Arctigenin Reduces Myofibroblast Activities in Oral Submucous Fibrosis by LINC00974 Inhibition

Abstract

Oral submucous fibrosis (OSF) is an oral precancerous condition associated with the habit of areca nut chewing and the TGF-β pathway. Currently, there is no curative treatment to completely heal OSF, and it is imperative to alleviate patients’ symptoms and prevent it from undergoing malignant transformation. Arctigenin, a lignan extracted from Arctium lappa, has been reported to have a variety of pharmacological activities, including anti-fibrosis. In the present study, we examined the effect of arctigenin on the cell proliferation of buccal mucosal fibroblasts (BMFs) and fibrotic BMFs (fBMFs), followed by assessment of myofibroblast activities. We found that arctigenin was able to abolish the arecoline-induced collagen gel contractility, migration, invasion, and wound healing capacities of BMFs and downregulate the myofibroblast characteristics of fBMFs in a dose-dependent manner. Most importantly, the production of TGF-β in fBMFs was reduced after exposure to arctigenin, along with the suppression of p-Smad2, α-smooth muscle actin, and type I collagen A1. In addition, arctigenin was shown to diminish the expression of LINC00974, which has been proven to activate TGF-β/Smad signaling for oral fibrogenesis. Taken together, we demonstrated that arctigenin may act as a suitable adjunct therapy for OSF.

The role of Interleukin 1 receptor antagonist in mesenchymal stem cell‐based tissue repair and regeneration

“…Rheumatoid arthritis (RA) is characterized by TNF‐α and IL‐1β‐driven synovial inflammation that results in the bone and cartilage destruction . Despite the fact that TNF‐α is a pivotal inflammatory cytokine in acute joint swelling, IL‐1β is considered as the dominant cartilage destructive cytokine and its production may occur in TNF‐α‐independent manner .…”

“…IL, interleukin; IL-1Ra, IL-1 receptor antagonist; MSC, mesenchymal stem cell; PGE2, prostaglandin E2; TNF-α, tumor necrosis factor alpha; TLR, toll-like receptor 6 | THERAPEUTIC POTENTIAL OF IL-1RA PRODUCING MSCS IN THE TREATMENT OF JOINT DISEASES Rheumatoid arthritis (RA) is characterized by TNF-α and IL-1β-driven synovial inflammation that results in the bone and cartilage destruction. 66,67 Despite the fact that TNF-α is a pivotal inflammatory cytokine in acute joint swelling, IL-1β is considered as the dominant cartilage destructive cytokine and its production may occur in TNF-α-independent manner. 66 Therefore, IL-1Ramediated inhibition of IL-1β-driven synovial inflammation has crucially important protective role in the pathogenesis of RA.…”

Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway

“…Due to their chemical structure, phytoestrogens can be classed as isoflavones and lignins. Arctigenin (Ar, Figure 1) is a lignin phytoestrogen extracted from Arctium lappa (Gao, Li, Zhang, & Zeng, 2008) that displays anti-inflammatory (Gao, Yang, & Zuo, 2018), antioxidant (Wu et al, 2014), antifibrosis (Lin et al, 2019), and antitumor effects (Maxwell, Chun, Lee, Kim, & Nam, 2017). In preliminary experiments, we found that arctigenin promotes the differentiation of bone marrow mesenchymal stem cells (BMSCs) of ovariectomized (OVX) rats into osteoblasts, leading to anti-osteoporosis effects.…”

Oral Submucous Fibrosis: A Review on Etiopathogenesis, Diagnosis, and Therapy

“…Transforming growth factor-β (TGF-β) is a major cytokine involved in OSF progression. It regulates the expression of α-SMA and type 1 collagen in myofibroblasts [47][48][49]. Studies have shown arecoline induced connective tissue growth factor (CTGF) biosynthesis via reactive oxygen species (ROS) and the NF-κB, JNK, and p38 MAPK pathways in buccal mucosal fibroblasts [35,48].…”