Vascular dementia (VD) is a serious sequela of cerebrovascular diseases that can significantly affect memory, emotion, and language. In severe cases, patients lose their normal survival ability, leading to a sharp decline in quality of life (Gorelick et al., 2016; Kalaria et al., 2016; Lee and Kim, 2020; Smith, 2017). However, because of the complex pathogenesis of VD, there is currently no effective treatment for this condition. Therefore, timely treatment of cerebrovascular diseases is crucial to prevent the progression to VD and delay the development of VD (Hobert et al., 2020). Floralozone is a colorless liquid first discovered in Lagotis Gaertn, and is now mainly synthesized industrially. In recent years, its medicinal value has been increasingly recognized (Cook et al., 2009). Our previous study has reported that the floraozone-regulated transient receptor potential melastatin 2 (TRPM2) and N-methyl-d-aspartate receptor (NMDAR) signaling pathways improved cognitive dysfunction in rats with VD (Yin et al., 2022). However, the specific mechanism by which Floralozone regulates TRPM2 and NMDAR to ameliorate VD remains unclear and requires further investigation.

AMP-activated protein kinase (AMPK) is a regulator of energy balance in vivo, with AMPKα2 as the main regulatory subunit (Hardie, 2011; Lin and Hardie, 2018; Salt and Hardie, 2017). Previous studies have demonstrated that AMPK activation is beneficial (Kuramoto et al., 2007); however, a growing body of evidence suggests a clear relationship between AMPK activation and neuronal death in focal stroke (Li et al., 2007; Nakatsu et al., 2008). Therefore, the role of AMPK in cerebral ischemia requires further investigation. Ion concentration disorders can also occur when ischemia and hypoxia lead to energy metabolism disorders. Ca2+ overload can cause neuronal death, leading to cognitive dysfunction (Ludhiadch et al., 2022). TRPM2 and NMDAR are two important ion channels that regulate Ca2+ flow into and out of cells. TRPM2 is an important channel that regulates toxic Ca2+ influx into cells discovered in recent years (Wang et al., 2021; Zhan et al., 2016). However, the current understanding of TRPM2 remains limited and needs further investigation. Many studies have demonstrated that NMDAR-mediated excitatory amino acid toxicity initiates and executes neuronal apoptosis. NR2B is the main regulatory subunit of this receptor and determines the permeability of NMDAR ion channels to Ca2+ (Lai et al., 2014). NR2B is not only involved in mediating ischemic brain injury, but is also the main regulator of synaptic plasticity and long-term potentiation effect of cortical and hippocampal neurons; thus, it is also known as the “smart gene” (Picconi et al., 2006). Therefore, the mechanism of action of NMDAR in VD requires further study. In recent years, non-coding small RNAs have been suggested to play important roles in the occurrence and development of diseases. Studies have indicated that injecting miR-7 mimics into rats with transient cerebral ischemia can greatly reduce lesion volume in the brain, improve motor function, and promote the recovery of cognitive function (Mehta et al., 2023). However, the biological role and function of miR-7 in ischemic brain injury remain unclear. Minichromosome maintenance complex component 2(MCM2) protein is a gene replication-related protein that exists in the nucleus and is a common marker for detecting hippocampal neurogenesis(von Bohlen und Halbach, 2011).

This study aimed to explore whether Floralozone can regulate the level of miR-7 in vivo through the activation of AMPKα2, affect the expression levels of TRPM2 and NR2B, and improve the symptoms of VD. Mouse nerve growth factor (mNGF) is a neuron-active agent developed using modern medical technology. mNGF improves cognitive function in rats with VD (Yin et al., 2022). In the present study, mNGF was used as a protective drug against neuronal damage.