Natural Products and Bioprospecting (Feb 2024)

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

  • Jie Cao,
  • Lanqin Li,
  • Runge Zhang,
  • Zhou Shu,
  • Yaxin Zhang,
  • Weiguang Sun,
  • Yonghui Zhang,
  • Zhengxi Hu

DOI
https://doi.org/10.1007/s13659-024-00438-y
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 14

Abstract

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Abstract Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1β production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

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