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Last update 23 Jan 2025

TRPV2

Last update 23 Jan 2025

Basic Info

Synonyms

Osm-9-like TRP channel 2, OTRPC2, Transient receptor potential cation channel subfamily V member 2

+ [6]

Introduction

Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by IGF-I, PDGF and neuropeptide head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH.

Drugs associated with TRPV2

HG-1249

Target

TRPV1 x TRPV2

Mechanism

TRPV1 modulators [+1]

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Nervous System Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRPV2

100 Translational Medicine associated with TRPV2

0 Patents (Medical) associated with TRPV2

669

Literatures (Medical) associated with TRPV2

01 Feb 2025·Journal of Ethnopharmacology

Qisheng wan decoction alleviates the inflammation of CCI rats via TRP channels

Article

Author: Xiang, Chunxiao ; Li, Zaiqi ; Wei, Guihua ; Wang, Haoyan ; Yan, Zhiyong ; Wu, Yating ; Li, Xi

ETHNOPHARMACOLOGICAL RELEVANCEQisheng wan decoction (QWD), a traditional Chinese medicine, has promising potential anti-inflammatory effects against neuropathic pain (NP). However, its valid ingredients and specific anti-inflammatory mechanisms are still unclear.AIM OF THE STUDYThis study aimed to identify the active ingredients of QWD responsible for its anti-inflammatory effect by combining liquid chromatography with network pharmacology, and to explore its anti-inflammatory mechanism by chronic constriction injury (CCI) model rats.MATERIALS AND METHODSThe UHPLC-Q Exactive Orbitrap-MS technique was used to identify the active ingredients of QWD. The potential ingredients of QWD, which targeted to the pathways of treating NP, were performed by network pharmacology, molecular docking and molecular dynamics simulations. After CCI rats-induced NP model operation, QWD (5.6 g/kg/d, 11.2 g/kg/d, 22.4 g/kg/d) and Pregabalin (10 g/kg/d) as positive controls, were administered to the rats for 7 days. The behaviors of the different groups were tested at 0, 1, 3, 5, 7, 12 days, respectively. And the inflammatory factor including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was detected by ELISA. Meantime, the inflammation of the sciatic nerve was evaluated by the hematoxylin-eosin staining. Ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) were detected by immunohistochemistry. Moreover, the expressions of TRPA1, TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and P38 mitogen-activated protein kinase (MAPK) were tested by RT-PCR, Western blot, and immunohistochemistry.RESULTSAfter screening by the liquid chromatography and network pharmacology approach, seventy ingredients of QWD were identified, and seven core targets including oncogene tyrosine-protein kinase (SRC), mitogen-activated protein kinase 3 (MAPK3), signal transducer and activator of transcription 1 (STAT1), protein-serine-threonine kinase 1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), TNF-α, and IL-6 were confirmed. Six active ingredients exhibited binding energies less than -5 kcal/mol, and the complexes were structurally stable within 50 ns. Pathway analysis indicated that transient receptor potential (TRP) channels were mainly responsible for anti-inflammatory mediator regulation. Compared with the CCI group, the behavioral tests showed that QWD-L, QWD-M, and QWD-H group alleviated mechanical, thermal and cold hyperalgesia (p < 0.05). HE staining results found out QWD-L, QWD-M, and QWD-H group decreased the inflammation of the sciatic nerve (p < 0.05). Similarly, compared with the CCI group, the serum level of TNF-α and IL-6 of QWD groups decreased conformably (p < 0.05). This reduction was downtrend with the inhibition of Iba-1, GFAP, and the TRP channel signaling pathway and p38 MAPK.CONCLUSIONSThis study provides a primary investigation of the composition of QWD for its anti-inflammation effect and its molecular mechanism in CCI model rats. And this therapeutic efficacy of QWD was achieved by decreasing the inflammation. QWD also inhibited the level TNF-α and IL-6 and decreasing the activation of Iba-1 and GFAP in glia. And this anti-inflammation mechanism involved in inhibiting the TRPA1, TRPV1, TRPV2, TRPV4, and TRPM8 and p38 MAPK signaling pathways. These findings provide a scientific and theoretical basis for the prevention and treatment of NP with QWD.

01 Jan 2025·Journal of Ethnopharmacology

Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms

Article

Author: Zakaria, Zainul Amiruddin ; Jabbari, Sajjad ; Mohammadi, Saeed

ETHNOPHARMACOLOGICAL RELEVANCETrifolium resupinatum L. (Fabaceae), known as Persian clover, ethnomedicinally used in Persian folk medicine to treat peritoneal inflammation, rheumatism, and back pain.AIM OF THE STUDYTo investigate the antineuropathic and antinociceptive activities of Trifolium resupinatum leaves essential oil (TREO) in male Wistar rats, as well as to explore the potential mechanisms of action.MATERIALS AND METHODSThe antinociceptive activity of TREO and its main constituents, quercetin (Qc) was assessed using the formalin-induced paw licking test. Moreover, the potential mechanisms of antinociception were evaluated through various competitive and non-competitive antagonisms. Additionally, the antineuropathic potential was investigated using the cervical spinal cord hemi-contusion (CCS) model, and the role of phosphorylated Stat-3 was analyzed using Western blotting.RESULTSTREO exerted significant antinociceptive activity (P < 0.01) in both phases of the formalin-induced test; however, its effects were more pronounced in the second phase. Modulators of the NO-cGMP-K⁺ channel pathway significantly reversed the antinociceptive activity of TREO (P < 0.05). Additionally, antagonists of TRPV1 and TRPV2, as well as CB1 and GABA_A receptors, significantly reversed the antinociceptive effects of TREO (P < 0.05). In another study, both TREO and Qc significantly attenuated hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced nociception model. Notably, TREO also reduced the expression levels of interleukin-1 beta, interleukin-2, and tumor necrosis factor alpha in CCS-induced rats (P < 0.05).CONCLUSIONTREO and Qc exhibit both antinociceptive and anti-neuropathic activities. The antinociceptive effects are partially mediated through the NO-cGMP-K⁺ channel pathways, along with the activation of TRPV, GABA, and cannabinoid receptors. Furthermore, the anti-neuropathic activity of TREO may be partially regulated through the inhibition of cytokines.

01 Jan 2025·British Journal of Pharmacology

Plumbagin, a novel TRPV2 inhibitor, ameliorates microglia activation and brain injury in a middle cerebral artery occlusion/reperfusion mouse model

Article

Author: Xue, Shuwen ; Ding, Meihuizi ; Wei, Ziyi ; Zhang, Fan ; Cao, Zhengyu ; Han, Rui ; Xie, Yiming

Background and PurposeTransient receptor potential vanilloid 2 (TRPV2) is a Ca2+‐permeable non‐selective cation channel. Despite the significant roles of TRPV2 in immunological response, cancer progression and cardiac development, pharmacological probes of TRPV2 remain to be identified. We aimed to discover TRPV2 inhibitors and to elucidate their molecular mechanism of action.Experimental ApproachFluorescence‐based Ca2+ assay in HEK‐293 cells expressing murine TRPV2 was used to identify plumbagin as a novel TRPV2 inhibitor. Patch‐clamp, in silico docking and site‐directed mutagenesis were applied to investigate the molecular mechanisms critical for plumbagin interaction. ELISA and qPCR were used to assess nitric oxide release and mRNA levels of inflammatory mediators, respectively. si‐RNA interference was used to knock down TRPV2 expression, which was validated by western blotting. Neurological and histological analyses were used to examine brain injury of mice following middle cerebral artery occlusion/reperfusion (MCAO/R).Key ResultsPlumbagin is a potent TRPV2 negative allosteric modulator with an IC50 value of 0.85 μM, exhibiting >14‐fold selectivity over TRPV1, TRPV3 and TRPV4. Plumbagin suppresses TRPV2 activity by decreasing the channel open probability without affecting the unitary conductance. Moreover, plumbagin binds to an extracellular pocket formed by the pore helix and flexible loop between transmembrane helices S5 and S6 of TRPV2. Plumbagin effectively suppresses LPS‐induced inflammation of BV‐2 microglia and ameliorates brain injury of MCAO/R mice.Conclusion and ImplicationsPlumbagin is a novel pharmacological probe to study TRPV2 pathophysiology. TRPV2 is a novel molecular target for the treatment of neuroinflammation and ischemic stroke.

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TRPV2

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