Abstract
Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD’s effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1β, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.
Highlights
Brain aging is the main factor inducing aging-related neurodegenerative diseases (Fung et al, 2020)
Once the AMPK/silent information regulator of transcription 1 (SIRT1) signaling pathway is activated, NF-κB is inhibited and alleviating cognitive impairment and neurodegenerative changes induced by D-gal
Starting from the fourth day, the D-gal treatment significantly increased the escape latency, whereas this phenomenon was significantly reversed by the metformin, M-Qiangji Decoction (QJD), and high dose of QJD group (H-QJD) (p < 0.05 or 0.01; Figures 1B, C)
Summary
Brain aging is the main factor inducing aging-related neurodegenerative diseases (Fung et al, 2020). With the rapid escalation of the aging population all over the world, the prevalence of chronic neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is increasing rapidly. We have made encouraging progress in the research of MCI and AD, its high prevalence has resulted in a heavy burden on the economy and society of the world. The increasing researches have confirmed that neuroinflammation can damage the structure and function of the brain and result in hippocampal-dependent learning and memory impairment (Lima Giacobbo et al, 2019; Yahfoufi et al, 2020; Salami et al, 2021). The inhibition of neuroinflammation has been regarded as an effective therapeutic intervention to alleviate the progression of chronic neurodegenerative diseases
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