Platycodin D Inhibits Inflammatory Response in LPS-Stimulated Primary Rat Microglia Cells through Activating LXRα–ABCA1 Signaling Pathway

Abstract

Platycodin D (PLD), an effective triterpenesaponin extracted from Platycodon grandiflorum, has been known to have anti-inflammatory effect. In the present study, we investigate the anti-inflammatory effects of PLD on LPS-induced inflammation in primary rat microglia cells. The results showed that PLD significantly inhibited LPS-induced ROS, TNF-α, IL-6, and IL-1β production in primary rat microglia cells. PLD also inhibited LPS-induced NF-κB activation. Furthermore, our results showed that PLD prevented LPS-induced TLR4 translocation into lipid rafts via disrupting the formation of lipid rafts by inducing cholesterol efflux. In addition, PLD could activate LXRα–ABCA1 signaling pathway which induces cholesterol efflux from cells. The inhibition of inflammatory cytokines by PLD could be reversed by SiRNA of LXRα. In conclusion, these results indicated that PLD prevented LPS-induced inflammation by activating LXRα–ABCA1 signaling pathway, which disrupted lipid rafts and prevented TLR4 translocation into lipid rafts, thereby inhibiting LPS-induced inflammatory response.

Biocatalysis of Platycoside E and Platycodin D3 Using Fungal Extracellular β-Glucosidase Responsible for Rapid Platycodin D Production

“…3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed no obvious cytotoxicity of PD (up to 10 μM) toward mouse macrophage cells in the presence of LPS although a trend toward decreased cell viability was observed ( Figure 6 b ( n = 3, p > 0.05)). The findings of this work concur with the previous data and suggest that PD inhibited inflammatory marker production in RAW 264.7 cells [ 49 , 50 , 51 , 52 , 53 ].…”

Lipid rafts in glial cells: role in neuroinflammation and pain processing

“…The mechanism involves reduction of lipid raft abundance and inhibition of LPS-induced TLR4 translocation into lipid rafts. The inhibition of cholesterol efflux mechanism (110).…”

“…SHP1 and SHP2, upon recruitments to lipid rafts, dephosphorylate their targets and help prevent steady-state inflammatory activation. Reversal of inflammarafts back into lipid rafts of a non-activated cell can be achieved by augmented cholesterol efflux regulated by the LXR-ABCA1 pathway (102)(103)(104)110), beta-cyclodextrins and AIBP (33); inhibition of ganglioside synthases (125)(126)(127)(128); and delicate control of sphingomyelinases, which hydrolyze sphingomyelin but produce inflammatory and raft-residing ceramides (129,132). For illustrative purposes, all protein components are depicted as residing in one large, shared inflammaraft.…”

Platycodin D inhibits platelet function and thrombus formation through inducing internalization of platelet glycoprotein receptors

“…As a triterpenoid saponin, platycodin D is one of the major bioactive components of the roots of P. grandiflorum, a traditional Chinese medicinal herb [ 7 , 8 ]. Several studies have shown that platycodin D affects cell biological behaviors through exerting multiple functions, such as anti-nociceptive [ 10 ], antiviral [ 11 ], anti-inflammatory [ 12 ], anti-cancer [ 13 ], immunomodulatory [ 14 , 15 ], and hepatoprotective activities [ 8 ]. However, whether platycodin D plays a role in platelet function and thrombus formation remains poorly understood.…”

“…Several monomers of P. grandiflorum have been identified, including platycodin A, B, C, D, D2, D3, and polygalacin D, D2 [ 9 ]. Previous studies have demonstrated that platycodin D possesses multiple biological and pharmacological properties, such as anti-nociceptive [ 10 ], antiviral [ 11 ], anti-inflammatory [ 12 ], anti-cancer [ 13 ], immunomodulatory [ 14 , 15 ], and hepatoprotective activities [ 8 ]. Moreover, platycodin D could be a potential approach to treat obesity as it can inhibit lipogenesis in 3T3-L1 cells and modulate fat accumulation in obese mice [ 16 ].…”