Elaboration of the Comprehensive Metabolic Profile of Salvianolic Acid A in Vivo and in Vitro Using UFLC-Q/TOF-MS

2019 ◽  
Vol 67 (44) ◽  
pp. 12199-12207
Author(s):  
Fuqiong Zhou ◽  
Linxin Teng ◽  
Yu Liu ◽  
Yanxia Ma ◽  
Weiping Chen ◽  
...  
Keyword(s):  
Metabolic Profile ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Tof Ms

scholarly journals Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

2018 ◽  
Vol 49 (6) ◽  
pp. 2320-2332 ◽  
Author(s):  
Guo Zu ◽  
Tingting Zhou ◽  
Ningwei Che ◽  
Xiangwen Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Glutathione Peroxidase ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Tnf Α

Background/Aims: Ischemia-reperfusion (I/R) adversely affects the intestinal mucosa. The major mechanisms of I/R are the generation of reactive oxygen species (ROS) and apoptosis. Salvianolic acid A (SalA) is suggested to be an effective antioxidative and antiapoptotic agent in numerous pathological injuries. The present study investigated the protective role of SalA in I/R of the intestine. Methods: Adult male Sprague-Dawley rats were subjected to intestinal I/R injury in vivo. In vitro experiments were performed in IEC-6 cells subjected to hypoxia/ reoxygenation (H/R) stimulation to simulate intestinal I/R. TNF-α, IL-1β, and IL-6 levels were measured using enzyme-linked immunosorbent assay. Malondialdehyde and myeloperoxidase and glutathione peroxidase levels were measured using biochemical analysis. Apoptosis was measured by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining or flow cytometry in vivo and in vitro. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. Western blotting was performed to determine the expression of heme oxygenase-1 (HO-1), Nrf2 and proteins associated with apoptosis. The mRNA expressions of Nrf2 and HO-1 were detected by quantitative real-time polymerase chain reaction in vivo and in vitro. Results: Malondialdehyde level and myeloperoxidase and glutathione peroxidase, TNF-α, IL-1β, and IL-6 levels group in intestinal tissue decreased significantly in the SalA pretreatment groups compared to the I/R group. SalA markedly abolished intestinal injury compared to the I/R group. SalA significantly attenuated apoptosis and increased Nrf2/HO-1 expression in vivo and in vitro. However, Nrf2 siRNA treatment partially abrogated the above mentioned effects of SalA in H/R-induced ROS and apoptosis in IEC-6 cells. Conclusion: The present study demonstrated that SalA ameliorated oxidation, inhibited the release of pro-inflammatory cytokines and alleviated apoptosis in I/R-induced injury and that these protective effects may partially occur via regulation of the Nrf2/ HO-1 pathways.

scholarly journals RGD-Modified Multifunctional Nanoparticles Encapsulating Salvianolic Acid A for Targeted Treatment of Choroidal Neovascularization

2021 ◽  
Author(s):  
Junxiu Zhang ◽  
Jingyi Zhu ◽  
Lingzhou Zhao ◽  
Ke Mao ◽  
Qing Gu ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fluorescein Isothiocyanate ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Low Cytotoxicity ◽  
Arginine Glycine Aspartic Acid

Abstract Background: The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4’-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA. Results: We showed that RGD-PEI/SAA complexes displayed desirable water dispersibility, low cytotoxicity, and sustainable release of SAA under different pH conditions. It could be specifically taken up by ɑvβ5 integrin receptors expressing retinal pigment epithelium (RPE) cells in vitro and selectively accumulated in CNV lesions in vivo. Moreover, the complexes displayed specific therapeutic efficacy in a mouse model of laser induced CNV, and the slow elimination of the complexes in the vitreous cavity was verified by SPECT imaging after 131I radiolabeling. The histological examinations further confimed the biocompatibility of RGD-PEI/SAA.Conclusions: The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases.

scholarly journals The Cardiotoxicity Induced by Arsenic Trioxide is Alleviated by Salvianolic Acid A via Maintaining Calcium Homeostasis and Inhibiting Endoplasmic Reticulum Stress

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 543 ◽  
Author(s):  
Ruiying Wang ◽  
Jingyi Zhang ◽  
Shan Wang ◽  
Min Wang ◽  
Tianyuan Ye ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Arsenic Trioxide ◽  
Calcium Homeostasis ◽  
In Vitro Study ◽  
Protective Effects ◽  
Salvianolic Acid ◽  
Salvianolic Acid A

Arsenic trioxide (ATO) has been verified as a breakthrough with respect to the management of acute promyelocytic leukemia (APL) in recent decades but associated with some serious adverse phenomena, particularly cardiac functional abnormalities. Salvianolic acid A (Sal A) is a major effective component in treating ATO-induced cardiotoxicity. Therefore, the objective of our study was to assess whether Sal A had protective effects by the regulation of calcium homeostasis and endoplasmic reticulum (ER) stress. For the in vivo study, BALB/c mice were treated with ATO and/or Sal A via daily tail vein injections for two weeks. For the in vitro study, we detected the effects of ATO and/or Sal A in real time using adult rat ventricular myocytes (ARVMs) and an IonOptix MyoCam system. Our results showed that Sal A pretreatment alleviated cardiac dysfunction and Ca2+ overload induced by ATO in vivo and vitro. Moreover, Sal A increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity and expression, alleviated [Ca2+]ER depletion, and decreased ER stress-related protein expression. Sal A protects the heart from ATO-induced injury and its administration correlates with the modulation of SERCA, the recovery of Ca2+ homeostasis, and the down-regulation of ER stress-mediated apoptosis.

scholarly journals Salvianolic acid A ameliorates renal ischemia/reperfusion injury by activating Akt/mTOR/4EBP1 signaling pathway

2018 ◽  
Vol 315 (2) ◽  
pp. F254-F262 ◽  
Author(s):  
Ying Song ◽  
Weihai Liu ◽  
Yi Ding ◽  
Yanyan Jia ◽  
Jinyi Zhao ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Initiation Factor ◽  
Salvianolic Acid ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Salvianolic Acid A

Salvianolic acid A (Sal A) has been shown to prevent and treat ischemic cardiovascular, as well as cerebral vascular diseases. However, little is known about Sal A in renal ischemia/reperfusion (I/R) injury. In this study, a renal I/R injury model in rats and a hypoxia/reoxygenation (H/R) model to damage proximal renal tubular cells (HK-2) were used to assess whether Sal A halts the development and progression of renal I/R injury. As compared with vehicle treatment, Sal A significantly attenuated kidney injury after renal I/R injury, accompanied by decreases in plasma creatinine, blood urea nitrogen levels, the number of apoptosis-positive tubular cells, and kidney oxidative stress. Sal A also activated phosphorylated protein kinase B (p-Akt) and phosphorylated-mammalian target of rapamycin (p-mTOR) compared with vehicle-treated I/R injury rats. In H/R-injured HK-2 cells, Sal A can reduce the levels of reactive oxygen species in a dose-related manner. Similar to the results from in vivo experiments, in vitro Sal A also increased the protein expression of phosphorylated-eukaryotic initiation factor 4E binding protein 1 (p-4EBP1) compared with vehicle. Furthermore, the cytoprotective activity of Sal A was inhibited by LY294002 and rapamycin. These findings indicate that Sal A can ameliorate renal I/R injury and promote tubular cell survival partly via the Akt/mTOR/4EBP1pathway. Sal A could be a candidate compound to prevent ischemic tissue damage.

scholarly journals Salvianolic Acid A Has Anti-Osteoarthritis Effect In Vitro and In Vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Yifan Wu ◽  
Zhanghong Wang ◽  
Zeng Lin ◽  
Xin Fu ◽  
Jingdi Zhan ◽  
...  
Keyword(s):  
Salvianolic Acid ◽  
Salvianolic Acid A

scholarly journals Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling

2017 ◽  
Vol 44 (6) ◽  
pp. 2378-2394 ◽  
Author(s):  
Biyu Hou ◽  
Guifen Qiang ◽  
Yuerong Zhao ◽  
Xiuying Yang ◽  
Xi Chen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Early Stage ◽  
Cell Permeability ◽  
Glomerular Endothelial Cell ◽  
Salvianolic Acid ◽  
Structural Deterioration ◽  
Salvianolic Acid A

Background/Aims: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. Methods: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs. Type 2 diabetic nephropathy rats were induced by high-fat diet and low-dose streptozocin (STZ). After eight-week treatment with SalA 1 mg/kg/day, 24h-urine protein, creatinine clearance was tested and renal structural injury was assessed by PAS and PASM staining. Primary glomerular endothelial cell permeability was evaluated after exposed to AGEs. AGEs-induced RhoA/ROCK and subsequently activated disarrange of cytoskeleton were assessed by western blot and immunofluorescence. Results: Biochemical assay and histological examination demonstrated that SalA markedly reduced endothelium loss and glomerular hyperfiltration, suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced urinary albumin and ameliorated renal function. Further investigation suggested that SalA exerted its renoprotective effects through inhibiting AGE-RAGE signaling. It not only inhibited formation of AGEs and increased its breaking in vitro, but also reduced AGEs accumulation in vivo and downregulated RAGE expression. SalA restored glomerular endothelial permeability through suppressing AGEs-induced rearrangement of actin cytoskeleton via AGE-RAGE-RhoA/ ROCK pathway. Moreover, SalA attenuated oxidative stress induced by AGEs, subsequently alleviated inflammation and restored the disturbed autophagy in glomerular endothelial cell and diabetic rats via AGE-RAGE-Nox4 axis. Conclusion: Our study indicated that SalA restored glomerular endothelial function and alleviated renal structural deterioration through inhibiting AGE-RAGE, thus effectively ameliorated early-stage diabetic nephropathy. SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.

A novel salvianolic acid A analog with resveratrol structure and its antioxidant activities in vitro and in vivo

2020 ◽  
Author(s):  
Jin‐Mei Qiu ◽  
Chang‐Feng Qin ◽  
Shen‐Gen Wu ◽  
Tong‐Ying Ji ◽  
Guo‐Tao Tang ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Salvianolic Acid ◽  
Salvianolic Acid A

scholarly journals RGD-modified multifunctional nanoparticles encapsulating salvianolic acid A for targeted treatment of choroidal neovascularization

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Junxiu Zhang ◽  
Jingyi Zhu ◽  
Lingzhou Zhao ◽  
Ke Mao ◽  
Qing Gu ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fluorescein Isothiocyanate ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Low Cytotoxicity ◽  
Arginine Glycine Aspartic Acid

Abstract Background The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4′-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA. Results We showed that RGD-PEI/SAA complexes displayed desirable water dispersibility, low cytotoxicity, and sustainable release of SAA under different pH conditions. It could be specifically taken up by retinal pigment epithelium (RPE) cells which highly expressed ɑvβ5 integrin receptors in vitro and selectively accumulated in CNV lesions in vivo. Moreover, the complexes displayed specific therapeutic efficacy in a mouse model of laser induced CNV, and the slow elimination of the complexes in the vitreous cavity was verified by SPECT imaging after 131I radiolabeling. The histological examinations further confirmed the biocompatibility of RGD-PEI/SAA. Conclusions The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases. Graphic abstract

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