Anti-osteoporosis effect of Semen Cuscutae in ovariectomized mice through inhibition of bone resorption by osteoclasts. 2022

Yun Yang, and Qiu Wei, and Ran An, and Hua-Mei Zhang, and Jia-Yuan Shen, and Xiao-Yan Qin, and Xiao-Ling Han, and Jie Li, and Xiao-Wei Li, and Xiu-Mei Gao, and Jun He, and Hao-Ping Mao
Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, China.

BACKGROUND Semen Cuscutae, called Tu-si-zi in Chinese, is a kind of dried mature seed in the Convolvulaceae family. It mainly distributes in China, Korea, Pakistan, Vietnam, India and Thailand. It is used as a kidney-tonifying drug for treatment of aging related diseases such as osteoporosis in traditional Chinese medicine. However, the exact mechanisms on bone resorption are poorly studied. OBJECTIVE The aim of this study was to investigate the potential effect of Semen Cuscutae on ovariectomy (OVX)-induced osteoporosis in mice and clarify the exact mechanisms by which Semen Cuscutae exert the anti-osteoporosis effect. METHODS Qualitative and quantitative analyses of Semen Cuscutae were performed by UPLC-Q-TOF-MS and HPLC-MS/MS, respectively. Changes in bone mineral density (BMD) induced by OVX in mice were measured by dual-energy X-ray absorptiometry and micro-computed tomography (μCT). Tartrate-resistant acid phosphatase (TRAP) staining as well as hematoxylin and eosin (HE) staining were used to observe bone microarchitectural changes. ELISA kits were used to assess the therapeutic effects of Semen Cuscutae on the serum levels of osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP-5b), and receptor activator of nuclear factor-κB (RANKL). The effect of Semen Cuscutae on primary cell viability was assessed using CCK-8 and anti-tartrate phosphatase assays. TRAP staining and actin ring staining were used to observe the effect of Semen Cuscutae on osteoclast differentiation. Western blotting was used to measure the effects of Semen Cuscutae on expressions of NFATC1, c-Src kinase, and c-fos. RESULTS Results from UPLC-Q-TOF-MS showed that the main components of Semen Cuscutae were flavonoid compounds that included quercitrin, quercetin, hyperoside, caffeic acid, rutin, chlorogenic acid, luteolin, apigenin, kaempferol, isoquercetin, cryptochlorogenic acid, isorhamnetin-3-O-glucoside, and astragalin. After the Semen Cuscutae extract was orally administered to OVX mice, bone density increased (P < 0.01) and bone microstructure was significantly improved (P < 0.01 or 0.05). Additionally, Semen Cuscutae exhibited a significant descending effect in the levels of serum TRACP-5b and RANKL, while there was a significant increase in OPG in the Semen Cuscutae group compared with the OVX group, especially at high doses. Moreover, we found that increasing of c-fos, c-Src kinase, and NFATC1 protein expressions were reversed by Semen Cuscutae in vitro and in vivo. CONCLUSIONS Our results showed that Semen Cuscutae exhibited anti-osteoporosis effects through the c-fos/c-Src kinase/NFATC1 signaling pathway.

UI MeSH Term Description Entries
D010010 Osteoclasts A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption. Odontoclasts,Cementoclast,Cementoclasts,Odontoclast,Osteoclast
D010024 Osteoporosis Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis. Age-Related Osteoporosis,Bone Loss, Age-Related,Osteoporosis, Age-Related,Osteoporosis, Post-Traumatic,Osteoporosis, Senile,Senile Osteoporosis,Osteoporosis, Involutional,Age Related Osteoporosis,Age-Related Bone Loss,Age-Related Bone Losses,Age-Related Osteoporoses,Bone Loss, Age Related,Bone Losses, Age-Related,Osteoporoses,Osteoporoses, Age-Related,Osteoporoses, Senile,Osteoporosis, Age Related,Osteoporosis, Post Traumatic,Post-Traumatic Osteoporoses,Post-Traumatic Osteoporosis,Senile Osteoporoses
D010936 Plant Extracts Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard. Herbal Medicines,Plant Extract,Extract, Plant,Extracts, Plant,Medicines, Herbal
D001862 Bone Resorption Bone loss due to osteoclastic activity. Bone Loss, Osteoclastic,Osteoclastic Bone Loss,Bone Losses, Osteoclastic,Bone Resorptions,Loss, Osteoclastic Bone,Losses, Osteoclastic Bone,Osteoclastic Bone Losses,Resorption, Bone,Resorptions, Bone
D004365 Drugs, Chinese Herbal Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China. Chinese Herbal Drugs,Plant Extracts, Chinese,Chinese Drugs, Plant,Chinese Plant Extracts,Extracts, Chinese Plant,Herbal Drugs, Chinese
D000081247 CSK Tyrosine-Protein Kinase Protein tyrosine kinases that phosphorylate tyrosine residues located in the C-terminal tails of SRC-FAMILY KINASES. C-Terminal Src Kinase,Carboxy-Terminal Src Kinase,Protein Tyrosine Kinase p50(csk),Protein-Tyrosine Kinase C-Terminal Src Kinase,Protein-Tyrosine Kinase c-src,Tyrosine Protein Kinase p50csk,Tyrosine-Protein Kinase CSK,c-src Kinase,c-src Tyrosine Kinase,CSK-src,p50(csk),C Terminal Src Kinase,CSK Tyrosine Protein Kinase,CSK src,CSK, Tyrosine-Protein Kinase,Carboxy Terminal Src Kinase,Kinase CSK, Tyrosine-Protein,Kinase c-src, Protein-Tyrosine,Kinase, C-Terminal Src,Kinase, CSK Tyrosine-Protein,Kinase, Carboxy-Terminal Src,Kinase, c-src,Kinase, c-src Tyrosine,Protein Tyrosine Kinase C Terminal Src Kinase,Protein Tyrosine Kinase c src,Src Kinase, C-Terminal,Src Kinase, Carboxy-Terminal,Tyrosine Kinase, c-src,Tyrosine Protein Kinase CSK,Tyrosine-Protein Kinase, CSK,c src Kinase,c src Tyrosine Kinase,c-src, Protein-Tyrosine Kinase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015502 Absorptiometry, Photon A noninvasive method for assessing BODY COMPOSITION. It is based on the differential absorption of X-RAYS (or GAMMA RAYS) by different tissues such as bone, fat and other soft tissues. The source of (X-ray or gamma-ray) photon beam is generated either from radioisotopes such as GADOLINIUM 153, IODINE 125, or Americanium 241 which emit GAMMA RAYS in the appropriate range; or from an X-ray tube which produces X-RAYS in the desired range. It is primarily used for quantitating BONE MINERAL CONTENT, especially for the diagnosis of OSTEOPOROSIS, and also in measuring BONE MINERALIZATION. Absorptiometry, X-Ray,Dual-Photon Absorptiometry,Photodensitometry, X-Ray,Photon Absorptiometry,Single-Photon Absorptiometry,X-Ray Absorptiometry,Absorptiometry, Dual X-Ray,Absorptiometry, Dual-Energy Radiographic,Absorptiometry, Dual-Energy X-Ray,DEXA Scan,DPX Absorptiometry,DXA Scan,Densitometry, X-Ray,Densitometry, Xray,Dual X-Ray Absorptiometry,Dual-Energy Radiographic Absorptiometry,Dual-Energy X-Ray Absorptiometry,Dual-Energy X-Ray Absorptiometry Scan,Radiographic Absorptiometry, Dual-Energy,X-Ray Absorptiometry, Dual-Energy,X-Ray Photodensitometry,Absorptiometries, DPX,Absorptiometry, DPX,Absorptiometry, Dual Energy Radiographic,Absorptiometry, Dual Energy X Ray,Absorptiometry, Dual X Ray,Absorptiometry, Dual-Photon,Absorptiometry, Single-Photon,Absorptiometry, X Ray,DEXA Scans,DXA Scans,Densitometry, X Ray,Dual Energy Radiographic Absorptiometry,Dual Energy X Ray Absorptiometry,Dual Energy X Ray Absorptiometry Scan,Dual Photon Absorptiometry,Dual X Ray Absorptiometry,Photodensitometry, X Ray,Radiographic Absorptiometry, Dual Energy,Scan, DEXA,Scan, DXA,Scans, DEXA,Scans, DXA,Single Photon Absorptiometry,X Ray Absorptiometry,X Ray Absorptiometry, Dual Energy,X Ray Photodensitometry,X-Ray Absorptiometry, Dual,X-Ray Densitometry,Xray Densitometry
D016760 Proto-Oncogene Proteins c-fos Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes. Fos B Protein,Fos-Related Antigen,Fos-Related Antigens,c-fos Protein,c-fos Proteins,fos Proto-Oncogene Protein,fos Proto-Oncogene Proteins,p55(c-fos),Antigens, Fos-Related,FRAs,Proto-Oncogene Products c-fos,Proto-Oncogene Proteins fos,p55 c-fos,Antigen, Fos-Related,Fos Related Antigen,Fos Related Antigens,Protein, c-fos,Protein, fos Proto-Oncogene,Proto Oncogene Products c fos,Proto Oncogene Proteins c fos,Proto Oncogene Proteins fos,Proto-Oncogene Protein, fos,c fos Protein,c fos Proteins,fos Proto Oncogene Protein,fos Proto Oncogene Proteins,p55 c fos

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