Background Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown. Methods Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC–MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. Results We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. Conclusion Our findings demonstrated that flavonoids from Astragalus membranaceus ameliorated brain impairment, and its modulation on gut-brain axis plays a pivotal role. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.
Combining GIS measures and statistic methods, this paper selects the physiographic factors and climatic factors to study the influencing strength and its functional forms of all factors on population density in the LRGR. In addition, this paper simulates the status of population density distribution in the LRGR with the factors influencing the population density distribution. The findings indicate the following circumstances: (1) All natural factors have influence on the spatial pattern of population density in the LRGR, but the influencing extent and forms are quite different. Physiographic factors and traffic network density have great influence on population density, while such factors as temperature and precipitation have little influence on population distribution. The relationship between the population density and the altitude and traffic network density assumes the negative and positive linear correlation trends, while the influence of water system density and slope appears to be the exponential function and logarithmic function separately. (2) The population is scattered throughout LRGR and takes on such features as integral scattering and local concentration because of the influence of natural conditions. Thus, a high population density belt has been formed in the middle of LRGR, and a high population density patch comes into being in the south of LRGR. (3) There is a good linear regression relationship between population density and human activity index (HAI) in the LRGR, which reflects that population density can present the artificial disturbance on natural ecosystem in the LRGR. (4) The increase of population density leads to the decrease of NDVI index. population density, artificial disturbance, vegetation coverage, physiographic factor, LRGRThe LRGR is an area with the assembly of rich global species and a world-class biological gene bank [1] . It has become a hot spot in the academes of ecosystem succession and biodiversity protection. In these years, the population increases year by year greatly, which has violently influenced the succession process of regional ecosystem [2][3][4][5] . Therefore, it is of far reaching importance for studying the population density pattern in LRGR to discover the regional ecosystem succession rule, identify the key factors restricting spatial distribution and dynamic variation of the land system in LRGR, grope for a typical development model of mountainous resources in our country, and build up an evaluation system for regional ecological security.
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