Hyperoside ameliorates cerebral ischaemic-reperfusion injury by opening the TRPV4 channel in vivo through the IP3-PKC signalling pathway

Pharm Biol. 2023 Dec;61(1):1000-1012. doi: 10.1080/13880209.2023.2228379.

Abstract

Context: Hyperoside (Hyp), one of the active flavones from Rhododendron (Ericaceae), has beneficial effects against cerebrovascular disease. However, the effect of Hyp on vasodilatation has not been elucidated.

Objective: To explore the effect of Hyp on vasodilatation in the cerebral basilar artery (CBA) of Sprague-Dawley (SD) rats suffering with ischaemic-reperfusion (IR) injury.

Materials and methods: Sprague-Dawley rats were randomly divided into sham, model, Hyp, Hyp + channel blocker and channel blocker groups. Hyp (50 mg/kg, IC50 = 18.3 μg/mL) and channel blocker were administered via tail vein injection 30 min before ischaemic, followed by 20 min of ischaemic and 2 h of reperfusion. The vasodilation, hyperpolarization, ELISA assay, haematoxylin-eosin (HE), Nissl staining and channel-associated proteins and qPCR were analysed. Rat CBA smooth muscle cells were isolated to detect the Ca2+ concentration and endothelial cells were isolated to detect apoptosis rate.

Results: Hyp treatment significantly ameliorated the brain damage induced by IR and evoked endothelium-dependent vasodilation rate (47.93 ± 3.09% vs. 2.99 ± 1.53%) and hyperpolarization (-8.15 ± 1.87 mV vs. -0.55 ± 0.42 mV) by increasing the expression of IP3R, PKC, transient receptor potential vanilloid channel 4 (TRPV4), IKCa and SKCa in the CBA. Moreover, Hyp administration significantly reduced the concentration of Ca2+ (49.08 ± 7.74% vs. 83.52 ± 6.93%) and apoptosis rate (11.27 ± 1.89% vs. 23.44 ± 2.19%) in CBA. Furthermore, these beneficial effects of Hyp were blocked by channel blocker.

Discussion and conclusions: Although Hyp showed protective effect in ischaemic stroke, more clinical trial certification is needed due to the difference between animals and humans.

Keywords: Traditional Chinese medicine; cerebral vasodilation; ischaemic stroke.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Brain Ischemia* / drug therapy
  • Endothelial Cells
  • Humans
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / prevention & control
  • Stroke* / metabolism
  • TRPV Cation Channels / metabolism
  • Vasodilation

Substances

  • TRPV Cation Channels
  • hyperoside
  • Antineoplastic Agents
  • TRPV4 protein, human

Grants and funding

This work was supported by the National Natural Science Foundation of China [Grant No. 81173596], the Major Project of Natural Science Foundation of the Department of Education of Anhui Province [Grant No. KJ2019ZD32], the Key Project of the Natural Science Foundation of the Department of Education of Anhui Province [Grant No. KJ2015A157] and the Academic Support Project for Top-Notch Talents in Disciplines (Majors) of Universities in Anhui Province [gxbjZD2022043].