Skip to main content
Log in

Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages.

Methods

M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86.

Results

TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01).

Conclusion

TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Dalbeth N, Gosling AL, Gaffo A, Abhishek A. Gout. Lancet 2021;397:318–328.

    Article  Google Scholar 

  2. Singh JA, Gaffo A. Gout epidemiology and comorbidities. Semin Arthritis Rheum 2020;50:S11–S16.

    Article  Google Scholar 

  3. Pillinger MH, Mandell BF. Therapeutic approaches in the treatment of gout. Semin Arthritis Rheum 2020;50:S24–S30.

    Article  CAS  Google Scholar 

  4. Zhang Y, Jin LJ, Liu JC, Wang W, Yu HY, Li J, et al. Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia. J Enthnopharmacol 2018;214:29–36.

    Article  CAS  Google Scholar 

  5. Wang X, Wang YG. Progress in the treatment of gout using Western and Chinese medicine. Chin J Integr Med 2020;26:8–13.

    Article  CAS  Google Scholar 

  6. Zhou Q, Yu DH, Zhang C, Liu SM, Lu F. Total saponins from Discorea nipponica ameliorate urate excretion in hyperuricemic mice. Planta Med 2014;80:1259–1268.

    Article  CAS  Google Scholar 

  7. Zhou Q, Yu DH, Zhang N, Liu SM. Anti-inflammatory effect of total saponins from Dioscorea nipponica Makino on gouty arthritis and its influence on NALP3 inflammasome. Chin J Integr Med 2019;25:663–670.

    Article  CAS  Google Scholar 

  8. Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS−) vs. alternatively activated macrophages. Front Immunol 2019;10:1084.

    Article  CAS  Google Scholar 

  9. Li SP, Li LZ, Yan H, Jiang X, Hu WW, Han N, et al. Anti-gouty arthritis and anti-hyperuricemia properties of celery seed extracts in rodent models. Mol Med Rep 2019;19:4523–4633.

    Google Scholar 

  10. Tardito S, Martinelli G, Soldano S, Paolino S, Pacini G, Patane M, et al. Macrophage M1/M2 polarization and rheumatoid arthritis: a systematic review. Autoimmun Rev 2019;18:102397.

    Article  CAS  Google Scholar 

  11. Liu XY, Liu L. Research progress on the regulation of metabolism and pro-inflammation related macrophage polarization. J Transl Med 2018;5:92–96.

    CAS  Google Scholar 

  12. Liu YZ, Tang HL, Liu XX, Chen HL, Feng N, Zhang J, et al. Reprogramming COX-2, 5-LOX, and CYP4A-mediated arachidonic acid metabolism in macrophages by salidroside alleviated gouty arthritis. J Leukoc Biol 2019;195:11–24.

    Article  Google Scholar 

  13. Borghi C. The management of hyperuricemia: back to the pathophysiology of uric acid. Curr Med Res Opin 2017;33:1–4.

    Article  Google Scholar 

  14. Qaseem A, Harris RP, Forciea MA, Clinical Guidelines Committee of the American College of Physicians, Denberg TD, Barry MJ, et al. Management of acute and recurrent gout: a clinical guideline from the American College of Physicians. Ann Intem Med 2017;166:58–68.

    Article  Google Scholar 

  15. Liu YZ, Duan CF, Chen HL, Wang CL, Liu XX, Qiu M, et al. Inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate crystal-induced inflammation. Toxicol Appl Pharmacol 2018;351:1–11.

    Article  CAS  Google Scholar 

  16. Chen Y, Chen X. Ancient herbal component may be a novel therapeutic for gouty arthritis. J Leukoc Biol 2019;105:7–9.

    Article  CAS  Google Scholar 

  17. Zhou Q, Lin FF, Liu SM, Sui XF. Influence of the total saponin fraction from Dioscorea nipponica Makino on TLR2/4-1R receptor signal pathway in rats of gouty arthritis. J Ethnopharmacol 2017;206:274–282.

    Article  CAS  Google Scholar 

  18. Pang YM, Gan L, Wang XZ, Su Q, Guo Z, He P. Influence of celecoxib on inflammatory cytokines of inflammation model in RAW264.7 macrophages induced by lipopolysaccharide. Chin Modern Med (Chin) 2017;24:4–7.

    Google Scholar 

  19. Wang XY, Liu BY, Wang S, Sui MH. Effects of acupuncture at Shu, Yuan, and Mu acupoints on blood serum uric acid and xanthine oxidase levels in a rat model of gout and hyperuricemia. J Tradit Chin Med 2017;37:841–845.

    Article  Google Scholar 

  20. Wang WW, Liu CX, Li HW, Tian S, Liu YX, Wang NX, et al. Discovery of novel and potent P2Y14R antagonists via structure-based virtual screening for the treatment of acute gouty arthritis. J Adv Res 2020;23:133–142.

    Article  Google Scholar 

  21. Zhang HJ, Li LN, Zhou J, Yang QQ, Liu PG, Xu P, et al. Effects of Gnaphalium affine D. Don on hyperuricemia and acute gouty arthritis. J Ethnopharmacol 2017;203:304–311.

    Article  CAS  Google Scholar 

  22. Zhou Q, Sun HJ, Liu SM, Jiang XH, Wang QY, Zhang S, et al. Anti-inflammation effects of the total saponin fraction from Dioscorea nipponica Makino on rats with gouty arthritis by influencing MAPK signaling pathway. BMC Complement Med Ther 2020;20:261.

    Article  CAS  Google Scholar 

  23. Zhou Q, Yu DH, Zhang N, Wang XY, Zhang N, Lin FF, et al. Therapeutic effects of total saponins from Dioscorea nipponica Makino on gouty arthritis based on the MAPK-PPAR γ signaling pathway: an in vitro study. Nat Prod Commun 2020;15:1–13.

    Google Scholar 

  24. Zhou Q, Liu SM, Yu DH, Zhang N. Therapeutic effect of total saponins from Dioscorea nipponica Makino on gouty arthritis based on the NF- κ B signal pathway: an in vitro study. Pharmacogn Mag 2016;12:235–240.

    Article  CAS  Google Scholar 

  25. Mei JT, Zhou F, Qiao H, Li HJ, Tang TT. Nerve modulation therapy in gouty arthritis: targeting increased sFRP2 expression in dorsal root ganglion regulates macrophage polarization and alleviates endothelial damage. Theranostics 2019;9:3707–3722.

    Article  CAS  Google Scholar 

  26. Deng JP, Wu XC, Chen C, Zhao ZL, Li YF, Su ZQ, et al. Chinese medicine Huzhen Tongfeng Formula effectively attenuates gouty arthritis by inhibiting arachidonic acid metabolism and inflammatory mediators. Mediat Inflamm 2020;2020:6950206.

    Article  Google Scholar 

  27. Zhang M, Zhang XL, Tian TR, Zhang Q, Wen YT, Zhu JY, et al. Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis. Bioact Mater 2021;8:368–380.

    Article  CAS  Google Scholar 

  28. Zhu LN, Yang T, Li LJ, Sun L, Hou YZ, Hu XL, et al. TSC1 controls macrophage polarization to prevent inflammatory disease. Nat Commun 2014;5:4696.

    Article  CAS  Google Scholar 

  29. Napagoda M, Gerstmeier J, Butschek H, Lorenz S, Kanatiwela D, Qader M, et al. Lipophilic extracts of Leucas zeylanica, a multi-purpose medicinal plant in the tropics, inhibit key enzymes involved in inflammation and gout. J Ethnopharmacol 2018;224:474–481.

    Article  Google Scholar 

  30. Li YY, Zhou HM. Clinical research progress of TCM external therapy for rGERD. Acta Chin Med Pharmacol (Chin) 2020;48:73–77.

    Google Scholar 

  31. Cai YW, Liu JH, Ma N. Research status of arachidonic acid-targeted metabonomics in inflammation. Chin J Clin Pharmacol 2021;37:2721–2728.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Zhou Q designed and carried out the experiment and wrote this paper, Sun HJ carried part of the experiment, and Liu SM helped writing this paper.

Corresponding author

Correspondence to Shu-min Liu.

Ethics declarations

The authors declare that they have no conflicts of interest.

Additional information

Supported by Joint Guidance Project of Heilongjiang Natural Science Foundation (No. LH2021H099), Start Fund of Postdoctoral Research in Heilongjiang Province (No. LBH-Q19188), Outstanding Youth Development Fund of Heilongjiang University of Chinese Medicine (No. 2019JC06), Project of Heilongjiang Administration of Traditional Chinese Medicine (No. ZHY202094), Graduate Innovative Scientific Research Project of Heilongjiang University of Chinese Medicine (No. 2020yjscx057), Natural Science Foundation of Heilongjiang Province (Key project, No. ZD2020H006)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, Q., Sun, Hj. & Liu, Sm. Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study. Chin. J. Integr. Med. 29, 44–51 (2023). https://doi.org/10.1007/s11655-022-3721-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-022-3721-6

Keywords

Navigation