ArticleFrontiers in pharmacology2020
Icariside II, a PDE5 Inhibitor, Suppresses Oxygen-Glucose Deprivation/Reperfusion-Induced Primary Hippocampal Neuronal Death Through Activating the PKG/CREB/BDNF/TrkB Signaling Pathway.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 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
- Icariside II in Neurological Disorders: Mechanistic Insights Into Alzheimer's Disease, Cerebral Ischemia and Parkinson's Disease.Journal of biochemical and molecular toxicology · 2026Review
- Pathological mechanisms and therapeutic potential of MSC-Exos in ischemic stroke management.Stem cell research & therapy · 2026Review
- Endothelial C-type natriuretic peptide/guanylyl cyclase-B signaling prevents pulmonary arterial hypertension.Nature communications · 2026Article
- Review
- GATA1-mediated macrophage polarization via TrkB/cGMP-PKG signaling pathway to promote the development of preeclampsia.European journal of medical research · 2025Article
- Pharmacological and Therapeutic Potential of a Natural Flavonoid Icariside II in Human Complication.Current drug targets · 2025Review
- Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function.Experimental and therapeutic medicine · 2024Article
- Neurotrophic Natural Products.Progress in the chemistry of organic natural products · 2024Article
- Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2023Review
- Photobiomodulation treatment inhibits neurotoxic astrocytic polarization and protects neurons in in vitro and in vivo stroke models.Neurochemistry international · 2023Article
- Article
- How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme.Pharmacological reports : PR · 2022Review
- Icariside II Attenuates Methamphetamine-Induced Neurotoxicity and Behavioral Impairments via Activating the Keap1-Nrf2 Pathway.Oxidative medicine and cellular longevity · 2022Article
- The mitochondrial regulator PGC1α is induced by cGMP-PKG signaling and mediates the protective effects of phosphodiesterase 5 inhibition in heart failure.FEBS letters · 2022Article
- TPPU Downregulates Oxidative Stress Damage and Induces BDNF Expression in PC-12 Cells.Computational and mathematical methods in medicine · 2022Article
- Trilobatin, a Naturally Occurring Food Additive, Ameliorates Exhaustive Exercise-Induced Fatigue in Mice: Involvement of Nrf2/ARE/Ferroptosis Signaling Pathway.Frontiers in pharmacology · 2022Article
- Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIschemic stroke remains the leading cause of death and adult disability. Cerebral ischemic/reperfusion (I/R) injury is caused by ischemic stroke thereafter aggravates overwhelming neuronal apoptosis and even the death of neurons. Of note, hippocampus is more susceptive to cerebral I/R injury than the other brain region. This study was designed to explore the effects and mechanism of icariside II (ICS II), a pharmacologically active compound exists in herbal
methodsEffects of ICS II on primary hippocampal neuronal impairment and apoptosis induced by OGD/R were examined by MTT, lactate dehydrogenase (LDH) release, TUNEL staining, and flow cytometry, respectively. Activation of memory-related signaling pathways was measured using Western blot analysis. The direct interaction between ICS II and PDE5 was further evaluated by molecular docking.
resultsICS II (12.5, 25, 50 μM) markedly abrogated OGD/R-induced hippocampal neuronal death as suggested by the increase in neurons viability and the decrease in cellular LDH release. Furthermore, ICS II not only effectively decreased the protein expression and activity of PDE5, restored the 3'5'-cyclic guanosine monophosphate (cGMP) level and its downstream target protein kinase G (PKG) activity but also increased the phosphorylation of cAMP response element binding protein (CREB) level, expressions of brain derived neurotrophic factor (BDNF), and tyrosine protein kinase B (TrkB). Mechanistically, the inhibitory effects of ICS II were abrogated by Rp-8-Br-cGMP (a PKG inhibitor) or ANA-12 (a TrkB inhibitor), which further confirmed that the favorable effects of ICS II were attributed to its activation of the PKG/CREB/BDNF signaling pathways. Intriguingly, ICS II might effectively bind and inhibited PDE5 activity as demonstrated by relatively high binding scores (-6.52 kcal/mol).
conclusionsICS II significantly rescues OGD/R-induced hippocampal neuronal injury. The mechanism is, at least partly, due to inhibition of PDE5 and activation of PKG/CREB/BDNF/TrkB signaling pathway. Hence it is thought that ICS II might be a potential naturally PDE5 inhibitor to combat cerebral I/R injury.
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