3D QSAR of novel estrogen–RGD peptide conjugates: Getting insight into structural dependence of anti-osteoporosis activity and side effect of estrogen in ERT

Zhao, Ming; Liu, Jiangyuan; Zhang, Xiaoyi; P, Li; Li, Chunyu; Peng, Shiqi

doi:10.1016/j.bmc.2009.03.057

Cited by 10 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these therapies are associated with high cost and side effects, including gastrointestinal toxicity, jaw osteonecrosis, atypical fractures, breast cancer and thromboembolism, which limit their clinical application. 38,39 The present study is the first to show that STA inhibits osteoclast formation and bone resorption by suppressing RANKL-induced activation of NF-κB-NFATc1 signalling in vitro. In addition, this study showed that STA attenuates LPS-induced bone loss in a murine model, suggesting its potential for treating inflammatory bone loss and osteoclastrelated diseases.…”

Section: Discussionmentioning

confidence: 57%

“…In the previous two decades, significant advances have been made in osteolytic disease treatment by using osteoclast‐targeting therapies such as bisphosphonates, oestrogens and denosumab. However, these therapies are associated with high cost and side effects, including gastrointestinal toxicity, jaw osteonecrosis, atypical fractures, breast cancer and thromboembolism, which limit their clinical application . The present study is the first to show that STA inhibits osteoclast formation and bone resorption by suppressing RANKL‐induced activation of NF‐κB–NFATc1 signalling in vitro.…”

Section: Discussionmentioning

confidence: 66%

See 1 more Smart Citation

Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Meng

Zhou

Zhang

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Osteoclast overactivation‐induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti‐inflammatory, anticancer and cardioprotective properties. However, its effects on osteoclast formation and function have been rarely described. In the present study, we found that STA suppressed receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast formation and bone resorption, and reduced osteoclast‐related gene expression in vitro. Mechanistically, STA inhibited RANKL‐induced activation of NF‐κB and Akt signalling, thus suppressing nuclear factor of activated T cells c1 induction and nuclear translocation. In addition, STA alleviated bone loss and reduced osteoclast number in a murine model of LPS‐induced inflammatory bone loss. STA also inhibited the activities of NF‐κB and NFATc1 in vivo. Together, these results suggest that STA effectively inhibits osteoclastogenesis both in vitro and in vivo and therefore is a potential option for treating osteoclast‐related diseases.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 66%

Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Meng

Zhou

Zhang

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Following our previous work,20,21 RGDS was synthesized using liquid-phase peptide synthesis according to Scheme 2. Boc-Arg(Tos) and Boc-Asp(OBzl) were first linked with HCl·Gly-OBzl and HCl·Ser-OBzl, respectively, and then the OBzl group of Boc-Arg(Tos)-Gly-OBzl and the Boc group of Boc-Asp(OBzl)-Ser-OBzl were removed by hydrogenesis and acidolysis.…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis and evaluation of VEGF-siRNA/CRS as a novel vector for gene delivery

Zhao¹,

Zhang²,

Jiang³

et al. 2016

DDDT

View full text Add to dashboard Cite

Small interfering RNA (siRNA) delivery is a prospective method in gene therapy, but it has application limitations such as negative charge, water solubility and high molecular weight. In this study, a safe and efficient nano-vector, CRS, was designed and synthesized to facilitate siRNA delivery. Physical and chemical properties of VEGF-siRNA/CRS were characterized by methods including scanning electron microscopy (SEM), transmission electron microscopy, zeta potential (ζ) measurement, drug-releasing rate measurement, gel electrophoresis and confocal microscopy. The biological activities were evaluated using cell viability assay, gene-silencing efficacy assay in vitro, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and antitumor tests in vivo. The mean nanoparticle size of VEGF-siRNA/CRS was 121.4±0.3 nm with positive ζ potential of 7.69±4.47 mV. The release rate of VEGF-siRNA from VEGF-siRNA/CRS was 82.50% sustained for 48 h in Tris-ethylenediaminetetraacetic acid buffer (pH 8.0). Real-time polymerase chain reaction was used to analyze the efficiency of the transfection, and the result showed that VEGF mRNA expression had been knocked down by 82.36%. The expression of VEGF protein was also recorded to be downregulated to 14.83% using ELISA. The results of cytotoxicity measured by Cell Counting Kit-8 assay showed that VEGF-siRNA/CRS had significant inhibitory effect on HeLa cells. The results of antitumor assays indicated that VEGF-siRNA/CRS exhibited tumor cell growth inhibition in vivo. The results demonstrated that VEGF-siRNA could be delivered and transported by the designed carrier, while siRNA could be released constantly and led to an increasing gene-silencing effect against VEGF gene. In conclusion, VEGF-siRNA/CRS is a promising carrier for siRNA delivery, and further studies are warranted.

show abstract

“…Serum calcium content and alkaline phosphatase (ALP) levels in mice given 110.3 nmol/kg of these compounds orally were significantly lower than those of mice receiving control estrogen, and both femur weight and femur ash and mineral levels of mice receiving control estrogen were lower than those receiving conjugates. Finally, these compounds showed a lower risk of endometrial hyperplasia and thromboembolic events [65]. In addition to these conjugates, 17-estradiol-RGD octapeptides (such as 12 , Fig.…”

Section: Update On Chemical Classes Comprising Erα and Erβ Modulatorsmentioning

confidence: 99%

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

et al. 2014

View full text Add to dashboard Cite

Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications.

show abstract

3D QSAR of novel estrogen–RGD peptide conjugates: Getting insight into structural dependence of anti-osteoporosis activity and side effect of estrogen in ERT

Cited by 10 publications

References 30 publications

Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Design, synthesis and evaluation of VEGF-siRNA/CRS as a novel vector for gene delivery

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

Contact Info

Product

Resources

About