Deciphering the Efficacy and Mechanism of Astragalus membranaceus on High Altitude Polycythemia by Integrating Network Pharmacology and In Vivo Experiments

Abstract

Hypoxic exposure makes plateau migrators susceptible to high altitude polycythemia (HAPC). Astragalus membranaceus (AM) is an edible and medicinal plant with remarkable immunomodulatory activities. The purpose of this study was to discover if AM could be a candidate for the prevention of HAPC and its mechanism. Here, network pharmacology was applied to screen active compounds, key targets, and enriched pathways of AM in the treatment of HAPC. Molecular docking evaluated the affinity between compounds and core targets. Subsequently, the mechanisms of AM were further verified using the hypoxia exposure-induced mice model of HAPC. The network pharmacology analysis and molecular docking results identified 14 core targets of AM on HAPC, which were predominantly mainly enriched in the HIF-1 pathway. In the HAPC animal models, we found that AM inhibited the differentiation of hematopoietic stem cells into the erythroid lineage. It also suppressed the production of erythrocytes and hemoglobin in peripheral blood by reducing the expression of HIF-1α, EPO, VEGFA, and Gata-1 mRNA. Furthermore, AM downregulated the expression of IL-6, TNF-α, and IFN-γ mRNA, thereby alleviating organ inflammation. In conclusion, AM supplementation alleviates hypoxia-induced HAPC in mice, and TNF-α, AKT1, HIF-1α, VEGFA, IL-6, and IL-1B may be the key targets.

Unraveling the Role of Scutellaria baicalensis for the Treatment of Breast Cancer Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

“…The BC and CC represented the shortest path crossing a single node and the ease of communication between nodes. A value greater than twice the median of Degree and the median of the BC and CC was used as the criterion to screen the core compound targets of Scutellaria baicalensis and disease and to create a PPI network interaction map [ 51 ].…”

Correlation between serum inflammatory factors and cognitive function in patients with high-altitude polycythemia: A case–control study

“…[2,3] It has also been found that HAPC is closely related to hematopoietic factors and inflammatory factors. [3,4] HAPC can cause blood vessel damage, microvascular lesions, cerebral arteriosclerosis, cerebral perfusion, cerebral metabolism, and inflammatory responses in the brain promoting the release of inflammatory cytokines, peripheral blood cells, and peripheral blood of inflammatory cytokines, also changing the permeability of the blood-brain barrier and promoting inflammation factors and white blood cells into the brain, with decreased cognitive function. [5][6][7] At present, there are few reports on the correlation between inflammatory factors and cognitive impairment in patients with polycythemia in altitude hypoxia environments worldwide.…”

A novel microbial and hepatic biotransformation-integrated network pharmacology strategy explores the therapeutic mechanisms of bioactive herbal products in neurological diseases: the effects of Astragaloside IV on intracerebral hemorrhage as an example

“…However, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of many herbal products are too poor to bind the putative targets in the lesions sufficiently, especially in the brain [5][6][7]. In this regard, most studies exclude the ingredients with low oral bioavailability (OB), drug-likeness (DL), or blood-brain barrier (BBB) permeability to reduce the false positive results in network pharmacology [8][9][10][11][12]. However, this strategy ignored the therapeutic effects and mechanisms of the low-OB compounds.…”