Tanshinone IIA alleviates the damage of neurocytes by targeting GLUT1 in ischaemia reperfusion model (in vivo and in vitro experiments)

Abstract

Stroke is partial or complete brain dysfunction combined with acute cerebral circulatory disorders, and it affects millions of individuals around the world each year. A total of 70-80% of patients experience ischaemic stroke caused by disturbances in cerebral circulation, leading to cerebral ischaemia, neuronal apoptosis, and necrosis. Tanshinone IIA is a natural compound extracted from Salvia miltiorrhiza and has been proven to assist in recovery from cerebral ischaemia reperfusion injury. GLUT1 is ubiquitously expressed in all types of tissues in the human body and has important physiological functions due to its glucose uptake ability. This experiment was performed to detect the effect of GLUT1 in promoting the therapeutic effect of tanshinone IIA. Here, we found that tanshinone IIA treatment increased the viability of neurons and promoted the recovery of brain function, and that the concentration of glucose in serum and cultured medium was also increased. We noticed that these effects might be mediated by an increased glucose uptake ability. In addition, we further found that the PI3K/mTOR/HER3 signalling pathway played an important role in regulating these effects. Thus, we thought that overexpression of GLUT1 might be an important target in the treatment of cerebral ischaemia-reperfusion.

Mechanism of Salvia miltiorrhiza Bge. for the Treatment of Ischemic Stroke Based on Bioinformatics and Network Pharmacology

“…In vitro , mainly using Neuro-2A cells cultured in Dulbecco's modified Eagle's medium and supplemented with 10% fetal bovine serum at 37°C and humidified in a 5% CO 2 atmosphere and divided into different groups treated in different ways, pretreatment with Tanshinone I could increase cell viability of HT-22 cell following oxygen-glucose deprivation (OGD) [ 10 ]. The effect of Tanshinone IIA on cellular viability results showed that the viability was significantly increased in the Tanshinone IIA treatment group groups compared with the operation group ( P < 0.05) [ 14 ]. the PI3K/mTOR signaling pathway was activated after treatment with Tanshinone IIA by detecting the expression of GLUT1 and HIF-1a and the ratio of p-AKT/AKT, p-mTOR/mTOR, and p-HER3/HER3 in cell model using western blotting analysis [ 14 ].…”

The PI3K/AKT Pathway—The Potential Key Mechanisms of Traditional Chinese Medicine for Stroke

“…Tanshinone IIA , a natural component derived from Salvia miltiorrhiza (Dan-Shen in Chinese), has been proven to have therapeutic effects in cerebrovascular and cardiovascular diseases. Tanshinone IIA treatment promotes the recovery of brain function and increases neuronal viability; furthermore, the glucose concentration in the serum and cultured medium was increased, possibly regulated by an increased glucose uptake ability and activation of the PI3K/AKT/mTOR pathway ( 19 ). Sodium tanshinone IIA sulfonate is a water-soluble derivative of tanshinone IIA, which suppresses the expression of HIF-1 and hemoglobin genes via inhibition of the PI3K/AKT/mTOR pathway, thereby protecting against hypoxia in cerebral hemorrhage in zebrafish ( 20 ).…”

Research progress of natural products for the treatment of ischemic stroke

“…Tanshinone IIA is extracted from the dried rhizome of Salvia miltiorrhiza Bge., and is commonly used in the treatment of cerebrovascular diseases. Tanshinone IIA can promote the recovery of cerebral ischemia-reperfusion injury, increase glucose uptake and energy supply of neurons by targeting GLUT1, and reducing the expression of inflammatory factors COX-2, IL-1β, prostaglandin E2 (PGE2) and monocyte chemoattractant protein-1 (MCP-1) [102].…”