Neuroprotective effect of Buyang Huanwu Decoction against focal cerebral ischemia/reperfusion injury in rats – Time window and mechanism

Zhao, Liandong; Wang, Jianhua; Jin, Guoxi; Zhao, Ying; Zhang, Haijun

doi:10.1016/j.jep.2012.01.026

Cited by 59 publications

(44 citation statements)

References 28 publications

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“…BYHWD augmented this effect, which was in accordance with the theory of Chinese Medicine and provided more evidence for elucidating its mechanisms of anti-cerebral ischemia. However, certain investigators have reported that the effect of BYHWD on decreasing glutamate peaked at 3 h after administration (6,7), but there should be other mechanisms, as BYHWD absorption and changes of protein expression possibly require a longer period of time. Although upregulation of GLT-1 and GS in the present study did not appear earlier to prevent ischemic injury efficiently, they could be beneficial for subsequent strokes, later regeneration and functional restoration, as GLT-1 was reported to be involved in synaptic plasticity and associative fear memory (23).…”

Section: Discussionmentioning

confidence: 99%

“…The neuroprotective effects of BYHWD following ischemia are involved in multiple pathways, such as reducing the infarct volume (2), decreasing apoptotic cells (3), inhibiting the oxidative stress/nitration stress reaction (4) and stimulating neural proliferation (5). Recent studies showed that BYHWD greatly suppressed the level of glutamate (6,7); however, the potential mechanisms are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Buyang Huanwu decoction increases the expression of glutamate transporter-1 and glutamate synthetase in association with PACAP-38 following focal ischemia

Ding

Liu

et al. 2015

Biomedical Reports

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Abstract. The neuroprotective role of Buyang Huanwu decoction (BYHWD) in focal ischemia is associated with decreasing glutamate concentration. However, the mechanisms are not fully understood. The present study aimed to explore whether glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) participated in the decreased level of glutamate and whether pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) was involved in this process. BYHWD was found to significantly upregulate the expression of GLT-1 and GS in the hippocampal CA1 area compared to the ischemia group, with the difference on day 3 being most significant. BYHWD increased the level of PACAP-38, and PACAP-(6-38) (PACAP receptor antagonist) significantly attenuated the effect of BYHWD on GLT-1 and GS, suggesting that PACAP-38 was involved in the upregulation of GLT-1 and GS induced by BYHWD. In addition, as GLT-1 and GS are mainly located in astrocytes, the changes of astrocytes were detected by glial fibrillary acidic protein (GFAP; an astrocytic marker) immunostaining. The results showed that BYHWD inhibited the expression of GFAP compared with the ischemia group, however, co-administration with PACAP-(6-38), which inhibited the effect of BYHWD on GLT-1 and GS in astrocytes, attenuated this effect, indicating that astrocytes participated in the protective role of BYHWD following focal ischemia. These results provided the evidence for the first time that not only neurons but also astrocytes contribute to the protective role of BYHWD, which opposes previous studies and may be a starting point for traditional medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Buyang Huanwu decoction increases the expression of glutamate transporter-1 and glutamate synthetase in association with PACAP-38 following focal ischemia

Ding

Liu

et al. 2015

Biomedical Reports

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“…Many investigations showed the neuroprotective effects of BYHWD against cerebral ischaemiareperfusion injury (Cai et al, 2007;Wang et al, 2011;Zhao et al, 2012). The neuroprotection of BYHWD may involve different mechanisms, including increased nerve proliferation (Cai et al, 2007), improved nerve regeneration (Li et al, 2003), reduced inflammatory cytokine and neuronal apoptosis (Chen et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanisms of this drug for stroke treatment are still unclear. Recent investigations showed its neuroprotective effects and mechanisms against cerebral ischaemia-reperfusion injury (Cai et al, 2007;Wang et al, 2011;Zhao et al, 2012). However, few studies have been performed to promote angiogenesis with BYHWD treatment, and the mechanisms of this drug for angiogenesis are unknown.…”

Section: Introductionmentioning

confidence: 99%

Buyang Huanwu decoction increases angiopoietin-1 expression and promotes angiogenesis and functional outcome after focal cerebral ischemia

Shen

Zhu

Hai

et al. 2014

J. Zhejiang Univ. Sci. B

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Buyang Huanwu decoction (BYHWD), a traditional Chinese herbal prescription, has been widely used clinically to treat stroke in China for hundreds of years; however, the mechanisms of this drug for stroke treatment are still unclear. This study aims to observe the cerebral angiogenesis effects of BYHWD on chronic brain injury after focal cerebral ischemia in rats and to explore its possible mechanisms. The ischemia was induced by occlusion of the right middle cerebral artery for 90 min. BYHWD (12.5 and 25.0 g/(kg·d), equivalent to the dry weight of the raw materials) was orally administered twice a day beginning 2 h after surgery. BYHWD significantly attenuated the neurological dysfunction, infarct volume, and brain atrophy after ischemia. There was a significant increase in the microvessel density, as assessed by immunofluorescence CD31, and a significant increase in angiopoietin-1 (Ang-1) in the penumbra areas of the rats was shown by immunohistochemical staining and Western blotting. The results indicate that the neurorestorative effects of BYHWD are associated with angiogenesis and the enhancement of the expressions of Ang-1 on chronic brain injury after focal cerebral ischemia.

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“…BYHWD is a traditional Chinese herbal medicine that is used to treat SCI. Its neuroprotective effects have been demonstrated in cerebral ischemia-reperfusion injury, 28,29 and may involve a number of mechanisms, including increased nerve proliferation, improved nerve regeneration, and reduced inflammatory cytokine and neuronal apoptosis. 30 These mechanisms are strongly associated with the pathophysiology and clinical outcome of the acute and subacute phases of cerebral ischemia.…”

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confidence: 99%

Neuroprotective effects of the Buyang Huanwu decoction on functional recovery in rats following spinal cord injury

Dong

Gao

2014

The Journal of Spinal Cord Medicine

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Background: The Buyang Huanwu decoction (BYHWD) is a traditional Chinese herbal prescription and has been used in China to treat spinal cord injury (SCI) for hundreds of years. Clinical trials have shown that BYHWD improves the outcome of SCI in clinical trials, but the mechanisms are not known. This study observed the neuroprotective effects of BYHWD on spinal nerve cells after SCI and investigated possible mechanisms. Materials and methods: Forty female Wistar rats were randomized equally to four groups treated by sham injury, SCI, BYHWD, or methylprednisolone (MP). The Basso, Beattie, and Bresnahan (BBB) score was used to evaluate hind-limb locomotor function. Neuron apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining and caspase-3, Bax, and Bcl-2 mRNA and protein expression were evaluated by real-time quantitative polymerase chain reaction and Western blotting, respectively. Results: In the sham group, walking was mildly abnormal after anesthesia but recovered completely in 2 days. The BBB score in the SCI model group was significantly different from that in the sham group. The BBB scores of rats in both the BYHWD and MP groups were significantly higher than scores of rats in the SCI group. BYHWD had an antiapoptosis effect, as shown by significant decreases in expression of caspase-3 and Bax and increase in Bcl-2 expression. Conclusion: BYHWD treatment restored hind-limb motor function of rats with SCI. The neuroprotective effect of BYHWD was associated with modulation of the expression of apoptosis-related proteins.

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Neuroprotective effect of Buyang Huanwu Decoction against focal cerebral ischemia/reperfusion injury in rats – Time window and mechanism

Cited by 59 publications

References 28 publications

Buyang Huanwu decoction increases the expression of glutamate transporter-1 and glutamate synthetase in association with PACAP-38 following focal ischemia

Buyang Huanwu decoction increases the expression of glutamate transporter-1 and glutamate synthetase in association with PACAP-38 following focal ischemia

Buyang Huanwu decoction increases angiopoietin-1 expression and promotes angiogenesis and functional outcome after focal cerebral ischemia

Neuroprotective effects of the Buyang Huanwu decoction on functional recovery in rats following spinal cord injury

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