Work

Huang-Lian-Jie-Du decoction alleviates cognitive impairment in periodontitis rats through restoring microbiota-gut-brain axis and inhibiting neuroinflammation via TLR4/NF-κB pathway

Year: 2025

Type: article

Abstract: BACKGROUND: Huang-Lian-Jie-Du decoction (HLJDD), a typical formulation for heat clearance and detoxification, shows therapeutic potential for oral diseases and cognitive impairment. Nevertheless, the mechanism by which HLJDD influences periodontitis-induced cognitive impairment via the microbiota-gut-brain axis remains unknown. AIM OF THE STUDY: We investigated HLJDD's neuroprotective effects in periodontitis rats, focusing on its modulation of the microbiota-gut-brain axis and underlying molecular mechanisms. MATERIALS AND METHODS: Chemical profiling of HLJDD was performed via UHPLC-Q-Exactive Orbitrap HRMS. Periodontitis was induced in SD rats using ligatures and Porphyromonas gingivalis for 2 weeks, followed by 8-week treatments with HLJDD (0.75/1.5/3 g/kg/day), doxycycline (10 mg/kg/day), or vehicle. Alveolar bone loss was assessed via micro-CT, while cognitive function was assessed via the Morris water maze (MWM). Hippocampal and colon pathology was analyzed via H&E, Nissl staining, and immunohistochemistry. The composition of gut microbiota was analyzed by 16S rDNA sequencing. The tight junction proteins in hippocampus and colon were examined by RT- qPCR and immunofluorescence (IF). Inflammatory cytokine levels in intestinal and hippocampus tissue and serum were quantified by ELISA. Network pharmacology predicted potential mechanisms, and Western blotting assessed TLR4/NF-κB pathway proteins. RESULTS: HLJDD contained 94 bioactive compounds and significantly attenuated alveolar bone loss, improved cognitive function, and reduced neuronal damage and Aβ deposition. It restored gut microbiota homeostasis, enhanced intestinal and blood-brain barrier integrity, and suppressed neuroinflammation by modulating pro- and anti-inflammatory cytokines. Mechanistically, HLJDD inhibited TLR4/NF-κB signaling, suggesting its therapeutic potential in periodontitis-related cognitive impairment. CONCLUSION: HLJDD ameliorates cognitive impairment in periodontitis by modulating the microbiota-gut-brain axis, reducing neuroinflammation, and inhibiting TLR4/NF-κB activation. These findings support its potential as a novel therapeutic strategy for periodontitis-associated cognitive impairment.

Source: Chinese Medicine

DOI: 10.1186/s13020-025-01235-6