Department of Oral & Maxillofacial Regeneration, Graduate School, Kyung Hee University, Seoul, 130-701, Republic of Korea.
Department of Dental Hygiene, College of Health Science, Gachon University, Incheon, 406-799, Republic of Korea.
Arch Pharm Res. 2017 Aug;40(8):933-942. doi: 10.1007/s12272-017-0932-z. Epub 2017 Jul 24.
Magnolol, honokiol, and obovatol are well known bioactive constituents of the bark of Magnolia officinalis and have been reported to have beneficial effects in various diseases. We recently isolated a novel active compound, 4-O-methylhonokiol (4-O-MH) from the ethanol extract of M. officinalis, which was previously reported to have pharmacological effects including anti-inflammatory, anti-oxidative, and anti-aging activities. Here, we examined the pharmacological properties of 4-O-MH on osteoblast (bone-forming cells) and osteoclast (bone-resorbing cells) differentiation, and its underlying signaling pathways in primary cultured pre-osteoblasts and bone marrow macrophages. Our results showed that 4-O-MH did not affect cell viability in pre-osteoblasts and did not influence osteoblast differentiation and mineralized nodule formation, as assessed by alkaline phosphatase activity and Alizarin red staining. However, 4-O-MH significantly inhibited TRAP-positive multinuclear osteoclasts and F-actin ring formation during Receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis without cytotoxicity. In addition, 4-O-MH suppressed RANKL-induced critical factors (c-Fos, NF-ATc1, TRAP, and ITB3) for osteoclast differentiation and function. Furthermore, RANKL-mediated signaling, including ERK1/2, AKT, and NF-kB pathways was attenuated by 4-O-MH. Taken together, 4-O-MH has an inhibitory role in RANKL-mediated osteoclastogenesis but not osteoblast differentiation, and our findings also suggest that 4-O-MH is a potential therapeutic agent for bone-destructive diseases such as osteoporosis, alveolar bone resorption, and osteoarthritis.
厚朴酚、和厚朴酚和蝙蝠葛碱是厚朴树皮中的几种众所周知的生物活性成分，据报道它们对各种疾病具有有益作用。我们最近从厚朴乙醇提取物中分离出一种新型活性化合物 4-O-甲基厚朴酚（4-O-MH），据报道它具有抗炎、抗氧化和抗衰老等药理学作用。在此，我们研究了 4-O-MH 对原代培养的成骨细胞和破骨细胞分化的药理作用及其在原代成骨细胞和骨髓巨噬细胞中的潜在信号通路。结果表明，4-O-MH 不影响成骨细胞的细胞活力，也不影响成骨细胞分化和矿化结节形成，如碱性磷酸酶活性和茜素红染色所示。然而，4-O-MH 在核因子-κB 受体激活剂配体（RANKL）介导的破骨细胞分化过程中，可显著抑制破骨细胞的形成，抑制破骨细胞的形成和破骨细胞的 F-肌动蛋白环形成，且无细胞毒性。此外，4-O-MH 还抑制 RANKL 诱导的破骨细胞分化和功能的关键因子（c-Fos、NF-ATc1、TRAP 和 ITB3）。此外，4-O-MH 还抑制 RANKL 介导的信号通路，包括 ERK1/2、AKT 和 NF-kB 通路。总之，4-O-MH 对 RANKL 介导的破骨细胞生成具有抑制作用，但对成骨细胞分化没有作用，我们的研究结果还表明，4-O-MH 可能是骨质疏松症、牙槽骨吸收和骨关节炎等破坏骨骼疾病的潜在治疗药物。
