Hydroxysafflor Yellow A - An Important Natural Pigment for Treating Metabolic Diseases

References

• Ekin, Z. Resurgence of Safflower (Carthamus Tinctorius L.) Utilization: A Global View. J. Agron. 2005, 4(2), 83–87. DOI:10.3923/ja.2005.83.87.
   Google Scholar
• Hussain, M. L.; Lyra, D. A.; Farooq, M.; Nikoloudakis, N.; Khalid, N. Salt and Drought Stresses in Safflower: A Review. Agronom. Sust. Develop. 2015, 36(4), 1–31. DOI: 10.1007/s13593-015-0344-8.
   Google Scholar
• FAOSTAT (Food and Agriculture Organization of the United Nations). FAOSTAT Online Database. http://www.fao.org/faostat/zh/#data/QC/visualize. ( accessed Nov 14, 2019).
   Google Scholar
• Li, D. J.; Mündel, H. H. Safflower Carthamus Tinctorius L; Institute of Plant Genetics and Crop Plant Research, Gatersleben/International Plant Genetic Resources Institute: Rome, Italy, 1996.
   Google Scholar
• Smith, J. R. Safflowe; American Oil Chemists’ Society: California, America: Los Altos, 1996.
   Google Scholar
• Bozan, B.; Temelli, F. Chemical Composition and Oxidative Stability of Flax, Safflower and Poppy Seed and Seed Oils. Bioresour. Technol. 2008, 99(14), 6354–6359. DOI: 10.1016/j.biortech.2007.12.009.
   PubMed Web of Science ®Google Scholar
• Han, X. J.; Cheng, L. M.; Zhang, R.; Bi, J. C. Extraction of Safflower Seed Oil by Supercritical CO2. J. Food Eng. 2009, 92(4), 370–376. DOI: 10.1016/j.jfoodeng.2008.12.002.
   Web of Science ®Google Scholar
• Ny, A. S.; Rah, E. D.; Ah, K.; Yahia, N. Characteristics and Oxidative Stability of Some Safflower (Carthamus Tinctorius L.). J. Nutr. Food Sci. 2015, s14(1), 1–6. DOI: 10.4172/2155-9600.S14-001.
   Google Scholar
• Ao, H.; Feng, W.; Peng, C. Hydroxysafflor Yellow A: A Promising Therapeutic Agent for A Broad Spectrum of Diseases. Evid. Based Complement. Altern. Med. 2018, 2018(2), 1–17. DOI: 10.1155/2018/8259280.
   Google Scholar
• Meselhy, M. R.; Kadota, S.; Momose, Y.; Hatakeyama, N.; Kusai, A.; Hattori, M.; Namba, T. Two New Quinochalcone Yellow Pigments from Carthamus Tinctorius and Ca2+++ Antagonistic Activity of Tinctormine. Chem. Pharm. Bull. 1993, 41(10), 1796–1802. DOI: 10.1248/cpb.41.1796.
   PubMed Web of Science ®Google Scholar
• Feng, Z. M.; He, J.; Jiang, J. S.; Chen, Z.; Yang, Y. N.; Zhang, P. C. NMR Solution Structure Study of the Representative Component Hydroxysafflor Yellow A and Other Quinochalcone C-Glycosides from Carthamus Tinctorius. J. Nat. Prod. 2013, 76(2), 270–274. DOI: 10.1021/np300814k.
   PubMed Web of Science ®Google Scholar
• Watanabe, T.; Hasegawa, N.; Yamamoto, A.; Nagai, S.; Terabe, S. Separation and Determination of Yellow and Red Safflower Pigments in Food by Capillary Electrophoresis. Biosci. Biotechnol. Biochem. 1997, 61(7), 1179–1183. DOI: 10.1271/bbb.61.1179.
   PubMed Web of Science ®Google Scholar
• Yoon, J. M.; Cho, M. H.; Park, J. E.; Kim, Y. H.; Hahn, T. R.; Paik, Y. S. Thermal Stability of the Pigments Hydroxysafflor Yellow A, Safflor Yellow B, and Precarthamin from Safflower (Carthamus Tinctorius). Food Chem. Toxicol. 2003, 68(63), 839–843. DOI: 10.1111/j.1365-2621.2003.tb08252.x.
   Google Scholar
• Li, Y.; Zhang, Z.-Y.; Zhang, J.-L. Determination of Hydroxysafflor Yellow A in Rat Plasma and Tissues by High-performance Liquid Chromatography after Oral Administration of Safflower Extract or Safflor Yellow. Biomed. Chromatogr. 2007, 21(3), 326–334. DOI: 10.1002/bmc.769.
   PubMed Web of Science ®Google Scholar
• Wang, S.; Sun, M.; Ping, Q. Enhancing Effect of Labrafac Lipophile WL 1349 on Oral Bioavailability of Hydroxysafflor Yellow A in Rats. Int. J. Pharmaceutics. 2008, 358(1–2), 198–204. DOI: 10.1016/j.ijpharm.2008.03.006.
   PubMed Web of Science ®Google Scholar
• Qi, J. P.; Sun, M. J.; Ping, Q. E.; Zhuang, J. E.; Li, J. R.; Peddie, F.; Song, Y. M. The Mechanisms for Enhanced Oral Absorption of Hydroxysafflor Yellow A by Chuanxiong Volatile Oil. Planta Med. 2010, 76(8), 786–792. DOI: 10.1055/s-0029-1240705.
   PubMed Web of Science ®Google Scholar
• Li, J. R.; Sun, M. J.; Ping, Q. N.; Chen, X. J.; Qi, J. P.; Han, D. E. Metabolism, Excretion and Bioavailability of Hydroxysafflor Yellow A after Oral Administration of Its Lipid-Based Formulation and Aqueous Solution in Rats. Chin. J. Nat. Med. 2010, 8(3), 0233–0240. DOI:10.3724/SP.J.1009.2010.00233.
   Google Scholar
• Qi, J. P.; Ping, Q. Enhanced Effect and Mechanism of Water-in-oil Microemulsion as an Oral Delivery System of Hydroxysafflor Yellow A. Int. J. Nanomed. 2011, 2011(6), 985–991. DOI: 10.2147/Ijn.S18821.
   Google Scholar
• Lv, L. Z.; Tong, C. Q.; Lv, Q.; Tang, X. J.; Li, L. M.; Fang, Q. X.; Yu, J.; Han, M.; Gao, J. Q. Enhanced Absorption of Hydroxysafflor Yellow A Using A Self-double-emulsifying Drug Delivery System: In Vitro and in Vivo Studies. Int. J. Nanomed. 2012, 2012(7), 4099–4107. DOI: 10.2147/Ijn.S33398.
   Google Scholar
• Ma, G. N.; Yu, F. L.; Wang, S.; Li, Z. P.; Xie, X. Y.; Mei, X. G. A Novel Oral Preparation of Hydroxysafflor Yellow A Base on A Chitosan Complex: A Strategy to Enhance the Oral Bioavailability. AAPS PharmSciTech. 2015, 16(3), 675–682. DOI: 10.1208/s12249-014-0255-z.
   PubMed Web of Science ®Google Scholar
• Zhou, J.; Li, M.; Jin, W. F.; Li, X. H.; Fan, H. J.; Zhang, Y. Y. Pharmacokinetic Study on Protocatechuic Aldehyde and Hydroxysafflor Yellow A of Danhong Injection in Rats with Hyperlipidemia. Pharmacology. 2018, 102(3–4), 154–160. DOI: 10.1159/000491020.
   PubMed Web of Science ®Google Scholar
• Han, D.; Wei, J.; Zhang, R.; Ma, W. H.; Shen, C.; Feng, Y. D.; Xiao, N.; Xu, D.; Cai, D. C.; Li, Y. M., et al. Hydroxysafflor Yellow A Alleviates Myocardial Ischemia/reperfusion in Hyperlipidemic Animals through the Suppression of TLR4 Signaling. Sci. Rep. 2016, 6(1), 35319. DOI: 10.1038/srep35319.
   PubMedGoogle Scholar
• Zhu, H. J.; Wang, L. J.; Wang, X. Q.; Pan, H.; Li, N. S.; Yang, H. B.; Jin, M.; Zang, B. X.; Gong, F. Y. Hormone-sensitive Lipase Is Involved in the Action of Hydroxysafflor Yellow A (HYSA) Inhibiting Adipogenesis of 3T3-L1 Cells. Fitoterapia. 2014, 93, 182–188. DOI: 10.1016/j.fitote.2014.01.001.
   PubMed Web of Science ®Google Scholar
• Zhu, H.-J.; Wang, L.-J.; Wang, X.-Q.; Pan, H.; Li, N.-S.; Yang, H.-B.; Jin, M.; Zang, B.-X.; Gong, F.-Y. Hydroxysafflor Yellow A (HYSA) Inhibited the Proliferation and Differentiation of 3T3-L1 Preadipocytes. Cytotechnology. 2015, 67(5), 885–892. DOI: 10.1007/s10616-014-9783-3.
   PubMed Web of Science ®Google Scholar
• Liu, J.; Yue, S. J.; Yang, Z. R.; Feng, W. W.; Meng, X. T.; Wang, A. T.; Peng, C.; Wang, C. Y.; Yan, D. Oral Hydroxysafflor Yellow A Reduces Obesity in Mice by Modulating the Gut Microbiota and Serum Metabolism. Pharmacol. Res. 2018, 134, 40–50. DOI: 10.1016/j.phrs.2018.05.012.
   PubMed Web of Science ®Google Scholar
• Yan, K. M.; Wang, X.; Pan, H.; Wang, L. J.; Yang, H. B.; Liu, M. J.; Zhu, H. J.; Gong, F. Y. Safflower Yellow and Its Main Component HSYA Alleviate Diet-Induced Obesity in Mice: Possible Involvement of the Increased Antioxidant Enzymes in Liver and Adipose Tissue. Front. Pharmacol. 2020, 11(482). DOI: 10.3389/fphar.2020.00482.
   Google Scholar
• Lee, M. S.; Li, H. L.; Zhao, H. X.; Suo, M.; Liu, D. L. Effects of Hydroxysafflor Yellow A on the PI3K/AKT Pathway and Apoptosis of Pancreatic β-Cells in Type 2 Diabetes Mellitus Rats. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020, 13, 1097–1107. DOI: 10.2147/DMSO.S246381.
   PubMed Web of Science ®Google Scholar
• Xu, Y. Y.; Lee, J.; Park, Y.-D.; Yang, J.-M.; Zheng, J. M.; Zhang, Q. Molecular Dynamics Simulation Integrating the Inhibition Kinetics of Hydroxysafflor Yellow A on α-glucosidase. J. Biomol. Struct. Dyn. 2018, 36(4), 830–840. DOI: 10.1080/07391102.2017.1300544.
   PubMed Web of Science ®Google Scholar
• Kajimoto, Y.; Kaneto, H. Role of Oxidative Stress in Pancreatic β-Cell Dysfunction. Ann. N.Y. Acad. Sci. 2004, 1011(1), 168–176. DOI: 10.1196/annals.1293.017.
   PubMedGoogle Scholar
• Zhao, Y.; Sun, H. C.; Li, X. S.; Zha, Y. M.; Hou, W. K. Hydroxysafflor Yellow A Attenuates High Glucose-induced Pancreatic Beta-cells Oxidative Damage via Inhibiting JNK/c-jun Signaling Pathway. Biochem. Biophys. Res. Commun. 2018, 505(2), 353–359. DOI: 10.1016/j.bbrc.2018.09.036.
   PubMed Web of Science ®Google Scholar
• Lee, M. S.; Zhao, H. X.; Liu, X. M.; Liu, D. L.; Chen, J. P.; Li, Z. Y.; Chu, S. F.; Kou, X. H.; Liao, S.; Deng, Y. X., et al. Protective Effect of Hydroxysafflor Yellow A on Nephropathy by Attenuating Oxidative Stress and Inhibiting Apoptosis in Induced Type 2 Diabetes in Rat. Oxid. med. cell. longevity. 2020, 2020(1), 1–11. DOI: 10.1155/2020/7805393.
   Google Scholar
• He, S.; Zhao, T.; Guo, H.; Meng, Y. Z.; Qin, G. J.; Goukassian, D. A.; Han, J. H.; Gao, X. M.; Zhu, Y.; Wang, X. Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice. Plos One. 2016, 11(12), e0167305. DOI: 10.1371/journal.pone.0167305.
   PubMed Web of Science ®Google Scholar
• Ni, Z.; Zhuge, Z.; Li, W.; Xu, H.; Zhang, Z.; Dai, H. Inhibitory Effects of Hydroxysafflor Yellow A on the Formation of Advanced Glycation End Products in Vitro. Biol. Pharm. Bull. 2012, 35(11), 2050–2053. DOI: 10.1248/bpb.b12-00249.
   PubMed Web of Science ®Google Scholar
• Chen, S.; Ma, J.; Zhu, H.; Deng, S.; Gu, M.; Qu, S. Hydroxysafflor Yellow A Attenuates High Glucose-induced Human Umbilical Vein Endothelial Cell Dysfunction. Human Exp. Toxicol. 2019, 38(6), 685–693. DOI:10.1177/0960327119831065.
   PubMed Web of Science ®Google Scholar
• Gao, S.-Q.; Chang, C.; Niu, X.-Q.; Li, L.-J.; Zhang, Y.; Gao, J.-Q. Topical Application of Hydroxysafflor Yellow A Accelerates the Wound Healing in Streptozotocin Induced T1DM Rats. Eur. J. Pharmacol. 2018, 823, 72–78. DOI: 10.1016/j.ejphar.2018.01.018.
   PubMed Web of Science ®Google Scholar
• Gao, S. Q.; Chang, C.; Li, J. J.; Li, Y.; Niu, X. Q.; Zhang, D. P.; Li, L. J.; Gao, J. Q. Co-delivery of Deferoxamine and Hydroxysafflor Yellow A to Accelerate Diabetic Wound Healing via Enhanced Angiogenesis. Drug Delivery. 2018, 25(1), 1779–1789. DOI: 10.1080/10717544.2018.1513608.
   PubMed Web of Science ®Google Scholar
• He, H.; Liu, Q.; Shi, M.; Zeng, X.; Yang, J.; Wu, L.; Li, L. Cardioprotective Effects of Hydroxysafflor Yellow A on Diabetic Cardiac Insufficiency Attributed to Up-regulation of the Expression of Intracellular Calcium Handling Proteins of Sarcoplasmic Reticulum in Rats. Phytotherapy Res. 2009, 23(5), 746–746. DOI: 10.1002/ptr.2885.
   Web of Science ®Google Scholar
• Li, Y.; Zheng, D.; Shen, D.; Zhang, X.; Zhao, X.; Liao, H. Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization. J. Immunol. Res. 2020, 2020(1), 2462039. DOI: 10.1155/2020/2462039.
   PubMedGoogle Scholar
• Feng, X. J.; Lia, L.; Wang, Y. N.; Lia, L. L.; Little, P. J.; Xu, S. W.; Liu, S. Danhong Injection in Cardiovascular and Cerebrovascular Diseases: Pharmacological Actions, Molecular Mechanisms, and Therapeutic Potential. Pharmacol. Res. 2019, 139, 62–75. DOI: 10.1016/j.phrs.2018.11.006.
   PubMed Web of Science ®Google Scholar
• Guoa, Y.; Yanga, J.-H.; Caob, S.-D.; Gaob, C.-X.; Hec, Y.; Wangb, Y.; Wanb, H.-T.; Jinb, B. Effect of Main Ingredients of Danhong Injection against Oxidative Stress Induced Autophagy Injury via miR-19a/SIRT1 Pathway in Endothelial Cells. Phytomedicine. 2021, 83, 153480. DOI: 10.1016/j.phymed.2021.153480.
   PubMed Web of Science ®Google Scholar
• Lv, Y. N.; Fu, L. S. The Potential Mechanism for Hydroxysafflor Yellow A Attenuating Blood-brain Barrier Dysfunction via Tight Junction Signaling Pathways Excavated by an Integrated Serial Affinity Chromatography and Shotgun Proteomics Analysis Approach. Neurochem. Int. 2018, 112, 38–48. DOI: 10.1016/j.neuint.2017.10.012.
   PubMed Web of Science ®Google Scholar
• Sun, Y.; Xu, D. P.; Qin, Z.; Wang, P. Y.; Hu, B. H.; Yu, J. G.; Zhao, Y.; Cai, B.; Chen, Y. L.; Lu, M., et al. Protective Cerebrovascular Effects of Hydroxysafflor Yellow A (HSYA) on Ischemic Stroke. Eur. J. Pharmacol. 2018, 818, 604–609. DOI: 10.1016/j.ejphar.2017.11.033.
   PubMed Web of Science ®Google Scholar
• Xu, J.; Zhan, T.; Zheng, W.; Huang, Y. K.; Chen, K.; Zhang, X. H.; Ren, P.; Huang, X. Hydroxysafflor Yellow A Acutely Attenuates Blood-brain Barrier Permeability, Oxidative Stress, Inflammation and Apoptosis in Traumatic Brain Injury in Rats. Acta Cirúrgica Brasileira. 2021, 3512(12), e351202. DOI: 10.1590/acb351202.
   Google Scholar
• Ye, F.; Wang, J. H.; Meng, W.; Qian, J. R.; Jin, M. Proteomic Investigation of Effects of Hydroxysafflor Yellow A in Oxidized Low-density Lipoprotein-induced Endothelial Injury. Sci. Rep. 2017, 7(1), 17981. DOI: 10.1038/s41598-017-18069-4.
   PubMedGoogle Scholar
• Huber, G. A.; Priest, S. M.; Geisbuhler, T. P. Cardioprotective Effect of Hydroxysafflor Yellow A via the Cardiac Permeability Transition Pore. Planta Med. 2018, 84(8), 507–518. DOI: 10.1055/s-0043-122501.
   PubMed Web of Science ®Google Scholar
• Zou, J.; Wang, N.; Liu, M. T.; Bai, Y. P.; Wang, H.; Liu, K.; Zhang, H.; Xiao, X. Z.; Wang, K. K. Nucleolin Mediated Pro-angiogenic Role of Hydroxysafflor Yellow A in Ischaemic Cardiac Dysfunction: Post-transcriptional Regulation of VEGF-A and MMP-9. J. Cellular Mol. Med. 2018, 22(5), 2692–2705. DOI: 10.1111/jcmm.13552.
   PubMed Web of Science ®Google Scholar
• Tian, W.; Feng-Hua, F. H.; Bing, H.; Gui-Sheng, G. S.; Lei-Ming, Z.; Ke, L. Hydroxysafflor Yellow A Reduces Myocardial Infarction Size after Coronary Artery Ligation in Rats. Pharm. Biol. 2009, 47(5), 458–462. DOI: 10.1080/13880200902822612.
   Web of Science ®Google Scholar
• Wang, J. P.; Zhang, Q.; Mei, X. H.; Zhang, X. Z. Hydroxysafflor Yellow A Attenuates Left Ventricular Remodeling after Pressure Overload-induced Cardiac Hypertrophy in Rats. Pharm. Biol. 2014, 52(1), 31–35. DOI: 10.3109/13880209.2013.805791.
   PubMed Web of Science ®Google Scholar
• Chen, M. C.; Wang, M. M.; Yang, Q.; Wang, M.; Wang, Z. P.; Zhu, Y. R.; Zhang, Y. K.; Wang, C.; Jia, Y. Y.; Li, Y. W., et al. Antioxidant Effects of Hydroxysafflor Yellow A and Acetyl-11-keto–boswellic Acid in Combination on Isoproterenol-induced Myocardial Injury in Rats. Int.J. Mol. Med. 2016, 37(6), 1501–1510. DOI: 10.3892/ijmm.2016.2571.
   PubMed Web of Science ®Google Scholar
• Min, J.; Wei, C. Hydroxysafflor Yellow A Cardioprotection in Ischemia–reperfusion (I/R) Injury Mainly via Akt/hexokinase II Independent of ERK/GSK-3β Pathway. Biomed. Pharmacother. 2017, 87, 419–426. DOI: 10.1016/j.biopha.2016.12.113.
   PubMed Web of Science ®Google Scholar
• Zhou, D. L.; Ding, T. T.; Ni, B.; Jing, Y. Y.; Liu, S. X. Hydroxysafflor Yellow A Mitigated Myocardial Ischemia/reperfusion Injury by Inhibiting the Activation of the JAK2/STAT1 Pathway. Int.J. Mol. Med. 2019, 44(2), 405–416. DOI: 10.3892/ijmm.2019.4230.
   PubMed Web of Science ®Google Scholar
• Cao, J. Y.; Wang, K.; Lei, L.; Bai, L.; Liang, R. M.; Qiao, Y.; Duan, J. L.; Gao, K.; Cao, S. S.; Zhao, C., et al. Astragaloside And/or Hydroxysafflor Yellow A Attenuates Oxygen-Glucose Deprivation-Induced Cultured Brain Microvessel Endothelial Cell Death through Downregulation of PHLPP-1. Evid. Based Complement. Altern. Med. 2020, 2020, 3597527. DOI: 10.1155/2020/3597527.
   PubMed Web of Science ®Google Scholar
• Ye, J.; Lu, S.; Wang, M.; Ge, W.; Sun, X.; Qi, Y.; Fu, J.; Zhang, Q.; Zhang, B.; Sun, G. Hydroxysafflor Yellow a Protects against Myocardial Ischemia/reperfusion Injury via Suppressing Nlrp3 Inflammasome and Activating Autophagy. Front. Pharmacol. 2020, 11, 1170. DOI: 10.3389/fphar.2020.01170.
   PubMed Web of Science ®Google Scholar
• Yang, G.; Wang, N.; Seto, S. W.; Chang, D.; Liang, H. Z. Hydroxysafflor Yellow A Protects Brain Microvascular Endothelial Cells against Oxygen Glucose Deprivation/reoxygenation Injury: Involvement of Inhibiting Autophagy via Class I PI3K/Akt/mTOR Signaling Pathway. Brain Res. Bull. 2018, 140, 243–257. DOI: 10.1016/j.brainresbull.2018.05.011.
   PubMed Web of Science ®Google Scholar
• Ni, B.; Zhou, D. L.; Jing, Y. Y.; Liu, S. X. Hydroxysafflor Yellow A Protects against Angiotensin II-induced Hypertrophy. Mol. Med. Rep. 2018, 18(4), 3649–3656. DOI: 10.3892/mmr.2018.9399.
   PubMed Web of Science ®Google Scholar
• Wei, G.; Yin, Y.; Duan, J. L.; Guo, C.; Zhu, Y. R.; Wang, Y. H.; Xi, M. M.; Wen, A. D. Hydroxysafflor Yellow A Promotes Neovascularization and Cardiac Function Recovery through HO-1/VEGF-A/SDF-1α Cascade. Biomed. Pharmacother. 2017, 88, 409–420. DOI: 10.1016/j.biopha.2017.01.074.
   PubMed Web of Science ®Google Scholar
• Sun, X.; Wei, X. B.; Qu, S. F.; Zhao, Y. X.; Zhang, X. M. Hydroxysafflor Yellow A Suppresses Thrombin Generation and Inflammatory Responses following Focal Cerebral Ischemia–reperfusion in Rats. Bioorg. Med. Chem. Lett. 2010, 20(14), 4120–4124. DOI:10.1016/j.bmcl.2010.05.076.
   PubMed Web of Science ®Google Scholar
• Gong, Z.; Pan, J.; Li, X.; Wang, H.; He, L.; Peng, Y. Hydroxysafflor Yellow A Reprograms TLR9 Signalling Pathway in Ischaemic Cortex after Cerebral Ischaemia and Reperfusion. Cns Neurol. Disord-drug Targets. 2018, 17(5), 370–382. DOI:10.2174/1871527317666180502110205.
   PubMed Web of Science ®Google Scholar
• Lv, Y.; Qian, Y.; Fu, L.; Chen, X.; Zhong, H.; Wei, X. Hydroxysafflor Yellow A Exerts Neuroprotective Effects in Cerebral Ischemia Reperfusion-injured Mice by Suppressing the Innate Immune TLR4-inducing Pathway. Eur. J. Pharmacol. 2015, 769, 324–332. DOI: 10.1016/j.ejphar.2015.11.036.
   PubMed Web of Science ®Google Scholar
• Bayat, M.; Sharifi, M. D.; Haghani, M.; Shabani, M. Enriched Environment Improves Synaptic Plasticity and Cognitive Deficiency in Chronic Cerebral Hypoperfused Rats. Brain Res. Bull. 2015, 119, 34–40. DOI: 10.1016/j.brainresbull.2015.10.001.
   PubMed Web of Science ®Google Scholar
• Sun, L.; Yang, L.; Xu, Y.-W.; Liang, H.; Han, J.; Zhao, R.-J.; Cheng, Y. Neuroprotection of Hydroxysafflor Yellow A in the Transient Focal Ischemia: Inhibition of Protein Oxidation/nitration, 12/15-lipoxygenase and Blood-brain Barrier Disruption. Brain Res. 2012, 1473, 227–235. DOI: 10.1016/j.brainres.2012.07.047.
   PubMed Web of Science ®Google Scholar
• Thomas, G. M.; Huganir, R. L. MAPK Cascade Signalling and Synaptic Plasticity. Nat. Rev. Neurosci. 2004, 5(3), 173–183. DOI: 10.1038/nrn1346.
   PubMed Web of Science ®Google Scholar
• Yu, L.; Duan, Y. H.; Zhao, Z.; He, W. D.; Xia, M.; Zhang, Q. J.; Cao, X. H. Hydroxysafflor Yellow A (HSYA) Improves Learning and Memory in Cerebral Ischemia Reperfusion-Injured Rats via Recovering Synaptic Plasticity in the Hippocampus. Front. Cell. Neurosci. 2018, 12, 371. DOI: 10.3389/fncel.2018.00371.
   PubMed Web of Science ®Google Scholar
• Xing, M. Y.; Sun, Q. N.; Wang, Y. Y.; Cheng, Y.; Zhang, N. Hydroxysafflor Yellow A Increases BDNF and NMDARs in the Hippocampus in A Vascular Dementia Rat Model. Brain Res. 2016, 1642, 419–425. DOI: 10.1016/j.brainres.2016.04.030.
   PubMed Web of Science ®Google Scholar
• Zhang, N.; Xing, M. Y.; Wang, Y. Y.; Liang, H.; Yang, Z.; Shi, F. D.; Cheng, Y. Hydroxysafflor Yellow A Improves Learning and Memory in A Rat Model of Vascular Dementia by Increasing VEGF and NR1 in the Hippocampus. Neurosci. Bull. 2014, 30(3), 417–424. DOI:10.1007/s12264-013-1375-2.
   PubMed Web of Science ®Google Scholar
• Li, L.; Dong, P. D.; Hou, C. J.; Cao, F. Y.; Sun, S. L.; He, F.; Song, Y. P.; Li, S.; Bai, Y. H.; Zhu, D. L. Hydroxysafflor Yellow A (HSYA) Attenuates Hypoxic Pulmonary Arterial Remodelling and Reverses Right Ventricular Hypertrophy in Rats. J. Ethnopharmacol. 2016, 186, 224–233. DOI: 10.1016/j.jep.2016.04.004.
   PubMed Web of Science ®Google Scholar
• Han, X. T.; Zhang, Y. X.; Zhou, Z.; Zhang, X. W.; Long, Y. F. Hydroxysafflor Yellow A Improves Established Monocrotaline-induced Pulmonary Arterial Hypertension in Rats. J. Int. Med. Res. 2016, 44(3), 569–584. DOI: 10.1177/0300060515597931.
   PubMed Web of Science ®Google Scholar
• Xi, S.-Y.; Zhang, Q.; Liu, C.-Y.; Xie, H.; Yue, L.-F.; Gao, X.-M. Effects of Hydroxy Safflower Yellow-A on Tumor Capillary Angiogenesis in Transplanted Human Gastric Adenocarcinoma BGC-823 Tumors in Nude Mice. J. Traditional Chin. Med. 2012, 32(2), 243–248. DOI: 10.1016/S0254-6272(13)60019-9.
   PubMed Web of Science ®Google Scholar
• Xi, S. Y.; Zhang, Q.; Liu, C. Y.; Sun, H. M.; Ge, G. L.; Cui, W.; Jei, H.; Liu, L. T.; Gao, X. M. Inhibitory Effect of Hydroxy saffloryellow-A on Transplantation Tumor of Human Gastric Adenocarcinoma Cell Line BGC-823 in Nude Mice. J. Beijing Univ. Traditional Chin. Med. 2009, 32(5), 331–335. DOI:10.1007/978-1-4020-9623-5_5.
   Google Scholar
• Liu, L.; Si, N.; Ma, Y. C.; Ge, D. Y.; Yu, X.; Fan, A. R.; Wang, X.; Hu, J. H.; Wei, P.; Chen, Z. W., et al. Hydroxysafflor-Yellow A Induces Human Gastric Carcinoma BGC-823 Cell Apoptosis by Activating Peroxisome Proliferator-Activated Receptor Gamma (PPARγ). Med. Sci. Monit. 2018, 24, 803–811. doi:10.12659/Msm.905587.
   PubMed Web of Science ®Google Scholar
• Chen, X.; Wang, Y.; Zhang, L.; Gao, Y. J. Hydroxysafflor Yellow A of Carthamus Tinctorius L., Represses the Malignant Development of Esophageal Cancer Cells via Regulating NF-κB Signaling Pathway. Cell Biochem. Biophys. 2020, 78(4), 511–520. DOI: 10.1007/s12013-020-00934-1.
   PubMed Web of Science ®Google Scholar
• Ma, L.; Liu, L.; Ma, Y.; Xie, H.; Yu, X.; Wang, X.; Fan, A.; Ge, D. Y.; Xu, Y. Y.; Zhang, Q., et al. The Role of E-Cadherin/beta-Catenin in Hydroxysafflor Yellow A Inhibiting Adhesion, Invasion, Migration and Lung Metastasis of Hepatoma Cells. Biol. Pharm. Bull. 2017, 40(10), 1706–1715. DOI: 10.1248/bpb.b17-00281.
   PubMed Web of Science ®Google Scholar
• Jiang, M.; Zhou, L.-Y.; Xu, N.; An, Q. Hydroxysafflor Yellow A Inhibited Lipopolysaccharide-induced Non-small Cell Lung Cancer Cell Proliferation, Migration, and Invasion by Suppressing the PI3K/AKT/mTOR and ERK/MAPK Signaling Pathways. Thoracic Cancer. 2019, 10(6), 1319–1333. DOI: 10.1111/1759-7714.13019.
   PubMed Web of Science ®Google Scholar
• Wu, N.; Li, J. M.; Luo, H. L.; Wang, D.; Bai, X. Y. Hydroxysafflor Yellow A Promotes Apoptosis via Blocking Autophagic Flux in Liver Cancer. Biomed. Pharmacother. 2021, 136, 111227. DOI: 10.1016/j.biopha.2021.111227.
   PubMed Web of Science ®Google Scholar
• Yang, G. S.; Zhou, X. Y.; Chen, T.; Deng, Y. D.; Yu, D.; Pan, S. Y.; Song, Y. M. Hydroxysafflor Yellow A Inhibits Lipopolysaccharide-induced Proliferation and Migration of Vascular Smooth Muscle Cells via Toll-like Receptor-4 Pathway. Int. J. Clin. Exp. Med. 2015, 8(4), 5295–5302.
   PubMed Web of Science ®Google Scholar
• Wang, J.; Wang, J. J.; Wang, X. X.; Liu, L.; Hu, J. H.; Yu, X.; Xu, Y. Y.; Niu, X. Y.; Lin, Z.; Zhang, Y., et al. Molecular Mechanism of Inhibition of the Abnormal Proliferation of Human Umbilical Vein Endothelial Cells by Hydroxysafflor-yellow A. Pharm. Biol. 2016, 54(9), 1800–1807. DOI: 10.3109/13880209.2015.1129541.
   PubMed Web of Science ®Google Scholar
• Yang, F. F.; Li, J. M.; Zhu, J. H.; Wang, D.; Chen, S. S.; Bai, X. Y. Hydroxysafflor Yellow A Inhibits Angiogenesis of Hepatocellular Carcinoma via Blocking ERK/MAPK and NF-κB Signaling Pathway in H22 Tumor-bearing Mice. Eur. J. Pharmacol. 2015, 754, 123–132. DOI: 10.1016/j.ejphar.2015.02.015.
   Web of Science ®Google Scholar
• Zhang, J. Y.; Li, J. M.; Song, H. R.; Xiong, Y. L.; Liu, D. S.; Bai, X. Y. Hydroxysafflor Yellow A Suppresses Angiogenesis of Hepatocellular Carcinoma through Inhibition of P38 MAPK Phosphorylation. Biomed. Pharmacother. 2019, 109, 806–814. DOI: 10.1016/j.biopha.2018.09.086.
   PubMed Web of Science ®Google Scholar
• Konishi, M.; Tabata, Y.; Kariya, M.; Hosseinkhani, H.; Suzuki, A.; Fukuhara, K.; Mandai, M.; Takakura, K. J.; Fujii, S. In Vivo Anti-tumor Effect of Dual Release of Cisplatin and Adriamycin from Biodegradable Gelatin Hydrogel. J. Controlled Release. 2005, 103(1), 7–19. DOI: 10.1016/j.jconrel.2004.11.014.
   PubMed Web of Science ®Google Scholar
• Ma, Y. T.; Li, M. M.; Wu, Q.; Xu, W. F.; Lin, S.; Chen, Z. W.; Li, L.; Long, L.; Sheng, Q.; Li, T. T., et al. Hydroxysafflor Yellow A Sensitizes Ovarian Cancer Cells to Chemotherapeutic Agent by Decreasing WSB1 Expression. Eur. J. Int. Med. 2019, 25, 6–12. DOI: 10.1016/j.eujim.2018.11.007.
   Google Scholar
• Jin, C. Y. Hydroxysafflor Yellow a Reverse Chemotherapy Resistance via Jnk and P38 Mapk Signal Pathway in Ovarian Cancer Cells. Farmacia. 2019, 67(2), 331–336. DOI: 10.31925/farmacia.2019.2.19.
   Web of Science ®Google Scholar
• Liu, L.; Tao, W.; Pan, W.; Lici, L.; Yu, Q.; Zhang, D.; Jiang, J. Hydroxysafflor Yellow A Promoted Bone Mineralization and Inhibited Bone Resorption Which Reversed Glucocorticoids-Induced Osteoporosis. Biomed Res. Int. 2018, 2018, 1–8. DOI: 10.1155/2018/6762146.
   Web of Science ®Google Scholar
• Min, F.; Sun, H. Q.; Wang, B.; Ahmad, N.; Guo, H.; Gao, H. T.; Gao, Y. Y.; Liu, X.; Li, H. Y. Hepatoprotective Effects of Hydroxysafflor Yellow A in D-galactose-treated Aging Mice. Eur. J. Pharmacol. 2020, 881, 173214. DOI: 10.1016/j.ejphar.2020.173214.
   PubMed Web of Science ®Google Scholar