Trichosanthis Semen Suppresses Lipopolysaccharide-Induced Neuroinflammation by Regulating the NF-κB Signaling Pathway and HO-1 Expression in Microglia

Abstract

Neuroinflammation, which is mediated by microglia that release various inflammatory cytokines, is a typical feature of neurodegenerative diseases (NDDs), such as Alzheimer’s disease and Parkinson’s disease. Hence, alleviating neuroinflammation by downregulating pro-inflammatory action, and upregulating anti-inflammatory action of microglia is an efficient therapeutic target for NDDs. In this study, we evaluated whether trichosanthis semen (TS), a dried ripe seed of Trichosanthes kirilowii Maximowicz, reduces lipopolysaccharide (LPS)-induced neuroinflammation by regulating microglial responses in vitro and in vivo. Our results presented that TS reduced the release of pro-inflammatory mediators, such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin-1β, and interleukin-6 via inhibition of the nuclear factor kappa B (NF-κB) signaling pathway in LPS-treated BV2 microglial cells. Moreover, TS induced anti-inflammatory mediators, such as interleukin-10, found in inflammatory zone 1, and chitinase 3-like 3 by the upregulation of heme oxygenase 1 (HO-1). We further confirmed that TS administration suppressed microglial activation, but enhanced HO-1 expression in LPS-injected mice. These results suggest that TS has anti-neuroinflammatory effects via inhibition of NF-κB signaling through the activation of HO-1, and that TS may be a therapeutical candidate for NDDs treatment.

Suppressive Effect of Tetrahydrocurcumin on Pseudomonas aeruginosa Lipopolysaccharide-Induced Inflammation by Suppressing JAK/STAT and Nrf2/HO-1 Pathways in Microglial Cells

“…Nrf2 is a key factor in protecting cells from oxidative stress and inflammationinduced damage, which modulates the levels of antioxidants and detoxification enzymes, such as HO-1, superoxide dismutase 1, NAD(P)H dehydrogenase 1, and glutathione peroxidase 1 [33]. A recent study has shown that a dried ripe seed of Trichosanthes kirilowii Maximowicz, Trichosanthis semen, could inhibit LPS-induced inflammation in BV2 7 Oxidative Medicine and Cellular Longevity microglial cells through activating HO-1 and inhibiting NF-κB signaling [34]. Our findings reveal that THC treatment reduces nitrite production (Figure 2(e)).…”

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

“…Lipopolysaccharides have the ability to directly induce neuroinflammation and are frequently employed in constructing neuroinflammation models for numerous animal and cell culture experiments. Research has illustrated that lipopolysaccharide-induced neuroinflammation exerts its effects through the NF-κB pathway in cells such as microglia and neurons [130][131][132].…”

Role of NRF2 in Colorectal Cancer Prevention and Treatment

“…The activation of NRF2 leads to the expression of HO-1, and the upregulation of HO-1 expression decreased the release of proinflammatory cytokines such as TNF-α, IL-6, etc. 18 HO-1 converts heme into biliverdin and CO, which play an important role in cytoprotection against oxidative stress. 19 Low concentration of CO can attenuate NF-κB p65 nuclear translocation.…”