Hydroxysafflor Yellow A Protects Against Cerebral Ischemia–Reperfusion Injury by Anti-apoptotic Effect Through PI3K/Akt/GSK3β Pathway in Rat

Chen, Lin; Xiang, Yuzhi; Kong, Lingjun; Zhang, Xiumei; Sun, Bo; Wei, Xinbing; Liu, Huiqing

doi:10.1007/s11064-013-1135-8

Cited by 87 publications

(72 citation statements)

References 31 publications

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“…The ability of HSYA to increase Ang 1 expression may be a mechanism by which HSYA protects cells from the effects of various injuries, such as ischemia [35,47], hypoxia [18,24], and methylglyoxal exposure [48], by inhibiting apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway

Chen¹,

Chen

Pang

et al. 2016

J Vasc Res

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Background: The flowers of Carthamus tinctorius L. are widely used in traditional Chinese medicine to treat cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA), the main constituent of C. tinctorius L. flowers, is known for its multiple biological activities. The present study investigated the effects of HSYA on angiogenesis in vitro and in a mouse hindlimb ischemia model. Methods: Using human umbilical vein endothelial cells (HUVEC) in vitro and a mouse hindlimb ischemia model in vivo, the angiogenic role of HSYA was evaluated. Results: HSYA significantly increased the capillary-like tube formation and migration of HUVEC. HSYA not only induced a rise in the expression of angiopoietin 1 and Tie-2 but it also increased phosphorylation of Tie-2, Akt, and extracellular signal-regulated kinase 1/2. Furthermore, an anti-Tie-2 neutralizing antibody significantly inhibited HSYA-induced HUVEC tube formation and migration. In vivo, the recovery of perfusion of ischemic hindlimb tissue after femoral artery interruption was significantly increased in HSYA-treated mice compared to vehicle controls. Consistent with these results, the arteriole and capillary densities in ischemic gastrocnemius muscles were significantly increased in HSYA-treated mice. Conclusions: These results indicate the potential utility of HSYA for the treatment of ischemic diseases.

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Section: Discussionmentioning

confidence: 99%

Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway

Chen¹,

Chen

Pang

et al. 2016

J Vasc Res

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“…Studies showed that HSYA plays a protective role in animal models of pulmonary inflammatory injury [19, 20], cardiac failure [21, 22], and liver fibrosis [23, 24]. HSYA features extreme neuroprotection in animal models of acute and chronic central nervous system (CNS) injuries, including spinal cord ischemia, ischemia-reperfusion injury [17, 25, 26], and Parkinson’s disease [27]. Accumulated data suggest that HSYA can cure CNS lesions through mechanisms involving anti-inflammation and anti-oxidation.…”

Section: Introductionmentioning

confidence: 99%

HSYA alleviates secondary neuronal death through attenuating oxidative stress, inflammatory response, and neural apoptosis in SD rat spinal cord compression injury

Pei¹,

Fan²,

Nan³

et al. 2017

J Neuroinflammation

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BackgroundHydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo. However, underlying mechanism of HSYA is not fully elucidated. The present study investigated the protective effects of HSYA in rat spinal cord compression injury model and related mechanisms involved.MethodsSprague–Dawley rats were divided as Sham, Control, and HSYA groups (n = 30 per group). Spinal cord injury (SCI) model was induced by application of vascular clips (force of 50 g, 1 min) to the dura at T9–T10 level of vertebra. Injured animals were administered with either HSYA (8 mg/kg at 1 and 6 h after injury, then 14 mg/kg, for a total of 7 days at 24-h time intervals) or equal volume of saline by intraperitoneal injection.ResultsFrom this experiment, we discovered that SCI in rats resulted in severe trauma, which is characterized by tissue damage, lipid peroxidation, neutrophil infiltration, inflammation mediator release, and neuronal apoptosis. However, HSYA treatment significantly reduced the following: (1) degree of tissue injury (histological score) and edema; (2) neutrophil infiltration (myeloperoxidase activity); (3) oxidative stress (superoxide dismutase, malondialdehyde, and nitric oxide); (4) pro-inflammatory cytokine expression (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2); (5) nuclear factor-κB activation; (6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining and cysteine-aspartic protease-3 activity). Moreover, in a separate set of experiments, we clearly demonstrated that HSYA treatment significantly ameliorated recovery of limb function (as evaluated by Basso, Beattie, and Bresnahan behavioral recovery scores).ConclusionsTreatment with HSYA restrains development of oxidative stress, inflammation response, and apoptotic events associated with SCI of rats, demonstrating that HSYA is a potential neuroprotectant for human SCI therapy.

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“…Wortmannin is a specific PI3K inhibitor, which was widely used to study the PI3K/Akt signal pathway (39,40). We also used wortmannin in our study to further examine whether 4-MCPC produces neuroprotective effects by activating the PI3K/Akt signal pathway.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of 4-Methylcyclopentadecanone on Focal Cerebral Ischemia/Reperfusion Injury in Rats

Zhang³

et al. 2014

J Pharmacol Sci

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Abstract. The present study aimed to investigate the effect of 4-methylcyclopentadecanone (4-MCPC) on local cerebral ischemia-reperfusion and the possible mechanisms involved. For this purpose, the focal cerebral ischemia rat model was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (4 or 8 mg·kg −1 , p.o.) just 0.5 h before reperfusion. The neurological deficit scores and the ischemic infarct volume were recorded 24 h after the MCAO. In addition, the number of apoptotic cells was measured by TUNEL assay, and the expression of apoptosis-regulatory proteins and the PI3K/Akt neuroprotective signaling pathway were investigated by western blotting. Our results indicated that 4-MCPC (4 or 8 mg·kg −1 ) remarkably alleviated cerebral I/R injury by decreasing infarct volume and neurological deficit scores. 4-MCPC also decreased the number of apoptotic cells, regulated the expression of Bcl-2 and Bax, and increased the ratio of Bcl-2/Bax. Further study revealed that 4-MCPC treatment also increased the level of p-Akt and p-GSK-3b. Wortmannin (PI3K inhibitor) markedly abolished the effects of 4-MCPC. Taken together, our results suggest that 4-MCPC protects against cerebral I/R injury through the inhibition of apoptosis, and this neuroprotective effect may be partly related to the activation of the PI3K/Akt signal pathway.

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Hydroxysafflor Yellow A Protects Against Cerebral Ischemia–Reperfusion Injury by Anti-apoptotic Effect Through PI3K/Akt/GSK3β Pathway in Rat

Cited by 87 publications

References 31 publications

Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway

Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway

HSYA alleviates secondary neuronal death through attenuating oxidative stress, inflammatory response, and neural apoptosis in SD rat spinal cord compression injury

Neuroprotective Effect of 4-Methylcyclopentadecanone on Focal Cerebral Ischemia/Reperfusion Injury in Rats

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