Correlative study of Parnassia palustris extract on orthotopic glioma suppression and gut microbiota modulation in mice.

OBJECTIVE: The gut microbiota is associated with brain tumor development and prognosis. Natural products are increasingly recognized for their therapeutic potential. Based on previously observed anti-glioma effects of Parnassia palustris (MHC) in vitro, this study evaluates the efficacy of its oral extract in an orthotopic glioma model and explores the correlative relationship between its antitumor activity and alterations in gut microbiota composition, without inferring causation. METHODS: Four-week-old female Balb/c nude mice underwent intracranial implantation of RFP-U87 MG or U87 MG cells. Mice received intragastric administration of MHC extract (25 mg/kg every other day from day 6 to 24 post-implantation, n = 7) or PBS (n = 7). Untreated healthy mice served as controls (n = 6). Tumor growth was monitored via in vivo fluorescence imaging. Brain tissues and gliomas were collected for weighing, H&E, and IHC staining. Fecal samples were collected for gut microbiota analysis using Illumina high-throughput sequencing. RESULTS: In vivo imaging and tumor weight measurements demonstrated that MHC significantly suppressed orthotopic glioma proliferation. H&E staining showed reduced tumor cell density, normalized nuclear-to-cytoplasmic ratio, and decreased nuclear atypia in the MHC group. IHC indicated that MHC inhibited the PI3K/Akt pathway, leading to decreased KI67 and increased p53 expression. MHC did not alter α-diversity but modulated the abundance of specific bacterial taxa, notably increasing Muribaculum intestinale, Bacteroides faecichinchillae, and Klebsiella oxytoca, while decreasing Lachnospiraceae bacterium A4 and Helicobacter japonicus. Compared to healthy controls, tumor-bearing mice exhibited distinct microbial profiles. CONCLUSION: MHC extract significantly inhibits orthotopic glioma growth and is associated with compositional changes in the gut microbiota, including enrichment of Muribaculum intestinale and Bacteroides faecichinchillae. These correlational findings indicate a potential link between microbial shifts and anti-glioma effects; however, causality remains to be established. Future studies employing fecal microbiota transplantation, antibiotic depletion, or germ-free models are required to determine whether microbiota modulation directly mediates MHC's antitumor activity.