Research Article: Effects of icariside II on brain tissue oxidative stress and Nrf2/HO-1 expression in rats with cerebral ischemia-reperfusion injury1

Date Published: February 28, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em
Cirurgia

Author(s): Yan Li, Fanjun Meng.

http://doi.org/10.1590/s0102-8650201900208

Abstract

To investigate the effects of icariside II on brain tissue oxidative stress
and Nrf2/HO-1 expression in rats with cerebral ischemia-reperfusion injury
(CIRI).

One hundred SD rats were randomly divided into sham-operated, model, and 5,
10 and 20 mg/kg icariside II groups, 20 rats in each group. The middle
cerebral artery occlusion model (ischemia for 2 h followed by reperfusion
for 24 h) was established in the later 4 groups. In later 3 groups, at
reperfusion beginning, the rats were intragastrically administrated with 5,
10 and 20 mg/kg icariside II, respectively. After 24 h of reperfusion, the
neurological severity score, cerebral water content and cerebral infarction
volume, brain tissue oxidative stress indexes and Nrf2 and HO-1 protein
expressions were determined.

Compared with model group, in 20 mg/kg icariside II group the neurological
severity score, cerebral water content and cerebral infarction volume, brain
tissue ROS content and MDA level were significantly decreased (P<0.05), and the brain tissue SOD, GSH-Px and catalase levels and Nrf2 and HO-1 protein levels were significantly increased (P<0.05). Icariside II can alleviate the CIRI in rats through reducing brain tissue oxidative stress and improving Nrf2/HO-1 expression.

Partial Text

Cerebral ischemia reperfusion injury (CIRI) refers to the more serious injury and
dysfunction of ischemic brain tissue after restoring the blood perfusion, compared
with before perfusion. The mechanism of CIRI includes several aspects, in which the
oxidative stress and cytotoxic injury caused by endogenous and exogenous
electrophiles are one of the important mechanisms1. After cerebral ischemia, the production of reactive oxygen species (ROS) in
cells is increased sharply, thus leading to the oxidative stress2. In traumatic brain injury, Nrf2/HO-1 pathway has been found to be one of
the most important antioxidant and cytotoxic defense mechanisms in cells.
Up-regulation of this signaling pathway can induce a variety of antioxidant enzymes
and detoxifying enzymes, accelerate the enzymatic reaction, increase the expression
of superoxide dismutase (SOD), glutathione and other antioxidant substances,
scavenge free radicals and other oxides, and maintain the normal intracellular
potential level, thus playing a role in cell protection3,4. Herba Epimedii is a Berberidacae medicinal plant in Asia.
Icariside II
(5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yloxychromen-4-one)
is one of the main active ingredients of Herba Epimedii (Fig. 1).

This study was approved by the ethics committee of the Jinan City Central Hospital
Affiliated to Shandong University. All animal procedures followed the Principles of
Laboratory Animal Care and were in accordance with the Guide for the Care and Use of
Laboratory Animals by the National Institutes of Health.

In treatment of ischemic cerebrovascular diseases, restoring the blood flow in
ischemic area or strengthening the blood supply to ischemic area is the prerequisite
for alleviating the damage to the structure and function of central nervous system
cells. However, if the dredging and restoring of cerebral blood flow exceed a
certain time point, they cannot alleviate the tissue damage and dysfunction caused
by ischemia, and even cause further aggravation of nerve injury, which is called
CIRI13. Inhibiting the reperfusion injury is an important link in the treatment of
ischemic cerebrovascular diseases. This study has established the CIRI model of
rats, and investigated the effects of icariside II on the oxidative stress and
Nrf2/HO-1 expression in CIRI rats. Results showed that, the neurological severity
score, cerebral water content and cerebral infarction volume in model group were
significantly higher than those in sham-operated group. Compared with model group,
the neurological severity score, cerebral water content and cerebral infarction
volume in 10 mg/kg icariside II and 20 mg/kg icariside II groups were significantly
decreased, respectively. This indicates that, icariside II has the protective
effects on CIRI in rats.

Icariside II can alleviate the CIRI in rats through reducing brain tissue oxidative
stress and improving Nrf2/HO-1 expression. This study has provided an experimental
reference for the clinical application of icariside II to prevention and treatment
of CIRI.

 

Source:

http://doi.org/10.1590/s0102-8650201900208

 

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