Lycium barbarum glycopeptide attenuates intracerebral hemorrhage-induced inflammation and oxidative stress via activation of the Sirt3 signaling pathway

Int Immunopharmacol. 2025 May 8:154:114518. doi: 10.1016/j.intimp.2025.114518. Epub 2025 Mar 28.

Abstract

Background: Intracerebral hemorrhage (ICH) is a severe neurological condition characterized by high morbidity and mortality rates, with no effective treatment currently available. Lycium barbarum glycopeptide (LbGP), derived from the further purification of Lycium barbarum polysaccharides (LBP), has demonstrated anti-inflammatory effects, suggesting its potential as a therapeutic agent for ICH. However, the role and mechanisms of LbGP in ICH remain unclear. This study aimed to investigate the effects of LbGP on ICH and its underlying mechanisms.

Methods: A collagenase injection-induced mouse model of ICH was used to evaluate the therapeutic effects of LbGP. Mice were treated with varying doses of LbGP, and outcomes were assessed based on hemorrhage volume, neurological function, inflammation, and oxidative stress markers. Apoptosis was analyzed using TUNEL staining. Mechanistic studies focused on mitochondrial acetylation homeostasis and the expression of Sirt3, a mitochondrial deacetylase. Statistical analyses were performed using one-way ANOVA with Tukey's post hoc tests.

Results: LbGP administration reduced hemorrhage volume and improved neurological function in a dose-dependent manner. It significantly decreased pro-inflammatory cytokines (IL-18, TNF-α, IL-1β) and oxidative stress markers (malondialdehyde and reactive oxygen species) while increasing superoxide dismutase activity and total antioxidant capacity. LbGP treatment also mitigated apoptosis and promoted mitochondrial acetylation homeostasis. Mechanistically, LbGP upregulated mitochondrial Sirt3 expression, and blocking Sirt3 disrupted mitochondrial acetylation homeostasis, resulting in increased inflammation and oxidative stress.

Conclusions: LbGP alleviates inflammation and oxidative stress in hemorrhagic brain injury by activating Sirt3 and maintaining mitochondrial acetylation homeostasis. These findings highlight the therapeutic potential of LbGP in treating ICH, providing a foundation for further clinical applications.

Keywords: Inflammation; Intracerebral hemorrhage (ICH); Lycium barbarum glycopeptide (LbGP); Oxidative stress; Sirt3.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents* / therapeutic use
  • Apoptosis / drug effects
  • Cerebral Hemorrhage* / chemically induced
  • Cerebral Hemorrhage* / drug therapy
  • Cerebral Hemorrhage* / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Glycopeptides* / pharmacology
  • Glycopeptides* / therapeutic use
  • Inflammation / drug therapy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Sirtuin 3* / metabolism

Substances

  • Sirtuin 3
  • Glycopeptides
  • Sirt3 protein, mouse
  • Anti-Inflammatory Agents
  • Drugs, Chinese Herbal
  • Cytokines
  • lycium barbarum polysaccharide