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CC BY 4.0 · Pharmaceutical Fronts 2020; 02(04): e168-e178
DOI: 10.1055/s-0041-1726301
Original Article

Serum Pharmacochemistry Analysis Combined with Network Pharmacology Approach to Investigate the Antiosteoporosis Effect of Xianlinggubao Capsule in vivo

Yun-Hui Xu‡   #
1   State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Yi-Chun Sun‡   #
2   Sinopharm Group Tongjitang (Guizhou) Pharmaceutical Co., Ltd., Guiyang, People's Republic of China
3   Guangdong Efong Pharmaceutical Co., Ltd, Guangzhou, People's Republic of China
,
Jie Liu
1   State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Hui-Xin Li
2   Sinopharm Group Tongjitang (Guizhou) Pharmaceutical Co., Ltd., Guiyang, People's Republic of China
,
Chun-Yue Huang
1   State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Yuan-Yuan Pang
2   Sinopharm Group Tongjitang (Guizhou) Pharmaceutical Co., Ltd., Guiyang, People's Republic of China
,
Tong Wu   #
1   State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Xiao Hu   #
1   State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   Sinopharm Group Tongjitang (Guizhou) Pharmaceutical Co., Ltd., Guiyang, People's Republic of China
› Author Affiliations Funding Statement This research was funded by the Project of Standardization of Chinese Materia Medica (Grant No. ZYBZH-C-GZ-10), China Postdoctoral Science Foundation (Grant No. 2018M633022), and National Science and Technology Major Project (Grant No. 2018ZX09731-016).
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Abstract

Xianlinggubao capsule (XLGB) is a traditional Chinese medicine multi-component herbal prescription and has been widely used in osteoporosis (OP) treatment. However, the underlying anti-OP mechanisms of XLGB have not been fully studied. In this study, an ovariectomized rat model of OP was established. The OP rats were orally administrated with XLGB, and then the main absorbed components in serum sample were assessed based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, the potential anti-OP markers in XLGB were screened based on a network pharmacology strategy. Molecular docking analysis was used for confirmation. LC-MS showed 22 absorbed components in the serum sample of OP rat with XLGB treatment. Network pharmacology and pathway analysis suggested 19 potential anti-OP markers in XLGB. According to molecular docking process, most of the potential markers displayed strong interactions with the 22 absorbed components mentioned above. Besides, an absorbed component–potential marker–pathway network was further established. In conclusion, our data suggested the possible mechanisms for XLGB in OP treatment, in which the “multicomponents, multitargets, and multipathways” participated. Our article provided possible direction for drug discovery in OP and could help for exploring novel application of XLGB in clinical setting.

Keywords

xianlinggubao capsule - osteoporosis - mechanism - serum pharmacochemistry analysis - network pharmacology - molecular docking

Author Contributions

Xiao Hu designed the experiments and checked the final manuscript. Yun-Hui Xu performed the experiments, analyzed and interpreted the results, and wrote the manuscript. Yi-Chun Sun performed some experiments, contributed materials, and checked the data. Jie Liu searched the relevant literature. Hui-Xin Li, Chun-Yue Huang, and Yuan-Yuan Pang provided helpful discussions. Tong Wu directed the research. All authors have read and approved the final version of this manuscript.


# These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 28 December 2020

Accepted: 10 February 2021

Article published online:
08 April 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Awasthi H, Mani D, Singh D, Gupta A. The underlying pathophysiology and therapeutic approaches for osteoporosis. Med Res Rev 2018; 38 (06) 2024-2057
    CrossrefPubMedGoogle Scholar
  • 2 Madrasi K, Li F, Kim MJ. et al. Regulatory perspectives in pharmacometric models of osteoporosis. J Clin Pharmacol 2018; 58 (05) 572-585
    CrossrefPubMedGoogle Scholar
  • 3 Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res 2007; 22 (03) 465-475
    CrossrefPubMedGoogle Scholar
  • 4 Chen P, Li Z, Hu Y. Prevalence of osteoporosis in China: a meta-analysis and systematic review. BMC Public Health 2016; 16 (01) 1039
    CrossrefPubMedGoogle Scholar
  • 5 Mithal A, Bansal B, Kyer CS, Ebeling P. The Asia-Pacific regional audit-epidemiology, costs, and burden of osteoporosis in India 2013: a report of International Osteoporosis Foundation. Indian J Endocrinol Metab 2014; 18 (04) 449-454
    CrossrefPubMedGoogle Scholar
  • 6 Cooper C, Cole ZA, Holroyd CR. et al; IOF CSA Working Group on Fracture Epidemiology. Secular trends in the incidence of hip and other osteoporotic fractures. Osteoporos Int 2011; 22 (05) 1277-1288
    CrossrefPubMedGoogle Scholar
  • 7 Liu K, Tan LJ, Wang P. et al. Functional relevance for associations between osteoporosis and genetic variants. PLoS One 2017; 12 (04) e0174808
    CrossrefPubMedGoogle Scholar
  • 8 Liu Y, Liu JP, Xia Y. Chinese herbal medicines for treating osteoporosis. Cochrane Database Syst Rev 2014; 6 (03) CD005467
    Google Scholar
  • 9 Zhu HM, Qin L, Garnero P. et al. The first multicenter and randomized clinical trial of herbal Fufang for treatment of postmenopausal osteoporosis. Osteoporos Int 2012; 23 (04) 1317-1327
    CrossrefPubMedGoogle Scholar
  • 10 Qin L, Zhang G, Hung WY. et al. Phytoestrogen-rich herb formula “XLGB” prevents OVX-induced deterioration of musculoskeletal tissues at the hip in old rats. J Bone Miner Metab 2005; 23 (Suppl): 55-61
    CrossrefPubMedGoogle Scholar
  • 11 State Food and Drug Administration of China, Xianlinggubao Capsule, WS-10269 (ZD-0269)-2002. National Standards Assembly of Chinese Patent Medicine, 2002.
    Google Scholar
  • 12 Dai Y, Tu FJ, Yao ZH. et al. Rapid identification of chemical constituents in traditional Chinese medicine fufang preparation xianling gubao capsule by LC-linear ion trap/Orbitrap mass spectrometry. Am J Chin Med 2013; 41 (05) 1181-1198
    CrossrefPubMedGoogle Scholar
  • 13 Bao H, Guo H, Feng Z, Li X. Deciphering the underlying mechanism of Xianlinggubao capsule against osteoporosis by network pharmacology. BMC Complement Med Ther 2020; 20 (01) 208
    CrossrefPubMedGoogle Scholar
  • 14 Lee AY, Park W, Kang TW, Cha MH, Chun JM. Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis. J Ethnopharmacol 2018; 221: 151-159
    CrossrefPubMedGoogle Scholar
  • 15 Cheng M, Wang Q, Fan Y. et al. A traditional Chinese herbal preparation, Er-Zhi-Wan, prevent ovariectomy-induced osteoporosis in rats. J Ethnopharmacol 2011; 138 (02) 279-285
    CrossrefPubMedGoogle Scholar
  • 16 Bahlous A, Kalai E, Hadj Salah M, Bouzid K, Zerelli L. Biochemical markers of bone remodeling: recent data of their applications in managing postmenopausal osteoporosis [in French]. Tunis Med 2006; 84 (11) 751-757
    PubMedGoogle Scholar
  • 17 Lei T, Liang Z, Li F. et al. Pulsed electromagnetic fields (PEMF) attenuate changes in vertebral bone mass, architecture and strength in ovariectomized mice. Bone 2018; 108: 10-19
    CrossrefPubMedGoogle Scholar
  • 18 Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1 (04) 337-341
    CrossrefPubMedGoogle Scholar
  • 19 Ru J, Li P, Wang J. et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6: 13
    CrossrefPubMedGoogle Scholar
  • 20 Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4 (01) 44-57
    CrossrefPubMedGoogle Scholar
  • 21 Lang PT, Brozell SR, Mukherjee S. et al. DOCK 6: combining techniques to model RNA-small molecule complexes. RNA 2009; 15 (06) 1219-1230
    CrossrefPubMedGoogle Scholar
  • 22 Missiuro PV, Liu K, Zou L. et al. Information flow analysis of interactome networks. PLOS Comput Biol 2009; 5 (04) e1000350
    CrossrefPubMedGoogle Scholar
  • 23 Tang Y, Li M, Wang J, Pan Y, Wu FX. CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems 2015; 127: 67-72
    CrossrefPubMedGoogle Scholar
  • 24 Geng JL, Dai Y, Yao ZH. et al. Metabolites profile of Xian-Ling-Gu-Bao capsule, a traditional Chinese medicine prescription, in rats by ultra performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis. J Pharm Biomed Anal 2014; 96: 90-103
    CrossrefPubMedGoogle Scholar
  • 25 Zhang D, Liu L, Jia Z, Yao X, Yang M. Flavonoids of Herba Epimedii stimulate osteogenic differentiation and suppress adipogenic differentiation of primary mesenchymal stem cells via estrogen receptor pathway. Pharm Biol 2016; 54 (06) 954-963
    CrossrefPubMedGoogle Scholar
  • 26 Wu Y, Xia L, Zhou Y, Xu Y, Jiang X. Icariin induces osteogenic differentiation of bone mesenchymal stem cells in a MAPK-dependent manner. Cell Prolif 2015; 48 (03) 375-384
    CrossrefPubMedGoogle Scholar
  • 27 Zhai YK, Guo XY, Ge BF. et al. Icariin stimulates the osteogenic differentiation of rat bone marrow stromal cells via activating the PI3K-AKT-eNOS-NO-cGMP-PKG. Bone 2014; 66: 189-198
    CrossrefPubMedGoogle Scholar
  • 28 You L, Chen L, Pan L, Chen JY. New insights into the gene function of osteoporosis. Front Biosci 2013; 18: 1088-1097
    CrossrefPubMedGoogle Scholar
  • 29 Xu F, Ding Y, Guo Y. et al. Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level approach. J Ethnopharmacol 2016; 177: 148-160
    CrossrefPubMedGoogle Scholar
  • 30 Higuchi C, Myoui A, Hashimoto N. et al. Continuous inhibition of MAPK signaling promotes the early osteoblastic differentiation and mineralization of the extracellular matrix. J Bone Miner Res 2002; 17 (10) 1785-1794
    CrossrefPubMedGoogle Scholar
  • 31 Peng S, Zhou G, Luk KD. et al. Strontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway. Cell Physiol Biochem 2009; 23 (1-3): 165-174
    CrossrefPubMedGoogle Scholar
  • 32 David JP, Sabapathy K, Hoffmann O, Idarraga MH, Wagner EF. JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms. J Cell Sci 2002; 115 (Pt 22): 4317-4325
    CrossrefPubMedGoogle Scholar
  • 33 Ikeda F, Nishimura R, Matsubara T. et al. Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. J Clin Invest 2004; 114 (04) 475-484
    CrossrefPubMedGoogle Scholar
  • 34 Xi JC, Zang HY, Guo LX. et al. The PI3K/AKT cell signaling pathway is involved in regulation of osteoporosis. J Recept Signal Transduct Res 2015; 35 (06) 640-645
    CrossrefPubMedGoogle Scholar
  • 35 Ke K, Li Q, Yang X. et al. Asperosaponin VI promotes bone marrow stromal cell osteogenic differentiation through the PI3K/AKT signaling pathway in an osteoporosis model. Sci Rep 2016; 6: 35233
    CrossrefPubMedGoogle Scholar
  • 36 Zhong H, Cao C, Yang J, Huang Q. Research on Relationship of HIF-1 Signaling Pathway and Postmenstrual Osteoporosis [in Chinese]. Sichuan Da Xue Xue Bao Yi Xue Ban 2017; 48 (06) 862-868
    PubMedGoogle Scholar
  • 37 Xu Q, Chen G, Liu X, Dai M, Zhang B. Icariin inhibits RANKL-induced osteoclastogenesis via modulation of the NF-κB and MAPK signaling pathways. Biochem Biophys Res Commun 2019; 508 (03) 902-906
    CrossrefPubMedGoogle Scholar
  • 38 Amjadi-Moheb F, Akhavan-Niaki H. Wnt signaling pathway in osteoporosis: Epigenetic regulation, interaction with other signaling pathways, and therapeutic promises. J Cell Physiol 2019; 234 (09) 14641-14650
    CrossrefPubMedGoogle Scholar