Dl-3-n-butylphthalide promotes angiogenesis in ischemic stroke mice through upregulating autocrine and paracrine sonic hedgehog

Dai, Meijie; Gui, Xingxing; Jia, Sujuan; Dou, Haoran; Cui, Wei

doi:10.1038/s41401-023-01137-z

Cited by 7 publications

(2 citation statements)

References 65 publications

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“…The tMCAO procedure was carried out in accordance with the methods described previously 29 . To mitigate the influence of hormonal disturbances in female mice post-tMCAO surgery: only male mice were studied.…”

Section: Methodsmentioning

confidence: 99%

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Zheng,

Zhu,

Qiu

et al. 2024

Sci Rep

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Blood–brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.

show abstract

Section: Methodsmentioning

confidence: 99%

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Zheng,

Zhu,

Qiu

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The tMCAO procedure was carried out in accordance with the methods described previously. 15 . To mitigate the in uence of hormonal disturbances in female mice post-tMCAO surgery, only male mice were studied.…”

Section: Establishment Of the Transient Middle Cerebral Artery Occlus...mentioning

confidence: 99%

Neferine inhibits BMECs pyroptosis and maintains blood-brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Zheng,

Zhu,

Qiu

et al. 2024

Preprint

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Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.

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Efficacy and safety of DL‐3‐N‐butylphthalide in the treatment of ischemic poststroke aphasia: A randomized clinical trial

Tian,

Yang,

Yang

et al. 2024

Ann Clin Transl Neurol

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ObjectivePoststroke aphasia (PSA) has a high prevalence and requires a long recovery period, severely impairing life and work. Its existing behavioral interventions, principally speech and language therapy, are limited by numerous factors. The aims of this study are to evaluate the efficacy and safety of DL‐3‐N‐butylphthalein (NBP) and explore its mechanism in the treatment of ischemic PSA.MethodsPatients hospitalized in the Second Hospital of Hebei Medical University in China were randomly administered NBP soft capsules or placebo orally for 6 months from July 1, 2021, to February 25, 2023. Language skills were assessed using the Western Aphasia Battery‐Aphasia Quotient (WAB‐AQ). We collected plasma samples and detected neurotransmitters by liquid chromatography‐mass spectrometry.ResultsIn total, 118 out of 124 patients were included in the outcome analysis. Compared with the control group, AQ values in the NBP group significantly improved at 6 months (U = 1187.5, p = 0.003). After eliminating baseline interference, NBP treatment was independently associated with the 6‐month AQ improvement [mean difference (MD) 0.106, 95% confidence interval (CI) 0.018, 0.195, p = 0.019]. We observed no statistically significant difference between the groups in abnormal liver function at 1 month [relative risk (RR) 1.07, 95% CI 0.89, 1.28] and 6 months [RR 0.99, 95% CI 0.86, 1.42]. Statistically significant differences were observed in tyrosine (p = 0.043) and 5‐hydroxytryptophan (p = 0.041) between the two groups.InterpretationNBP treatment might promote the recovery of WAB‐AQ in patients with ischemic PSA by increasing levels of monoamine neurotransmitters.

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Dl-3-n-butylphthalide promotes angiogenesis in ischemic stroke mice through upregulating autocrine and paracrine sonic hedgehog

Cited by 7 publications

References 65 publications

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Neferine inhibits BMECs pyroptosis and maintains blood-brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α

Efficacy and safety of DL‐3‐N‐butylphthalide in the treatment of ischemic poststroke aphasia: A randomized clinical trial

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