ArticleMolecules (Basel, Switzerland)2020
Costunolide Plays an Anti-Neuroinflammation Role in Lipopolysaccharide-Induced BV2 Microglial Activation by Targeting Cyclin-Dependent Kinase 2.
Article in Molecules (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- [Paeoniflorin alleviates cancer-related fatigue during chemotherapy for breast cancer by targeting EZH2/CCNE1 to regulate cell cycle and inflammatory microenvironment].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Recent advances in proteomic strategies for target identification of traditional Chinese medicine.Journal of pharmaceutical analysis · 2026Review
- Inhibition of Neuroinflammation by Costunolide Attenuates Hypoxic-Ischemic Brain Damage via the PI3K/AKT Pathway in Neonatal Rats.Molecular neurobiology · 2025Article
- Small-molecule probes based on natural products: Elucidation of drug-target mechanisms in stroke.Journal of pharmaceutical analysis · 2025Review
- Costunolide normalizes neuroinflammation and improves neurogenesis deficits in a mouse model of depression through inhibiting microglial Akt/mTOR/NF-κB pathway.Acta pharmacologica Sinica · 2025Article
- Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural-Mesenchymal Transition.Biomedicines · 2025Review
- Review
- Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking.World journal of clinical cases · 2024Article
- Effects of Lactobacillus-fermented low-protein diets on the growth performance, nitrogen excretion, fecal microbiota and metabolomic profiles of finishing pigs.Scientific reports · 2024Article
- Costunolide alleviates hyperglycaemia-induced diabetic cardiomyopathy via inhibiting inflammatory responses and oxidative stress.Journal of cellular and molecular medicine · 2023Article
- Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases.Acta pharmaceutica Sinica. B · 2023Article
- An update of label-free protein target identification methods for natural active products.Theranostics · 2022Review
- Back to the Roots-An Overview of the Chemical Composition and Bioactivity of Selected Root-Essential Oils.Molecules (Basel, Switzerland) · 2021Review
- Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2021Article
- Mogroside V Alleviates Lipopolysaccharide-Induced Neuroinflammation via Inhibition of TLR4-MyD88 and Activation of AKT/AMPK-Nrf2 Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer.Frontiers in cell and developmental biology · 2021Article
- A study on comprehensive bibliometric analysis of natural medicines for Alzheimer's disease (1999-2025).Journal of Alzheimer's disease reportsReview
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Hyperactivation of microglia in the brain is closely related to neuroinflammation and leads to neuronal dysfunction. Costunolide (CTL) is a natural sesquiterpene lactone with wide pharmacological activities including anti-inflammation and antioxidation. In this study, we found that CTL significantly inhibited the production of inflammatory mediators including nitric oxide, IL-6, TNF-α, and PGE2 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Moreover, CTL effectively attenuated IKKβ/NF-κB signaling pathway activation. To identify direct cellular target of CTL, we performed high-throughput reverse virtual screening assay using scPDB protein structure library, and found cyclin-dependent kinase 2 (CDK2) was the most specific binding protein for CTL. We further confirmed the binding ability of CTL with CDK2 using cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assays. Surface plasmon resonance analysis also supported that CTL specifically bound to CDK2 with a dissociation constant at micromole level. Furthermore, knocking down CDK2 obviously reversed the anti-inflammation effect of CTL via AKT/IKKβ/NF-κB signaling pathway on BV-2 cells. Collectively, these results indicate that CTL inhibits microglia-mediated neuroinflammation through directly targeting CDK2, and provide insights into the role of CDK2 as a promising anti-neuroinflammation therapeutic target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.