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. 2021 Oct 18;11(1):20558.
doi: 10.1038/s41598-021-00071-6.

Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota

Yingchun Zhao #  1 , Xinglong Liu #  1 , Yinan Zheng #  1   2 , Wencong Liu  3   4 , Chuanbo Ding  5
Affiliations

Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota

Yingchun Zhao et al. Sci Rep. .

Abstract

Aronia melanocarpa is a natural medicinal plant that has a variety of biological activities, its fruit is often used for food and medicine. Aronia melanocarpa polysaccharide (AMP) is the main component of the Aronia melanocarpa fruit. This research evaluated the delay and protection of AMP obtained from Aronia melanocarpa fruit on aging mice by D-Galactose (D-Gal) induction and explored the effect of supplementing AMP on the metabolism of the intestinal flora of aging mice. The aging model was established by intraperitoneal injection of D-Gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks. AMP (100 and 200 mg/kg) was given daily by oral gavage after 6 weeks of D-Gal-induced. The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice determined by the eight-arm maze test. H&E staining showed that AMP significantly reversed brain tissue pathological damage and structural disorders. AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating the PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family. Importantly, 16S rDNA analysis indicated the AMP treatment significantly retarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammation and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Analysis of the structure of AMP. (A) The standard monosaccharides. (B) The monosaccharide composition. (C) FI-IR analysis of A. melanocarpa polysaccharide. The IR spectra was analyzed on JASCO FT/IR-620 spectrometer (http://www.jasco.co.jp/).
Figure 2
Figure 2
AMP improves the general condition of mice. (A) Experimental design of the D-Gal-induced liver fibrosis model in mice. (B,C) AMP improved the appearance of the whole brain of aging mice and H&E staining showed the pathological damage of the hippocampus. Images were obtained using Canon EOS 1600D\u002F 200D II (http://www.canon.com.cn/), and processed with Adobe Photoshop CC 2018 (https://www.adobe.com/products/photoshop.html). The drawing was created using Adobe Illustrator CS 11.0 (https://www.adobe.com/cn/products/illustrator.html). The stained sections were collected by light- microscope Leica DM750 (https://www.leica-microsystems.com.cn/cn/products/light-microscopes/).
Figure 3
Figure 3
AMP improves D-Gal-induced spatial learning and memory. (A,B) Latent period and track length of mice in the maze. (C) Percentage of time spent by mice in each quadrant. (D) Action trajectory diagram of mice in the maze. (E) AchE level in mouse brain tissue. (F–H) The brain levels of MDA, SOD, and CAT in D-Gal-induced senescence. (I,J) Nrf2 and HO-1 protein expression and heat map analysis of Nrf2 and HO-1 protein expression levels. Data are expressed as the mean ± standard deviation (S.D), n = 10. *p < 0.05 or **p < 0.01 vs. normal group; #p < 0.05 or ##p < 0.01 vs. D-Gal group. The figures were created by using GraphPad Prism Software version 6.04 (https://www.graphpad.com/). Chemical imaging was collected using Bio-Rad Imaging System version VersaDoc 3000 (https://www.bio-rad.com/). The heatmap was constructed using the online tool Morpheus (https://software.broadinstitute.org/morpheus/). Trajectory imaging was taken using Thermal Imaging Analysis software version RMT-100 (https://tmvmc.com/).
Figure 4
Figure 4
AMP improves D-Gal-induced oxidative stress. (A–D) AMPK, SIRT1, and P53 proteins expression, and heat map analysis of AMPK signaling pathway expression levels. (E–K) Inflammasome proteins expression of GSDMD, Caspase 1, IL-1β, ASC, and NALP3, and heat map analysis of inflammasome protein expression levels. Data are expressed as the mean ± standard deviation (S.D), n = 10. *p < 0.05 or **p < 0.01 vs. normal group; #p < 0.05 or ##p < 0.01 vs. D-Gal group. Chemical imaging was collected using Bio-Rad Imaging System version VersaDoc 3000 (https://www.bio-rad.com/). The heatmap was constructed using the online tool Morpheus (https://software.broadinstitute.org/morpheus/).
Figure 5
Figure 5
AMP exerts an anti-aging effect in mice by regulating NF-κB-mediated inflammation and PI3K/AKT/mTOR anti-apoptotic pathway. (A,B) The proteins expression of NF-κB and IκB-α in mice of brain tissue, and heat map analysis of NF-κB signaling pathway expression protein levels. (C–H) The proteins expression of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, Bax, Caspase 3 and Bcl-2 in mice of brain tissue, and heat map analysis of PI3K/AKT/mTOR and its downstream protein levels. Data are expressed as the mean ± standard deviation (S.D), n = 10. *p < 0.05 or **p < 0.01 vs. normal group; #p < 0.05 or ##p < 0.01 vs. D-Gal group. Chemical imaging was collected using Bio-Rad Imaging System version VersaDoc 3000 (https://www.bio-rad.com/). The heatmap was constructed using the online tool Morpheus (https://software.broadinstitute.org/morpheus/).
Figure 6
Figure 6
AMP improves D-Gal-induced aging by regulating the intestinal flora of mice. (A) Venn diagram; (B) Phylum lever barplot. (C,D) Alpha diff boxplot. (E) Unweighted UniFrac ANOSIM. (F,G) Relative abundance and unweighted Unifrac. Data are expressed as the mean ± standard deviation (S.D), n = 10. *p < 0.05 or **p < 0.01 vs. normal group; #p < 0.05 or ##p < 0.01 vs. D-Gal group. OTUs were clustered using UPARSE version 7.1 (http://drive5.com/uparse/). The images were generated using R 3.6.3 (https://www.r-project.org/) and pheatmap package (https://cran.r-project.org/web/packages/pheatmap/).
Figure 6
Figure 6
AMP improves D-Gal-induced aging by regulating the intestinal flora of mice. (A) Venn diagram; (B) Phylum lever barplot. (C,D) Alpha diff boxplot. (E) Unweighted UniFrac ANOSIM. (F,G) Relative abundance and unweighted Unifrac. Data are expressed as the mean ± standard deviation (S.D), n = 10. *p < 0.05 or **p < 0.01 vs. normal group; #p < 0.05 or ##p < 0.01 vs. D-Gal group. OTUs were clustered using UPARSE version 7.1 (http://drive5.com/uparse/). The images were generated using R 3.6.3 (https://www.r-project.org/) and pheatmap package (https://cran.r-project.org/web/packages/pheatmap/).
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