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. 2023 Jan;29(1):44-51. doi: 10.1007/s11655-022-3721-6. Epub 2022 Jul 12.

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.

Keywords: Dioscorea nipponica Makino; M1/M2 polarization; arachidonic acid; gouty arthritis; signaling pathway.

MeSH terms

  • Arachidonic Acid / adverse effects
  • Arachidonic Acid / metabolism
  • Arthritis, Gouty*
  • Dioscorea*
  • Lipopolysaccharides
  • Macrophages
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saponins* / pharmacology
  • Signal Transduction
  • Uric Acid / metabolism

Substances

  • Uric Acid
  • Arachidonic Acid
  • Lipopolysaccharides
  • Saponins
  • RNA, Messenger