Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways

Abstract

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.

FAEE exerts a protective effect against osteoporosis by regulating the MAPK signalling pathway

“…The MAPK signalling pathway includes ERK, JNK, and p38 pathways (Yang et al. 2021 ). In addition, the phosphorylation of MAPKs (ERK, JNK and p38) is conducive to RANKL-stimulated osteoclastogenesis and bone resorption.…”

Gut Metabolite Urolithin A Inhibits Osteoclastogenesis and Senile Osteoporosis by Enhancing the Autophagy Capacity of Bone Marrow Macrophages

“…Classically, the MAPK signaling pathway is highly involved in osteoclast differentiation and actively regulates osteoclast maturity ( Fang et al, 2021 ; Yang et al, 2021 ). To explore the response mechanism by which Uro-A inhibits osteoclasts, we tested the expression of the MAPK family after Uro-A treatment.…”

An Insight into Sesamolin: Physicochemical Properties, Pharmacological Activities, and Future Research Prospects

“…Only sesamol gave the 50% inhibitory concentration (IC 50 ) against melanoma despite required a high treatment concentration (1893.1 ± 170.7 µM). It was mentioned in the study that sesamolin could not be dissolved well in cell culture media at a concentration higher than 200 µM that causing the limit investigation at a higher concentration [ 65 ]. These findings suggest that although sesamolin had the potency to inhibit melanoma cell growth, the limitation related to the solubility hindered the cytotoxic effect.…”

“…Several studies have used animal models to study the pharmacological activity of sesamolin and other lignans in sesame seeds or oils. However, they did not report the pharmacokinetic profile of sesamolin after administration [43,[63][64][65]. Two studies reported the bioavailability of sesamolin in in vivo models.…”