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Loganin Modulates Sigma-1 Receptor to Alleviate Depression: Animal, Cellular, and Computational Evidence.

Man-Ni Wang1, Cong-Yuan Xia2, Yu-Xuan Guo1

  • 1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People's Republic of China.

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Loganin, an iridoid glycoside, shows antidepressant effects by reducing neuroinflammation. It targets the Sigma-1 receptor (Sigma-1R) to alleviate depression-like behaviors and inhibit the NLRP3 inflammasome pathway.

Keywords:
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Area of Science:

  • Neuroscience
  • Pharmacology
  • Immunology

Background:

  • Inflammation exacerbates depressive symptoms, but mechanisms are unclear.
  • Loganin, from Cornus officinalis, has antidepressant and anti-inflammatory properties.
  • Sigma-1 receptor (Sigma-1R) is implicated in depression and neuroinflammation.

Purpose of the Study:

  • Investigate loganin's potential to treat inflammation-related depression.
  • Determine if loganin modulates Sigma-1R to achieve its effects.
  • Elucidate the underlying molecular pathways involved.

Main Methods:

  • Used social isolation and LPS-induced models for depressive-like behaviors.
  • Assessed behavioral outcomes, neuroinflammation markers, oxidative stress, and NLRP3 inflammasome.
  • Employed molecular docking, cellular thermal shift assay, and Sigma-1R inhibition (BD1047).

Main Results:

  • Loganin improved depressive-like behaviors and reduced neuroinflammation and oxidative stress.
  • Confirmed loganin binds to Sigma-1R and increases its hippocampal expression.
  • Sigma-1R inhibition reversed loganin's antidepressant and anti-inflammatory effects.
  • Loganin downregulated the NLRP3 inflammasome via the Sigma-1R/IRE1α/TXNIP pathway.

Conclusions:

  • Loganin alleviates inflammation-associated depression through Sigma-1R modulation.
  • The Sigma-1R/IRE1α/TXNIP pathway is crucial for loganin's therapeutic effects.
  • Loganin shows potential as a novel therapeutic agent for depression linked to inflammation.