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A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated

Tsong-Hai Lee1, Jiun-Liang Chen2, Chuan-Hsin Chang3

  • 1Stroke Center and Stroke Section, Department of Neurology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

Biomedicines
|January 26, 2024
PubMed

Insights

A novel soft coral sterol, 4p3f, reduces matrix metalloproteinase-9 (MMP-9) expression in brain astrocytes. This compound shows potential for anti-inflammatory and neuroprotective effects by inhibiting MMP-9-mediated pathways.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Marine Natural Products Chemistry

Background:

  • Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in blood-brain barrier disruption and neuroinflammation.
  • Marine-derived compounds are explored for anti-inflammatory drug development.
  • The neuroprotective potential of the soft coral sterol 4p3f on brain astrocytes is unknown.

Purpose of the Study:

  • To investigate the effects of 4p3f on lipopolysaccharide (LPS)-induced MMP-9 expression in rat brain astrocytes (RBAs).
  • To elucidate the signaling mechanisms underlying 4p3f's action on MMP-9 expression.
  • To assess 4p3f's impact on MMP-9-triggered astrocyte migration.

Main Methods:

  • Zymography, qRT-PCR, Western blot, and immunofluorescence staining were used to analyze MMP-9 expression.
  • Promoter-reporter assays and cell migration analyses were employed.
  • Rat brain astrocytes were treated with LPS and varying concentrations of 4p3f.

Main Results:

  • 4p3f significantly inhibited LPS-induced MMP-9 expression in RBAs.
  • LPS-induced MMP-9 expression involved the ERK1/2, p38 MAPK, and JNK1/2 pathways, linked to STAT3-mediated NF-κB signaling.
  • 4p3f attenuated LPS-induced RBA cell migration.

Conclusions:

  • The soft coral-derived sterol 4p3f exhibits anti-inflammatory and neuroprotective potential.
  • 4p3f acts by inhibiting MMP-9 expression and related signaling pathways in brain astrocytes.
  • 4p3f is a promising candidate for neuroprotective drug development.
Keywords:
anti-inflammationbrain astrocytescell migrationlipopolysaccharidematrix metalloproteinase-9soft coral

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