Apigetrin Abrogates Lipopolysaccharide-Induced Inflammation in L6 Skeletal Muscle Cells through NF-κB/MAPK Signaling Pathways

Abstract

Apigetrin is a glycosidic flavonoid derived from Teucrium gnaphalodes that has a wide range of biological activities, including antioxidant, anti-inflammatory, and anticancer. Inflammation is a kind of defense mechanism in the body. Flavonoids are natural phytochemicals that exert anti-inflammatory effects in numerous cells. In the present study, we investigated the anti-inflammatory effect of apigetrin and its underlying mechanism of activity in skeletal muscle cells (L6). The determination of cytotoxicity was performed by MTT assay. We treated L6 cells with apigetrin, and nontoxic concentrations were chosen to perform further experimentation. Apigetrin inhibited the expression of iNOS and COX-2 induced by LPS in a dose-dependent manner. iNOS and COX-2 are inflammatory markers responsible for enhancing the inflammatory response. Apigetrin also inhibited the LPS-induced phosphorylation of p65 and IκB-α. NF-κB signaling regulates the inflammatory process by mediating various proinflammatory genes. Similarly, the MAPK signaling pathway consists of ERK, JNK, and p38, which plays a critical role in the production of cytokines and downstream signaling events leading to inflammation. Apigetrin significantly downregulated the phosphorylation of JNK and p38, but did not affect the phosphorylation of ERK in the LPS-stimulated cells. These findings indicate the correlation between the anti-inflammatory activity of NF-κB and the MAPK signaling pathway. Thus, our overall finding suggests that apigetrin has anti-inflammatory effects and it can be considered for further drug design on L6 skeletal muscle cells.

Effect of apigetrin in pseudo-SARS-CoV-2-induced inflammatory and pulmonary fibrosis in vitro model

“…4). Consistent with our data, apigetrin has been reported to lower TNF-α, IL-1β, and IL-6 production and mRNA expression in LPS-stimulated various cells [16, 17,51] and in mice with acute otitis media [19]. Similarly to our model, it has been reported that apigetrin inhibits IL-1α and TGF-β production induced by recombinant spike protein of SARS-CoV-2-stimulated RAW 264.7 cells [52].…”

Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy

“…After internalization of the drug‐loaded nanoparticles, IL‐1β‐treated IVD tissue showed a dramatic reduction in many inflammatory mediators (IL‐6, IL‐8, and PGE2), while remodeled ECM manifested by upregulation of ECM proteins (Collagen II and Aggrecan) and downregulation of matrix degrading enzymes (MMP1 and MMP3). 54 API shows excellent anti‐inflammatory effects on various cell types, including skeletal muscle cells, 55 microglia, 24 , 56 and adipocytes, 57 which makes it a promising treatment for inflammation‐related diseases. Similarly, our results demonstrated that API significantly downregulated proinflammatory factors, which may further reduce catabolic activity while increasing anabolism in IL‐1β‐stimulated NPCs.…”

The Anti-Muscle Atrophy Effects of Ishige sinicola in LPS-Induced C2C12 Myotubes through Its Antioxidant and Anti-Inflammatory Actions

“…Inflammation is an important factor that causes skeletal muscle atrophy [14]. Proinflammatory cytokines can trigger muscle atrophy mediated by the activating ubiquitinproteasome and NF-κB/MAPK signaling pathways [26,27]. MAPKs including ERK, c-Jun N-terminal kinase, and p38 regulate MAFbx and MuRF1 expression of muscles under oxidative stress and inflammatory conditions.…”