ArticleScientific reports2017
Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 101 citations in OpenAlex.
- Inhibition of endolysosomal two-pore channel 2 (TPC2) induces osteoblast differentiation and matrix mineralization while targeting autophagy.Journal of endocrinological investigation · 2026Article
- Lysosomal channel TPC2 modulates microglia-endothelial signaling in choroidal angiogenesis.Angiogenesis · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Modulation of Cognitive Function by TRPM3 Channels in the Dentate Gyrus of a Menopausal Rat Model: Effects of Naringenin Treatment and Ciliary Neurotrophic Factor.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Short-Term Efficacy and Safety of Haizao Yuhu Decoction Plus Methimazole versus Methimazole Monotherapy for Graves' Disease: A Prospective Study Using Propensity Score-Matching.International journal of general medicine · 2026Article
- Polymethoxyflavones from Kaempferia parviflora stimulate melanogenesis by blocking the TPC2 channel.Scientific reports · 2025Article
- The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology.International journal of molecular sciences · 2025Review
- Article
- Inhibition of TRPM3 channels in the medial prefrontal cortex mitigates OCD symptoms following traumatic brain injury.Inflammopharmacology · 2025Article
- A Comprehensive Review of Naringenin, a Promising Phytochemical with Therapeutic Potential.Journal of microbiology and biotechnology · 2024Review
- Rab7a is an enhancer of TPC2 activity regulating melanoma progression through modulation of the GSK3β/β-Catenin/MITF-axis.Nature communications · 2024Article
- Structural basis for inhibition of the lysosomal two-pore channel TPC2 by a small molecule antagonist.Structure (London, England : 1993) · 2024Article
- Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism.Frontiers in endocrinology · 2024Article
- Spice-Derived Phenolic Compounds: Potential for Skin Cancer Prevention and Therapy.Molecules (Basel, Switzerland) · 2023Review
- Anti-cancer effect of nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line.BMC complementary medicine and therapies · 2023Article
- Conformational rearrangements in the second voltage sensor domain switch PIPProceedings of the National Academy of Sciences of the United States of America · 2023Article
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- Expanding the Toolbox: Novel Modulators of Endolysosomal Cation Channels.Handbook of experimental pharmacology · 2023Article
- The Plant Vacuole as Heterologous System to Characterize the Functional Properties of TPC Channels.Handbook of experimental pharmacology · 2023Article
- Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization:Drug delivery · 2022Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our research introduces the natural flavonoid naringenin as a novel inhibitor of an emerging class of intracellular channels, Two-Pore Channel 2 (TPC2), as shown by electrophysiological evidence in a heterologous system, i.e. Arabidopsis vacuoles lacking endogenous TPCs. In view of the control exerted by TPC2 on intracellular calcium signaling, we demonstrated that naringenin dampens intracellular calcium responses of human endothelial cells stimulated with VEGF, histamine or NAADP-AM, but not with ATP or Angiopoietin-1 (negative controls). The ability of naringenin to impair TPC2-dependent biological activities was further explored in an established in vivo model, in which VEGF-containing matrigel plugs implanted in mice failed to be vascularized in the presence of naringenin. Overall, the present data suggest that naringenin inhibition of TPC2 activity and the observed inhibition of angiogenic response to VEGF are linked by impaired intracellular calcium signaling. TPC2 inhibition is emerging as a key therapeutic step in a range of important pathological conditions including the progression and metastatic potential of melanoma, Parkinson's disease, and Ebola virus infection. The identification of naringenin as an inhibitor of TPC2-mediated signaling provides a novel and potentially relevant tool for the advancement of this field of research.
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