[Qiangji Decoction regulates AMPKα/Drp1/Nrf2 pathway to ameliorate neural damage induced by D-galactose by suppressing oxidative stress and neuronal apoptosis].

This study aims to investigate the mechanism by which Qiangji Decoction(QJD) regulates the adenosine 5'-monophosphate(AMP)-activated protein kinase α(AMPKα)/dynamin-related protein 1(Drp1)/nuclear factor E2 related factor 2(Nrf2) pathway to ameliorate oxidative stress and neuronal apoptosis induced by D-galactose. Seventy-two C57BL/6 mice were randomized into the control, model, low-dose Qiangji Decoction(L-QJD), medium-dose Qiangji Decoction(M-QJD), high-dose Qiangji Decoction(H-QJD), and metformin(Met) groups. The mouse model of Alzheimer's disease(AD) was established by subcutaneous injection of D-galactose(0.1 g·kg~(-1)) into the mouse neck for 8 consecutive weeks. The control and model groups received equal volumes of normal saline by gavage at a dose of 20 mL·kg~(-1), and the L-QJD, M-QJD, and H-QJD groups were treated with QJD extract at doses of 12.48, 24.96, and 49.92 g·kg~(-1), respectively. The Met group was administrated with metformin sustained-release tablets by gavage at a dose of 0.2 g·kg~(-1). After 4 weeks of treatment, the Morris water maze test was carried out to evaluate the learning and memory abilities of mice. The pathological changes of the hippocampus were observed via hematoxylin-eosin staining. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining was employed to detect apoptotic neurons in the hippocampus. Immunofluorescence(IF) staining was employed to detect the expression levels of B cell lymphoma-2(Bcl-2) and Bcl2-associated X protein(Bax) in the hippocampus. Biochemical assay kits were used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), glutathione peroxidase(GSH-PX), and catalase(CAT) in the hippocampal tissue. Western blot was used to determine the expression levels of AMPKα, phosphorylated AMPKα(p-AMPKα-Thr172), Drp1, phosphorylated Drp1(p-Drp1-Ser616), cysteinyl aspartate-specific proteinase-3(caspase-3), cleaved caspase-3, Nrf2, heme oxygenase 1(HO-1), and NAD(P)H quinone oxidoreductase 1(NQO1) in the hippocampal tissue. The results showed that compared with the control group, the model group presented reduced learning and memory abilities, increased neurons with shrinkage or deep staining, increased apoptotic neurons(P<0.01), upregulated expression of Bax, MDA, p-Drp1-Ser616/Drp1, and cleaved caspase-3/caspase-3(P<0.01), and downregulated expression of Bcl-2, T-SOD, GSH-PX, CAT, p-AMPKα-Thr172/AMPKα, Nrf2, HO-1, and NQO1(P<0.01) in the hippocampus. Compared with the model group, the M-QJD, H-QJD, and Met groups showed improved learning and memory abilities, decreased neurons with shrinkage or deep staining and apoptotic neurons(P<0.05, P<0.01), downregulated expression of Bax, MDA, p-Drp1-Ser616/Drp1, and cleaved caspase-3/caspase-3 in the hippocampus(P<0.05, P<0.01), and upregulated expression of Bcl-2, T-SOD, GSH-PX, CAT, p-AMPKα-Thr172/AMPKα, Nrf2, HO-1, and NQO1 in the hippocampus(P<0.05, P<0.01). QJD could alleviate D-galactose-induced cognitive impairment, neuronal apoptosis, and oxidative stress by regulating the AMPKα/Drp1/Nrf2 pathway.