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This study explored the mechanism by which the classical prescription Baihe Dihuang Decoction alleviates neuronal injury in anxious depression, based on the Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) signaling pathway. Sprague-Dawley rats were randomly divided into a normal group, model group, venlafaxine group (13.5 mg·kg-1), and Baihe Dihuang Decoction high-, medium-, and low-dose groups (16, 8, and 4 g·kg-1, respectively). An anxious depression model was established using 28 days of chronic restraint stress (6 h/day) combined with corticosterone administration (30 mg·kg-1, ih). From day 8 of modeling, intragastric administration of the corresponding treatments was given for 21 consecutive days. Anxiety-and depression-like behaviors were evaluated. Golgi staining was used to observe dendritic spine morphology of hippocampal neurons, and Western blot was performed to detect hippocampal phosphorylated (p)-SHP2, synapsin 1 (SYN1), and postsynaptic density protein-95 (PSD-95). In cell experiments, primary hippocampal neurons were transfected with lentiviruses to specifically overexpress or knock down SHP2. Transfection efficiency was assessed by RT-PCR and Western blot. A corticosterone-induced neuronal injury model was established, followed by intervention with Baihe Dihuang Decoction-containing serum. Cell viability was measured using the MTT assay, apoptotic morphology was observed by Hoechst 33342 staining, apoptosis rates were determined via flow cytometry, and immunofluorescence was used to detect SHP2, p-SHP2, SYN1, and PSD-95 expression. The results showed that, compared with the normal group, model rats exhibited hippocampal dendritic spines with atrophy, loss, irregular morphology, and shortening, accompanied by significantly reduced SYN1 and PSD-95 expression and markedly increased p-SHP2/SHP2 levels. After Baihe Dihuang Decoction intervention, hippocampal neuronal injury was significantly alleviated, and p-SHP2/SHP2 levels were suppressed. In vitro, neuronal SHP2 overexpression (SHP2 OE) or corticosterone modeling led to a marked decrease in cell viability, increase in apoptosis rate, and downregulation of SYN1 and PSD-95. Following treatment with Baihe Dihuang Decoction-containing serum, SHP2 overexpression was inhibited, cell viability increased, apoptosis decreased, and SYN1 and PSD-95 expression significantly increased. In addition, SHP2 knockdown (SHP2 KD) via lentiviral transfection also mimicked the protective effects of Baihe Dihuang Decoction. In conclusion, Baihe Dihuang Decoction improves hippocampal neuronal injury in anxious depression by regulating the SHP2 signaling pathway.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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