Tricin attenuates cerebral ischemia/reperfusion injury through inhibiting nerve cell autophagy, apoptosis and inflammation by regulating the PI3K/Akt pathway

Abstract

To elucidate the effect of tricin in cerebral ischemia/reperfusion (I/R) injury and examine its possible underlying mechanisms. Rats were randomly divided into Sham (exposed the right internal carotid arteries), I/R, and tricin (administered at various doses) groups. After the cerebral I/R injury model was established, a Morris water maze test and a tetrazolium chloride assay were performed. Apoptosis and autophagy were assessed in the nerve cells of hippocampus tissue, and the levels of inflammatory markers within animal serum were detected. Proteins related to apoptosis and the PI3K/Akt pathway were evaluated. To further investigate the mechanisms by which tricin affects brain damage, mouse neuroblastoma cells N2a were divided into control, oxygen-glucose deprivation and reoxygenation (OGD/R), tricin, PI3K/Akt activator, and tricin + PI3K/Akt inhibitor groups. The cell viability, apoptosis, inflammatory factors, and PI3K/Akt pathway related proteins in N2a cells were also detected. The results revealed that I/R-induced learning and memory dysfunction was improved by tricin treatment. The area of cerebral infarction, the levels of apoptosis and autophagy in nerve cells, and the serum inflammatory marker content were all decreased following tricin treatment. Additionally, the expression of Beclin-1 protein was downregulated, while the expression of Bcl-2 protein, p-PI3K/PI3K and p-Akt/Akt was upregulated after tricin treatment. Mechanistically, tricin or PI3K/Akt activator ameliorated OGD/R-induced apoptosis, autophagy, and inflammation. However, these effects were reversed following PI3K/Akt inhibitor treatment in OGD/R-induced N2a cells. In summary, this study suggested that tricin can against I/R-induced brain injury by inhibiting autophagy, apoptosis and inflammation, and activating the PI3K/Akt signaling pathway.

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS

“…These results suggest that PI3K/AKT signaling pathway is involved in neuroprotection by E. bonariensis extract in OVX/D-Gal-induced neurotoxicity via α7-nAChR stimulation. Certain flavonoids or phenolic acids, such as cimicifugic acid (Wang et al 2017 ), caffeoyl-quinic acid (Yang et al 2022 ), casticin (Fan et al 2018 ), cirsimaritin (Kim et al 2015 ), tricin (Liu et al 2022 ), quercetin (Tu et al 2021 ), and luteolin (Park and Song 2013 ), are capable of modulating PI3K/AKT signaling, of which several were detected as major components in E. bonariensis extract using LC–MS with peak no. 18, 7, 30, 23, 27, and 14, respectively (Table 2 ).…”

Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets

“… 519 Zhao et al 509 and Li et al 510 have shown that treatment with Astragalus, 511 , 512 Salvia Miltiorrhiza, 513 , 514 Angelica Sinensis, 515 , 516 Harpagide, 517 Icariin, 518 pachymic acid, 519 and Lycopene 197 , 520 , 521 confer therapeutic effects against I/R injury in the heart, brain, and other organs. Moreover, Zhao et al 509 reported that TCM like Tricin, 522 Platycodin D, 523 Baicalein, 524 Lupeol, 525 Paeoniflorin, 526 and Bauhinia Championii 527 could activate the PI3K/Akt signaling pathway and mitigate brain I/R injury. Additionally, these TCM treatments have also been found to modulate the activity of the Wnt/β-catenin signaling pathway in different developmental or pathological contexts.…”

“…Additionally, these TCM treatments have also been found to modulate the activity of the Wnt/β-catenin signaling pathway in different developmental or pathological contexts. 528 – 537 Moreover, TCM have shown activation of PI3K/Akt, 522 – 526 NF-κB, 538 – 540 HIF-1α, 541 and Notch signaling pathways 542 during organ injury treatment, indicating their potential to alleviate I/R injury by targeting multiple signaling pathways. Exercise-based cardiac rehabilitation has demonstrated numerous benefits for patients with cardiac disease, including a reduced risk of MI.…”

Downregulation of TNFAIP1 alleviates OGD/R‑induced neuronal damage by suppressing Nrf2/GPX4‑mediated ferroptosis

“…OGD/R has been frequently used in research for induction of CIRI and has been reported to stimulate inflammation, apoptosis, autophagy and endoplasmic reticulum stress in cultured cortical neurons ( 20 , 21 ). In the present study, the OGD/R model was established to simulate CIRI in vitro .…”