The Neoflavonoid Latifolin Isolated from MeOH Extract ofDalbergia odoriferaAttenuates Inflammatory Responses by Inhibiting NF-κB ActivationviaNrf2-Mediated Heme Oxygenase-1 Expression

Abstract

In Korea and China, the heartwood of Dalbergia odorifera T. Chen is an important traditional medicine used to treat blood disorders, ischemia, swelling, and epigastric pain. In this study, we investigated the inhibitory effects of latifolin, a major neoflavonoid component isolated from the MeOH extract of D. odorifera, on the inflammatory reaction of thioglycollate-elicited peritoneal macrophages exposed to lipopolysaccharide, with a particular focus on heme oxygenase-1 (HO-1) expression and nuclear factor-κB (NF-κB) signaling. Latifolin significantly inhibited the protein and mRNA expression of inducible nitric oxide synthase and COX-2, reduced NO, prostaglandins E2, tumor necrosis factor-α, and interleukin-1β production in primary murine peritoneal macrophages exposed to lipopolysaccharide. Latifolin also suppressed inhibitor κB-α levels, NF-κB nuclear translocation, and NF-κB DNA-binding activity. Furthermore, latifolin upregulated HO-1 expression via nuclear transcription factor-E2-related factor 2 (Nrf2) nuclear translocation. In addition, using inhibitor tin protoporphyrin IX (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of latifolin on the proinflammatory mediators and NF-κB DNA-binding activity were associated with the HO-1 expression. These results suggested that the latifolin-mediated up-regulation of HO-1 expression played a critical role in anti-inflammatory effects in macrophages. This study therefore identified potent therapeutic effects of latifolin, which warrants further investigation as a potential treatment for inflammatory diseases.

Limb ischemic preconditioning protects against contrast-induced acute kidney injury in rats via phosphorylation of GSK-3β

“…Together, these data show that LIPC inhibits oxidative stress and inflammation in CI-AKI rats through the suppression of GSK-3β activity. These observations are consistent with other studies also showing that GSK-3β regulates Nrf2 activity [57][58][59][60][61], that Nrf2 has antioxidant effects [54,55,[60][61][62], and that Nrf2-mediated heme oxygenase-1 expression attenuates inflammatory responses by inhibiting NF-κB activation [63,64].…”

RETRACTED: BJ-1103, 6-aminopyridin-3-ol skeletal compound, modulates neuroprotective and anti-neuroinflammatory effects in murine hippocampal and microglial cells via Nrf2-mediated heme oxygenase-1 expression

“…HO-1 gene expression is induced by activation of mitogen-activated kinase (MAPKs) that play crucial roles in cellular processes, such as proliferation, apoptosis, and the stress response [5,6]. Recently many studies reported that small molecules, such as resveratrol [7], latifolin [8], sulfuretin [9] and curcumin [10] have inhibitory effects on oxidative stress-induced neuronal damage through induction of HO-1.…”

A Dalbergia odorifera extract improves the survival of endotoxemia model mice by inhibiting HMGB1 release

“…The anti-inflammatory effect of DOE may be due to its effects on cellular signaling cascades, as demonstrated in this study. In fact, the neoflavonoid latifolin isolated from a methanol extract of D. odorifera attenuates inflammatory responses by inactivating nuclear factor (NF)-κB through nuclear transcription factor-E2-related factor 2 (Nrf-2)-mediated upregulation of HO-1 [22]. In line with the present finding, isoliquiritigenin, another constituent of D. odorifera , is a powerful anti-inflammatory molecule that protects against the effects of LPS by inhibiting interleukin-1β, tumor necrosis factor-α, and NO production in RAW 264.7 cells [30].…”

“…Furthermore, epigallocatechin-3-gallate and tanshinone IIA stimulate autophagic degradation and endocytic uptake of HMGB1 in RAW264.7 cells, respectively [20, 21]. On the other hand, Dalbergia odorifera , a folk medicinal herb, exhibits a beneficial effect in inflammatory conditions via the induction of heme oxygenase (HO)-1, an anti-inflammatory protein, in murine RAW 264.7 macrophages and BV2 microglial cells [22, 23]. These anti-inflammatory activities of D. odorifera stem from a number of compounds such as flavonoids, phenolic constituents, and quinines isolated from its heartwood [24, 25].…”