Protection on brain injury |
HSYA (1) (0.036 and 0.072 mg/ml) |
Organotypic hippocampal slices from neonatal SD rats (in vitro) |
Increase organotypic hippocampal cells from neonatal SD rats (DAPI+, BrdU+ and Nestin+) with arranged in cords and migrated to the codex as compared to control (normal saline) |
Qin et al. (2012a)Qin, Z., Wang, X.F., Ye, H., Zheng, X.B., 2012a. Effects of hydroxysafflor yellow A on nerve regeneration of the organotypic hippocampal slices from neonatal SD rats. Shi Zhen Guo Yi Guo Yao 23, 1856-1858.
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HSYA (1) (0.036 and 0.072 mg/ml) |
Oxygen-glucose deprivation in hippocampal slice cultures from rats (in vitro) |
Reduce the proliferation of neural stem cell compared to normal saline |
Qin et al. (2012b)Qin, Z., Wang, X.F., Ye, H., Zheng, X.B., 2012b. Effects of hydroxysafflor yellow A on neurogenesis in a rat model of oxygen-glucose deprivation in hippocampal slice cultures. Int. J. Cerebrovasc. Dis. 20, 263-268.
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HSYA (1) (10-80 µmol/l) |
Ca2+-induced and H2O2-induced swelling of mitochondria isolated from rat brains (in vitro) |
Inhibited swelling and reactive oxygen species of mitochondria, improve mitochondrial energy metabolism and enhanced ATP levels and the respiratory control ratio compared to 50 µmol/l Ca2+-treated group |
Tian et al. (2008)Tian, J.W., Li, G.S., Liu, Z.F., Fu, F.H., 2008. Hydroxysafflor yellow A inhibits rat brain mitochondrial permeability transition pores by a free radical scavenging action. Pharmacology 82, 121-126.
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HSYA (1) (3.0 and 6.0 mg/kg, sublingular vein injection) |
Male Wistar-Kyoto rats with middle cerebral artery occlusion (MCAO) (in vivo) |
Decrease neurological deficit scores and reducing infarct area compared to the saline group and dosage of 6.0 mg/kg show a similar potency as nimodipine (0.2 mg/kg) |
Zhu et al. (2003)Zhu, H., Wang, Z., Ma, C., Tian, J., Fu, F., Li, C., Guo, D., Roeder, E., Liu, K., 2003. Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies. Planta Med. 69, 429-433.
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HSYA (1) (3.0 and 6.0 mg/kg, sublingular vein injection) |
MCAO rats (in vivo) |
Produce a dose-dependent reduction in infarct area (60% and 85% respectively), increase the ratio of 6-Keto-PGF1a and TXB2, reduce thrombotic weight |
Zhu et al. (2005)Gan, L., Wang, Z.H., Ma, C.J., Li, G., 2012. Protective effects of hydroxysafflor yellow A on brain injury in mice irradiated by 300 MeV/u 12C6+ ions. Nucl. Sci. Technol. 35, 624-629.
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HSYA (1) (10.0 mg/kg, ear intravenous injection) |
Rabbits with ischemia/reperfusion (I/R) injury (in vivo) |
Attenuate I/R induced necrosis in spinal cords, alleviate oxidative stress as indicated by decreased malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity and protected neurons from I/R-induced apoptosis in rabbits |
Shan et al. (2010)Shan, L.Q., Ma, S., Qiu, X.C., Zhou, Y., Zhang, Y., Zheng, L.H., Ren, P.C., Wang, Y.C., Fan, Q.Y., Ma, B.A., 2010. Hydroxysafflor yellow A protects spinal cords from ischemia/reperfusion injury in rabbits. BMC Neurosci. 11, 720-725.
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HSYA (1) (5 mg/kg, i.p.) |
Rats with lymphostatic encephalopathy-induced brain injury (in vivo) |
Alleviate the neurological deficits, attenuate cell apoptosis in the rostral ventrolateral medullus compared to saline group |
Pan et al. (2012)Pan, Y., Zheng, D.Y., Liu, S.M., Meng, Y., Xu, H.Y., Zhang, Q., Gong, J., Xia, Z.L., Chen, L.B., Li, H.Y., 2012. Hydroxysafflor yellow A attenuates lymphostatic encephalopathy-induced brain injury in rats. Phytother. Res. 26, 1500-1506.
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HSYA (1) (5,10 and 20 mg/kg, intraperitoneal injection) |
Mouse with brain injury induced by 12C6+particle therapy (in vivo) |
Dose-dependently improve the spatiomemory deficits and increase SOD activity and reduce malondialdehyde content in brain tissue |
Gan et al. (2012)Gan, L., Wang, Z.H., Ma, C.J., Li, G., 2012. Protective effects of hydroxysafflor yellow A on brain injury in mice irradiated by 300 MeV/u 12C6+ ions. Nucl. Sci. Technol. 35, 624-629.
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HSYA (1) (4 and 8 mg/kg, tail-vein injection) |
MCAO rats (in vivo) |
Diminish the number of apoptotic cells and increase the Bcl-2/Bax ratio as well as the phosphorylations of Akt and GSK3b |
Chen et al. (2013aChen, Y.S., Lee, S.M., Lin, C.C., Liu, C.Y., Wu, M.C., Shi, W.L., 2013a. Kinetic study on the tyrosinase and melanin formation inhibitory activities of carthamus yellow isolated from Carthamus tinctorius L. J. Biosci. Bioeng. 115, 242-245.
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b)Chen, L., Xiang, Y.X., Kong, L.J., Zhang, X.M., Sun, B.Z., Wei, X.B., Liu, H.Q., 2013b. Hydroxysafflor yellow A protects against cerebral ischemia-reperfusion injury by anti-apoptotic effect through PI3K/Akt/GSK3b pathway in rat. Neurochem. Res. 38, 2268-2275.
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N1,N5-(Z)-N10-(E)-tri-p-coumaroylspermidine (2) (0.04-100 µM) |
Chinese hamster ovary cells (in vitro) |
Inhibit serotonin uptake in S6 cells (IC50 = 0.74 ± 0.15 µM) and in synaptosomes (IC50 = 1.07 ± 0.23 µM) |
Zhao et al. (2009b)Zhao, G., Zheng, X.W., Gai, Y., Chu, W.J., Qin, G.W., Guo, L.H., 2009a. Safflower extracts functionally regulate monoamine transporters. J. Ethnopharmacol. 124, 116-124.
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Carthamin (3) (10 mg/kg) |
Rats with epileptic foci induced by iron (in vivo) |
Inhibit 8-hydroxy-2'-deoxyguanosine in the cerebral cortex of rats |
Hiramatsu et al. (2009)Hiramatsu, M., Takahashi, T., Komatsu, M., Kido, T., Kasahara, Y., 2009. Antioxidant and neuroprotective activities of Mogami-benibana (Safflower, Carthamus tinctorius Linne). Neurochem. Res. 34, 795-805.
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Kempferol-3-O-rutinoside (4) (2.5, 5 and 10 mg/kg, tail vein) |
Rats with permanent focal cerebral ischemia (in vivo) |
Dose-dependently reduce brain infarct volume and neurological deficits compared with nimodipin (positive control) |
Li et al. (2006a)Li, R.P., Guo, M.L., Zhang, G., Xu, X.F., Li, Q., 2006a. Neuroprotection of nicotiflorin in permanent focal cerebral ischemia and in neuronal cultures. Biol. Pharm. Bull. 29, 1868-1872.
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Kempferol-3-O-rutinoside (4) (25-100 µg/ml) |
Cultured neurons suffered hypoxia (in vitro) |
Attenuate cell death and reduce lactate dehydrogenase release |
Li et al. (2006a)Li, R.P., Guo, M.L., Zhang, G., Xu, X.F., Li, Q., 2006a. Neuroprotection of nicotiflorin in permanent focal cerebral ischemia and in neuronal cultures. Biol. Pharm. Bull. 29, 1868-1872.
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Anti-myocardial ischemia effect |
Ethanolic extract (62.5 and 125 µg/ml) |
H9c2 cardiomyoblast cells (in vitro) |
Reduce IkB degradation and NFkB activation, activate of anti-apoptotic proteins, Bcl-2 and Bcl-xL, stabilization the mitochondria membrane and the down-regulation of extrinsic and intrinsic pro-apoptotic proteins, such as TNFα, active caspases-8,9 and 3 t-Bid, Bax, compared to LPS |
Tien et al. (2010)Tien, Y.C., Lin, J.Y., Lai, C.H., Kuo, C.H., Lin, W.Y., Tsai, C.H., Tsai, F.J., Cheng, Y.C., Peng, W.H., Huang, C.Y., 2010. Carthamus tinctorius L. prevents LPS-induced TNFa signaling activation and cell apoptosis through JNK1/2-NFkB pathway inhibition in H9c2 cardiomyoblast cells. J. Ethnopharmacol. 130, 505-513.
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HSYA (1) (4 and 8 mg/kg, tail vein) |
Rats with coronary artery ligation (in vivo) |
Reduction of myocardial infarction size, superoxide dismutase activity, endothelial nitric oxide synthase activity and nitric oxide content, and inhibit elevation of creatine kinase activity and malondialdehyde content |
Wang et al. (2009aWang, T., Fu, F.H., Han, B., Li, G.S., Zhang, L.M., Liu, K., 2009a. Hydroxysafflor yellow A reduces myocardial infarction size after coronary artery ligation in rats. Pharm. Biol. 47, 458-462.
b)Wang, C.Y., Ma, H.M., Zhang, S.P., Wang, Y.F., Liu, J.T., Xiao, X.H., 2009b. Safflor yellow B suppresses pheochromocytoma cell (PC12) injury induced by oxidative stress via antioxidant system and Bcl-2/Bax pathway. N-Sarch. Pharmacol. 380, 135-142.
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HSYA (1) (0.1-3 mg/kg, intravenous injection) |
Rats with pentobarbitone-anesthetized normotensive and spontaneously hypertensive (in vivo) |
Dose-dependently reduce heart rate, mean arterial pressure, left ventricular systolic pressure, left ventricular end-diastolic pressure |
Nie et al. (2012)Nie, P.H., Zhang, L., Zhang, W.H., Rong, W.F., Zhi, J.M., 2012. The effects of hydroxysafflor yellow A on blood pressure and cardiac function. J. Ethnopharmacol. 139, 746-750.
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N-(p-coumaroyl) serotonin (6) (5 × 10-7M) |
Model of perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion (in vitro) |
Increase the NO level at the end of ischemia and show 63.2% recovery rate of left ventricular developed pressure compared to drug-free control (30.8%) |
Hotta et al. (2002)Hotta, Y., Nagatsu, A., Liu, W., Muto, T., Narumiya, C., Lu, X.L., Yajima, M., Ishikawa, N., Miyazeki, K., Kawai, N., Mizukami, H., Sakakibara, J., 2002. Protective effects of antioxidative serotonin derivatives isolated from safflower against postischemic myocardial dysfunction. Mol. Cell. Biochem. 238, 151-162.
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N-feruroylserotonin (5 × 10-7 M) (7) |
Similar to N-(p-coumaroyl) serotonin |
Show 61.0% recovery rate of left ventricular developed pressure and quench the activity of active radicals |
Hotta et al. (2002)Hotta, Y., Nagatsu, A., Liu, W., Muto, T., Narumiya, C., Lu, X.L., Yajima, M., Ishikawa, N., Miyazeki, K., Kawai, N., Mizukami, H., Sakakibara, J., 2002. Protective effects of antioxidative serotonin derivatives isolated from safflower against postischemic myocardial dysfunction. Mol. Cell. Biochem. 238, 151-162.
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Antithrombotic effect |
Aqueous extract (1 and 0.7 g/kg, oral) |
(a) Rats arterial thrombosis model (in vivo) (b) Rats venous (Wessler) thrombosis model (in vivo) (c) Mouses with collagen/epinephrine-induced pulmonary embolism (in vivo) (d) Mouses tail bleeding (in vivo) |
(a) Show a mild thrombosis inhibition but without difference with control when plus clopidogrel or not (b) Inhibit thrombus formation from 16.1 to 7.9 mg and led to a significant decrease in venous thrombus weight when added clopidogrel and also augment thrombin time and prothrombin time (c) Increase the number of non-paralyzed animals to 33.3% and surviving rates to 53.3% (d) Prolonged the bleeding time when added clopidogrel |
Li and Wang (2010)Li, Y.H., Wang, N.S., 2010. Antithrombotic effects of Danggui, Honghua and potential drug interaction with clopidogrel. J. Ethnopharmacol. 128, 623-628.
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Carthamins yellow (100 and 200 mg/kg, oral) |
Rats with blood stasis (in vivo) |
Decrease the whole blood viscosity, plasma viscosity, erythrocyte aggregation index, hematocrit and platelet aggregation when compared with aspirin |
Li et al. (2009)Li, H.X., Han, S.Y., Wang, X.W., Ma, X., Zhang, K., Wang, L., Ma, Z.Z., Tu, P.F., 2009. Effect of the carthamins yellow from Carthamus tinctorius L. on hemorheological disorders of blood stasis in rats. Food Chem. Toxicol. 47, 1797-1802.
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HSYA (1) (1 × 10-4 M) |
Human EC line (EAhy926) (in vitro) |
Attenuate cell cycle arrest and inhibit cell apoptosis in a concentration-dependent manner and increase the bcl-2/bax ratio, VEGF protein concentration, VEGF mRNA expression, HIF-1a protein accumulation and its transcriptional activity |
Ji et al. (2008)Ji, D.B., Zhu, M.C., Zhu, B., Zhu, Y.Z., Li, C.L., Ye, J., Zhu, H.B., 2008. Hydroxysafflor yellow A enhances survival of vascular endothelial cells under hypoxia via upregulation of the HIF-1a-VEGF pathway and regulation of Bcl-2/Bax. J. Cardiovasc. Pharm. 52, 191-202.
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HSYA (1) (1 × 10-6, 1 × 10-5and 1 × 10-4 M) |
Human umbilical vein endothelial cells (HUVEC) (in vitro) |
Inhibit cell apoptosis and cell cycle G1 arrest induced by hypoxia Increase the Bcl-2/Bax ratio of protein and NO content of cell supernatant Reduce p53 protein expression in cell nucleus |
Ji et al. (2009)Ji, D.B., Zhang, L.Y., Li, C.L., Ye, J., Zhu, H.B., 2009. Effect of hydroxysafflor yellow A on human umbilical vein endothelial cells under hypoxia. Vasc. Pharmacol. 50, 137-145.
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Anti-inflammatory |
Safflor yellow (25 and 50 mg/kg, intraperitoneal) |
Rats of pulmonary fibrosis induced by bleomycin (in vivo) |
(a) Alleviate the loss in bodyweight, the increase of hydroxyproline content in the lung tissues and pathologic changes of pulmonary fibrosis (b) Prevent the increase of a α-SMA positive cells and TGF-b b1 expression |
Wang et al. (2011aWang, L., Jin, M., Zang, B.X., Wu, Y., 2011a. Inhibitory effect of safflor yellow on pulmonary fibrosis. Biol. Pharm. Bull. 34, 511-516.
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b)Wang, X.H., Qin, Y.L., Yan, T., 2011b. Pharmacological research progress of Honghua injection. Acta Chin. Med. Pharmacol. 39, 109-110.
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Safflor yellow (0.05, 0.25 and 1.25 mg/ml) |
Human embryo lung fibroblast (in vitro) |
Dose-dependently inhibit the elevation of α-SMA expression and the morphological change |
Wang et al. (2011aWang, L., Jin, M., Zang, B.X., Wu, Y., 2011a. Inhibitory effect of safflor yellow on pulmonary fibrosis. Biol. Pharm. Bull. 34, 511-516.
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b)Wang, X.H., Qin, Y.L., Yan, T., 2011b. Pharmacological research progress of Honghua injection. Acta Chin. Med. Pharmacol. 39, 109-110.
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Methanol extract (10, 50 and 100 µg/ml) |
RAW 264.7 macrophages (in vitro) |
The increase HO-1 protein expression, the reduced production of NO, PGE2, iNOS and COX-2, and the inhibition of (TNF)-α-mediated VCAM-1 expression and NF-κB luciferase activity |
Jun et al. (2011)Jun, M.S., Ha, Y.M., Kim, H.S., Jang, H.J., Kim, Y.M., Lee, Y.S., Kim, H.J., Seo, H.G., Lee, J.H., Lee, S.H., Chang, K.C., 2011. Anti-inflammatory action of methanol extract of Carthamus tinctorius involves in heme oxygenase-1 induction. J. Ethnopharmacol. 133, 524-530.
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HSYA (1) (1, 4 and 16 µmol/l) |
Human alveolar epithelial A549 cells (in vitro) |
(a) Inhibit the expression of TLR-4, Myd88 ICAM-1, TNFα, IL-1β and IL-6 (b) Inhibit the phosphorylation of p38 MAPK, the adhesion of leukocytes to A549 cells and decrease NF-κB p65 nuclear translocation |
Song et al. (2013)Song, L.J., Zhu, Y., Jin, M., Zang, B.X., 2013. Hydroxysafflor yellow A inhibits lipopolysaccharide-induced inflammatory signal transduction in human alveolar epithelial A549 cells. Fitoterapia 84, 107-114.
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HSYA (1) (5 × 10-6, 10 × 10-6and 20 × 10-6 mol/l) |
Umbilical vein endothelial Eahy 926 cells (in vitro) |
Inhibit the increased expression of TLR-4, IL-6, IL-1β and TNFα |
Zhu et al. (2012)Zhu, Y., Song, L.J., Zang, B.X., Bian, B.L., Jin, M., 2012. Study of hydroxysafflow yellow A to attenuate acute lung injury model of endothenal cell inflammatory factor expression induced by LPS. J. Cardiovasc. Pulmonary Dis. 31, 484-487.
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HSYA (6, 15 and 37.5 mg/kg, i.v.) |
Mice with LPS-induced pulmonary inflammatory injury (in vivo) |
(a) Ameliorate pulmonary edema and inflammatory cell infiltration (b) Suppress p38 MAPK, NF-κB p65 activation and alter inflammatory cytokine expression (TNF-α, IL-1β, IL-6 and IL-10) |
Sun et al. (2010)Sun, C.Y., Pei, C.Q., Zang, B.X., Wang, L., Jin, M., 2010. The ability of HSYA to attenuate lipopolysaccharide-induced pulmonary inflammatory injury in mice. Phytother. Res. 24, 1788-1795.
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HSYA (1) (26.7, 40 and 60 mg/kg/day, intraperitoneal injection) |
Mice with bleomycin-induced pulmonary injury (in vivo) |
Attenuate the loss in body weight, the increase of myeloperoxidase activity and pathologic changes of pulmonary inflammation (c) Attenuate the increased expression of TNF-α, IL-1β and TGF-β1, the increased activation of NF-κB and phosphorylation of p38 MAPK |
Wu et al. (2012aWu, Z.Y., Jia, Y.L., Zhao, F.R., Li, P., Yi, Y.L., 2012a. Proliferation inhibition and induced differentiation effects of carthamin on Leukemic cells. An Hui Nong Ye Ke Xue 40, 5165-5166.
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b)>Wu, Y., Wang, L., Jin, M., Zang, B.X., 2012b. Hydroxysafflor yellow A alleviates early inflammatory response of bleomycin-induced mice lung injury. Biol. Pharm. Bull. 35, 515-522.
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Hepatoprotective effect |
HSYA (1) (5 mg/kg/day for 12 weeks, oral) |
Rats with CCl4-induced hepatic fibrosis (in vivo) |
The decrease in fibrosis and expression of α-SMA protein, MEF-2C gene, Tβ-RI, Tβ-RII, MEKK3, MEK5, and phosphorylation of ERk5 |
Zhang et al. (2011Zhang, Y.B., Guo, J., Dong, H.Y., Zhao, X.M., Fan, L., Zou, Y., Zhang, C., Li, G., Liu, J.C., Niu, Y.C., 2011. Hydroxysafflor yellow A protects against chronic carbon tetrachloride-induced liver fibrosis. Eur. J. Pharmcol. 660, 438-444.
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2012aZhang, Y.B., Dong, H.Y., Zhao, X.M., Fan, L., Zou, Y., Zhang, C., Li, G., Liu, J.C., Niu, Y.C., 2012a. Hydroxysafflor yellow A attenuates carbon tetrachloride-induced hepatic fibrosis in rats by inhibiting Erk5 signaling. Am. J. Chin. Med. 40, 481-494.
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b>Zhang, X.L., Cheng, X., Liu, Y., Shi, X.K., 2012b. Effects of safflower polysaccharide on gene transcription and protein express on of Bcl-2 and Bax in human hepatocarcinoma cell line SMMC-7721. Chin. J. Exp. Tradit. Med. Form. 18, 239-244.
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c)Zhang, L., Yue, Y.H., Chen, Y.C., Yang, G.Z., Li, X.R., 2012c. Study on the type I allergic reaction of safflower injection. Chin. Hosp. Pharm. J. 32, 1319-1321.
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HSYA (1) (10 mg/kg, intraperitoneal injection) |
Rats with hepatic fibrosis induced by oxidative stress (in vivo) |
(a) Increase the activities of antioxidant enzymes and reduce α-SMA level. (b) Up-regulating the expression of PPARr and MMP-2, and down regulating the expression of TGF-β1 and TIMP-1 |
Wan et al. (2013)Wan, L.W., Tan, L., Wang, Z.R., Liu, S.X., Wang, Y.L., Liang, S.Y., Zhong, J.B., Lin, H.S., 2013. Preventive and therapeutic effects of Danhong injection on lipopolysaccharide induced acute lung injury in mice. J. Ethnopharmacol. 149, 352-359.
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Carthamus red (5, 10 and 20 mg/kg, oral) |
Rats with CCl4-induced hepatic fibrosis (in vivo) |
(a) Lower the serum levels of ALT, AST, ALP and total protein in liver damage rat models (b) Up-regulate Nrf2, GSTα and NQO1 expressions were at the protein level (c) Elevate the activities of antioxidant enzymes and level of GSH and lessen the content of TBARS compared to silymarin |
Wu et al. (2013)Wu, S.C., Yue, Y., Tian, H., Li, Z.K., Li, X.F., He, W., Ding, H., 2013. Carthamus red from Carthamus tinctorius L. exerts antioxidant and hepatoprotective effect against CCl4-induced liver damage in rats via the Nrf2 pathway. J. Ethnopharmacol. 148, 570-578.
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