Polygonatum cyrtonema Hua Polysaccharides Protect BV2 Microglia Relief Oxidative Stress and Ferroptosis by Regulating NRF2/HO-1 Pathway

Abstract

Neuronal-regulated cell death (RCD) due to the accumulation of ROS within the central nervous system (CNS) is one of the crucial causes of central system diseases. Caspase-dependent apoptosis is the only form of RCD. As research progressed, several nonapoptotic cell death pathway RCDs were identified. Ferroptosis is a nonapoptotic RCD characterized by lipid peroxidation and plasma membrane damage. Polygonatum cyrtonema Hua. Polysaccharides (PCP) are an effective antioxidant. Based on this, the protective effect and mechanism of PCP against H2O2-induced microglial injury were investigated. Furthermore, the protective mechanism of PCP against ferroptosis in microglia was explored. Our results indicated that PCP could reduce oxidative stress-induced ROS accumulation by activating the NRF2/HO-1 signaling pathway, thus attenuating RCD in microglia. Subsequent studies have revealed that PCP alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. Therefore, we hypothesized that PCP exerts antioxidative and anti-ferroptosis effects by activating the expression of the NRF2/HO-1 pathway. This facilitates new ideas for clinically effective prevention and treatment of diseases due to accumulated reactive oxygen species in the CNS. Simultaneously, PCP has the development potential as a new drug candidate for treating CNS diseases.

Review on active components and mechanism of natural product polysaccharides against gastric carcinoma

“…Furthermore, astragalus polysaccharides can alshave been shown to treat ferroptosis in normal human cells and prevent the occurrence of diseases [ 53 ]. It is worth noting that various natural product polysaccharide components have been identified to inhibit ferroptosis, enhance immune function, provide neuroprotection, and exhibit anti-tumor effects [ [54] , [55] , [56] , [57] ].…”

Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway

“…Polysaccharide from Dendrobium officinale showed lung protection in LPS-induced BEAS-2B cells involved with increases of HO-1 and NQO1 protein expressions as well as nuclear/cytosol Nrf2 ratio ( 20 ). NPs from herbs displayed neuroprotection against MPP+-induced N2a cells ( 22 ), H 2 O 2 - ( 121 ), UVB- ( 122 ), and OGD/R-induced ( 144 ) PC12 cells, OGD/R-induced primary cortical neurons ( 65 ), and H 2 O 2 -induced microglia BV2 cells ( 145 ) or HT22 cells ( 123 ), which were correlated with promotions of mRNA and protein expressions of Keap1, Nrf2, HO-1, NQO1, GCLC, GCLM, and GSTP1 along with nuclear Nrf2, and reduction of cytosol Nrf2 protein expression. Moreover, Salvia miltiorrhiza polysaccharides protected PC12 cells from OGD/R-induced ferroptosis and lipid peroxidation by activating Nrf2/HO-1 pathway ( 144 ).…”

“…Moreover, Salvia miltiorrhiza polysaccharides protected PC12 cells from OGD/R-induced ferroptosis and lipid peroxidation by activating Nrf2/HO-1 pathway ( 144 ). Polygonatum cyrtonema Hua polysaccharides alleviated ferroptosis in H 2 O 2 -induced microglia BV2 cells by activating Nrf2/HO-1 signaling pathway ( 145 ). NPs from herbs revealed cardioprotection on hypoxia/reoxygenation- ( 124 ), ischemia/reperfusion- ( 19 ) or H 2 O 2 -induced ( 125 ) H9c2 cells by modulating protein and mRNA expressions of Nrf2, HO-1, and NQO1 as well as nuclear and cytosol Nrf2.…”

Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides

“…PCPS (4.24 × 10 4 Da) showed strong effects in preventing oxidative damage through activating erythroid 2-related factor 2 (Nrf2)/HO-1 antioxidant signaling [ 89 ]. PCP could reduce oxidative stress-induced ROS accumulation and alleviate ferroptosis via activating NRF2/HO-1 signaling pathway, thus attenuating neuronal-regulated cell death in microglia [ 90 ].…”