Potent Anti-inflammatory and Analgesic Actions of the Chloroform Extract of <i>Dendropanax morbifera</i> Mediated by the Nrf2/HO-1 Pathway

Abstract

Dendropanax morbifera LEVEILLE (DP) has been used in traditional Korean medicines to treat a variety of inflammatory diseases. Although the in vitro anti-inflammatory potential of this plant is understood, its in vivo efficacy and underlying molecular mechanism of anti-inflammatory effects are largely unknown. We elucidated the anti-inflammatory and analgesic activities and the underlying molecular mechanisms of DP using in vitro and in vivo models. Lipopolysaccharide (LPS)-stimulated murine macrophages were used to analyze the in vitro anti-inflammatory potential of DP extract and to elucidate the underlying mechanisms.In vivo animal models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and acetic acid-induced writhing response tests were used to analyze the in vivo anti-inflammatory effects and anti-nociceptive effects of DP extract, respectively. Methanolic extract of DP (DPME) significantly inhibited the release of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) in LPS-activated macrophages. Among the five sub-fractions, the chloroform fraction (DP-C) showed the most potent suppressive effects against pro-inflammatory mediators and cytokines in LPS-stimulated macrophages. These effects were attributed to inhibition of nuclear factor-κB (NF-κB) nuclear translocation and c-Jun N terminal kinase (JNK) 1/2 phosphorylation and to activation of NF-E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling. DP-C exhibited strong protective in vivo effects in TPA-induced ear edema mouse model and acetic acid-induced writhing response test. Our data suggest that DP-C has potent anti-inflammatory and analgesic activities and may be a promising treatment against a variety of inflammatory diseases.

Polydatin inhibits mast cell-mediated allergic inflammation by targeting PI3K/Akt, MAPK, NF-κB and Nrf2/HO-1 pathways

“…The reports by Yan et al . 49 and Dai et al . 50 show that inflammation could be affected through Nrf2/HO-1 pathways.…”

Inhibitory effect of 1-tetradecanol on Helicobacter pylori-induced production of interleukin-8 and vascular endothelial growth factor in gastric epithelial cells

“…However, limited data are available about the physiological effects of the compound 1-TD, isolated from the lower stem of D. morbifera. Only a few studies have examined its anti-inflammatory effects on cells such as microglial cells (6,7) and macrophages (3). Furthermore, IL-8, a member of the CXC chemokine family, is involved in inflammatory responses, leukocyte chemotaxis and cancer development (18,19).…”

“…Anti-cancer activities of methanol extracts have been reported in hepatocarcinoma, colon adenocarcinoma, biliary tract cancer and human osteosarcoma cells (5). Anti-inflammatory responses by D. morbifera extracts involve the suppression of NF-κB dependent pathways in LPS-stimulated macrophages (6) and microglia (7).…”

Cytotoxic Effects of Plant Sap-Derived Extracellular Vesicles on Various Tumor Cell Types

“…Specifically, we investigated plant sap-derived EVs from four endemic plants collected from Bogildo and Hekseongsan in Korea: Dendropanax Morbifera (DM), Pinus densiflora (PD), Thuja occidentalis (TO), and Chamaecyparis obtusa (CO). It is known that DM and PD extracts have anticancer, antioxidant, antidiabetic, and anti-inflammatory activities, anti-melanogenic effects [25][26][27][28][29][30][31][32][33][34], whereas TO and CO extracts have antioxidant, anti-inflammatory, antimicrobial, and anti-asthmatic effects [35][36][37][38]. EVs isolated from these four kinds of plant saps were investigated for their anticancer effects on normal, low metastatic, and malignant cells.…”