Effects of HSYA on the proliferation and apoptosis of MSCs exposed to hypoxic and serum deprivation conditions

Abstract

As a primary active ingredient of safflor yellow, hydroxysafflor yellow A (HSYA) exhibits notable antioxidative and neuroprotective effects. The aim of the present study was to investigate the protective effects of HSYA in mesenchymal stem cells (MSCs) exposed to hypoxia (5% O2) and serum deprivation (H/SD), and to explore the mechanisms underlying HSYA-mediated protection. Under H/SD conditions, HSYA was applied to protect MSCs against injury. Cell viability, proliferation, apoptosis and reactive oxygen species (ROS) levels were determined using an 5-ethynyl-2′-deoxyuridine assay, MTT assay, Hoechst 33342/propidium iodide and 2′,7′-dichlorodihydrofluorescein diacetate staining, respectively. The results revealed that 160 mg/l HSYA significantly reduced apoptosis and ROS levels compared with the H/SD group; however, HSYA demonstrated minimal effects on cell proliferation. A western blot assay demonstrated that HSYA reduced cleaved caspase-3 expression and cytC release from the mitochondria to the cytoplasm when compared with the H/SD group. In addition, western blotting and RT-qPCR analyses revealed that HSYA treatment significantly increased the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). In conclusion, the results of the current study demonstrated that HSYA exerts protective effects against H/SD-induced apoptosis in MSCs potentially via activation of the HIF-1α/VEGF signaling pathway and stabilization of the mitochondrial membrane.

Protective effect of hydroxysafflor yellow A on MSCs against senescence induced by -galactose

“…Nowadays, a great number of pharmacological researches revealed that HSYA exerted a prominent influence on anti-inflammation, anti-oxidation and inhibition of cell apoptosis. For instance, our previous study under the conditions of hypoxia and serum deprivation in vitro confirmed that HSYA treatment dramatically reduced the apoptosis rate of MSCs and enhanced their survival capability by activating HIF-α/VEGF signaling and reducing ROS production in cells ( Song et al, 2018 ). Meanwhile, HSYA was revealed to enhance the repairing effects on tissue traumas in animal models significantly ( Wang et al, 2016 , Sun et al, 2018 , Xu et al, 2017 ), through reducing the levels of malondialdehyde (MDA) and glutathione disulfide (GSSG), and concomitantly increasing the relative activity of superoxide dismutase (SOD) and catalase (CAT), the level of glutathione (GSH) and the ratio of GSH/GSSG.…”

Anti-aging effects exerted by Tetramethylpyrazine enhances self-renewal and neuronal differentiation of rat bMSCs by suppressing NF-kB signaling

“…In order to exhibit the morphology of bMSCs clearly, Diff-Quick staining agent (Beijing Propbs Biotechnology Co., Ltd.) was used to stain the bMSCs at passage 4 (P 4 ), in accordance with previous research [45]. Following washing with PBS, images were obtained under the multifunctional fluorescent microscope (×200) (Eclipse 90i; Tokyo Nikon Corporation).…”

Three Ingredients of Safflower Alleviate Acute Lung Injury and Inhibit NET Release Induced by Lipopolysaccharide

“…After five days, the cells were stimulated with PMA (MedChemExpress, Monmouth Junction, NJ, USA) (100 ng/ml, dissolved in DMSO) or medium or DMSO. Then, SYA, HSYA, and AHSYB (160 mg/l) were added into the medium [19]. Three hours later, cells were harvested after centrifugation while the supernatant was collected for other use.…”

“…Besides, it has been reported that HSYA inhibits the phosphorylation of NF-κB and p38 MAPK in BV2 cells in OGD/reoxygeneration (OGD/R) conditions [51]. In addition, HYSA has been reported to activate the HIF-1α/VEGF signaling pathway and then reduce the production of ROS and maintain the integrity of mitochondrial membrane [19]. Raf/MEK/ERK may be another target pathway of SYA, HSYA, and AHSYB to alleviate the inflammatory responses.…”