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

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), IK_Ca and SK_Ca 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
• ischaemic stroke
• cerebral vasodilation

Author contributions

Jun Han designed the study and drafted the manuscript. Lei Shi and Chenchen Jiang coordinated the experiments. Yuxiang He, Hanghang Xu, Xuebin Shen and Jiajun Lu conducted the animal studies. Xiuyun Yin participated in the data analyses. Zhuo Chen, Di Cao and Xuefeng Hou were involved in the discussion of the experiments and drafts of the manuscript. All authors have read and approved the final manuscript. All data were generated in-house and no paper mill was used. All authors agree to be accountable for all aspects of the work, thus ensuring its integrity and accuracy.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analysed during this study are included in the manuscript.

Additional information

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].