Magnesium Lithospermate B Suppresses Lipopolysaccharide-Induced Neuroinflammation in BV2 Microglial Cells and Attenuates Neurodegeneration in Lipopolysaccharide-Injected Mice

Abstract

Chronic inflammation in the brain plays a critical role in major neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Microglia, the resident macrophages and intrinsic components of the central nervous system (CNS), appear to be the main effectors in this pathological process. Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, which has been documented to protect neurons against multiple types of neuronal injury. However, its functions on microglia and the related neuroinflammation remain unknown. In the present study, BV2 microglial cells were used to assess the anti-neuroinflammatory capacity of MLB. Our data show that treatment with MLB could not only suppress lipopolysaccharide (LPS)-induced proliferation and morphological changes, but also interfere with cell cycle progression in BV2 cells. More strikingly, it attenuated the production of the inflammatory mediator nitric oxide (NO) and a panel of pro-inflammatory cytokine in LPS-stimulated BV2 cells, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1α, IL-1β, and IL-6, and also promoted a phenotypic switch from the M1 to the M2 phenotype. Additionally, an in vivo study showed that the administration of MLB could ameliorate lipopolysaccharide-induced neurodegeneration and microglial activation in the hippocampus of adult mice. Mechanistically, MLB blocked the activation of the NF-κB pathway upon LPS stimulation, indicating that the effects of MLB on microglia may be mediated by the NK-κB pathway. These results suggest the therapeutic potential of MLB as a novel anti-inflammatory and microglia-modulating drug for neurodegenerative diseases.

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

“…Imipramine [247] Isobavachalcone [248] Isochlorogenic acid [167] Isoquercetin (Isoquercitrin) [249] Kaempferol [128,160,193,194] Kaempferol, 3-O-a-l arabinofuranoside-7-O-a-l-rhamnopyranoside [214] KR33493 [250] Kukoamine [251] Lestaurtinib [164] Lipoic acid [252][253][254] Luteolin [128] LY354740 [115] M10 [24] M30 (VAR10303) [112,255] M99 [24] Macranthoin G [256] Magnesium lithospermate B [257] [160,193,194,267] [18F]MPPF [107] MSX-3 [268] Myricetin [128,269,270] Myricitrin [271] Naringenin [128,272] Naringin [117,273,274] Nicotinamide adenine dinucleotide phosphate (NADPH) [275,276] Nicotinamide mononucleotide [277] Nitecapone [278] Nordihydroguaiaretic [160,193,194] Oleuropein…”

The Effects of Crinum asiaticum var. japonicum Baker Seeds on Neuroprotection and Antineuroinflammation in Neuronal Cell Lines

“…Among them, NO is the most potent molecule in neuroprotection 45 and regulates the release of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in AD. 46 In our study, we utilized BV-2 microglia to examine the inhibitory effect of ECAS on neuroinflammation (Figure 3(A)). Under different ranges of nontoxic concentrations, the anti-inflammatory effects of ECAS were compared by measuring the amount of NO.…”

Synthetic 3',4'-Dihydroxyflavone Exerts Anti-Neuroinflammatory Effects in BV2 Microglia and a Mouse Model

“…Finally, to confirm whether 3′,4′-dihydroxyflavone reduces neuroinflammation in vivo , we injected LPS into mice, a well-known animal model of neuroinflammation cause by microglial activation ( Tai et al ., 2017 ; Zhang and Xu, 2017 ). We administered 3′,4′-dihydroxyflavone to mice orally for 3 days prior to the i.p.…”