Olive Oil Solution of Volatile Oil from Citri Reticulatae Pericarpium Viride Alleviates Slow-Transit Constipation via Regulating SCF/c-Kit Signaling Pathway and Intestinal Flora

Drug Des Devel Ther. 2025 May 22:19:4275-4295. doi: 10.2147/DDDT.S517114. eCollection 2025.

Abstract

Objective: The aroma of the aromatic class of traditional Chinese medicines can promote gastrointestinal peristalsis. This study aimed to explore the mechanisms by which volatile oil from Citri Reticulatae Pericarpium Viride (VOCRPV) alleviates slow-transit constipation (STC).

Methods: The main active ingredients in VOCRPV were determined by High-Performance Liquid Chromatography (HPLC). Due to poor stability, an olive oil solution was prepared to enhance the volatile oil's stability. A mouse model of STC was induced using loperamide hydrochloride. The mice's body weight was monitored weekly. The number of fecal pellets, fecal water content, and small intestinal propulsion rate were detected. The colon tissues were analyzed using HE staining. The serum content of gastrointestinal hormones was measured using the corresponding ELISA kit. The protein expressions of stem cell factor (SCF) and c-Kit in colon tissues were detected by Western blot and immunohistochemistry methods. The 16S rRNA gene sequencing was used to detect the intestinal flora.

Results: The contents of p-isopropyl toluene, γ-Terpinene, and d-Limonene were determined by HPLC. VOCRPV and its olive oil solution significantly enhanced body weight, increased the number of fecal pellets, improved fecal water content, and boosted small intestinal propulsion rate in mice with loperamide-induced STC, while also repairing colon mucosa damage. They also increased gastrin (Gas) and motilin (MTL) levels in treated mice, upregulated the expression of SCF and c-Kit proteins, and restored intestinal flora balance in STC mice.

Conclusion: VOCRPV could effectively alleviate STC, and olive oil enhances its therapeutic effect. VOCRPV alleviates STC by elevating Gas and MTL levels, activating the SCF/c-Kit signaling pathway, and modulating intestinal flora.

Keywords: intestinal flora; olive oil; slow-transit constipation; stem cell factor/c-Kit signaling pathway; volatile oil from Citri Reticulatae Pericarpium Viride.

MeSH terms

  • Animals
  • Citrus* / chemistry
  • Constipation* / chemically induced
  • Constipation* / drug therapy
  • Constipation* / metabolism
  • Disease Models, Animal
  • Gastrointestinal Microbiome* / drug effects
  • Male
  • Mice
  • Oils, Volatile* / administration & dosage
  • Oils, Volatile* / chemistry
  • Oils, Volatile* / isolation & purification
  • Oils, Volatile* / pharmacology
  • Olive Oil* / administration & dosage
  • Olive Oil* / chemistry
  • Olive Oil* / isolation & purification
  • Olive Oil* / pharmacology
  • Proto-Oncogene Proteins c-kit* / metabolism
  • Signal Transduction / drug effects
  • Stem Cell Factor* / metabolism

Substances

  • Oils, Volatile
  • Olive Oil
  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit