ArticleActa pharmacologica Sinica2020
Icariside II attenuates cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction in rats via regulating the balance of MMP9/TIMP1.
Article in Acta pharmacologica Sinica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Pharmacological mechanism and therapeutic efficacy of Icariside II in the treatment of acute ischemic stroke: a systematic review and network pharmacological analysis.BMC complementary medicine and therapies · 2022Pooled it
- Neuroprotective effect of 3',4'-dihydroxyflavonol on blood-brain barrier ıntegrity and matrix remodeling in rats with transient bilateral carotid occlusion-ınduced ıschemia-reperfusion.Journal of bioenergetics and biomembranes · 2026Article
- Icariside II in Neurological Disorders: Mechanistic Insights Into Alzheimer's Disease, Cerebral Ischemia and Parkinson's Disease.Journal of biochemical and molecular toxicology · 2026Review
- Actin polymerization drives endogenous MMP-9 upregulation and blood-brain barrier disruption in ischemic brain endothelial cells.Molecular and cellular biochemistry · 2026Article
- LncRNA-XIST Competitively Binds to MicroRNA-532-5p to Regulate PTEN Expression, Exacerbating Cerebral Ischemia-Reperfusion Injury.Advanced biology · 2026Article
- Endothelialized human umbilical cord mesenchymal stem cell-derived exosomes enhances angiogenesis and stabilizes the blood-spinal cord barrier after spinal cord injury.Journal of nanobiotechnology · 2026Article
- Neuroprotective mechanisms of cobalamin in ischemic stroke insights from network pharmacology and molecular simulations.Scientific reports · 2026Article
- L-Borneolum Attenuates Ischemic Stroke Through Remodeling BBB Transporter Function via Regulating MFSD2A/Cav-1 Signaling Pathway.Brain sciences · 2026Article
- Huazhuo Decoction Contributes to Immune Homeostasis and Attenuates Neuronal Inflammation and Demyelination in a Mouse Model of Multiple Sclerosis.Journal of inflammation research · 2026Article
- Verification of the predictive value of EV-associated biomarkers MMP9 and CEACAM1 in rehabilitation of ischemic stroke.Extracellular vesicles and circulating nucleic acids · 2026Article
- Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis.Journal of advanced research · 2025Article
- Synergistic Neuroprotection of Artesunate and Tetramethylpyrazine in Ischemic Stroke, Mechanisms of Blood-Brain Barrier Preservation.International journal of molecular sciences · 2025Article
- TIMP1 promotes microglia M2 polarization through MAPK pathway to ameliorate early brain injury after ischemia.Hereditas · 2025Article
- Upregulation of C1QC as a Mediator of Blood-Brain Barrier Damage in Type 2 Diabetes Mellitus.Molecular neurobiology · 2025Article
- Elucidating the Mechanism of Jisheng Shenqi Pills in the Treatment of Diabetic Kidney Disease: Network Pharmacology Combined with Experimental Verification.Endocrine, metabolic & immune disorders drug targets · 2025Article
- Pharmacological and Therapeutic Potential of a Natural Flavonoid Icariside II in Human Complication.Current drug targets · 2025Review
- TIMP1 protects against blood-brain barrier disruption after subarachnoid haemorrhage by inhibiting ubiquitination of astrocytic β1-integrin.Stroke and vascular neurology · 2024Article
- Transcription Factor TFAP2B Exerts Neuroprotective Effects Targeting BNIP3-Mediated Mitophagy in Ischemia/Reperfusion Injury.Molecular neurobiology · 2024Article
- Association between TIMP1 polymorphism and female neuromyelitis optica spectrum disorder in Chinese population.Heliyon · 2024Article
- Gallic acid pretreatment mitigates parathyroid ischemia-reperfusion injury through signaling pathway modulation.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood-brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which is derived from Herba Epimedii, attenuates cerebral I/R injury by inhibiting the GSK-3β-mediated activation of autophagy both in vitro and in vivo. However, the effect of ICS II on the BBB remains unclear. Thus, in this study, we investigated the regulation of BBB integrity by ICS II after cerebral I/R injury and further explored the underlying mechanism in rats. Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO), and the treatment groups were administered ICS II at a dose of 16 mg/kg by gavage twice a day for 3 days. The results showed that ICS II effectively prevented BBB disruption, as evidenced by Evans Blue staining. Moreover, ICS II not only significantly reduced the expression of MMP2/9 but also increased TIMP1 and tight junction protein (occludin, claudin 5, and ZO 1) expression. Intriguingly, ICS II may directly bind to both MMP2 and MMP9, as evidenced by molecular docking. In addition, ICS II also inhibited cerebral I/R-induced apoptosis and ameliorated the Bax/Bcl-2 ratio and cleaved-caspase 3 level. Collectively, our findings reveal that ICS II significantly ameliorates I/R-induced BBB disruption and neuronal apoptosis in MCAO rats by regulating the MMP9/TIMP1 balance and inhibiting the caspase 3-dependent apoptosis pathway.
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