Using bioinformatics analysis, network pharmacology, and cellular experiments, this study investigated the effects and potential mechanisms of Panax notoginseng saponins (PNS) on osteogenic induction of immortalized human aortic valve interstitial cells (hVICs). A calcific aortic valve disease (CAVD) cell model was established by treating hVICs with osteogenic induction medium (OM). Experimental groups included a control group, a model group, and PNS treatment groups (0.075, 0.05, and 0.025 mg·mL^-1). Cell viability was assessed by the CCK-8 assay. Calcification was evaluated by alkaline phosphatase (ALP) and alizarin red S staining. Western blot was performed to measure the expression of calcification-related proteins runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), and ALP. Transcriptomic datasets related to CAVD were obtained from the Gene Expression Omnibus (GEO) database, and CAVD disease targets were retrieved from GeneCards. Active components of PNS and their potential targets were collected from HERB, Batman-TCM 2.0, and ETCM databases. The intersecting genes were subjected to protein-protein interaction (PPI) network construction, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, identifying the spleen tyrosine kinase (SYK)/nuclear factor kappa-B (NF-κB) signaling pathway as a core pathway. Western blot was then used to assess the effects of PNS at the optimal concentration on SYK/NF-κB pathway-related proteins. NF-κB p65 nuclear translocation was examined by immunofluorescence co-localization, and ELISA was applied to measure tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels. Results showed that PNS reduced alizarin red S and ALP staining in calcification-induced hVICs and downregulated calcification-related proteins BMP2, ALP, and RUNX2 (P<0.05, P<0.01), with the most significant effect observed at 0.075 mg·mL^-1. A total of 1 416 differentially expressed genes were identified from GEO, while 5 646 CAVD-related targets were obtained from GeneCards. From HERB, Batman-TCM 2.0, and ETCM, 605 PNS targets were collected, with 130 overlapping genes identified. These were mainly involved in inflammatory responses, lipopolysaccharide-mediated signaling, transcriptional regulation, protein phosphorylation, and NF-κB pathway activation, occurring primarily in membrane rafts and the golgi apparatus, with molecular functions such as kinase activity regulation and protein binding, and enriched in lipid metabolism, atherosclerosis, and NF-κB signaling pathways. Experimental validation showed that PNS significantly decreased NF-κB p65 expression (P<0.05), significantly increased IκBα expression (P<0.01), and markedly suppressed expression of p-SYK (P<0.01), p-IκBα (P<0.01), p-NF-κB p65 (P<0.01), and p-NF-κB p50 (P<0.01). PNS also significantly reduced NF-κB p65 nuclear/cytoplasmic fluorescence intensity (P<0.01), decreased TNF-α secretion in the supernatant (P<0.01), and promoted IL-10 secretion (P<0.01). In conclusion, PNS ameliorates hVICs calcification by downregulating IκBα, NF-κB p65, and NF-κB p50 expression, inhibiting phosphorylation of SYK, IκBα, NF-κB p65, and NF-κB p50, reducing NF-κB p65 nuclear translocation, and suppressing TNF-α expression.

This study observed the effect of Chaihu Jia Longgu Muli Decoction on myocardial fibrosis in the rat model of myocardial infarction (MI) and explored the effect of this decoction on ventricular remodeling induced by myocardial fibrosis after MI based on transforming growth factor-β1 (TGF-β1)/Smad proteins (Smads) pathway, aiming to reveal the therapeutic mechanism of this decoction. MI model rats were established by coronary artery ligation and assigned into sham, model, and low-dose, medium-dose, and high-dose (2.09, 4.19, and 8.37 g·kg^-1, respectively) Chaihu Jia Longgu Muli Decoction groups, with 10 rats in each group. Chaihu Jia Longgu Muli Decoction groups were administrated with the decoction at different doses by gavage, and the sham and model groups received an equal volume of distilled water once daily for 4 weeks. The cardiac function of rats after MI was assessed via echocardiography. Myocardial fiber deposition and collagen volume fraction (CVF) were observed by Sirius red staining and Masson staining. Ultrastructure changes of myocardial cells were observed by transmission electron microscopy. Creatine kinase isoenzymes (CK-MB), cardiac troponin T (cTnT), and soluble growth stimulation expressed gene 2 (sST2) levels were measured by ELISA. Western blot was employed to assess the protein levels of collagen Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA) associated with myocardial fibrosis, and TGF-β1, Smad3, and Smad7 associated with the TGF-β1/Smads pathway. Compared with the sham group, the model group had significantly decreased body weight, compromised cardiac function, abnormal ventricular structure, collagen fiber deposition, increased fibrosis area and CVF, seriously damaged ultrastructure of myocardium, a part of mitochondria being swollen or even ruptured, disarrangement and lysis of myofibril, and broken myotome and myofilament with emergence of space. Furthermore, the model group showed risen levels of cTnT, sST2 and CK-MB, obvious myocardial fibrosis, up-regulated protein levels of pro-fibrotic cytokines TGF-β1 and Smad3, down-regulated protein level of the inhibitory cytokine Smad7, and increased expression of myocardial fibrosis-related proteins Col Ⅰ and α-SMA. Compared with the model group, Chaihu Jia Longgu Muli Decoction groups showed increased body weight, improved cardiac function and ventricular structure, reduced collagen fiber deposition, fibrosis area, and CVF, intact ultrastructure of myocardium, normal mitochondrial structure, and well-arranged myofibril and myofilament. In addition, Chaihu Jia Longgu Muli Decoction groups presented declined cTnT, sST2, and CK-MB levels, down-regulated protein levels of TGF-β1 and Smad3, up-regulated protein level of Smad7, and reduced expression of Col Ⅰ and α-SMA. Chaihu Jia Longgu Muli Decoction may reduce excessive deposition of extracellular matrix by regulating the expression of proteins in the TGF-β1/Smads pathway, thereby alleviating myocardial fibrosis and ameliorating ventricular remodeling.

This study aims to investigate the mechanism by which modified Xiangsha Liujunzi Decoction (M-XS) ameliorates hepatic inflammation in hyperlipidemic mice by regulating the intestinal high-density lipoprotein 3 (HDL3) level. Intestine-specific ATP-binding cassette transporter A1 (ABCA1) knockout mice (Abcal-Villin-cre-Tg) were randomized into 3 groups (n = 8): intestine-specific knockout group (Abcal^△Vill), intestine-specific knockout mice fed a high-fat diet group (Abcal^△Vill + HFD), and intestine-specific knockout with Chinese herbal medicine intervention group (Abcal^△Vill + HFD + M-XS). Littermate control mice were randomly allocated into 3 groups (n = 8): blank group (Abcal^fl/fl), high-fat diet group (Abcal^fl/fl+HFD), and Chinese herbal medicine intervention group (Abcal^fl/fl +HFD+M-XS). Except the Abcal^fl/fl and Abcal^△Vill groups, the other groups were fed a HFD for 10 weeks. Drug administration lasted for 6 weeks at a dose of 23.66 g·kg^-1·d^-1. Serum lipid profiles (four items), hepatic histopathology (HE and oil red O staining), and ileal histopathology (HE staining) were assessed. Ileal HDL3 levels were measured by ELISA, hepatic triacylglycerol (TG) levels by the GPO-PAP method, and co-localization of CD86 and Toll-like receptor 4 (TLR4) in the liver tissue by immunofluorescence. The mRNA levels of hepatic lipopolysaccharide-binding protein (LBP), nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), inhibitor of nuclear factor kappa-B alpha (IκBα), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were determined by real-time PCR. The protein levels of ABCA1 and apolipoprotein A-I (apoA-I) in the ileum, as well as LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β in the liver, were assessed by Western blot. Compared with the Abcal^fl/fl group, the Abcal^fl/fl +HFD group showed increased blood lipid levels, numerous vacuoles and lipid droplets in the liver, shortened intestinal villi, elevated hepatic TG level, reduced levels of HDL3, ABCA1, and apoA-I in the ileum, co-localization of CD86 and TLR4 in the liver, and up-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β as well as protein levels of LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β in the liver (P<0.05). Compared with the Abcal^fl/fl +HFD group, the Abcal^fl/fl +HFD+M-XS group showed decreased blood lipid levels, reduced vacuoles and lipid droplets in the liver, increased intestinal villus length, decreased hepatic TG level, elevated levels of HDL3, ABCA1, and apoA-I in the ileum, weakened co-localization of CD86 and TLR4 in the liver, and down-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β and protein levels of LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β (P<0.05). Compared with the Abcal^fl/fl+HFD group, the Abcal^△Vill+HFD group showed raised blood lipid levels, increased vacuoles and lipid droplets in the liver, elevated hepatic TG level, enhanced co-localization of CD86 and TLR4 in the liver, and up-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β and protein levels of LBP, p-NF-κB, p-IκBα, TNF-α, and IL-1β (P<0.05). Compared with the Abcal^fl/fl+HFD+M-XS group, the Abcal^△Vill+HFD+M-XS group showed raised blood lipid levels, increased vacuoles and lipid droplets in the liver, elevated hepatic TG level, enhanced co-localization of CD86 and TLR4 in the liver, and up-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β and protein levels of LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β (P<0.05). In conclusion, modified Xiangsha Liujunzi Decoction ameliorates hepatic inflammation and corrects dyslipidemia by modulating intestinal HDL3 levels.

This study explored the mechanism by which Suanzaoren Decoction (SZRD) ameliorates hippocampal neuronal damage in APP/PS1 mice by inhibiting Bax/Bcl-2/caspase-3-mediated apoptosis through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Differentially expressed genes (DEGs) in Alzheimer's disease (AD) were screened using the GEO database, and KEGG and GO enrichment analyses were performed using R software. Thirty 6-month-old APP/PS1 transgenic mice were randomly assigned to three groups: APP/PS1 group, low-dose SZRD group (12.96 g·kg^-1), and high-dose SZRD group (25.92 g·kg^-1), while ten age-matched male C57BL/6J mice served as the blank control group. The treatment groups received SZRD by gavage for 28 consecutive days. Following treatment, spatial learning and memory were assessed using the Morris water maze test. Neuronal numbers were evaluated by Nissl staining. Immunohistochemistry (IHC) was used to detect neuron-specific nuclear protein (NeuN) and assess amyloid-β (Aβ) deposition in hippocampal neurons. Western blot was performed to measure the expression levels of PI3K/Akt pathway proteins and apoptosis-related markers, including Bcl-2, Bax, caspase-3, and cleaved-caspase-3 in hippocampal tissues. Bioinformatics analysis identified 686 DEGs, with GO enrichment linked to synaptic function and neurotransmitter transport, and KEGG pathways including neuroactive ligand-receptor interaction and PI3K/Akt signaling. In vivo experiments showed that, compared with APP/PS1 mice, both low-and high-dose SZRD groups exhibited improved learning and memory, increased neuronal numbers, and decreased Aβ deposition. Furthermore, hippocampal levels of p-PI3K/PI3K, p-Akt/Akt, and Bcl-2 were upregulated, while Bax and cleaved-caspase-3/caspase-3 levels were downregulated. In conclusion, SZRD may improve hippocampal neuronal damage and cognitive function in APP/PS1 mice by regulating Bax/Bcl-2/caspase-3-mediated apoptosis through the PI3K/Akt signaling pathway.

This study investigated the asthma-alleviating effects of Poria cocos from the perspectives of immuno-inflammation and gut microbiota (GM), providing a theoretical basis for its rational clinical use. Male Balb/c mice were randomly divided into normal, model, positive control (montelukast sodium, 1.5 mg·kg^-1), low-dose P. cocos (0.057 g·kg^-1), medium-dose P. cocos (0.114 g·kg^-1), and high-dose P. cocos (0.227 g·kg^-1) group. Except for the normal group, the other groups were sensitized with ovalbumin (OVA) by intraperitoneal injection combined with nebulization to establish an asthma model, and treated with the corresponding drugs. After modeling, cough and wheezing indices, lung function, and asthma characteristic indicators including immunoglobulin E (IgE), interferon-γ (IFN-γ), interleukin 4 (IL4), and interleukin 10 (IL10) levels were measured. Lung tissue pathology was observed by hematoxylin-eosin (HE) and Masson staining. Quantitative real-time PCR (qRT-PCR) was used to detect airway inflammation-and remodeling-related mRNA levels in lung tissue. Levels of 12 inflammatory factors in serum and bronchoalveolar lavage fluid were detected by multiplex assay. Furthermore, the asthma-alleviating mechanism of P. cocos was analyzed by network pharmacology and GM 16S rRNA sequencing. Results showed that P. cocos reduced cough frequency in asthmatic mice, improved lung function, alleviated pathological damage in lung tissue, decreased serum IgE and IL 4 levels, increased IL 10 and IFN-γ levels, and multi-target regulated related inflammatory factors in serum and alveolar lavage fluid, maintaining immune homeostasis. Network pharmacology predicted that P. cocos exerts its asthma-alleviating effects via inflammation regulation pathways. GM sequencing showed that P. cocos effectively alleviated dysbiosis induced by OVA sensitization, significantly downregulated Muribaculum intestinale and Alistipes inops, and correlation analysis revealed both were positively correlated with pro-inflammatory factors. Therefore, it is speculated that P. cocos restores intestinal microecological homeostasis by reducing levels of M. intestinale and A. inops, decreases pro-inflammatory factor production, blocks the inflammatory cascade, and thereby exerts its asthma-alleviating effects.

This study established a hyperlipidemia model by feeding Sprague-Dawley rats a high-fat diet for 8 weeks. The rats were randomly assigned to the following groups: model group, atorvastatin calcium group (4.8 mg·kg^-1), low-, medium-, and high-dose Tanyu Tongzhi Optimization Decoction (TYTZD) groups (3.6, 7.2, and 14.4 g·kg^-1), and a normal diet control group. After 4 weeks of continuous administration, hematoxylin-eosin (HE) and oil red O staining were used to observe liver pathological changes and lipid infiltration. Automatic biochemical analyzer were performed to assess blood lipid profiles, coagulation function, and liver function. Transcriptomic and proteomic analyses were employed to identify differentially expressed genes (DEGs) and proteins (DEPs), followed by enrichment analysis. The MCODE algorithm was applied to classify DEGs and DEPs into modules, and network separation index (S_AB) was calculated to assess module separation, enabling construction of a gene-protein co-expression network for core target screening. The diagnostic accuracy of core targets was evaluated by area under the receiver operating characteristic (ROC) curve (AUC), and ELISA was used to measure core target expression. Western blot detected the expression of core pathway-related proteins in liver tissue. Results demonstrated that TYTZD significantly improved dyslipidemia, coagulation dysfunction, liver injury, hepatic pathology, and lipid infiltration in hyperlipidemic rats. Transcriptomic analysis identified 571 DEGs significantly reversed by TYTZD, mainly enriched in inflammatory signaling pathways such as Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB). Proteomic analysis identified 102 reversed DEPs, mainly involved in cholesterol metabolism pathways. Integrated analysis identified core targets including TLR4, tumor necrosis factor-α (TNF-α), integrin subunit alpha M (ITGAM), Toll-like receptor 2 (TLR2), matrix metalloproteinase 9 (MMP9), interleukin-1β (IL-1β), apolipoprotein E (APOE), and apolipoprotein C2 (APOC2), all with AUC values greater than 0.70. ELISA showed that TYTZD intervention significantly downregulated MMP9, TNF-α, IL-1β, TLR2, ITGAM, and TLR4, and upregulated APOC2 and APOE. Western blot indicated that TYTZD reduced TLR4, p-NF-κB, and IL-1β protein expression in liver tissue. In conclusion, TYTZD may exert anti-hyperlipidemic effects through regulation of core targets such as ITGAM, TLR4, and APOC2, and by modulating the TLR4/NF-κB signaling pathway to intervene in inflammatory responses and cholesterol metabolism, thereby achieving multi-target, multi-pathway therapeutic effects against hyperlipidemia.

Epilepsy is a common neurological disorder characterized by refractoriness and recurrence. In China, the prevalence rate is 0.4%-0.7%, with currently over nine million patients, among whom approximately 30% suffer from refractory epilepsy. Although antiepileptic drugs (AEDs) are the mainstay of treatment, they are associated with multi-system adverse reactions and drug resistance issues. In contrast, traditional Chinese medicine (TCM) treatment exhibits significant efficacy with lower toxicity and side effects, and integrated TCM and western medicine treatment can achieve complementary advantages. Studies have shown that integrated therapy demonstrates benefits in various types of epilepsy, including status epilepticus, post-stroke epilepsy, post-traumatic epilepsy, pediatric epilepsy, refractory epilepsy, and epilepsy comorbid with depression and anxiety. It exerts synergistic effects by enhancing AED bioavailability (borneol improves blood-brain barrier permeability), reducing seizure frequency, preventing recurrence, and minimizing western medicine toxicity (Dingxian Decoction decreases digestive/neurological adverse reactions). The underlying mechanisms involve regulating neurotransmitters (modulating glutamate and γ-aminobutyric acid levels) and ion channels (inhibiting sodium/calcium ion channels). In terms of preventive care, TCM plays an important role in preventing epileptic seizures by correcting biased constitutional states. In the future, integrated TCM and western medicine in epilepsy prevention and treatment will move toward individualized treatment, etiological treatment, preventive rehabilitation, and integration of scientific research with clinical practice, forming a three-dimensional development pattern of "technology empowerment, standard guidance, and whole-process management".

This study aimed to investigate whether Xihuang Pills (XHP) enhance the therapeutic efficacy of temozolomide (TMZ) against glioblastoma (GBM) U251 cells by inducing mitochondria-associated ferroptosis via regulation of Nrf2/HO-1/GPX4 signaling axis. The XHP-containing serum was prepared, and the effects of various concentrations of TMZ (0-200 μmol·L^-1) and XHP (0-20%) on U251 cell viability were assessed by CCK-8 assay. The optimal synergistic dose (200 μmol·L^-1 TMZ + 10% XHP) was identified via the SynergyFinder platform for establishing a combined intervention model. Control, XHP, TMZ, and XHP + TMZ groups were designed. Cell proliferation was evaluated by EdU staining and colony formation assay, and cell migration and invasion were assessed by Transwell and wound healing assays. FerroOrange and DCFH-DA fluorescent probes were used to measure the intracellular levels of Fe²⁺ and ROS, respectively. The JC-1 fluorescent probe was used to assess mitochondrial membrane potential, while Mito-PeDPP fluorescent probe to examine mitochondrial lipid peroxidation. Mito-Tracker Green and MitoSOX^TM Red were used to examine mitochondrial morphology and oxidative stress. Transmission electron microscopy was adopted to observe the mitochondrial ultrastructure. GSH and MDA levels were measured by colorimetric assays. Western blot was employed to assess the protein levels of Nrf2, HO-1, xCT, and GPX4. The results showed that, XHP + TMZ suppressed cell viability, proliferation, migration, and invasion (P<0.01), increased Fe²⁺ accumulation, ROS generation, GSH depletion, and lipid peroxidation (P<0.001), reduced mitochondrial membrane potential, caused severe structural damage, and down-regulated the protein levels of Nrf2, HO-1, GPX4, and xCT, which indicated that the antioxidant ferroptosis-protective pathway was co-inhibited. In conclusion, XHP enhances TMZ-induced ferroptosis in GBM cells by suppressing the Nrf2/HO-1/GPX4 signaling axis. The findings provide new mechanism insights into the synergistic antitumor effect of traditional Chinese medicine in glioblastoma therapy and offer experimental evidence for the treatment of refractory brain tumors with combined strategies.

This study aims to investigate whether the mitophagy receptor FUN14 domain-containing 1 (FUNDC1) serves as a molecular link between mitophagy and neuronal ferroptosis, and to determine whether salidroside (Sal) can inhibit neuronal ferroptosis after oxygen-glucose deprivation/reoxygenation (OGD/R) by inducing FUNDC1 expression and regulating mitophagy, thereby exerting neuroprotective effects. An in vitro model of neuronal ischemia-reperfusion injury was established with HT22 cells subjected to OGD/R. The experiment consisted of three parts: ① control, OGD/R, ferrostatin-1 (Fer-1), FUNDC1 overexpression (OV-FUNDC1), and OV-FUNDC1+Fer-1 groups; ② control, OGD/R, 3-methyladenine (3MA, an autophagy inhibitor), Sal, and Sal+3MA groups; ③control, OGD/R, Sal, FUNDC1 silencing (Si-FUNDC1), and Sal+Si-FUNDC1 groups. In the first part of the experiment, the survival rate of cells in each group was detected by the CCK-8 assay, and the protein levels of p62, microtubule-associated protein light chain 3 (LC3), acyl-CoA synthetase long-chain family 4 (ACSL4), and glutathione peroxidase 4 (GPX4) were measured by Western blot. The results showed that compared with the control group, the OGD/R group had down-regulated protein levels of p62 and GPX4 (P<0.05, P<0.01) and up-regulated protein level of ACSL4 (P<0.01); compared with the OGD/R group, the OV-FUNDC1 group showed increased protein levels of LC3 and GPX4 (P<0.05, P<0.01) and decreased protein levels of p62 and ACSL4 (P<0.05, P<0.01). In the second part of the experiment, after Sal intervention, the protein levels of FUNDC1, p62, LC3, ACSL4, and GPX4 were determined by Western blot, and changes in mitochondrial membrane potential were measured via JC-1. The results showed that compared with the OGD/R group, the Sal group had up-regulated protein levels of FUNDC1, LC3, and GPX4 (P<0.01), down-regulated protein levels of p62 and ACSL4 (P<0.01), and increased mitochondrial membrane potential (P<0.01); the 3MA group showed decreased mitochondrial membrane potential (P<0.01). In the third part of the experiment, after silencing of FUNDC1, the intracellular Fe²⁺ content was measured via a ferrous ion assay kit; reactive oxygen species (ROS) levels were measured by flow cytometry; the mitochondrial function was assessed via MitoTracker Red; adenosine triphosphate (ATP) and glutathione (GSH) levels were detected using assay kits; the expression of ACSL4 and GPX4 was detected by immunofluorescence; the protein levels of p62, LC3, ACSL4, and GPX4 were measured by Western blot. The results showed that compared with the Si-FUNDC1 group, the Sal group had decreased Fe²⁺ concentration (P<0.01), reduced ROS level (P<0.01), increased MitoTracker Red fluorescence intensity (P<0.01) and GSH content (P<0.01), weakened ACSL4 fluorescence intensity (P<0.01), enhanced GPX4 fluorescence intensity (P<0.01), up-regulated protein levels of LC3 and GPX4 (P<0.01), and down-regulated protein levels of p62 and ACSL4 (P<0.01). This study reveals that FUNDC1 may be a key protein linking mitochondrial autophagy and ferroptosis in neurons after ischemia-reperfusion injury, and Sal intervention can inhibit neuronal ferroptosis after ischemia-reperfusion by promoting the non-ubiquitinated FUNDC1-dependent mitophagy pathway.

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.