Diphlorethohydroxycarmalol (DPHC) Isolated from the Brown Alga Ishige okamurae Acts on Inflammatory Myopathy as an Inhibitory Agent of TNF-α

Abstract

Inflammation affects various organs of the human body, including skeletal muscle. Phlorotannins are natural biologically active substances found in marine brown algae and exhibit anti-inflammatory activities. In this study, we focused on the effects of phlorotannins on anti-inflammatory activity and skeletal muscle cell proliferation activity to identify the protective effects on the inflammatory myopathy. First, the five species of marine brown algal extracts dramatically inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells without toxicity at all the concentrations tested. Moreover, the extracts collected from Ishige okamurae (I. okamurae) significantly increased cell proliferation of C2C12 myoblasts compared to the non-treated cells with non-toxicity. In addition, as a result of finding a potential tumor necrosis factor (TNF)-α inhibitor that regulates the signaling pathway of muscle degradation in I. okamurae-derived natural bioactive compounds, Diphlorethohydroxycarmalol (DPHC) is favorably docked to the TNF-α with the lowest binding energy and docking interaction energy value. Moreover, DPHC down-regulated the mRNA expression level of pro-inflammatory cytokines and suppressed the muscle RING-finger protein (MuRF)-1 and Muscle Atrophy F-box (MAFbx)/Atrgoin-1, which are the key protein muscle atrophy via nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPKs) signaling pathways in TNF-α-stimulated C2C12 myotubes. Therefore, it is expected that DPHC isolated from IO would be developed as a TNF-α inhibitor against inflammatory myopathy.

Effect of Pinoresinol and Vanillic Acid Isolated from Catalpa bignonioides on Mouse Myoblast Proliferation via the Akt/mTOR Signaling Pathway

“…Next, the proliferation effect of skeletal muscle cells was measured during the differentiation period by BrdU cell proliferation assay [ 19 , 20 , 21 , 22 ], except for compound 9 , which was excluded because of its toxicity. Compared to the control conditions, most compounds triggered approximately a 1.2-fold increase in cell proliferation ( Figure 2 B).…”

Ishophloroglucin A, Isolated from Ishige okamurae, Alleviates Dexamethasone-Induced Muscle Atrophy through Muscle Protein Metabolism In Vivo

“…Previous studies have reported the various biological activities mediated by IO, including anti-obesity, anti-diabetes, and anti-inflammatory properties [ 28 , 29 ]. A previous study showed that IO downregulated pro-inflammatory cytokines and muscle atrophy proteins against TNF-α, thereby demonstrating its potential as a TNF-α inhibitor for inflammatory myopathy [ 21 ]. In addition, IO improved the proliferation of C2C12 myoblasts [ 20 ].…”

“…Ishige okamurae extract (IO) has been reported to activate skeletal muscle cell proliferation without inducing cytotoxicity in C2C12 myoblasts [ 20 ]. In addition, IO can potentially inhibit tumor necrosis factor (TNF)-α in muscle-degradation-induced inflammatory myopathy [ 21 ]. However, the underlying mechanism of action of IPA, which is the equivalent content of IPA in IO, on muscle function in Dexa-induced muscle atrophy remains unknown.…”

The Anti-Allergic and Anti-Inflammatory Effects of Phlorotannins from the Edible Brown Algae, Ecklonia sp. and Eisenia sp

“…Resulting from those effects, they suppressed the production of PGE 2 , IL-1β, IL-6, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) and expression of COX-2 and iNOS. [93][94][95][96][97] Although PFF-B's effects were mentioned above, there are reports by other research groups. PFF-B suppressed expression of COX-2 and iNOS and production of NO, IL-1β, and IL-6 and the effect was attributed to the degradation of the NF-κB signaling pathway through the suppression of Akt, ERK, and JNK phosphorylation.…”