Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Structural Characterization and Antidepressant-Like Effects of Polygonum sibiricum Polysaccharides Associated with Regulating Microglial Polarization in Cums-Induced Zebrafish

Version 1 : Received: 27 December 2023 / Approved: 27 December 2023 / Online: 27 December 2023 (05:03:49 CET)

A peer-reviewed article of this Preprint also exists.

Zhang, Y.; Wang, D.; Liu, J.; Bai, Y.; Fan, B.; Lu, C.; Wang, F. Structural Characterization and Antidepressant-like Effects of Polygonum sibiricum Polysaccharides on Regulating Microglial Polarization in Chronic Unpredictable Mild Stress-Induced Zebrafish. Int. J. Mol. Sci. 2024, 25, 2005. Zhang, Y.; Wang, D.; Liu, J.; Bai, Y.; Fan, B.; Lu, C.; Wang, F. Structural Characterization and Antidepressant-like Effects of Polygonum sibiricum Polysaccharides on Regulating Microglial Polarization in Chronic Unpredictable Mild Stress-Induced Zebrafish. Int. J. Mol. Sci. 2024, 25, 2005.

Abstract

: Background: The polysaccharides are one of the main active ingredients of Polygonum sibiricum (PSP), which is a traditional food and medicine homologues in China. The antidepressant-like effects of PSP and its underlying mechanisms remain to be studied in depth, especially the regulation of microglial polarization. Methods: The chemical composition and structural characteristics of PSP was determined firstly. The CUMS procedure was carried out to the zebrafish for 5 weeks and PSP were immersed administration for 9 days (1 h/d). The body weight of zebrafish was monitored and the behavioral tests, including the novel tank test and light and dark tank test, were performed to evaluate the antidepressant-like effects of PSP. Then the function of HPI axis, the levels of peripheral inflammation, neuronal and blood-brain barrier damage in mesencephalon and telencephalon and the mRNA expression of M1/M2 phenotype genes in brain were examined. Results: PSP samples had the typical structure characteristics of polysaccharide, consisting of glucose, mannose and galactose with the average Mw 20.48 kDa, which owned a porous and agglomerated morphology. Compared with untreated zebrafish, the depression-like behaviors of CUMS-induced zebrafish were significantly attenuated. PSP significantly decreased the levels of cortisol and the pro-inflammatory cytokines and increased the levels of the anti-inflammatory cytokines in the body of CUMS-induced depressive zebrafish. Furthermore, neuronal and blood-brain barrier damage in mesencephalon and telencephalon and the mRNA expression of M1/M2 phenotype genes in brain were remarkably reversed by PSP. Conclusion: These findings indicated that the antidepressant-like effects of PSP were related to alter the HPI axis hyperactivation, suppress peripheral inflammation, inhibit neuroinflammation induced by microglia hyperactivation, and modulate microglial M1/M2 polarization. The current study provides foundation to the future exploitation of PSP in the functional foods of emotional regulation.

Keywords

depression; Polygonati Rhizoma polysaccharides; microglia polarization

Subject

Biology and Life Sciences, Neuroscience and Neurology

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