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

Pharm Biol. 2022 Dec;60(1):467-478. doi: 10.1080/13880209.2022.2039216.

Abstract

Context: Ferulic acid ethyl ester (FAEE) is abundant in Ligusticum chuanxiong Hort. (Apiaceae) and grains, and possesses diverse biological activities; but the effects of FAEE on osteoporosis has not been reported.

Objective: This study investigated whether FAEE can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating mitogen-activated protein kinase (MAPK).

Materials and methods: We stimulated RAW 264.7 cells with receptor activator of NF-κB ligand (RANKL) followed by FAEE. The roles of FAEE in osteoclast production and osteogenic resorption of mature osteoclasts were evaluated by tartrate resistant acid phosphatase (TRAP) staining, expression of osteoclast-specific genes, proteins and MAPK. Ovariectomized (OVX) female Sprague-Dawley rats were administered FAEE (20 mg/kg/day) for 12 weeks to explore its potential in vivo, and then histology was undertaken in combination with cytokines analyses.

Results: FAEE suppressed RANKL-induced osteoclast formation (96 ± 0.88 vs. 15 ± 1.68) by suppressing the expression of osteoclast-specific genes, proteins and MAPK signalling pathway related proteins (p-ERK/ERK, p-JNK/JNK and p-P38/P38) in vitro. In addition, OVX rats exposed to FAEE maintained their normal calcium (Ca) (2.72 ± 0.02 vs. 2.63 ± 0.03, p < 0.05) balance, increased oestradiol levels (498.3 ± 9.43 vs. 398.7 ± 22.06, p < 0.05), simultaneously reduced levels of bone mineral density (BMD) (0.159 ± 0.0016 vs. 0.153 ± 0.0025, p < 0.05) and bone mineral content (BMC) (0.8 ± 0.0158 vs. 0.68 ± 0.0291, p < 0.01).

Discussion and conclusions: These findings suggested that FAEE could be used to ameliorate osteoporosis by the MAPK signalling pathway, suggesting that FAEE could be a potential therapeutic candidate for osteoporosis.

Keywords: Ferulic acid ethyl ester; osteoclast; postmenopausal osteoporosis.

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Caffeic Acids / pharmacology*
  • Disease Models, Animal
  • Female
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Osteoporosis, Postmenopausal / prevention & control*
  • Ovariectomy
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Caffeic Acids
  • ethyl ferulate

Grants and funding

This work was supported by the Yunnan provincial key programs of Yunnan Eco-friendly Food International Cooperation Research Centre project under Grant [2019ZG00904, 2019ZG00909], the Science and Technology Plan Project of Yunnan Province [2018IA060] and Yunnan Provincial Science and Technology Project [2018FG001-035].