Formononetin is a type of phytoestrogen obtained from the Chinese medical herb Red Clover. It exhibits anti-neoplastic hepatoprotective, and neuroprotective properties. However, the anti-inflammatory effect of formononetin in cerebral ischemia-reperfusion injury has not been reported. To explore the potential mechanism of action of formononetin in cerebral ischemia-reperfusion injury with regard to the JAK2/STAT3 signaling pathway. Male SD rats were used to establish a middle cerebral artery occlusion (MCAO) model and randomly divided into 5 groups: Sham, MCAO, JAK2 Inhibitor (Ag490), Formononetin, Inhibitor + Formononetin. The protective effect of formononetin in MCAO rats was detected by performing neurological deficit testing, TTC staining, H&E staining, Nissl staining, ELISA, RT-PCR, western blotting and immunofluorescence. Formononetin significantly alleviated the neurological deficit and the pathological state of brain tissues, and reduced the volume of cerebral infarction, levels of IL-18 and TNF-α inflammatory factors in plasma, mRNA levels of IL-6 and IL-1β in rat brain tissue, and the protein levels of p-JAK2, p-STAT3, NLRP3, ASC, cl-Caspase-1, and cl-IL-1β in the MCAO rat brain tissue. Formononetin has anti-inflammatory effects. It may inhibit the relevant targets in the JAK2/STAT3 signaling pathway, thereby having a certain protective effect against cerebral ischemia-reperfusion injury.

Many traditional Chinese medicines, including Danhong injection (DHI), can be used to treat cerebral ischemia-reperfusion injury and have neuroprotective effects on the brain; however, few studies have explored the mechanism by which this effect is generated. In this study, we investigated the neuroprotective effect of DHI against cerebral ischemia-reperfusion injury mediated via the PI3K-Akt signaling pathway. After establishing the model of middle cerebral artery occlusion (MCAO), 60 male Sprague–Dawley rats were allocated to six groups as follows: sham, MCAO, DHI (MCAO + DHI), LY294002 (MCAO + LY294002 [PI3K-Akt pathway specific inhibitor]), DHI + LY294002 (MCAO + DHI + LY294002), and NMDP + LY294002 (MCAO + NMDP [nimodipine] + LY294002). Hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate the pathological changes of brain tissue and the degree of neuronal apoptosis. Real-time quantitative polymerase chain reaction (qRT-PCR), western blot analysis and enzyme-linked immunosorbent assays were used to measure the expression of Bad, Bax, Bcl-2, Bim, P53, MDM2, Akt, PI3K, p-Akt, p-PI3K, and Cyt-C. Compared with the MCAO group, brain tissue cell apoptosis was significantly reduced in the DHI group, and the brain function score was significantly improved. In addition, the expression of pro-apoptotic factors (Bad, Bax, and Bim) was significantly downregulated in the DHI group, while expression of the anti-apoptotic factor Bcl-2 was significantly upregulated, and expression of the apoptotic gene p53 was also significantly attenuated. Moreover, this neuroprotective effect was attenuated by the PI3K-Akt signaling pathway inhibitor (LY294002). Thus, our results confirmed the neuroprotective effects of DHI in rats with ischemia-reperfusion injury and indicate that these effects on the brain are partly generated by activation of the PI3K-Akt signaling pathway.

Neurodegenerative diseases are a class of disorders with the gradual loss of the central nervous system and peripheral nervous system. Neurodegenerative diseases manifest primarily as cognitive and behavioral disorders that adversely affect the lives of millions of people worldwide. Therefore, it is necessary to elucidate the mechanism of neurodegenerative diseases further and find effective new therapies. In recent years, increasing evidence has shown that the immune system plays a significant role in the pathophysiology of neurodegenerative diseases and regulates this process. The central and peripheral immune systems exert different roles in the disease progression. The development of neurodegenerative diseases is influenced by interactions between them. This review focuses on how the immune system, including microglia mediated nucleotide-binding oligomerization domainlike receptor protein 3 inflammation activation and T cell-mediated neuroinflammation, interactions with neurodegenerative diseases by modulating protein aggregation and blood-brain barrier permeability. Besides, we gave particular attention to glial cell-centered multicellular interactions and the inflammatory signaling pathway. Insight into the immune system’s functions and cellular interactions is essential for progressing disease research. In addition, the functions and mechanisms of these immune cells also suggest new ideas and targets for treatment. Therefore, this review summarizes some of the existing treatment strategies for amyloid-beta, tau, neuroinflammation, α-synuclein, associated microbiota, immune modulation, and neural injury repair. In addition, this review summarizes and compares animal models of different common neurodegenerative diseases and clinical research progress. In view of the current research status, new research directions and suggestions are proposed.