Mechanism of Tiaogeng decoction (调更汤) in a cognitive dysfunction mouse model

doi:10.19852/j.cnki.jtcm.2025.05.006

Abstract

Abstract:

OBJECTIVE: To explore the mechanism of action of Tiaogeng decoction (调更汤, TG) in alleviating oxidative stress damage in the hippocampus of a mouse model of cognitive impairment.

METHODS: Amyloid precursor protein/presenilin-1 (APP/PS1) transgenic female mice were randomly divided into model, estradiol valerate, low-, medium-, and high-dose TG groups, female C57 mice were used as the control group (n = 12/group). After 12 weeks of treatment, the behavior of mice was tested with the Morris water maze, and brain tissue samples were collected, and changes in hippocampal neurons were observed using electron microscopy. The deposition of beta-amyloid protein (Aβ) amyloid plaques in the hippocampus was determined by light microscopy. Aβ1-42 protein levels were detected through immunofluorescence. Oxidative stress indicators in the hippocampus were detected by enzyme linked immunosorbent assay. The expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), c-Jun N-terminal kinase (JNK), phospho-JNK (p-JNK), B-cell lymphoma-2 (Bcl-2), caspase-9, and cleaved caspase-9 were detected by Western blot. Hippocampal cell apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated nick end Labeling.

RESULTS: TG improved the cognitive function of APP/PS1 mice, as judged by improvements in several indices from the Morris water maze test. TG increased Nrf2, superoxide dismutase, and heme oxygenase-1 protein expression and reduced malondialdelyde and reactive oxygen species expression. TG also inhibited the expression of JNK proteins, upregulated the expression of Bcl-2, and downregulated the expression of caspase-9, reducing cell apoptosis. TG decreased the percentage of the hippocampal cornu ammonis 1 area positive for Aβ1-42, reducing mitochondrial damage caused by oxidative stress and Aβ protein deposition.

CONCLUSIONS: TG may improve memory ability while reducing oxidative stress and apoptosis. It also reduces Aβ protein deposition in the hippocampus, protecting the central nervous system and improving memory function. TG may reduce the risk of AD.

Key words: Alzheimer disease, oxidative stress, apoptosis, Tiaogeng decoction

NI Shuang, LIU Xiaofei, GUO Xiaoyan, GU Zuxi, WU Panqing, CONG Chao, LI Shengnan, GAO Xianwei, XU Lianwei. Mechanism of Tiaogeng decoction (调更汤) in a cognitive dysfunction mouse model[J]. Journal of Traditional Chinese Medicine, 2025, 45(5): 987-997.

Figures/Tables 4

Figure 1 Water maze test results A: comparison of escape latency; B: times of crossing the platform; C: percentage of the target quadrant movement distance; D: percentage of the target quadrant movement time; E: track chart for comparison of times of crossing platforms in each group. E1: control group; E2: model group; E3: E2 group; E4: L-TG group; E5: M-TG group; E6: H-TG group. Control group: give purified water 0.3 mL/d; Model group: give purified water 0.3 mL/d; E2 group: give estradiol valerate 0.152 mg·kg?1·d?1; L-TG group: give Tiaogeng decoction 0.82 g·kg?1·d?1; M-TG group: give Tiaogeng decoction 1.64 g·kg?1·d?1; H-TG group: give Tiaogeng decoction 3.28 g·kg?1·d?1. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. The data are expressed as mean ± standard deviation (n = 12). Compared with control group, aP < 0.01; compared with model group, bP < 0.05; compared with L-TG group, cP < 0.05; compared with E2 group, dP < 0.05.

Figure 2 Observation on the structure of hippocampal neuronal organelles in each group under electron microscope A: control group; A1: magnified 4500 times, green arrow indicates neuron nucleus; A2: magnified 11500 times, green arrow indicates mitochondrion; B: model group; B1: magnified 4500 times, green arrow indicates cell nuclear membrane; B2: magnified 11500 times, green arrow indicates mitochondrion; C: E2 group; C1: magnified 4500 times; C2: magnified 11500 times, Green arrow indicates mitochondrion; D: L-TG group; D1: magnified 4500 times; D2: magnified 11500 times, green arrow indicates mitochondrion; E: M-TG group; E1: magnified 4500 times; E2: magnified 11500 times, green arrow indicates mitochondrion; F: H-TG group; F1: magnified 4500 times; F2: magnified 11500 times, green arrow indicates mitochondrion. Control group: give purified water 0.3 mL/d; Model group: give purified water 0.3 mL/d; E2 group: give estradiol valerate 0.152 mg·kg-1·d?1; L-TG group: give Tiaogeng decoction 0.82 g·kg-1·d?1; M-TG group: give Tiaogeng decoction 1.64 g·kg-1·d?1; H-TG group: give Tiaogeng decoction 3.28 g·kg-1·d?1.

Figure 3 Immunofluorescence detection of hippocampal CA1 area Aβ1-42 A: control group; A1: Aβ1-42 expression; A2: cell nuclear blue fluorescence staining; A3: merge; B: model group; B1: Aβ1-42 expression; B2: cell nuclear blue fluorescence staining; B3: merge; C: E2 group; C1: Aβ1-42 expression; C2: cell nuclear blue fluorescence staining; C3: merge; D: L-TG group; D1: Aβ1-42 expression; D2: cell nuclear blue fluorescence staining; D3: merge; E: M-TG group; E1: Aβ1-42 expression; E2: cell nuclear blue fluorescence staining; E3: merge; F: H-TG group; F1: Aβ1-42 expression; F2: cell nuclear blue fluorescence staining; F3: merge; G: Aβ1-42 percentage of positive area. Control group: give purified water 0.3 mL/d; Model group: give purified water 0.3 mL/d; E2 group: give estradiol valerate 0.152 mg·kg-1·d?1; L-TG group: give Tiaogeng decoction 0.82 g·kg-1·d?1; M-TG group: give Tiaogeng decoction 1.64 g·kg-1·d?1; H-TG group: give Tiaogeng decoction 3.28 g·kg-1·d?1. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. The data are expressed as mean ± standard deviation (n = 3). Compared with control group, aP < 0.05; compared with model group, bP < 0.05.

Figure 4 Oxidative stress indicators in the hippocampus A: SOD; B: MDA; C: ROS; D: HO-1. Control group: give purified water 0.3 mL/d; Model group: give purified water 0.3 mL/d; E2 group: give estradiol valerate 0.152 mg·kg-1·d?1; L-TG group: give Tiaogeng decoction 0.82 g·kg-1·d?1; M-TG group: give Tiaogeng decoction 1.64 g·kg-1·d?1; H-TG group: give Tiaogeng decoction 3.28 g·kg-1·d?1. SOD: superoxide dismutase; MDA: malondialdehyde; ROS: reactive oxygen species; HO-1: heme oxygenase-1. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. The data are expressed as mean ± standard deviation (n = 6). Compared with control group, aP < 0.01; compared with model group, bP < 0.05.

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