Polysaccharides from Polygonatum cyrtonema Hua Reduce Depression-Like Behavior in Mice by Inhibiting Oxidative Stress-Calpain-1-NLRP3 Signaling Axis

Abstract

Polysaccharides from Polygonatum cyrtonema Hua (PSP) exert antioxidant, anti-inflammatory, and antidepressant effects. Production of reactive oxygen species (ROS) and activation of the calpain system and the NOD-like receptor protein 3 (NLRP3) inflammasome are closely related to the pathogenesis of depression. However, the relationships among those pathways and the protective effects of PSP have not been characterized. In this study, lipopolysaccharide (LPS) and chronic unpredictable mild stress- (CUMS-) induced depression models were used to evaluate the protective mechanisms of PSP against depression. ROS levels were measured in HT-22 cells using flow cytometry. Brain tissues were collected to determine the levels of oxidation-related indicators and inflammatory cytokines. The protein levels of calpain-1, calpain-2, calpastatin, phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), suprachiasmatic nucleus circadian oscillatory protein (SCOP), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, cleaved-caspase-1, ionized calcium binding adapter molecule 1 (Iba1), phosphorylation of extracellular signal-regulated kinase (p-ERK), nuclear factor-kappa B (NF-κB), interleukin-1β (IL-1β), and glial fibrillary acidic protein (GFAP) were measured using western blotting or immunofluorescence. In cellular experiments, we showed that PSP attenuated LPS-induced production of ROS in HT-22 cells. In animal experiments, we found that LPS increased the expression of calpain-1, NLRP3, ASC, caspase-1, cleaved-caspase-1, Iba1, p-ERK, NF-κB, and GFAP and reduced the expression of calpastatin, PTEN, SCOP, and Nrf2. Administration of PSP reversed these changes. N-Acetyl-L-cysteine (NAC) administration also inhibited oxidative stress and activation of the calpain system and the NLRP3 inflammasome. Furthermore, PSP, calpeptin, MCC950 (a selective NLRP3 inflammasome inhibitor), and NAC reduced LPS-induced proinflammatory cytokine release. We also showed that PSP prevented CUMS-induced changes in the calpain system and the Nrf2 and NLRP3 signaling pathways and reduced depression-like behavior. These results indicate that PSP exerts antidepressant effects through regulation of the oxidative stress-calpain-1-NLRP3 signaling axis.

Use of Steaming Process to Improve Biochemical Activity of Polygonatum sibiricum Polysaccharides against D-Galactose-Induced Memory Impairment in Mice

“…These changes in monosaccharide content after steaming might explain the enhanced biological activity. Additionally, in a previous study we analyzed the monosaccharide composition of non-steamed PSP by UHPLC [ 18 ], and our findings were consistent with the literature. Therefore, we did not repeat this part of experiment.…”

“…For example, Li et al have pointed out that the structural properties and antioxidant activity of PSP change after steaming [ 17 ]. Our previous studies have shown that PSP can ameliorate inflammation and relieve oxidative stress to prevent depression-like behaviors in mice [ 18 , 19 ]. However, the effect of steaming on the biochemical activity of PSP against memory impairment has not been studied, and its mechanism remains unclear.…”

Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides

“…In mice with lung injury, raw and honey-processed PCP could increase levels of SOD, inhibit pulmonary inflammation through the NF-κB pathway, and reduce the occurrence of pulmonary oxidative stress via the AMPK-Nrf2 pathway [ 133 ]. The protective effect in lung injury may be tightly related to the antioxidant and anti-inflammatory activities of PCP [ 134 , 135 ].…”

A Review of Polygonatum Mill. Genus: Its Taxonomy, Chemical Constituents, and Pharmacological Effect Due to Processing Changes

“…PCP exerted antidepressant effects by regulating the oxidative stress-calpain-1- NOD-like receptor protein 3 (NLRP3) signaling axis. PCP prevented chronic unpredictable mild stress-induced changes in the calpain system and reduced depression-like behavior [ 84 ]. Moreover, methanol extract from P. odoratum administration reversed intestinal microbiota compositions, inhibiting H 2 S-related bacteria, a lower level of H 2 S, and higher content of short-chain fatty acid-related bacteria [ 85 ].…”