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

Abstract

Stroke is associated with a high disability and fatality rate, and adversely affects the quality of life of patients and their families. Traditional Chinese Medicine (TCM) has been used effectively in the treatment of stroke for more than 2000 years in China and surrounding countries and regions, and over the years, this field has gleaned extensive clinical treatment experience. The Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway is important for regulation of cell migration, proliferation, differentiation, and apoptosis, and plays a vital role in vascularization and oxidative stress in stroke. Current Western medicine treatment protocols for stroke include mainly pharmacologic or mechanical thrombectomy to restore blood flow. This review collates recent advances in the past 5 years in the TCM treatment of stroke involving the PI3K/AKT pathway. TCM treatment significantly reduces neuronal damage, inhibits cell apoptosis, and delays progression of stroke via various PI3K/AKT-mediated downstream pathways. In the future, TCM can provide new perspectives and directions for exploring the key factors, and effective activators or inhibitors that affect occurrence and progression of stroke, thereby facilitating treatment.

A Pharmacological Review of Tanshinones, Naturally Occurring Monomers from Salvia miltiorrhiza for the Treatment of Cardiovascular Diseases

“…In addition to DHT, it has been confirmed that Tan I could also promote nuclear Nrf2 protein to increase the expression of related enzymes to combat oxidative stress by the Akt/Nrf2 pathway upregulation [ 41 ]. The classical pathway, phosphatidylinositol-3 kinase (PI3K)/Akt, is essential to regulate various biological processes such as oxidative stress and cellular apoptosis [ 42 , 43 ]. Tan IIA was reported to activate the PI3K/Akt pathway, followed by the upregulation of its downstream mammalian target of rapamycin (mTOR) and endothelial nitric oxide synthase (eNOS) to prevent cellular oxidative stress and apoptosis [ 44 ].…”

Network pharmacology and experimental study of phenolic acids in salvia miltiorrhiza bung in preventing ischemic stroke

“…Inflammation is a hallmark of stroke pathology, and the cytokines is related with infarct evolution (Lambertsen et al, 2012). Akt-related pathways is associated with cell migration, proliferation, apoptosis, oxidative stress, etc., during stroke (Gu et al, 2022). VEGFs participated in the process of cerebral edema, neuroprotection, angiogenesis, etc., in ischemic stroke rats (Greenberg and Jin, 2013).…”

Exploring the mechanism of Ginkgo biloba L. leaves in the treatment of vascular dementia based on network pharmacology, molecular docking, and molecular dynamics simulation

“…[29,30] The repair of various organs in the human body usually proceeds through the PI3K/Akt pathway, especially in the central nervous system. [31] After being phosphorylated by upstream signals, the PI3K/Akt pathway can stimulate downstream proteins to induce a cascade response that is involved in neuroprotection by inhibiting apoptosis, alleviating inflammation and oxidative stress, stimulating angiogenesis, improving cerebral circulation, and many other biological processes (Fig. 9).…”