title: Ophiopogonin D: A new herbal agent against osteoporosis.
abstract: Excessive reactive oxygen species (ROS) play an important role in the development of osteoporosis. Ophiopogonin D (OP-D), isolated from the traditional Chinese herbal agent Radix Ophiopogon japonicus, is a potent anti-oxidative agent. We hypothesized that OP-D demonstrates anti-osteoporosis effects via decreasing ROS generation in mouse pre-osteoblast cell line MC3T3-E1 subclone 4 cells and a macrophage cell line RAW264.7 cells. We investigated OP-D on osteogenic and osteoclastic differentiation under oxidative status. Hydrogen peroxide (H2O2) was used to establish an oxidative damage model. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Then, we searched the molecular mechanism of OP-D against osteoporosis. Our results revealed that OP-D significantly promoted the proliferation of MC3T3-E1 cells and improved some osteogenic markers. Moreover, OP-D reduced TRAP activity and the mRNA expressions of osteoclastic genes in RAW264.7 cells. OP-D suppressed ROS generation in both MC3T3-E1 and RAW264.7 cells. OP-D treatment reduced the activity of serum bone degradation markers, including CTX-1 and TRAP. Further research showed that OP-D displayed anti-osteoporosis effects via reducing ROS through the FoxO3a-β-catenin signaling pathway. In summary, our results indicated that the protective effects of OP-D against osteoporosis are linked to a reduction in oxidative stress via the FoxO3a-β-catenin signaling pathway, suggesting that OP-D may be a beneficial herbal agent in bone-related disorders, such as osteoporosis.
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Air Force General Hospital, People's Liberation Army, Beijing 100142, People's Republic of China.
authors.forename: Jin-Kang
authors.initials: JK
authors.lastname: Zhang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Zhuo-Jing
authors.initials: ZJ
authors.lastname: Luo
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China. Electronic address: liujianhq@sina.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy; D008517:Phytotherapy; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013150:Spirostans / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012503:Saponins; D013150:Spirostans; D051176:beta Catenin; C046996:ophiopogonin D; D006861:Hydrogen Peroxide
keywords: FoxO3a; Ophiopogonin D; Osteoclastogenesis; Osteogenesis; Reactive oxygen species; β-Catenin