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High-altitude polycythemia (HAPC) occurs in high-altitude (HA) environments and involves an imbalance between erythropoiesis and eryptosis. Spleen/splenic macrophages are an important primary tissue/cell of eryptosis and iron recycling. However, the role of the spleen in the pathogenesis of HAPC and the effect of hypobaric hypoxia (HH) on the biology of the spleen and splenic macrophages are still unclear. We used a mouse hypobaric hypoxia (HH) exposure model to simulate anin vivostudy of 6000 m HA exposure. Forin vitrostudies, we used a primary splenic macrophage model treated with 1% hypoxia. We found that the HH-treated mouse model promoted erythropoiesis and led to erythrocytosis. In addition, HH exposure resulted in marked splenic contraction followed by splenomegaly for up to 14 days. HH exposure impaired the red blood cell (RBC) handling capacity of the spleen, which was caused by a decrease in splenic macrophages in the red pulp. Moreover, HH treatment for 7 and 14 days promoted iron mobilization and ferroptosis in the spleen, as reflected by the expression of metabolism-related proteins and ferroptosis-related proteins. All of the protein expression levels were similar to the gene expression levels in human peripheral blood mononuclear cells. Single-cell sequencing of the spleen further demonstrated a significant decrease in macrophages in the spleen 7 days after HH exposure. Inin vitrostudies, we confirmed that primary splenic macrophages decreased and induced ferroptosis following hypoxic treatment, which was reversed by pre-treatment with the ferroptosis inhibitor ferrostatin-1. Taken together, HH exposure induces splenic ferroptosis, especially in red pulp macrophages, which further inhibits the clearance of RBCs from the spleen. As such, it promotes the retention of RBCs in the spleen and causes splenomegaly, which may further lead to the persistent production of RBCs and ultimately to the development of HAPC.

Inonotus obliquus (Fr.) Pilat is an edible mushroom which is used to produce tea and syrup due to its medicinal properties.

An investigation of the fruiting bodies of edible mushroom Ganoderma lucidum produced 13 steroids, containing one new lanostane-type triterpene compound, named ganoderterpene A (1). Nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data were used to deduce these structures. All the isolates were evaluated for their ability to suppress NO generation in BV-2 microglial cells treated with lipopolysaccharide (LPS) and exhibited moderate to strong inhibition effects, with IC50 values in the range 7.15-36.88 μM. Among the tested compounds, compound 1 exhibited the most marked activity with an IC50 value of 7.15 μM, and the structure-activity relationships were studied. This study showed that compound 1 significantly suppressed the activation of MAPK and TLR-4/NF-κB signaling pathways, as evidenced by an immunofluorescence assay and a molecular docking experiment. Furthermore, compound 1 effectively improved the LPS-induced mitochondrial membrane potential and apoptosis. These findings suggest that ganoderterpene A could exert protective effects in microglial cells from apoptosis by restraining the inflammatory response. Hence, G. lucidum could be used as a novel preventative agent for neurodegenerative disorders.

An investigation of the fruiting bodies of edible mushroom

Ganoderma resinaceum, as a traditional edible mushroom, has been widely reported to improve neurodegenerative diseases characterized by oxidative stress and inflammation. In this study, five new terpenoids, including four lanostane triterpenoids, named ganoresinoid A-D (1-4) and one meroterpenoid, named ganoresinoid E (5), along with 27 known compounds (6-32), were isolated from the fruiting bodies of edible mushroom G. resinaceum. These structures were identified by NMR, HRESIMS data analysis. All metabolites were evaluated for anti-inflammatory, antioxidative and anti-apoptosis activities. Among them, ganoresinoid A showed notably restrained nitric oxide (NO), IL-1β, IL-6 and TNF-α levels in LPS-activated BV-2 microglial cells via suppressing TLR-4/ NF-κB and MAPK signaling pathway. Simultaneously, ganoresinoid A remarkably alleviated LPS-induced apoptosis by means of the decrease of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). In addition, ganoresinoid A demonstrated antioxidant effects in H

Ganorbifates C–I, seven undescribed biosynthetically related polyoxygenated 3,4-seco-27-norlanostanoid congeners, were isolated from the edible mushroom, Ganoderma orbiforme. Ganorbifate C features a unique cyclobutene ring constructed at C19/C11, and both D and E incorporate an unusual cyclopropane ring formed by C-19/C-9 linkage. Their structures, including the absolute configurations, were determined by spectroscopic methods and ECD calculations. The proposed Norrish-Yang cyclization-based key biosynthetic pathway for ganorbifates C-E is revealed by density functional theory (DFT) calculations. The computational studies uncover the formation of both cyclobutene and cyclopropane rings in the isolates and the stereoselectivity centers of these steps are consistent with those in the natural products. All compounds exhibited NO generation inhibition in LPS-induced BV-2 microglial cells, among them ganorbifate C was the most promising one with the IC50 values of 4.37 μM.

Eucommia ulmoides (EU) Oliver seeds are rich in oil and serve as a potential edible oil, but little is known about its phytochemical substances. In this study, the sterol profiles of the supercritical CO2 fluid extracted EU seed oil and its contents were first evaluated by GC-MS analysis, and fifteen sterols and three triterpene alcohols were determined. β-sitosterol was detected as the most abundant phytosterol in the seed oil. Additionally, seven iridoid glycosides (1–7), namely aucubin (1), bartsioside (2), linaride (3), geniposidic acid (4), one dimer scyphiphin D (5), two trimers ulmoidoside A (6) and ulmoidoside B (7) were identified from the defatted seed flour, and the compound 3 was reported in E. ulmoides for the first time. Natural and two acetylated compounds (1–9) were evaluated for their inhibitory effects on NO production in the lipopolysaccharide (LPS)-stimulated microglial cells, and 1–3 exerted significant inhibition of NO generation with IC50 values of 3.60, 7.09, and 10.52 μM, respectively. The structure-activity relationships (SARs) of these iridoids indicated that OH groups on C-10 and C-6 were more effective and the COOH group at C-4 position was highly detrimental to the activity. The results suggest that the edible EU seeds could be a potential dietary source of aucubin and β-sitosterol for reducing the risk of neurodegenerative diseases.