ArticleMolecular neurobiology2024
Total Flavonoids of Aurantii Fructus Immaturus Regulate miR-5100 to Improve Constipation by Targeting Fzd2 to Alleviate Calcium Balance and Autophagy in Interstitial Cells of Cajal.
Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Traditional herbal medicine for opioid-induced constipation in patients with cancer: a systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2025Pooled it
- Lianxia Xiaopi Granules for Treatment of Functional Dyspepsia: A Multicenter, Randomized, Double-Blind and Placebo-Controlled Trial.Chinese journal of integrative medicine · 2026Trial
- Deficiency of METTL3 alleviates excessive autophagy and apoptosis in mice with slow transit constipation and glutamic acid-induced interstitial cells of Cajal via the activation of PI3K/AKT pathway.Journal of molecular histology · 2026Article
- Article
- Article
- Therapeutic Mechanism of Zhishi Decoction Regulating P38/MAPK Signaling Pathway on Functional Constipation (FC).Combinatorial chemistry & high throughput screening · 2025Article
- Combined UPLC-Q-TOF-MS/MS and Network Pharmacology to Analyze the Potential Mechanism of Jieyu Fuwei Powder for Functional Dyspepsia Treatment.Current topics in medicinal chemistry · 2025Article
- Hesperidin facilitating gastrointestinal motility by "Gut-brain axis" and "SCF/C-Kit signaling pathways".Poultry science · 2024Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Aurantii Fructus Immaturus total flavonoids (AFIF) is the main effective fraction extracted from AFI, which has a good effect on promoting gastrointestinal motility. This study aimed to investigate AFIF which regulates miR-5100 to improve constipation symptoms in mice by targeting Frizzled-2 (Fzd2) to alleviate interstitial cells of Cajal (ICCs) calcium ion balance and autophagy apoptosis. The constipated mouse model was induced by an antibiotic suspension, and then treated with AFIF. RNA-seq sequencing, luciferase assay, immunofluorescence staining, transmission electron microscopy, ELISA, flow cytometry, quantitative polymerase chain reaction (PCR), and Western blot were applied in this study. The results showed that AFIF improved constipation symptoms in antibiotic-induced constipated mice, and decreased the autophagy-related protein Beclin1 levels and the LC3-II/I ratio in ICCs. miR-5100 and its target gene Fzd2 were screened as key miRNAs and regulator associated with autophagy. Downregulation of miR-5100 caused increased expression of Fzd2, decreased proliferation activity of ICCs, increased apoptotic cells, and enhanced calcium ion release and autophagy signals. After AFIF treatment, miR-5100 expression was upregulated and Fzd2 was downregulated, while autophagy-related protein levels and calcium ion concentration decreased. Furthermore, AFIF increased the levels of SP, 5-HT, and VIP, and increased the expression of PGP9.5, Sy, and Cx43, which alleviated constipation by improving the integrity of the enteric nervous system network. In conclusion, AFIF could attenuate constipation symptoms by upregulating the expression of miR-5100 and targeting inhibition of Fzd2, alleviating calcium overload and autophagic death of ICCs, regulating the content of neurotransmitters, and enhancing the integrity of the enteric nervous system network.
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