Scandoside Exerts Anti-Inflammatory Effect Via Suppressing NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

Abstract

The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 messenger RNA (mRNA) expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

Asperuloside and Asperulosidic Acid Exert an Anti-Inflammatory Effect via Suppression of the NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

“…To date, numerous natural products have been identified as potential anti-inflammatory agents that can scavenge inflammatory mediators [ 18 , 19 , 20 , 21 , 22 ]. Among them, iridoids play an important role in inflammatory treatment and are considered as the major bioactive constituents of H. diffusa [ 16 , 17 ]. In a phytochemical analysis, ASP, ASPA, DAA, SME, and CSME were found by ultra performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS) methods and identified by comparison with their reference substances [ 17 ].…”

“…RAW 264.7 cells were cultured in DMEM supplemented with 10% FBS, 100 units/mL penicillin, and 100 μg/mL streptomycin, and maintained in a carbon dioxide incubator (Thermo Fisher Scientific, Waltham, MA, USA) at 37 °C in 5% CO 2 with a humidified atmosphere of 95% air. RAW 264.7 cells were induced with LPS (50 ng/mL) for 24 h after being incubated with iridoids for 1 h [ 16 ].…”

“…Iridoids, flavonoids, and anthraquinones are the main constituents responsible for the multiple bioactivities of H. diffusa [ 14 , 15 ]. Scandoside, an iridoid isolated from H. diffusa , has been proven to be an anti-inflammatory compound [ 16 ]. Previously, we confirmed that the aqueous extract of H. diffusa , mainly containing asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E -6- O - p -coumaroyl scandoside methyl ester (CSME), showed a protective effect on LPS-induced renal inflammation in mice ( Figure 1 ) [ 17 ].…”

Geniposide, a component of Gardenia jasminoides Ellis, inhibits NF-ĸB to attenuate LPS-induced injury in intestinal epithelial cells

“…After binding the corresponding site on specific DNA, it can induce the transcription of related genes and promote the release of cytokines, thus generating a systemic inflammatory response [21]. The research shows that GD could reduce the level of inflammatory cytokines in the injury model and had anti-inflammatory effects on tissues [3].…”

Anti‐inflammatory effect of alkaloids extracted from Dendrobium aphyllum on macrophage RAW 264.7 cells through NO production and reduced IL‐1, IL‐6, TNF‐α and PGE2 expression

“…Inflammation is a defence response of living tissues to injurious stimuli and a protective attempt by the organism to remove the stimulus and then initiate the tissue healing process. LPS – a common endotoxin derived from the outer membrane of Gram‐negative bacteria – can induce a series of inflammatory reactions in which macrophages are recruited to inflammatory sites and initiate intracellular cascades (He et al, ). Macrophages play an important role in the response of organisms (via the secretion of a series of pro‐inflammatory cytokines, NO, signalling proteins and various other inflammatory mediators) and are activated by stimuli such as pro‐inflammatory cytokines, including tumour necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), and IL‐1 (Ahn et al, ).…”