Skip to content
2000
image of Unveiling the Therapeutic Targets and Active Components of Xianlinggubao Capsule in Osteoarthritis and Osteoporosis through Network Pharmacology and Bioinformatic Analysis

Abstract

Introduction

The Xianling Gubao capsule (XLGB), a traditional Chinese medicine formulation approved by the China Food and Drug Administration, has been effectively used to treat two common medical conditions: osteoarthritis (OA) and osteoporosis (OP). However, due to the complex ingredients, the molecular mechanisms underlying its therapeutic effects for OA and OP remain unknown.

Methods

This study identified XLGB-related therapeutic target genes and pathways for OA and OP by using bioinformatics and network pharmacology. Molecular docking assessed the interactions between core genes and compounds, while quantitative real-time PCR and Western blotting analyses validated the mRNA and protein expression of key target genes.

Results

Bioinformatics analysis identified 473 unique genes common to OA and OP. Network pharmacology analysis identified 30 intersecting genes as the principal target genes for anti-OA and anti-OP effects. Ten hub genes were identified using protein-protein interaction as potential therapeutic targets. These genes were related to transcription regulation and enriched in certain signaling pathways, such as interleukin-17 and tumor necrosis factor. Molecular docking analysis revealed danshenxinkun B to exhibit a strong affinity for , , and , while miltirone displayed a strong affinity for . The experimental results have been verified using cellular experiments.

Discussion

This study showed , , and to be mainly enriched in interleukin-17 and tumor necrosis factor signaling pathways. Moreover, danshenxinkun B and miltirone significantly modulated the expression levels of these genes.

Conclusion

This study has demonstrated that danshenxinkun B and miltirone may be pivotal agents in treating OA and OP by down-regulating the expressions of , , and .

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128406157250911093530
2025-10-08
2025-11-09

  • From This Site

    /content/journals/cpd/10.2174/0113816128406157250911093530
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Chen X. Li Y. Zhang Z. Xianling Gubao attenuates high glucose-induced bone metabolism disorder in MG63 osteoblast-like cells. PLoS One 2022 17 12 e0276328 10.1371/journal.pone.0276328 36548302
    [Google Scholar]
  2. Zeng J. Li C. Gu Z. A network pharmacological study to unveil the mechanisms of xianlinggubao capsule in the treatment of osteoarthritis and osteoporosis. Arch. Med. Sci. 2020 20 2 557 566 10.5114/aoms.2020.92931 38757042
    [Google Scholar]
  3. Kumavat R. Kumar V. Malhotra R. Biomarkers of joint damage in osteoarthritis: Current status and future directions. Mediators Inflamm. 2021 2021 1 15 10.1155/2021/5574582 33776572
    [Google Scholar]
  4. Allen K.D. Thoma L.M. Golightly Y.M. Epidemiology of osteoarthritis. Osteoarthritis Cartilage 2022 30 2 184 195 10.1016/j.joca.2021.04.020 34534661
    [Google Scholar]
  5. Macías I. Alcorta-Sevillano N. Rodríguez C.I. Infante A. Osteoporosis and the potential of cell-based therapeutic strategies. Int. J. Mol. Sci. 2020 21 5 1653 10.3390/ijms21051653 32121265
    [Google Scholar]
  6. Adejuyigbe B. Kallini J. Chiou D. Kallini J.R. Osteoporosis: Molecular pathology, diagnostics, and therapeutics. Int. J. Mol. Sci. 2023 24 19 14583 10.3390/ijms241914583 37834025
    [Google Scholar]
  7. Kim D. Pirshahid A.A. Li Y. Varghese T. Pope J.E. Prevalence of osteoporosis in osteoarthritis: A systematic review and meta-analysis. Osteoporos. Int. 2022 33 8 1687 1693 10.1007/s00198‑022‑06376‑0 35380214
    [Google Scholar]
  8. Edgar R. Domrachev M. Lash A.E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002 30 1 207 210 10.1093/nar/30.1.207 11752295
    [Google Scholar]
  9. Xia L. Gong N. Identification and verification of ferroptosis-related genes in the synovial tissue of osteoarthritis using bioinformatics analysis. Front. Mol. Biosci. 2022 9 992044 10.3389/fmolb.2022.992044 36106017
    [Google Scholar]
  10. Davis A.P. Wiegers T.C. Johnson R.J. Sciaky D. Wiegers J. Mattingly C.J. Comparative toxicogenomics database (CTD): Update 2023. Nucleic Acids Res. 2023 51 D1 D1257 D1262 10.1093/nar/gkac833 36169237
    [Google Scholar]
  11. Liu X. Liu J. Fu B. DCABM-TCM: A database of constituents absorbed into the blood and metabolites of Traditional Chinese Medicine. J. Chem. Inf. Model. 2023 63 15 4948 4959 10.1021/acs.jcim.3c00365 37486750
    [Google Scholar]
  12. Szklarczyk D. Kirsch R. Koutrouli M. The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023 51 D1 D638 D646 10.1093/nar/gkac1000 36370105
    [Google Scholar]
  13. Sherman B.T. Panzade G. Imamichi T. Chang W. DAVID Ortholog: An integrative tool to enhance functional analysis through orthologs. Bioinformatics 2024 40 10 btae615 10.1093/bioinformatics/btae615 39412445
    [Google Scholar]
  14. Torres P.H.M. Sodero A.C.R. Jofily P. Silva-Jr F.P. Key topics in molecular docking for drug design. Int. J. Mol. Sci. 2019 20 18 4574 10.3390/ijms20184574 31540192
    [Google Scholar]
  15. Fan Y. Yin L. Zhong X. An integrated network pharmacology, molecular docking and experiment validation study to investigate the potential mechanism of Isobavachalcone in the treatment of osteoarthritis. J. Ethnopharmacol. 2024 326 117827 10.1016/j.jep.2024.117827 38310989
    [Google Scholar]
  16. Burley S.K. Impact of structural biologists and the Protein Data Bank on small-molecule drug discovery and development. J. Biol. Chem. 2021 296 100559 10.1016/j.jbc.2021.100559 33744282
    [Google Scholar]
  17. Kim S. Chen J. Cheng T. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 2021 49 D1 D1388 D1395 10.1093/nar/gkaa971 33151290
    [Google Scholar]
  18. Pinzi L. Rastelli G. Molecular docking: Shifting paradigms in drug discovery. Int. J. Mol. Sci. 2019 20 18 4331 10.3390/ijms20184331 31487867
    [Google Scholar]
  19. Zhang J. Fan F. Liu A. Icariin: A potential molecule for treatment of knee osteoarthritis. Front. Pharmacol. 2022 13 811808 10.3389/fphar.2022.811808 35479319
    [Google Scholar]
  20. Li J.X. Han Z.X. Cheng X. Combinational study with network pharmacology, molecular docking and preliminary experiments on exploring common mechanisms underlying the effects of weijing decoction on various pulmonary diseases. Heliyon 2023 9 5 e15631 10.1016/j.heliyon.2023.e15631 37153415
    [Google Scholar]
  21. Saikia S. Bordoloi M. Molecular docking: Challenges, advances and its use in drug discovery perspective. Curr. Drug Targets 2019 20 5 501 521 10.2174/1389450119666181022153016 30360733
    [Google Scholar]
  22. Ho W.C. Chang C.C. Wu W.T. Effect of osteoporosis treatments on osteoarthritis progression in postmenopausal women: A review of the literature. Curr. Rheumatol. Rep. 2024 26 5 188 195 10.1007/s11926‑024‑01139‑8 38372871
    [Google Scholar]
  23. Chu L. Liu X. He Z. Articular cartilage degradation and aberrant subchondral bone remodeling in patients with osteoarthritis and osteoporosis. J. Bone Miner. Res. 2020 35 3 505 515 10.1002/jbmr.3909 31692085
    [Google Scholar]
  24. Liu W. Xu D. Qi Q. Li J. Ou L. Chinese herbal medicine Xianling Gubao capsule for knee osteoarthritis. Medicine 2022 101 3 e28634 10.1097/MD.0000000000028634 35060547
    [Google Scholar]
  25. Cheng B.R. Wu R.Y. Gao Q.Y. Chinese proprietary medicine xianling gubao capsule for osteoporosis: A systematic review and meta-analysis of randomized clinical trials. Front. Endocrinol. 2022 13 870277 10.3389/fendo.2022.870277 35464071
    [Google Scholar]
  26. Wu J. Li W. Ye B. Yao Y. The efficacy and safety of Xianling Gubao capsules in the treatment of knee osteoarthritis. Medicine 2021 100 36 e27086 10.1097/MD.0000000000027086 34516497
    [Google Scholar]
  27. Xiao J. Zhang G. Mai J. Bioinformatics analysis combined with experimental validation to explore the mechanism of XianLing GuBao capsule against osteoarthritis. J. Ethnopharmacol. 2022 294 115292 10.1016/j.jep.2022.115292 35447200
    [Google Scholar]
  28. Qiu Z. Tang X. Wu Q. A new strategy for discovering effective substances and mechanisms of traditional Chinese medicine based on standardized drug containing plasma and the absorbed ingredients composition, a case study of Xian-Ling-Gu-Bao capsules. J. Ethnopharmacol. 2021 279 114396 10.1016/j.jep.2021.114396 34246738
    [Google Scholar]
  29. Yu B. Wang C.Y. Osteoporosis and periodontal diseases – An update on their association and mechanistic links. Periodontol. 2000 2022 89 1 99 113 10.1111/prd.12422 35244945
    [Google Scholar]
  30. Martel-Pelletier J. Barr A.J. Cicuttini F.M. Osteoarthritis. Nat. Rev. Dis. Primers 2016 2 1 16072 10.1038/nrdp.2016.72 27734845
    [Google Scholar]
  31. Li Q. Tian C. Liu X. Li D. Liu H. Anti-inflammatory and antioxidant traditional Chinese Medicine in treatment and prevention of osteoporosis. Front. Pharmacol. 2023 14 1203767 10.3389/fphar.2023.1203767 37441527
    [Google Scholar]
  32. Cheng Y. Liu X. Qu W. Amentoflavone alleviated cartilage injury and inflammatory response of knee osteoarthritis through PTGS2. Naunyn Schmiedebergs Arch. Pharmacol. 2024 397 11 8903 8916 10.1007/s00210‑024‑03222‑4 38856914
    [Google Scholar]
  33. Richard M.J. Driban J.B. McAlindon T.E. Pharmaceutical treatment of osteoarthritis. Osteoarthritis Cartilage 2023 31 4 458 466 10.1016/j.joca.2022.11.005 36414224
    [Google Scholar]
  34. Zhang C. Li X. Wen P. Li Y. Ellagic acid improves osteoarthritis by inhibiting PGE2 production in M1 macrophages via targeting PTGS2. Clin. Exp. Pharmacol. Physiol. 2024 51 10 e13918 10.1111/1440‑1681.13918 39188023
    [Google Scholar]
  35. Wang D. Xie D. Meng S. Role and molecular mechanisms of HuangQiSiJunZi decoction for treating triple-negative breast cancer as explored via network pharmacology and bioinformatics analyses. BMC Cancer 2024 24 1 1217 10.1186/s12885‑024‑12957‑5 39350059
    [Google Scholar]
  36. Matsuoka K. Bakiri L. Bilban M. Metabolic rewiring controlled by c-Fos governs cartilage integrity in osteoarthritis. Ann. Rheum. Dis. 2023 82 9 1227 1239 10.1136/ard‑2023‑224002 37344157
    [Google Scholar]
  37. Lu J. Kuang Z. Chen T. Isoalantolactone inhibits RANKL-induced osteoclast formation via multiple signaling pathways. Int. Immunopharmacol. 2020 84 106550 10.1016/j.intimp.2020.106550 32388216
    [Google Scholar]
  38. Lee S.H. Park S.Y. Kim J.H. Kim N. Lee J. Ginsenoside Rg2 inhibits osteoclastogenesis by downregulating the NFATc1, c-Fos, and MAPK pathways. BMB Rep. 2023 56 10 551 556 10.5483/BMBRep.2023‑0100 37605614
    [Google Scholar]
  39. Wu Y. He X. Huang N. Yu J. Shao B. A20: A master regulator of arthritis. Arthritis Res. Ther. 2020 22 1 220 10.1186/s13075‑020‑02281‑1 32958016
    [Google Scholar]
  40. Martens A. Hertens P. Priem D. A20controls RANK ‐dependent osteoclast formation and bone physiology. EMBO Rep. 2022 23 12 e55233 10.15252/embr.202255233 36194667
    [Google Scholar]
  41. Liu T. Li X. Cui Y. Bioinformatics analysis identifies potential ferroptosis key genes in the pathogenesis of intracerebral hemorrhage. Front. Neurosci. 2021 15 661663 10.3389/fnins.2021.661663 34163322
    [Google Scholar]
  42. Su M. Guo C. Liu M. Liang X. Yang B. Therapeutic targets of vitamin C on liver injury and associated biological mechanisms: A study of network pharmacology. Int. Immunopharmacol. 2019 66 383 387 10.1016/j.intimp.2018.11.048 30530052
    [Google Scholar]
  43. Liu H. Yuan S. Zheng K. IL-17 signaling pathway: A potential therapeutic target for reducing skeletal muscle inflammation. Cytokine 2024 181 156691 10.1016/j.cyto.2024.156691 38986253
    [Google Scholar]
  44. Li H. Deng Y. Wang T. Huang K. Yu C. Chen C. Danshenxinkun B protects human umbilical vein endothelial cells against ox-LDL-induced injury by inhibiting pyroptosis and the NF-κB/NLRP3 pathway. Nan Fang Yi Ke Da Xue Xue Bao 2023 43 8 1425 1431 10.12122/j.issn.1673‑4254.2023.08.21 37712281
    [Google Scholar]
  45. Lee S.R. Jeon H. Kwon J.E. Anti-osteoporotic effects of Salvia miltiorrhiza Bunge EtOH extract both in ovariectomized and naturally menopausal mouse models. J. Ethnopharmacol. 2020 258 112874 10.1016/j.jep.2020.112874 32311485
    [Google Scholar]
  46. Huang J Zhang J Sun C,et al Adjuvant role of Salvia miltiorrhiza bunge in cancer chemotherapy: A review of its bioactive components,health-promotion effect and mechanisms. J Ethnopharmacol 2024 318 (Pt B) 117022 10.1016/j.jep.2023.117022 37572929
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128406157250911093530
Loading
Unveiling the Therapeutic Targets and Active Components of Xianlinggubao Capsule in Osteoarthritis and Osteoporosis through Network Pharmacology and Bioinformatic Analysis
Bentham Science Publishers ; https://doi.org/10.2174/0113816128406157250911093530
/content/journals/cpd/10.2174/0113816128406157250911093530
/content/journals/cpd/10.2174/0113816128406157250911093530
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: osteoarthritis ; osteoporosis ; homeotherapy for heteropathy ; Xianling Gubao capsules ; network pharmacology ; Western blotting

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test