Galangin suppresses RANKL‐induced osteoclastogenesis via inhibiting MAPK and NF‐κB signalling pathways

Abstract

Osteoporosis is a group of diseases in which the bone mass is significantly reduced, predisposing patients to spontaneous bone fragility and bone fractures. It has been reported that more than 70 million people worldwide are affected by this life-threatening problem. 1 The integrity and structure of the skeleton are precisely regulated by osteoclastogenesis (mediated by osteoclasts) coupled with osteogenesis (mediated by osteoblasts). 2,3 However, excessive bone resorption by osteoclasts destabilizes this balance, ultimately causing chronic lytic diseases such as osteoporosis. 4 Therefore, identification of agents that can modulate the formation and activity of osteoclasts is important for the treatment of osteoporosis. Osteoclasts, if not exclusive, are the primary bone-resorbing cells. During the process of osteoclastogenesis, osteoclasts degrade the bone matrix by producing and secreting cathepsin K (CtsK) and tartrate-resistant acid phosphatase

Anti-Inflammatory Effects of Geniposidic Acid on Porphyromonas gingivalis-Induced Periodontitis in Mice

“…However, IL-6 production was not increased in the osteoclast differentiation assay with sRANKL and M-CSF ( Figure 5 b). Previous studies have shown that activation of p38 and ERK phosphorylation in the MAPK signaling pathway, as well as downstream factors of NFATc1, c-Fos, and C-Jun are important [ 37 ]. As GPA suppresses activation of the MAPK, AP-1, and NF-κB signaling pathways in macrophages [ 38 ], alveolar bone resorption may occur in vivo through the indirect action of IL-6 suppression because of its anti-inflammatory effect and its direct effects on BMMCs.…”

The molecular mechanisms underlying anti‐inflammatory effects of galangin in different diseases

“…Importantly, through inhibition of NF‐κB, GAL exerts significant anti‐inflammatory effects in different models such as osteoclastogenesis (Huh et al, 2013; X. Li et al, 2021), cardiometabolic disorders (Prasatthong et al, 2021), vascular remodelling (Chaihongsa et al, 2021), renal inflammation (H. Lu et al, 2019), rheumatoid arthritis (RA) (Fu et al, 2018), and psoriasis‐like skin inflammation (Sangaraju et al, 2021).…”

“…In human osteoarthritis chondrocytes, GAL increased ECM synthesis and decreased ECM degradation, and the intra‐articular GAL injection slowed the progression of osteoarthritis in rat models (Lin et al, 2022). Through inhibition of MAPK and NF‐κB signaling pathways, Li et al (2021) reported that GAL is a promising therapeutic agent for osteoporosis. GAL decreased NFATc1, C‐Jun, and C‐Fos in addition to inhibition of ERK and p38MAPK phosphorylation.…”

Receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis signaling pathway and related therapeutic natural compounds

“…Galangin, a natural bioflavonoid extracted from a traditional Chinese herb, has a variety of biological activities, including antiinflammatory and antioxidant properties. (Li et al (2021a) showed that during the differentiation of bone marrow macrophages Frontiers in Pharmacology frontiersin.org studying osteoporosis, which has the characteristics of single modeling factor, great repeatability, high reliability of experimental results, and can successfully simulate postmenopausal osteoporosis in vivo. In vivo studies have shown that Vinp significantly reduces the number of osteoclasts and attenuates ovariectomy-induced bone loss.…”

“…Galangin, a natural bioflavonoid extracted from a traditional Chinese herb, has a variety of biological activities, including anti-inflammatory and antioxidant properties. ( Li et al (2021a) showed that during the differentiation of bone marrow macrophages (BMMs) to OCs, galangin inhibited the phosphorylation of p38 and ERK in the MAPK signaling pathway, as well as downstream factors such as NFATc1, c-Jun and c-Fos. It also inhibits bone resorption by inhibiting lipopolysaccharide (LPS)-induced differentiation of OCs.…”