PUBLICATION

Integrated pathological cell fishing and network pharmacology approach to investigate main active components of Er-Xian decotion for treating osteoporosis

Authors
Wang, N., Xu, P., Wang, X., Yao, W., Yu, Z., Wu, R., Huang, X., Si, Y., Shou, D.
ID
ZDB-PUB-190529-6
Date
2019
Source
Journal of ethnopharmacology   241: 111977 (Journal)
Registered Authors
Keywords
Berberine, Curculigoside, Epimedin A, Epimedin B, Epimedin C, Ferulic acid, Icariin, Monotropein, Network pharmacology, Obaculactone, Orcinol glucoside, Osteoblast, Osteoporosis, Oxidative stress, Timosaponin AIII, Timosaponin BII, Timosaponin C, Traditional Chinese herbal prescription
MeSH Terms
  • Animals
  • Bone Morphogenetic Protein 2/blood
  • Bone and Bones/drug effects
  • Bone and Bones/metabolism
  • Cell Line
  • Cell Survival/drug effects
  • Drugs, Chinese Herbal/pharmacology*
  • Drugs, Chinese Herbal/therapeutic use*
  • Female
  • Hydrogen Peroxide/pharmacology
  • Mice
  • Osteoblasts/drug effects
  • Osteoblasts/metabolism
  • Osteocalcin/metabolism
  • Osteoporosis/drug therapy*
  • Osteoporosis/metabolism*
  • Oxidative Stress/drug effects
  • Rats, Wistar
  • Zebrafish
PubMed
31136804 Full text @ J. Ethnopharmacol.
Abstract
Oxidative damage to osteoblasts was a key factor in the development of osteoporosis. Er-Xian Decotion (EXD) is widely used in China for the treatment of osteoporosis, which has a variety of antioxidant active ingredients. EXD may be an important source of protection against oxidative damage in osteoblasts, but the anti-osteoporotic active components of EXD is currently unclear.
This work established an effective and reliable drug screening method to find main active ingredients in EXD (M-EXD) that can protect osteoblasts against oxidative stress and achieve anti-osteoporosis effects.
H2O2-induced osteoblast cell fishing with UHPLC-QTOF/MS was firstly used to discover the potential active components from EXD. Afterword, the EXD compound-osteoporosis target network was constructed using network pharmacology, thus potentially anti-osteoporosis ingredients were founded, and their combination were defined as the M-EXD. Finally, pharmacology effects of M-EXD was evaluated by ovariectomized rats, prednisolone induced-zebrafish and H2O2-induced osteoblasts.
40 candidate active ingredients in EXD were initially screened out via pathological cell fishing. According to network pharmacology result, M-EXD consisted of 13 ingredients since they had a close relationship with 65 osteoporosis-related targets. Pharmacological evaluation showed that M-EXD significantly ameliorated oxidative stress in H2O2-induced osteoblast model, evidently reversed the activity of ALP, ROS, GSH-px, NO and MDA compared with the model group. M-EXD showed better anti-oxidative activities than individual ingredients, presenting obvious synergetic effects. In osteoporosis rat and zebrafish models, M-EXD also demonstrated good anti-osteoporotic properties by mitigating the osteoporosis bone loss and increasing serum bone morphogenetic protein 2, and reversing osteocalcin expression in bone tissue. It significantly ameliorated oxidative stress in the in-vivo models. Moreover, M-EXD and EXD showed similar anti-osteoporotic and anti-oxidative properties, while the rest components of EXD had no satisfactory anti-osteoporotic efficacy.
Our work successfully identified the main active components in EXD, which could represent the efficacy of EXD on treating osteoporosis, and meanwhile, it also provided an effective strategy to investigate active ingredients from natural medicines, which might be helpful for drug development and application.
Genes / Markers
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Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes