Microglia are permanent immune cells of the central nervous system. Microglia play an important role in the pathological process of Alzheimer's disease (AD). They are mainly involved in the uptake and clearance of amyloid‐β (Aβ), as well as the formation of neuroinflammation. We found that overactivated microglia increase Aβ and Tau, and Aβ and Tau in turn act as activators of microglia. Additionally, various cytokines and proteins, high cholesterol, and telomere shortening are all associated with microglia activation. More activated microglia induce the release of inflammatory and anti‐inflammatory factors to regulate inflammation, while microglia express multiple homologous receptors that bind to neuroimmunomodulators to prevent microglia overactivation. Moreover, aging of the body promotes neuroinflammation by increasing the response to IFN‐γ (interferon‐γ), and aging of the microglia themselves promotes AD by inducing the accumulation of large amounts of iron and reducing autophagy by regulating protein levels. Cognitive dysfunction occurs when activated microglia induce an increase in beta oligomers, promoting the production of pro‐inflammatory factors that alter the shape, composition, and density of synapses. Based on their correlation, microglia‐mediated AD therapy as well as the corresponding targets and drugs are discussed. In contrast to similar reviews, this article also summarizes some novel microglia‐mediated AD treatment methods over the recent years.

To investigate the effect of scutellarin (SCU) in diabetic retinopathy (DR) and explore the associated molecular network mechanism. The animal model of DR was established from diabetic mellitus (DM) rats by intraperitoneally injected streptozotocin (STZ) at dosage 55 mg/kg. Meanwhile, SCU was intraperitoneally administrated to protect retina from cell pyroptosis induced by DM, and cell pyroptosis was detected by using HE, Nissl staining, and immunofluorescence recognition. Moreover, the hub gene involving in pyroptosis in DR was screened by bioinformatics and network pharmacology, designated as Venny intersection screen, GO and KEGG analysis, PPI protein interaction, and molecular docking. Lastly, the expressional change of hub genes were validated with experimental detection. Cell pyroptosis of the DR, specifically in retina ganglion cells (RGC), was induced in DM rats; SCU administration results in significant inhibition in the cell pyroptosis in DR. Mechanically, 4084 genes related to DR were screened from GeneCards and OMIM databases, and 120 SCU therapeutic targets were obtained, by using GeneCards, TCMSP with Swiss Target Prediction databases. Moreover, 357 targets related to pyroptosis were found using GenenCards database, and Drug, disease and phenotypic targets were analyzed online using the Draw Venn Diagram website, and 12 cross targets were obtained. Through GO function and KEGG pathway enrichment analysis, 659 BP related items, 7 CC related items, 30 MF related items, and 70 signal pathways were screened out; Of these, eleven proteins screened from cross-target PPI network were subsequently docked with the SCU, and their expressions including caspase-1, IL-1β, IL-18, GSDMD and NLRP3 in RGC indicated by immunofluorescence, and the mRNA expression for caspase-1 in DR indicated by quantitative PCR, were successfully validated. SCU can effectively protect RGC pyroptosis in DR, and underlying mechanisms are involved in the inhibition of caspase-1, GSDMD, NLRP3, IL-1β and IL-18. Our findings therefore provide crucial evidence to support the clinic practice of SCU for the treatment of DR, and explained the underlying molecular network mechanism.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by neurodegeneration, nerve loss, neurofibrillary tangles and Aβ plaques. Different process of the AD pathology present more opportunities for treatment. In addition, the holistic approaches involving network pharmacology with traditional Chinese medicine (TCM) may be viable options for AD treatment, and lead to an effective cure for AD in the future. Therefore, this study explored the therapeutic effect and mechanism of Rosmarinus officinalis L(rosemary) in the treatment of Alzheimer’s disease on basis of cell experiments, network pharmacology and molecular docking. We performed cell experiments, to investigate the therapeutic effects of Rosmarinus officinalis L on AD in vitro using CCK8 assay, flow cytometry and TMRE Kit. In addition, carnosic acid is a major antioxidant diterpenoid in Rosmarinus officinalis L. We performed cell experiments, to investigate the neuroprotective effects of carnosic acid on AD in virto using CCK8 assay and flow cytometry. Furthermore, the main antioxidant compounds of rosemary ware collected through literature reviews, PharmMapper and Swiss Target prediction ware used to identify their potential targets. Targets of AD were obtained from Genecards and OMIM. The intersection targets of the main active components of rosemary and the therapeutic targets of Alzheimer’s disease were subsequently obtained by using online Venn diagram. Protein–protein interaction, Cytoscape, Gene Ontology, and Kyoto Encyclopedia of Genes were used to analyze potential targets and key pathways of rosemary in AD. Besides, through molecular docking, the interactions of the main active components of rosemary, and the predicted candidate targets were verified. Finally, quantitative Real-Time PCR (RT-qPCR) was performed to confirm the effectiveness of the genes. It was found that rosemary could reversed Aβ25–35 induced damage to mouse hippocampal neuron HT22 cells, significantly improved the viability of damaged cells, and reduced apoptosis. The results of fluorescent staining with Hoechst 33,342 and TMRE suggested that rosemary inhibited the reduction of mitochondrial membrane potential levels induced by Aβ25–35, which had a specific protective effect on AD in vitro. Additionally, a main antioxidant compound in rosemary, carnosic acid, also has neuroprotective effects. Eight main antioxidant compounds of rosemary ware collected. Network pharmacology and molecular docking, revealed that rosemary plays a therapeutic role in the treatment of Alzheimer’s disease through the main active carnosic acid, carnosol, rosmarinol, rosmadial, genkwanin, cirsimaritin, rosmarinic acid and caffeic acid in Rosmarinus officinalis L, which affects the gene regulation of HRAS, ESR1, RHOA, IGF1, SRC, ANXA5, MMP9, MAPK14, NOS3, and PIK3R1, and participates in the PI3K-Akt, Rap1, MAPK, and estrogen signaling pathways. RT-qPCR indicated that rosemary could elevated expression of IGF1, MMP9 and decreased mRNA levels of SRC, MAPK14, compared with the control group. Rosemary is an important economic plant with multi-component, multi-target and multi-pathway synergistic effects.The findings highlight the effectiveness of rosemary in helping to increase cell viability and reduce apoptosis when treating mouse hippocampal neuron HT22 cells, thereby supporting its therapeutic potential in treating Alzheimer’s disease.

Spinal cord injury (SCI) is a severe complication of spinal trauma with high disability and mortality rates. Effective therapeutic methods to alleviate neurobehavioural deficits in patients with SCI are still lacking. In this study, we established a spinal cord contusion (SCC) model in adult Sprague Dawley rats. Induced pluripotent stem cell-derived A2B5⁺ oligodendrocyte precursor cells (iP-A2B5⁺OPCs) were obtained from mouse embryonic fibroblasts and injected into the lesion sites of SCC rats. Serological testing and magnetic resonance imaging were employed to determine the effect of iP-A2B5⁺OPCs cell therapy. The Basso-Beattie-Bresnahan score and inclined plane test were performed on days 1, 3, 7, and 14 after cell transplantation, respectively. Differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were detected by microarray analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyse the biological functions of these lncRNAs and mRNAs. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify variations in the expression of crucial target genes. The results demonstrated that induced pluripotent stem cells exhibited embryonic stem cell-like morphology and could differentiate into diverse neural cells dominated by oligodendrocytes. The neurobehavioural performance of rats treated with iP-A2B5⁺OPCs transplantation was better than that of rats with SCC without cell transplantation. Notably, we found that 22 lncRNAs and 42 mRNAs were concurrently altered after cell transplantation, and the key lncRNA (NR_037671) and target gene (Cntnap5a) were identified in the iP-A2B5⁺OPCs group. Moreover, RT-qPCR revealed that iP-A2B5⁺OPCs transplantation reversed the downregulation of NR_037671 induced by SCC. Our findings indicated that iP-A2B5⁺OPCs transplantation effectively improves neurological function recovery after SCC, and the mechanism might be related to alterations in the expression of lncRNAs and mRNAs, such as NR_037671 and Cntnap5a.