Cervus elaphus sibiricus (Deer antler) extract alleviates osteoporosis via dual modulation of osteoblast and osteoclast activity in ovariectomy-induced mice on network pharmacology.
You Yeon Choi, Seong Chul Jin, Minwoo Song, Seungyob Yi, Jieun Park, Hee Kyung Baek, Sung Hyo Park, Hyun Jung Yang, Jin Young Lee, Woong Mo Yang
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引用次数: 0
Abstract
Ethnopharmacological relevance: Cervus elaphus sibiricus (deer antler; Cervi Parvum Cornu; Nokyong) refers to the unossified antlers of young male deer and has been traditionally used in East Asian medicine to tonify the kidney and strengthen bone, supporting musculoskeletal health (osteoporosis, age-related frailty). Despite its long-standing use, the pharmacological mechanisms underlying its anti-osteoporotic effects remain largely unelucidated.
Aim of the study: This study aimed to evaluate the anti-osteoporotic effects of a dual-extraction deer antler extract (PKDE) and to elucidate its mechanism of action through an integrative approach combining network pharmacology with in vivo and in vitro models.
Materials and methods: Network pharmacology (KEGG, GO, PPI) was used to identify bone-related targets, and active compounds were verified by HPLC-MS. An ovariectomy (OVX)-induced osteoporosis mouse model was used to evaluate the in vivo efficacy of PKDE (48, 96, and 144 mg/kg, p.o., 4 weeks). Bone mineral density (BMD), bone mineral content (BMC), collagen deposition, and adipocyte size were assessed. Serum levels of TRACP-5b, CTX, and osteocalcin were measured. Osteogenic and osteoclastic gene expression in tibial tissue was analyzed by RT-PCR. In vitro, the effects of PKDE on osteoclastogenesis and osteoblast differentiation were investigated using RAW264.7 and SaOS-2 cells, respectively.
Results: PKDE increased BMD and BMC, restored collagen, and reduced marrow adiposity. Serum levels of TRACP-5b and CTX decreased, whereas osteocalcin increased. Gene expression analysis revealed downregulation of osteoclast markers (RANKL/OPG ratio) and upregulation of osteoblast markers (Col1a1, Bmp2, Spp1) in tibial tissue. In vitro, PKDE suppressed osteoclastogenesis in RANKL-induced RAW264.7 cells, as evidenced by a reduction in TRAP-positive multinucleated cells and downregulation of osteoclast-related genes such as Nfatc1 and Ctsk. In contrast, PKDE promoted osteoblast differentiation in AA/β-GP-induced SaOS-2 cells, as demonstrated by enhanced mineralization via Alizarin Red S staining and upregulated expression of osteogenic markers including COL1A1, BMP2, Runx2, SPP1, and IBSP. No hepatotoxicity or nephrotoxicity was observed.
Conclusion: PKDE exerts dual anti-osteoporotic effects by inhibiting osteoclastogenesis and promoting osteoblast differentiation via modulation of bone metabolism pathways, supporting the traditional use of PKDE and highlighting its potential as a natural-origin therapeutic for bone health.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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