Serum metabolomics analysis combined with network pharmacology reveals possible mechanisms of postoperative cognitive dysfunction in the treatment of Mongolian medicine Eerdun Wurile basic formula.

This study analyzed the endogenous metabolites and metabolic pathways in the serum of Sprague-Dawley (SD) rats gavaged with the Eerdun Wurile basic formula (EWB) using metabolomics methods and network pharmacology to explore the possible mechanism of action of the EWB in improving postoperative cognitive dysfunction (POCD). SD rats were divided into the basic formula group, which received the EWB, and the control group, which received equal amounts of distilled water. The blood was collected from the abdominal aorta and analyzed for metabolite profiles using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Network pharmacology predicts the targets of the differential metabolites and disease targets; takes the intersection and constructs a "metabolite-disease-target" network; and performs protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 56 metabolites were selected for significant differences between the groups, mainly affecting amphetamine addiction, alcoholism, and regulation of lipolysis in adipocytes. A total of 177 potential targets for differential metabolite action in POCD were selected. The PI3K-Akt pathway, the HIF-1 pathway, and the FoxO pathway were in key positions. The studies have shown that EWB could improve POCD through multicomponents, multitargets, and multipathways, providing new possibilities and reference values for the treatment of POCD.

Nutrients addition decreases soil fungal diversity and alters fungal guilds and co-occurrence networks in a semi-arid grassland in northern China.

Anthropogenic eutrophication is known to impair the diversity and stability of aboveground community, but its effects on the diversity, composition and stability of belowground ecosystems are not yet fully understood. In this study, we conducted a 9-year nitrogen (N) and phosphorus (P) addition experiment in a semi-arid grassland of Northern China to elucidate the impacts of nutrients addition on soil fungal diversity, functional guilds, and co-occurrence networks. The results showed that N addition significantly decreased soil fungal diversity and altered fungal community composition, whereas P addition had no impact on them. The relative abundance of arbuscular mycorrhizal fungi and leaf_saprotroph were reduced by N and P addition, but P addition enhanced the abundance of saprotrophic fungi. Co-occurrence network analysis revealed that N addition destabilized fungal network complexity and stability, while P addition slightly increased the network complexity. Additionally, the network analysis of N × P interaction revealed that P addition mitigated negative effects of N addition on network complexity and stability. Structural equation modeling (SEM) results suggested that nutrients addition directly or indirectly influenced the fungal community structure through the loss of plant richness and the increase of perennial grass biomass. These findings indicate that in comparison to P addition, N addition exhibits a pronounced negative effect on soil fungal communities. Our findings also suggest that changes in plant functional groups under nutrients deposition are pivotal in shaping soil fungal community structure in semi-arid grassland and highlight the need for a better understanding of the belowground ecosystem dynamics.

Study on the Mechanism of Eerdun Wurile's Effects on Post-operative Cognitive Dysfunction by the TLR4/NF-κB Pathway.

The object of our work was to observe whether the Mongolian medicine Eerdun Wurile (EW) improve postoperative cognitive dysfunction (POCD) by affecting the TLR4/NF-κB. Mice (6-8-week-old male C57BL/6 J) were selected to establish an animal model of POCD by combining intracerebroventricular injection of lipopolysaccharide and nephrectomy; EW formulation and EW basic formulation were administered intra-gastrically for 7 consecutive days. The cognitive performance was assessed by Morris water maze test. H&E staining was examined to detect alterations in hippocampal tissue. Immunohistochemical staining was performed to evaluate MyD88, NF-κB, TLR4, iNOS, and IBA-1 expressions; Western blotting and RT-qPCR were performed to evaluate MyD88, NF-κB, and TLR4. The expressions of IL-6, IL-1ß, and TNF-α were evaluated by ELISA. Intracerebroventricular injection of lipopolysaccharide combined with nephrectomy induced cognitive dysfunction in mice, stimulated TLR4/NF-κB and microglia, and promoted the secretion of murine TNF-α, IL-1ß, and IL-6. EW formulation and EW basic formulation treatment are able to suppress the TLR4/NF-κB pathway activation and microglia, and the serum cytokine secretions related to proinflammation, and restore the cognitive performance. EW formulation and EW basic formulation can improve POCD in mice, and TLR4/NF-κB pathway seems to be one of the important mechanisms in EW's improvement of POCD.

Mechanism of the Mongolian medicine Eerdun Wurile basic formula in improving postoperative cognitive dysfunction by inhibiting apoptosis through the SIRT1/p53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mongolian medicine Eerdun Wurile is a commonly used Mongolian in folk medicine used to treat cerebral nervous system diseases such as cerebral hemorrhage, cerebral thrombosis, nerve injury and cognitive function, cardiovascular diseases such as hypertension and coronary heart disease. Eerdun wurile may effect anti-postoperative cognitive function. AIM OF THE STUDY: To investigate the molecular mechanism of the Mongolian medicine Eerdun Wurile Basic Formula (EWB) in improving postoperative cognitive dysfunction (POCD) based on Network pharmacology, and to confirm involvement of the SIRT1/p53 signal pathway, one of the key signal pathways, by using the POCD mouse model. MATERIAL AND METHODS: Obtain compounds and disease-related targets through TCMSP, TCMID, PubChem, PharmMapper platforms, GeneCards, and OMIM databases, and screen intersection genes; Use Cytoscape software to build a "drug-ingredient-disease-target" network, and the STRING platform for protein interaction analysis.; R software was used to analyze the function of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment.; AutoDock Vina software for active components and core targets to Perform molecular docking. The POCD mouse model was prepared by intracerebroventricular injection of lipopolysaccharide (LPS), and the morphological changes of hippocampal tissue were observed by hematoxylin-eosin (HE) staining, Western blot, immunofluorescence and TUNEL were used to verify the results of network pharmacological enrichment analysis. RESULTS: There were 110 potential targets for improving POCD by EWB, 117 items were enriched by GO, and 113 pathways were enriched by KEGG, among which the SIRT1/p53 signaling pathway was related to the occurrence of POCD. Quercetin, kaempferol, vestitol, ß-sitosterol and 7-methoxy-2-methyl isoflavone in EWB can form stable conformations with low binding energy with core target proteins IL-6, CASP3, VEGFA, EGFR and ESR1. Animal experiments showed that compared with the POCD model group, the EWB group could significantly improve the apoptosis in the hippocampus of the mice, and significantly down-regulate the expression of Acetyl-p53 protein (P < 0.05). CONCLUSION: EWB can improve POCD with the characteristics of multi-component, multi-target, and multi-pathway synergistic effects. Studies have confirmed that EWB can improve the occurrence of POCD by regulating the expression of genes related to the SIRT1/p53 signal pathway, which provides a new target and basis for the treatment of POCD.

Research progress on the mechanism of chronic neuropathic pain.

Chronic neuropathic pain (CNP) refers to pain that lasts for more than three months due to a disease or an injury to the somatosensory nervous system. The incidence of CNP has been increasing in the world, causing it to become a global concern and patients often experience spontaneous pain, hyperalgesia, abnormal pain or even abnormal sensation as some of its main symptoms. In addition to serious pain and poor physical health, CNP also negatively affects patients' mental health, thus impacting the overall quality of their lives. The pathogenesis of CNP is not clear, but some studies have proved that central sensitization, peripheral sensitization, neuroinflammation, dysfunction in descending nociceptive modulatory systems, oxidative stress reaction, activation of glial cells and psychological factors play an important role in the occurrence and development of CNP. In this context, this article summarizes the current research progress on the mechanism of CNP to provide a basis for further research in preventing and treating the disease.

Mechanism of Mongolian Medicine Eerdun Wurile in Improving Postoperative Cognitive Dysfunction Through Activation of the PI3K Signaling Pathway.

OBJECTIVE: To study the effect of Eerdun Wurile (EW), a traditional Mongolian medicine, on the cognitive function of rats by activating the IRS-PI3K-AKT-GLUT4 pathway in an animal model of postoperative cognitive dysfunction (POCD). METHODS: Fifty clean-grade adults Sprague Dawley (SD) male rats were assigned to one of five groups: (1) a control group with no anesthesia (Group C), (2) a POCD model group with anesthesia only (Group P), (3) POCD group with low-dose EW treated (Group L), (4) a POCD group with high-dose EW treated (Group H), and (5) a POCD model group with dexmedetomidine treated (Group D) for positive control. The study started 7 days after all rats had acclimated to housing. Rats were trained in the Morris Water Maze navigation 5 days before surgery. All rats underwent the same maze for navigation and spatial exploration experiments on the preoperative day 1 and postoperative days 1, 3, 5, and their learning and memory abilities were assessed. At the end of the water maze experiment, rats were sacrificed to obtain hippocampal tissue. The mRNA levels of IRS-2, PI3K, AKT, and GLUT4 were measured in the hippocampus by real-time PCR, and the expression of IRS-2, PI3K, AKT, and GLUT4 protein in the hippocampus was determined by Western blotting to investigate the potential mechanisms at the molecular level. RESULTS: Compared to control Group C, Group P, L, H, and D showed prolonged escape latency (P < 0.05) and decreased number of times to cross the platform (P < 0.05) at 1, 3 and 5 days after surgery. Compared to Group P, Group L, H, and D showed a decrease in escape latency with an increased number of crossing the platform at all-time points after surgery (P < 0.05). Within individual P, L, H, and D groups, escape latencies decreased (P < 0.05) and the number of times that the platform was crossed increased (P < 0.05) between postoperative days 3 and 5 compared to postoperative 1 day. Compared to Group C, the mRNA expression of IRS-2, PI3K, AKT and GLUT4 in the hippocampus of P, L, H, and D groups were decreased (P < 0.05). Compared to Group P, IRS-2, PI3K, AKT, and GLUT4 in the hippocampus of L, H, and D groups were increased (P < 0.05). Compared with Group D, the expression levels of IRS-2 and AKT in both L and H groups were higher. The expression level of PI3K in Group L was also higher (P < 0.05) vs Group D. The expression of AKT mRNA in Group H was higher than in Group L (P < 0.05). Compared to Group C, the p-IRS-2/IRS-2 ratio in the hippocampus of Group P was higher than that of Group C (P < 0.05). Compared to Group P, the ratios of p-IRS-2/IRS-2 in Group L, Group H, and Group D were lower, and the ratios of the p-PI3K/PI3K, p-AKT/AKT, and p-GLUT4/GLUT4 were higher (P < 0.05). CONCLUSION: Administration of EW showed the effect on the signaling pathway in rats with POCD. The therapeutic effect was better in the low-dose group. This could be related to the insulin downstream signal molecule PI3K and the IRS-PI3K-AKT-GLUT4 signaling pathway.