitic acid-induced myocardial cell death and was accompanied by mitochondrial membrane potential and intracellular reactive oxygen species improvement. Analysis of the underlying mechanisms showed that SAA reversed myocardial TLR4 induction in HFD-fed mice and H9c2 cells. Palmitic acid-induced cell death was significantly reversed by CLI-95, a specific TLR4 inhibitor. TLR4 activation by LPS significantly suppressed SAA-mediated lipotoxicity protection. Additionally, SAA inhibited lipotoxicity-mediated expression of TLR4 target genes, including MyD88 and p-JNK/MAPK in HFD-fed mice and H9c2 cells. However, SAA did not exert any effect on palmitic acid-induced SIRT1 suppression and p-AMPK induction. In conclusion, our data shows that SAA protects against lipotoxicity-induced myocardial damage through a TLR4/MAPKs mediated mechanism.

Salvianolic Acid A, a Component of Salvia miltiorrhiza, Attenuates Endothelial–Mesenchymal Transition of HPAECs Induced by Hypoxia

2017 ◽  
Vol 45 (06) ◽  
pp. 1185-1200 ◽  
Author(s):  
Tianyi Yuan ◽  
Yucai Chen ◽  
Huifang Zhang ◽  
Lianhua Fang ◽  
Guanhua Du
Keyword(s):  
Salvia Miltiorrhiza ◽  
Mesenchymal Transition ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Downstream Effectors ◽  
Cytoskeleton Remodeling ◽  
Pulmonary Arterial ◽  
Underlying Mechanisms ◽  
Arterial Endothelial Cells ◽  
Endothelial Mesenchymal Transition

Salvianolic acid A (SAA), a polyphenols acid, is a bioactive ingredient from a traditional Chinese medicine called Dan shen (Salvia Miltiorrhiza Bunge). According to previous studies, it was shown to have various effects such as anti-oxidative stress, antidiabetic complications and antipulmonary hypertension. This study aimed to investigate the effect of SAA on pulmonary arterial endothelial–mesenchymal transition (EndoMT) induced by hypoxia and the underlying mechanisms. Primary cultured human pulmonary arterial endothelial cells (HPAECs) were exposed to 1% O2 for 48[Formula: see text]h with or without SAA treatment. SAA treatment improved the morphology of HPAECs and inhibited the cytoskeleton remodeling. A total of 3[Formula: see text][Formula: see text]M SAA reduced migration distances from 262.2[Formula: see text][Formula: see text]m to 198.4[Formula: see text][Formula: see text]m at 24[Formula: see text]h and 344.8[Formula: see text][Formula: see text]m to 109.3[Formula: see text][Formula: see text]m at 48[Formula: see text]h. It was observed that the production of ROS in cells was significantly reduced by the treatment of 3[Formula: see text][Formula: see text]M SAA. Meanwhile, SAA alleviated the loss of CD31 and slightly inhibited the expression of [Formula: see text]-SMA. The mechanisms study shows that SAA treatment increased the phosphorylation levels of Smad1/5, but inhibited that of Smad2/3. Furthermore, SAA attenuated the phosphorylation levels of ERK and Cofilin, which were enhanced by hypoxia. Based on these results, our study indicated that SAA treatment can protect HPAECs from endoMT induced by hypoxia, which may perform via the inhibition on ROS production and further through the downstream effectors of BMPRs or TGF[Formula: see text]R including Smads, ERK and ROCK/cofilin pathways.

scholarly journals Bioactive Phenolic Compounds from the Roots of Danshen (Salvia miltiorrhiza)

2018 ◽  
Vol 13 (10) ◽  
pp. 1934578X1801301
Author(s):  
Nguyen Huu Tung ◽  
Le Quoc Hung ◽  
Ha Van Oanh ◽  
Duong Thi Ly Huong ◽  
Phuong Thien Thuong ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Methyl Ester ◽  
Ethyl Ester ◽  
Rosmarinic Acid ◽  
Salvia Miltiorrhiza ◽  
Chemical Constituents ◽  
Acid Methyl Ester ◽  
Acid Ethyl Ester ◽  
Salvianolic Acid ◽  
Salvianolic Acid A

Danshen ( Salvia miltiorrhiza Bunge) is one of the most used medicinal plants in the Oriental medicine and has been well studied for application in modern medicine. In our continuing study on chemical constituents of danshen cultivated in Vietnam, using chromatography separation resulted in the isolation of six phenolic compounds including a benzophenone, iriflophenone 2- O- α-L-rhamnopyranoside (1), and five phenolic acids including rosmarinic acid (2), rosmarinic acid methyl ester (3), rosmarinic acid ethyl ester (4), salvianolic acid A methyl ester (5) and salvianolic acid A ethyl ester (6) from the butanol portion of the danshen crude extract. Beside the typically main phenolic acid components, to our knowledge, iriflophenone 2- O- α-L-rhamnopyranoside (1) was first isolated from salvia sp. On biological testing, compound 1 showed strong antiproliferative activity on HL-60 leukemia cells with the IC50 of 8.9 μM; compounds 1 and 3–6 inhibited markedly nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells.

scholarly journals Salvianolic Acid A Ameliorates Early-Stage Atherosclerosis Development by Inhibiting NLRP3 Inflammasome Activation in Zucker Diabetic Fatty Rats

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1089 ◽  
Author(s):  
Quanxin Ma ◽  
Qinqin Yang ◽  
Jiaojiao Chen ◽  
Chen Yu ◽  
Lizong Zhang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Salvia Miltiorrhiza ◽  
Blood Cholesterol ◽  
Inflammasome Activation ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats ◽  
Anti Inflammatory

Salvianolic acid A (SAA), an important bioactive polyphenolic acid found in Salvia miltiorrhiza Bunge, may be used for treating metabolic disorders due to its anti-inflammatory activity. Since chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM) complicated with atherosclerosis (AS), SAA may have beneficial effects on AS. Here, we evaluated the effects of SAA on metabolic disorders in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet and Vitamin D3 injections. Compared with the model group, the SAA high dosage (1 mg/kg) group exhibited decreased hemoglobin A1C levels but unchanged blood glucose levels. The disrupted lipid profiles were ameliorated by SAA, with significantly decreased levels of blood cholesterol, LDL-C and triglyceride. The protective effects of SAA against early AS were further confirmed by histopathological examination of aortic tissues. In addition, we observed that SAA decreased serum hs-CRP levels and suppressed the activation of NLRP3 inflammasome and NF-κB signaling in aortic tissues of ZDF rats. Collectively, our results demonstrate the potential of SAA to alleviate AS and T2DM in ZDF rats as a result of its anti-inflammatory effects.

scholarly journals Protective Effects of Active Compounds from Salviae miltiorrhizae Radix against Glutamate-Induced HT-22 Hippocampal Neuronal Cell Death

Processes ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 914
Author(s):  
Hung Manh Phung ◽  
Sullim Lee ◽  
Ki Sung Kang
Keyword(s):  
Cell Death ◽  
Rosmarinic Acid ◽  
Calcium Influx ◽  
Salvia Miltiorrhiza ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Salvianolic Acid B ◽  
Tanshinone Iia ◽  
Salvianolic Acid

Oxidative stress is considered one of the factors that cause dysfunction and damage of neurons, causing diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and Parkinson’s disease (PD).Recently, natural antioxidant sources have emerged as one of the main research areas for the discovery of potential neuroprotectants that can be used to treat neurological diseases. In this research, we assessed the neuroprotective effect of a 70% ethanol Salvia miltiorrhiza Radix (SMR) extract and five of its constituent compounds (tanshinone IIA, caffeic acid, salvianolic acid B, rosmarinic acid, and salvianic acid A) in HT-22 hippocampal cells. The experimental data showed that most samples were effective in attenuating the cytotoxicity caused by glutamate in HT-22 cells, except for rosmarinic acid and salvianolic acid B. Of the compounds tested, tanshinone IIA (TS-IIA) exerted the strongest effect in protecting HT-22 cells against glutamate neurotoxin. Treatment with 400 nM TS-IIA restored HT-22 cell viability almost completely. TS-IIA prevented glutamate-induced oxytosis by abating the accumulation of calcium influx, reactive oxygen species, and phosphorylation of mitogen-activated protein kinases. Moreover, TS-IIA inhibited glutamate-induced cytotoxicity by reducing the activation and phosphorylation of p53, as well as by stimulating Akt expression. This research suggested that TS-IIA is a potential neuroprotective component of SMR, with the ability to protect against neuronal cell death induced by excessive amounts of glutamate.

scholarly journals Salvianolic Acid A Protects H9c2 Cells from Arsenic Trioxide-Induced Injury via Inhibition of the MAPK Signaling Pathway

2017 ◽  
Vol 41 (5) ◽  
pp. 1957-1969 ◽  
Author(s):  
Jing-yi Zhang ◽  
Gui-bo Sun ◽  
Yun Luo ◽  
Min Wang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
Arsenic Trioxide ◽  
Mitochondrial Membrane ◽  
Mapk Signaling ◽  
H9c2 Cells ◽  
Salvianolic Acid ◽  
Mapk Pathways ◽  
Salvianolic Acid A ◽  
Mitochondrial Membrane Depolarization

Background/Aims: This study aimed to investigate whether Salvianolic acid A (Sal A) conferred cardiac protection against Arsenic trioxide (ATO)-induced cardiotoxicity in H9c2 cells by inhibiting MAPK pathways activation. Methods: H9c2 cardiac cells were exposed to 10 µM ATO for 24 h to induce cytotoxicity. The cells were pretreated with Sal A for 4 h before exposure to ATO. Cell viability was determined utilizing the MTT assay. The percentage of apoptosis was measured by a FITC-Annexin V/PI apoptosis kit for flow cytometry. Mitochondrial membrane potential (∆Ψm) was detected by JC-1. The intracellular ROS levels were measured using an Image-iTTM LIVE Green Reactive Oxygen Species Detection Kit. The apoptosis-related proteins and the MAPK signaling pathways proteins expression were quantified by Western blotting. Results: Sal A pretreatment increased cell viability, suppressed ATO-induced mitochondrial membrane depolarization, and significantly altered the apoptotic rate by enhancing endogenous antioxidative enzyme activity and ROS generation. Signal transduction studies indicated that Sal A suppressed the ATO-induced activation of the MAPK pathway. More importantly, JNK, ERK, and p38 inhibitors mimicked the cytoprotective activity of Sal A against ATO-induced injury in H9c2 cells by increasing cell viability, up-regulating Bcl-2 protein expression, and down-regulating both Bax and caspase-3 protein expression. Conclusion: Sal A decreases the ATO-induced apoptosis and necrosis of H9c2 cells, and the underlying mechanisms of this protective effect of Sal A may be connected with the MAPK pathways.

scholarly journals The Effect of Salvianolic Acid on Vascular Protection and Possible Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yalan Wu ◽  
Suowen Xu ◽  
Xiao Yu Tian
Keyword(s):  
Cardiovascular Diseases ◽  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Salvianolic Acid B ◽  
Drug Candidate ◽  
Protective Effects ◽  
Vascular Protection ◽  
Salvianolic Acid ◽  
Salvianolic Acid A

Salvia miltiorrhiza (Danshen), as an important traditional Chinese medicinal plant, has been used in China for the treatment of cardiovascular diseases for hundreds of years. Salvianolic acids (salvianolic acid A and salvianolic acid B) as the most abundant water-soluble component extracted from Salvia miltiorrhiza have attracted more and more attention from cardiovascular scientists due to its comprehensive cardiovascular actions. In vivo and in vitro studies have rendered salvianolic acid an excellent drug candidate for the treatment and prevention of cardiovascular diseases. In this review, we surveyed the protective effects of salvianolic acid A and salvianolic acid B against cardiovascular diseases and the pharmacological basis, providing a strong scientific rationale for elucidating the important role of Salvia miltiorrhiza in cardiovascular therapy. More importantly, we also hope to provide new inspiration and perspectives on the development and innovation of small-molecule cardiovascular drugs based on salvianolic acid.

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

2014 ◽  
Vol 42 (05) ◽  
pp. 1183-1198 ◽  
Author(s):  
Guifen Qiang ◽  
Xiuying Yang ◽  
Qi Xuan ◽  
Lili Shi ◽  
Hengai Zhang ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
Type I ◽  
High Fat ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Underlying Mechanisms ◽  
Tgf Β1

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.

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