Panax notoginseng saponins (PNS), the main active ingredient of herbal medicine Panax notoginseng, has been generally applied for the therapy of cardiovascular and cerebrovascular diseases, especially for stroke. It is believed that PNS has obvious anti-inflammatory effect, however, the roles of PNS on microglia after stroke have not been completely explored and the underlying mechanism of microglia-mediated inflammation remains to be clarified. In this study, cerebral ischemia injury was induced by photothrombotic (PT) stroke in mice. Two days after operation, PNS administration alleviated ischemic brain injury by increasing grip strength, relieving neurological deficits, improving local cerebral blood flow, and reducing pathological damage in the brain cortex and hippocampus. Moreover, microglial activation occurred in the acute stage after stroke and mediated inflammation, whereas PNS administration could inhibit microglial activation and inflammation. Meanwhile, we firstly demonstrated that PKM2 expression was upregulated in the nucleus of activated microglia after stroke, which could be inhibited after PNS administration. We hypothesized that suppression of nuclear PKM2 upregulation in microglia along with downregulation of HIF-1α/PKM2/STAT3 signaling could partially underlie the potential anti-inflammatory mechanism of PNS against ischemic brain injury. Our findings offer some new standpoints about PNS against microglia-mediated inflammation after stroke. Despite strengths, this study has limitation. PKM2 is not specifically expressed by microglia, but could be expressed by neurons, vascular endothelial cells, etc. Here we only explored the effect of PKM2 on activated microglia, and we would further investigate the impact of PKM2 expressed in other cells on stroke outcome in the future.

Background: Poststroke cognitive impairment (PSCI) is a common complication observed after stroke. Current pharmacologic therapies have no definitive evidence for cognitive recovery or disease progression. Recent studies have verified the positive effect of DL-3-n-butylphthalide (NBP). However, the clinical efficacy and safety are still unclear. The aim of this study was to assess the efficacy of NBP and its harmful effect in the treatment of PSCI.Method: Eligible randomized controlled trials (RCTs) were retrieved from inception to June 2021 from seven medical databases and two clinical registries. The revised Cochrane risk of bias tool (RoB 2.0) was used for methodological quality. RevMan v5.4.1 from Cochrane Collaboration was used for statistical analysis, and Hartung-Knapp-Sidik-Jonkman (HKSJ) method was used for post hoc testing depend on the number of studies. This study has been submitted to PROSPERO with registration number is CRD42021274123.Result: We identified 26 studies with a total sample size of 2,571 patients. The results of this study showed that NBP as monotherapy or combination therapy had better performance in increasing the MoCA (monotherapy: SMD_N = 1.05, 95% CI [0.69, 1.42], p < 0.00001; SMD_P = 1.06, 95% CI [0.59, 1.52], p < 0.00001. combination: SMD_O = 0.81, 95% CI [0.62, 1.01], p < 0.00001; SMD_N = 0.90, 95% CI [0.46, 1.33], p < 0.0001; SMD_D = 1.04, 95% CI [0.71, 1.38], p < 0.00001), MMSE (monotherapy: MD_N = 4.89, 95% CI [4.14, 5.63]), p < 0.00001). combination: SMD_O = 1.26, 95% CI [0.97, 1.56], p < 0.00001; SMD_C = 1.63, 95% CI [1.28, 1.98], p < 0.00001; SMD_N = 2.13, 95% CI [1.52, 2.75], p < 0.00001) and BI (monotherapy: MD_N = 13.53, HKSJ 95% CI [9.84, 17.22], p = 0.014. combination: SMD_O = 2.24, HKSJ 95%CI [0.37, 4.11], p = 0.032; SMD_C = 3.36, 95%CI [2.80, 3.93], p < 0.00001; SMD_D = 1.48, 95%CI [1.13, 1.83], p < 0.00001); and decreasing the NIHSS (monotherapy: MD_N = −3.86, 95% CI [−5.22, −2.50], p < 0.00001. combination: SMD_O = −1.15, 95% CI [−1.31, −0.98], p < 0.00001; SMD_C = −1.82, 95% CI [−2.25, −1.40], p < 0.00001) and CSS (combination: MD_O = −7.11, 95% CI [−8.42, −5.80], p < 0.00001), with no serious adverse reactions observed. The funnel plot verified the possibility of publication bias.Conclusion: NBP maintains a stable pattern in promoting the recovery of cognitive function and abilities of daily living, as well as reducing the symptoms of neurological deficits. However, there is still a need for more high-quality RCTs to verify its efficacy and safety.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, yet as of currently, there is no disease-modifying therapy that could delay its progression. Paeonia lactiflora Pall. is the most frequently used herb in formulas for PD in Traditional Chinese Medicine and also a potential neuroprotective agent for neurodegenerative diseases, while its mechanisms remain poorly understood. In this study, we aim to explore the underlying mechanism of P. lactiflora in treating PD utilizing a network pharmacology approach.Methods: The protein targets of P. lactiflora ingredients and PD were first obtained from several databases. To clarify the key targets, a Protein-Protein-Interaction (PPI) network was constructed and analyzed on the String database, and then enrichment analysis was performed by the Metascape platform to determine the main Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the Ingredient-Target-Pathway (I-T-P) network was constructed and analyzed by Cytoscape software.Results: Six active ingredients of P. lactiflora (kaempferol, ß-sitosterol, betulinic acid, palbinone, paeoniflorin and (+)-catechin) as well as six core targets strongly related to PD treatment [AKT1, interleukin-6, CAT, Tumor necrosis factor (TNF), CASP3, and PTGS2] were identified. The main pathways were shown to involve neuroactive ligand-receptor interaction, Calcium signaling pathway, PI3-Akt signaling pathway, TNF signaling pathway, and apoptosis signaling pathway. The main biological process included the regulation of neurotransmitter levels.Conclusion:P. lactiflora may retard neurodegeneration by reducing neuroinflammation, inhibiting intrinsic and extrinsic apoptosis, and may improve motor and non-motor symptoms by regulating the levels of neurotransmitters. Our study has revealed the mechanism of P. lactiflora in the treatment of PD and may contribute to novel drug development for PD.

Post-stroke cognitive impairment, is a major complication of stroke, characterized by cognitive dysfunction, which directly affects the quality of life. Post-stroke cognitive impairment highlights the causal relationship between stroke and cognitive impairment. The pathological damage of stroke, including the increased release of excitatory amino acids, oxidative stress, inflammatory responses, apoptosis, changed neurotrophic factor levels and gene expression, influence synaptic plasticity. Synaptic plasticity refers to the activity-dependent changes in the strength of synaptic connections and efficiency of synaptic transmission at pre-existing synapses and can be divided into structural synaptic plasticity and functional synaptic plasticity. Changes in synaptic plasticity have been proven to play important roles in the occurrence and treatment of post-stroke cognitive impairment. Evidence has indicated that Chinese herbal drugs have effect of treating post-stroke cognitive impairment. In this review, we overview the influence of pathological damage of stroke on synaptic plasticity, analyze the changes of synaptic plasticity in post-stroke cognitive impairment, and summarize the commonly used Chinese herbal drugs whose active ingredient or extracts can regulate synaptic plasticity. This review will summarize the relationship between post-stroke cognitive impairment and synaptic plasticity, provide new ideas for future exploration of the mechanism of post-stroke cognitive impairment, compile evidence of applying Chinese herbal drugs to treat post-stroke cognitive impairment and lay a foundation for the development of novel formulas for treating post-stroke cognitive impairment.

Elderly individuals living alone represent a vulnerable group with limited family support, making them more susceptible to mental health issues such as depression and anxiety. This study aims to construct a network model of depression and anxiety symptoms among older adults living alone, exploring the correlations and centrality of different symptoms. The goal is to identify core and bridging symptoms to inform clinical interventions. Using data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), this study constructed a network model of depression and anxiety symptoms among elderly individuals living alone. Depression and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale-10 (CESD-10) and the Generalized Anxiety Disorder Scale-7 (GAD-7), respectively. A Gaussian Graphical Model (GGM) was employed to build the symptom network, and the Fruchterman-Reingold algorithm was used for visualization, with the thickness and color of the edges representing partial correlations between symptoms. To minimize spurious correlations, the Least Absolute Shrinkage and Selection Operator (LASSO) method was applied for regularization, and the optimal regularization parameters were selected using the Extended Bayesian Information Criterion (EBIC). We further calculated Expected Influence (EI) and Bridge Expected Influence (Bridge EI) to evaluate the importance of symptoms. Non-parametric bootstrap methods were used to assess the stability and accuracy of the network. The Network centrality analysis revealed that GAD2 (Uncontrollable worry) and GAD4 (Trouble relaxing) exhibited the highest strength centrality (1.128 and 1.102, respectively), indicating their significant direct associations with other symptoms and their roles as core nodes in the anxiety symptom network. Other highly central nodes, such as GAD1 (Nervousness or anxiety) and GAD3 (Generalized worry), further underscore the dominance of anxiety symptoms in the overall network. Betweenness centrality results highlighted GAD1 (Nervousness or anxiety) and GAD2 (Uncontrollable worry) as critical bridge nodes facilitating information flow between different symptoms, while CESD3 (Feeling depressed) demonstrated a bridging role across modules. Weighted analyses further confirmed the central importance of GAD2 (Uncontrollable worry) and GAD4 (Trouble relaxing). Additionally, the analysis showed gender differences in the depression-anxiety networks of elderly individuals living alone. This study, through network analysis, uncovered the complex relationships between depression and anxiety symptoms among elderly individuals living alone, identifying GAD2 (Uncontrollable worry) and GAD4 (Trouble relaxing) as core symptoms. These findings provide essential insights for targeted interventions. Future research should explore intervention strategies for these symptoms to improve the mental health of elderly individuals living alone.