Mitigation of lipopolysaccharide-induced intestinal injury in rats by Chimonanthus nitens Oliv. essential oil via suppression of mitochondrial fusion protein mitofusin 2 (MFN2)-mediated mitochondrial-associated endoplasmic reticulum membranes (MAMs) formation

  • J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118856. doi: 10.1016/j.jep.2024.118856.
Shuying Huang  1 ,  Zhenguo Zeng  2 ,  Yuelei Chu  3 ,  Shichao Zhang  4 ,  Jia Zhou  4 ,  Zhiguo Hu  4 ,  Yuting Yang  4 ,  Chaoqi Zhou  4 ,  Wang Cheng  4 ,  Songyu Yang  5 ,  Shengbin Chen  5 ,  Wenjuan Li  6 ,  Cheng Qing  7
Affiliations
  • 1. Department of Reproductive Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang, 330000, China.
  • 2. Department of Intensive Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang, 330000, China; Key Laboratory of Critical Care Medicine, Jiangxi Provincial Health Commission, 17 Yongwai Zhengjie, Nanchang, 330000, China.
  • 3. State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, China.
  • 4. Department of Intensive Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang, 330000, China.
  • 5. The Fourth Clinical Medical College, Nanchang University, Nanchang, Jiangxi, 330027, China.
  • 6. State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, China. Electronic address: [email protected].
  • 7. Department of Intensive Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang, 330000, China; Key Laboratory of Critical Care Medicine, Jiangxi Provincial Health Commission, 17 Yongwai Zhengjie, Nanchang, 330000, China; Nanchang Key Laboratory of Diagnosis of Infectious Diseases of Nanchang University, Nanchang, Jiangxi, 330096, China. Electronic address: [email protected].
PMID: 39332614 DOI: 10.1016/j.jep.2024.118856
Abstract

Ethnopharmacological relevance: Chimonanthus nitens Oliv. is a traditional Chinese medicine with anti-inflammatory and antioxidant properties that has commonly been used for colds, fevers, and Other Diseases. However, its role and specific mechanism in sepsis-associated intestinal injury have not been reported.

Aim of the study: C. nitens Oliv. essential oil (CEO), an organic active compound extracted from the traditional Chinese medicine C. nitens Oliv. exhibits notable anti-inflammatory and antioxidant properties. Nevertheless, the therapeutic potential of CEO for septic intestinal injury remains undocumented. This study thus aims to elucidate the anti-inflammatory and antioxidant effects of CEO in the context of acute intestinal injury and to investigate its mechanisms of action in septic rats.

Materials and methods: Cell and animal models were established using LPS to investigate the impact of CEO on LPS-induced intestinal pathological injury and the secretion of inflammatory factor IL-1β. The effects of CEO on the expression of NLRP3, Caspase-1, and MFN2, p-p65 protein were also examined, as well as its influence on oxidative stress injury and mitochondrial-associated endoplasmic reticulum membrane (MAM) formation. Generation of an MFN2 knockout IEC-6 cell line allowed comprehensive investigation of the protective mechanism of CEO.

Results: In rat models, CEO reduced IL-1β secretion, inhibited Caspase-1, ZO-1 expression and NF-κB p65 phosphorylation, while also decreasing malondialdehyde levels and enhancing superoxide dismutase activity in intestinal tissues. Cellular experiments demonstrated its ability to decrease IL-1β secretion; NLRP3, Caspase-1, and MFN2 expression; NF-κB p65 phosphorylation; Reactive Oxygen Species (ROS) production, and mitochondrial dysfunction. MFN2 knockdown enhanced these effects synergistically with CEO, indicating potential therapeutic synergy. Further, MFN2 knockdown significantly mitigated LPS-induced NLRP3 and Caspase-1 expression, IL-1β secretion, ROS production, NF-κB p65 phosphorylation and MMP reduction in IEC-6 cells, while inhibiting MAM formation and NLRP3 localization on MAMs. Importantly, MFN2 downregulation and CEO synergistically reduced LPS-induced IL-1β secretion and ROS production while inhibiting MAM formation in IEC-6 cells, thus inhibiting NLRP3 inflammasome activation.

Conclusion: CEO mitigates inflammation and oxidative stress by inhibiting MAM formation and is thus a promising intervention for septic intestinal injury.

Keywords
Chimonanthus nitens Oliv. essential oil; Mitochondria-associated endoplasmic reticulum membranes (MAMs); NLRP3 inflammasome; Oxidative stress; Septic intestinal injury.
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