The volatile oil of Acorus tatarinowii Schott ameliorates Alzheimer's disease through improving insulin resistance via activating the PI3K/AKT pathway.

BACKGROUND: Alzheimer's disease (AD) presently stands as the most prevalent neurodegenerative disease. Existing research underscores the pivotal role of insulin signaling in the progression of AD. Acorus tatarinowii Schott (SCP), a traditional Chinese herbal, is employed for AD treatment in China. The volatile oil of Acorus tatarinowii Schott (SCP-oil) is the active component. However, its impact on AD-associated insulin resistance (AD-IR) remains inadequately investigated.

PURPOSE: This study used network pharmacology and experimental to investigate the effects and mechanisms of SCP-oil on cognitive improvement in AD by inhibiting IR.

MATERIALS AND METHODS: GC-Q/TOF-MS was employed to analyze the chemical composition of SCP-oil, while network pharmacology predicted the targets associated with SCP-oil in treating AD-IR to identify its regulatory mechanism. IR in the brain was simulated by intracerebroventricular streptozotocin administration (ICV-STZ). The neuroprotective and cognitive improvement effects of SCP-oil were assessed using the Morris water maze and hematoxylin and eosin, as well as Nissl staining. The expression levels of Neun and proteins related to p-tau, tau, amyloid-beta (Aβ), apoptosis, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were measured using immunohistochemistry and Western blotting, respectively. Dexamethasone (DXM)-induced HT22 cells were used for IR modeling. Chemical analysis determined the glucose consumption rate, and periodic acid Schiff staining was employed to detect glycogen deposition. Western Blots were utilized to investigate the expression of characteristic AD proteins, apoptosis-related proteins, and PI3K/AKT pathway-related proteins. The apoptosis rate was detected by flow cytometry. Reverse validation was further performed using LY294002 to evaluate the pharmacodynamic effects of SCP-oil after PI3K/AKT pathway inhibition.

RESULTS: A total of 25 chemical constituents were identified in SCP-oil. The network pharmacology findings indicated that SCP-oil holds the potential to ameliorate IR in the brain by activating the PI3K/AKT pathway, thereby improving AD. SCP-oil significantly improved ICV-STZ-induced cognitive dysfunction and pathological damage, reduced neuronal loss, Aβ deposition, and tau protein hyperphosphorylation, inhibited cell apoptosis, and activated the PI3K/AKT signaling pathway. Neuron loss, Aβ deposition, and tau protein hyperphosphorylation and cell apoptosis were further enhanced following treatment with LY294002, while the PI3K/AKT signaling pathway was further inhibited, and the protective effect of SCP-oil was weakened.

CONCLUSION: SCP-oil exhibited the potential to ameliorate brain IR, inhibiting cell apoptosis by activating the PI3K/AKT signaling pathway, thereby improving learning and memory ability.