Ferroptosis is a form of regulated nonapoptotic cell death associated with iron-dependent lipid peroxidation. Previous studies have shown that ferroptosis is involved in the occurrence and development of acute lung injury (ALI). In this study, a systems pharmacology approach was performed through the overall process of target acquisition, network construction, and further analysis. Then, the effects of astaxanthin on LPS-induced inflammation and ferroptosis were investigated in RAW264.7 cells induced by LPS in vitro and ALI mice induced by LPS in vivo. The enrichment analysis of astaxanthin-target gene is closely related to the occurrence and development mechanism of ferroptosis. GO and KEGG enrichment analysis of astaxanthin acting on ALI found that these intersection genes are associated with ALI inflammatory pathway. In addition, astaxanthin can effectively inhibit LPS-induced production of pro-inflammatory cytokines and ferroptosis in RAW264.7 cells. Consistently, administration of astaxanthin protected mice against LPS-induced ALI and significantly decreased the extent of lung edema, inflammatory cells infiltration, and ferroptosis in vivo, and Keap1-Nrf2/HO-1 pathway is involved in astaxanthin inhibits LPS-induced ALI and ferroptosis. Taken together, these results demonstrate that astaxanthin inhibit inflammation and ferroptosis by regulating Keap1-Nrf2/HO-1 pathway to reduce LPS-induced ALI. 

Astaxanthin attenuates ferroptosis via Keap1-Nrf2/HO-1 signaling pathways in LPS-induced acute lung injury.

Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms of IS. In particular, the early proinflammatory response resulting from the overactivation of resident microglia and the infiltration of circulating monocytes and macrophages in the brain after cerebral ischemia leads to secondary brain injury. Microglia are innate immune cells in the brain that constantly monitor the brain microenvironment under normal conditions. Once ischemia occurs, microglia are activated to produce dual effects of neurotoxicity and neuroprotection, and the balance of the two effects determines the fate of damaged neurons. The activation of microglia is defined as the classical activation (M1 type) or alternative activation (M2 type). M1 type microglia secrete pro-inflammatory cytokines and neurotoxic mediators to exacerbate neuronal damage, while M2 type microglia promote a repairing anti-inflammatory response. Fine regulation of M1/M2 microglial activation to minimize damage and maximize protection has important therapeutic value. This review focuses on the interaction between M1/M2 microglia and other immune cells involved in the regulation of IS phenotypic characteristics, and the mechanism of natural plant components regulating microglia after IS, providing novel candidate drugs for regulating microglial balance and IS drug development. 

/pdf/the-mechanism-of-microglia-mediated-immune-inflammation-in-gatxbwce.pdf

The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review

Abstract Background Icariin (ICA), an active ingredient extracted from Epimedium species, has shown promising results in the treatment of Alzheimer's disease (AD), although its potential therapeutic mechanism remains largely unknown. This study aimed to investigate the therapeutic effects and the underlying mechanisms of ICA on AD by an integrated analysis of gut microbiota, metabolomics, and network pharmacology (NP). Methods The cognitive impairment of mice was measured using the Morris Water Maze test and the pathological changes were assessed using hematoxylin and eosin staining. 16S rRNA sequencing and multi-metabolomics were performed to analyze the alterations in the gut microbiota and fecal/serum metabolism. Meanwhile, NP was used to determine the putative molecular regulation mechanism of ICA in AD treatment. Results Our results revealed that ICA intervention significantly improved cognitive dysfunction in APP/PS1 mice and typical AD pathologies in the hippocampus of the APP/PS1 mice. Moreover, the gut microbiota analysis showed that ICA administration reversed AD-induced gut microbiota dysbiosis in APP/PS1 mice by elevating the abundance of Akkermansia and reducing the abundance of Alistipe . Furthermore, the metabolomic analysis revealed that ICA reversed the AD-induced metabolic disorder via regulating the glycerophospholipid and sphingolipid metabolism, and correlation analysis revealed that glycerophospholipid and sphingolipid were closely related to Alistipe and Akkermansia . Moreover, NP indicated that ICA might regulate the sphingolipid signaling pathway via the PRKCA/TNF/TP53/AKT1/RELA/NFKB1 axis for the treatment of AD. Conclusion These findings indicated that ICA may serve as a promising therapeutic approach for AD and that the ICA-mediated protective effects were associated with the amelioration of microbiota disturbance and metabolic disorder. Graphical Abstract 

/pdf/anti-alzheimers-molecular-mechanism-of-icariin-insights-from-4zhkwyys.pdf

Anti-Alzheimers molecular mechanism of icariin: insights from gut microbiota, metabolomics, and network pharmacology

Potential treatment of COVID-19 with traditional chinese medicine: What herbs can help win the battle with SARS-CoV-2?

Therapeutic targeting of Ras/Raf/MAPK pathway by natural products: A systematic and mechanistic approach for neurodegeneration.

Icariin is a biologically active substance in Epimedii herba that is used for the treatment of neurologic disorders. However, a comprehensive analysis of the molecular mechanisms of icariin is lacking. In this review, we present a brief history of the use of icariin for medicinal purposes; describe the active chemical components of Epimedii herba; and examine the evidence from experimental studies that have uncovered molecular targets of icariin in different diseases. We also constructed a protein-protein interaction network and carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to predict the therapeutic actions of icariin in nervous system diseases including Alzheimer disease, Parkinson disease, ischemic stroke, depressive disorder, multiple sclerosis, glioblastoma, and hereditary spastic paraplegias. The results of our analyses can guide future studies on the application of icariin to the treatment of neurologic disorders.

/pdf/icariin-an-up-and-coming-bioactive-compound-against-3ykqnq3q75.pdf

Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review.

Background Since December 2019, coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has emerged in Wuhan and rapidly spread throughout China and even to other countries. Combined therapy with modern medicine and traditional Chinese medicine has been proposed, in which Shen Zhu San (SZS) was regarded as one of the basic prescriptions. Methods Network pharmacological approaches along with candidate compound screening, target prediction, target tissue location, protein-protein interaction network, gene ontology (GO), KEGG enrichment analyses, and gene microarray analyses were applied. Results A total of 627 targets of the 116 active ingredients of SZS were identified. Targets in immune cells and tissues were much more abundant than those in other tissues. A total of 597 targets were enriched in the GO biological cellular process, while 153 signaling pathways were enriched according to the KEGG analysis. A total of 450 SARS-related targets were integrated and intersected with the targets of SZS to identify 40 common targets that were significantly enriched in five immune function aspects of the immune system process during GO analysis. Several inflammation-related pathways were found to be significantly enriched throughout the study. Conclusions The therapeutic mechanisms of the effects of SZS on COVID-19 potentially involve four effects: suppressing cytokine storms, protecting the pulmonary alveolar-capillary barrier, regulating the immune response, and mediating cell death and survival.

/pdf/investigation-of-the-potential-mechanism-governing-the-3v0k85z0lk.pdf

Investigation of the Potential Mechanism Governing the Effect of the Shen Zhu San on COVID-19 by Network Pharmacology.

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Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review.

Investigation of the Potential Mechanism Governing the Effect of the Shen Zhu San on COVID-19 by Network Pharmacology.