Puerarin attenuates intracerebral hemorrhage‐induced early brain injury possibly by PI3K/Akt signal activation‐mediated suppression of NF‐κB pathway

Abstract

Intracerebral hemorrhage (ICH) can induce intensively oxidative stress, neuroinflammation, and brain cell apoptosis. However, currently, there is no highly effective treatment available. Puerarin (PUE) possesses excellent neuroprotective effects by suppressing the NF‐κB pathway and activating the PI3K/Akt signal, but its role and related mechanisms in ICH‐induced early brain injury (EBI) remain unclear. In this study, we intended to observe the effects of PUE and molecular mechanisms on ICH‐induced EBI. ICH was induced in rats by collagenase IV injection. PUE was intraperitoneally administrated alone or with simultaneously intracerebroventricular injection of LY294002 (a specific inhibitor of the PI3K/Akt signal). Neurological deficiency, histological impairment, brain edema, hematoma volume, blood–brain barrier destruction, and brain cell apoptosis were evaluated. Western blot, immunohistochemistry staining, reactive oxygen species (ROS) measurement, and enzyme‐linked immunosorbent assay were performed. PUE administration at 50 mg/kg and 100 mg/kg could significantly reduce ICH‐induced neurological deficits and EBI. Moreover, PUE could notably restrain ICH‐induced upregulation of the NF‐κB pathway, pro‐inflammatory cytokines, ROS level, and apoptotic pathway and activate the PI3K/Akt signal. However, LY294002 delivery could efficaciously weaken these neuroprotective effects of PUE. Overall, PUE could attenuate ICH‐induced behavioral defects and EBI possibly by PI3K/Akt signal stimulation‐mediated inhibition of the NF‐κB pathway, and this made PUE a potential candidate as a promising therapeutic option for ICH‐induced EBI.

Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage

“…In the discrimination trial, the novel object (%) and familiar object (%) in the sham + progesterone group increased compared with the sham + vehicle group [ 59 ]. In addition, LY294002, as a commonly used inhibitor of the PI3K/Akt pathway, has been used in ICH with relatively mature application, and it is generally believed that it will not cause side effects or benefits in non-ICH area [ 60 , 61 ]. Overall, the current study showed that progesterone and LY294002 had no significant effect on the neurological function in normal animals.…”

Puerarin Attenuates Oxidative Stress and Ferroptosis via AMPK/PGC1α/Nrf2 Pathway after Subarachnoid Hemorrhage in Rats

“…The neurological scores were assessed using the modified Garcia test and beam balance test [25]. The Modified Garcia score (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) was the sum of 6 separate trial scores, including spontaneous activity (scores 0-3), symmetry (0-3), forelimb extension (0-3), climbing (1-3), body proprioception (1-3), and response to vibrators (1-3). Beam balance test was used to record the distance rats walked on a balance beam in a quiet environment, scoring 0-4.…”

“…Puerarin is a type of flavonoid glycoside extracted from the Pueraria lobata root [ 8 ]. Studies have shown that puerarin has neuroprotective effects in several central nervous system diseases, including Parkinson’s disease [ 9 ], Alzheimer’s disease [ 10 ], acute spinal cord injury [ 11 ], brain ischemia/reperfusion injury [ 12 , 13 ], and intracerebral hemorrhage [ 14 ]. As an antioxidant to protect the cells against apoptosis caused by oxidative stress [ 15 ], Puerarin was shown to preserve the activities of antioxidant enzymes [ 16 , 17 ].…”

Upregulation of Small Ubiquitin-Like Modifier 2 and Protein SUMOylation as a Cardioprotective Mechanism Against Myocardial Ischemia-Reperfusion Injury

“…Figure 5 showed that puerarin was well bound to ER protein with the binding energy of −7.3 kcal/mol and induced the expression of reporter luciferase through an ER-mediated mechanism. Nevertheless, botanic drug puerarin may exhibit antiinflammatory and cytoprotective activities through regulating different signaling pathways, including phosphoinositide 3kinase (PI3K)/Akt pathway, NF-κB pathway and peroxisome proliferator-activated receptor (PPAR) pathway (He et al, 2019;Zeng et al, 2021). Our group previously found that puerarin might exhibit neuroprotective and neurorestorative activities via progesterone receptor (PR) signaling (Zhao et al, 2020b).…”