Aloperine improves osteoporosis in ovariectomized mice by inhibiting RANKL-induced NF-κB, ERK and JNK approaches

Rong Hu; Libo Chen; Xiaolong Chen; Zhong Xie; Chao Xia; Yong Chen

doi:10.1016/j.intimp.2021.107720

Aloperine improves osteoporosis in ovariectomized mice by inhibiting RANKL-induced NF-κB, ERK and JNK approaches

Int Immunopharmacol. 2021 Aug:97:107720. doi: 10.1016/j.intimp.2021.107720. Epub 2021 May 1.

Authors

Rong Hu¹, Libo Chen², Xiaolong Chen¹, Zhong Xie³, Chao Xia³, Yong Chen⁴

Affiliations

¹ Department of Radiology, the First Affiliated Hospital, University of South China, Hengyang, Hunan 421000, China.
² Department of Urology, the First Affiliated Hospital, University of South China, Hengyang, Hunan 421000, China.
³ Department of Spinal Surgery, the First Affiliated Hospital, University of South China, Hengyang, Hunan 421000, China.
⁴ Department of Spinal Surgery, the First Affiliated Hospital, University of South China, Hengyang, Hunan 421000, China. Electronic address: yongchen110@sina.com.

PMID: 33945918
DOI: 10.1016/j.intimp.2021.107720

Abstract

Presently, postmenopausal osteoporosis mainly caused by excessive activation of in vivo osteoclasts has become a global public health burden. Natural compounds have gradually become the potential drugs for the treatment of postmenopausal osteoporosis. Aloperine is a new alkaloid extracted from the leaves and seeds of sophora bean. The current studies have proved that aloperine has many biological activities, including anti-inflammatory, antiviral and anticancer activities. This study shows that aloperine can inhibit activity and formation of osteoclast mediated by RANKL in a dose-dependent manner without affecting the activity of bone marrow macrophages (BMM). In addition, it is found that aloperine can inhibit the expression of osteoclast specific marker genes, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP), matrix metallopeptidase 9 (MMP9), cathepsin K (Ctsk), V-ATPase d2 and calcitonin receptor. The in vitro experiment of aloperine proved that aloperine can inhibit the degradation of IκBα and the phosphorylation of P65, ERK and JNK. Additionally, aloperine improves bone loss in ovariectomized (OVX) mice by inhibiting osteoclast activity. This project proved that aloperine can affect the formation of osteoclasts by inhibiting RANKL signaling channel, and it is indicated that aloperine has the potential to be developed as a new drug for the prevention and treatment of postmenopausal osteoporosis.

Keywords: Aloperine; NF-κB; Osteoclast; Postmenopausal osteoporosis; RANKL.

MeSH terms

Animals
Disease Models, Animal
Drug Evaluation, Preclinical
Female
Femur / drug effects
Femur / pathology
Humans
Janus Kinases / antagonists & inhibitors
Janus Kinases / metabolism
MAP Kinase Signaling System / drug effects
Mice
NF-kappa B / antagonists & inhibitors
NF-kappa B / metabolism
Osteoclasts / drug effects
Osteogenesis / drug effects*
Osteoporosis, Postmenopausal / diagnosis
Osteoporosis, Postmenopausal / drug therapy*
Osteoporosis, Postmenopausal / etiology
Osteoporosis, Postmenopausal / pathology
Ovariectomy
Quinolizidines / pharmacology*
Quinolizidines / therapeutic use
RANK Ligand / antagonists & inhibitors
RANK Ligand / metabolism
X-Ray Microtomography

Substances

NF-kappa B
Quinolizidines
RANK Ligand
Tnfsf11 protein, mouse
aloperine
Janus Kinases