Mogrosides from S. grosvenorii ameliorate acute pharyngitis via the PI3K/AKT-NF-κB-NLRP3 signaling pathway and oxidative stress modulation.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Acute pharyngitis is described as "acute throat impediment" in TCM, characterized by sudden, severe throat pain with redness and swelling of the pharyngeal region; in severe cases it can cause dysphagia and respiratory compromise, substantially degrading quality of life. Total mogrosides (TMG) are the active constituents of Siraitia grosvenorii and are commonly used to treat respiratory disorders, exerting throat-soothing and anti-swelling effects. These compounds display pronounced antioxidant and anti-inflammatory activities. Although these bioactivities have been confirmed, the precise mechanisms by which TMG alleviate pharyngitis have not yet been fully elucidated. AIM OF THE STUDY: The present study evaluates the therapeutic potential of TMG in acute pharyngitis and elucidates its underlying mechanism, with particular emphasis on the PI3K/AKT-NF-κB-NLRP3 signaling axis and the regulation of oxidative stress. MATERIALS AND METHODS: The chemical composition of TMG was characterized using UPLC-Q-TOF-MS/MS analysis. An ammonia-irritated mice model of acute pharyngitis was established and divided into control, model, positive drug, and TMG treatment groups at varying doses. Histopathological and molecular evaluations were employed to assess alterations in pharyngeal tissue, inflammatory mediators, signaling proteins, and oxidative stress markers. In parallel, LPS-stimulated RAW264.7 cells were used to examine the influence of TMG-containing serum on cell viability, nitric oxide production, reactive oxygen species generation, and NLRP3 inflammasome activation. Moreover, untargeted metabolomics was conducted to investigate the modulatory effects of TMG on serum metabolic profiles in the mouse model. RESULTS: A total of 41 mogroside constituents were identified in TMG. Treatment with TMG markedly alleviated pharyngeal tissue injury in pharyngitis mice, suppressed the production of pro-inflammatory cytokines, enhanced the anti-inflammatory cytokine IL-10, and reduced the expression of relative inflammation proteins. Mechanistic analysis revealed that TMG downregulated the PI3K/AKT-NF-κB pathway and inhibited NLRP3 inflammasome activation while simultaneously triggering the Nrf2/HO-1-mediated antioxidant response, thereby mitigating oxidative stress. Metabolomic profiling demonstrated that TMG modulated amino acid metabolism, particularly phenylalanine, tyrosine, and tryptophan metabolic pathway contributing to restoration of systemic metabolic balance. CONCLUSION: TMG significantly attenuates inflammation and oxidative injury associated with acute pharyngitis by concurrently suppressing the PI3K/AKT-NF-κB-NLRP3 inflammatory cascade and promoting activation of the Nrf2/HO-1 antioxidant defense system. These results highlight a multi-component synergistic mechanism and provide pharmacological evidence supporting the clinical potential of S. grosvenorii in the treatment of pharyngitis.

Key Findings

• Total mogrosides (TMG) from Siraitia grosvenorii contain 41 identified constituents with antioxidant and anti-inflammatory properties.
• TMG treatment significantly alleviated pharyngeal tissue injury and reduced pro-inflammatory cytokine production in an ammonia-induced acute pharyngitis mouse model.
• TMG modulated the PI3K/AKT-NF-κB-NLRP3 signaling pathway and oxidative stress markers, suppressing NLRP3 inflammasome activation and reactive oxygen species generation in LPS-stimulated RAW264.7 cells.

Clinical Significance

Citation

Wu Juanjiang, Huang Huaxue, Mao Jiananet al.. Mogrosides from S. grosvenorii ameliorate acute pharyngitis via the PI3K/AKT-NF-κB-NLRP3 signaling pathway and oxidative stress modulation. Journal of ethnopharmacology. 2026-Apr-10.