2. Academic Validation
  3. Monotropein induces autophagy through activation of the NRF2/PINK axis, thereby alleviating sepsis-induced colonic injury

Monotropein induces autophagy through activation of the NRF2/PINK axis, thereby alleviating sepsis-induced colonic injury

  • Int Immunopharmacol. 2023 Dec 23:127:111432. doi: 10.1016/j.intimp.2023.111432.
Jingchao Qiang 1,  Rongrong Yang 2,  Xueqing Li 1,  Xuhui Xu 1,  Mengyuan Zhou 1,  Xiaomeng Ji 1,  Yingzhi Lu 3,  Zibo Dong 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
  • 2 Department of Oncology, The Second People's Hospital of Lianyungang (The Oncology Hospital of Lianyungang), Lianyungang 222000, China.
  • 3 Department of Oncology, The Second People's Hospital of Lianyungang (The Oncology Hospital of Lianyungang), Lianyungang 222000, China. Electronic address: [email protected].
  • 4 Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China. Electronic address: [email protected].
PMID: 38142644 DOI: 10.1016/j.intimp.2023.111432
Abstract

Sepsis is a systemic inflammatory disease that is caused by a dysregulated host response to Infection and is a life-threatening organ dysfunction that affects many organs, which includes the colon. Mounting evidence suggests that sepsis-induced colonic damage is a major contributor to organ failure and cellular dysfunction. Monotropein (MON) is the major natural compound in the iris glycoside that is extracted from Morendae officinalis radix, which possesses the potent pharmacological activities of anti-inflammatory and antioxidant properties. This research evaluated whether MON is able to alleviate septic colonic injury in mice by cecal ligation and puncture. Colonic tissues were analyzed using histopathology, immunofluorescence, quantitative real-time polymerase chain reaction, and Western blot methods. It was initially discovered that MON reduced colonic damage in infected mice, in addition to inflammation, Apoptosis, and oxidative stress in colonic tissues, while it activated Autophagy, with the NRF2/keap1 and PINK1/Parkin pathways also being activated. Through the stimulation of NCM460 cells with lipopolysaccharides, an in vitro model of sepsis was created as a means of further elucidating the potential mechanisms of MON. In the in vitro model, it was found that MON could still activate the NRF2/keap1, PINK1/Parkin, and Autophagy pathways. However, when MON was paired with the NRF2 inhibitor ML385, it counteracted MON-induced activation of PINK1/Parkin and Autophagy, while also promoting inflammatory response and Apoptosis in NCM460 cells. Therefore, the data implies that MON could play a therapeutic role through the activation of the NFR2/PINK pathway as a means of inducing Autophagy to alleviate the oxidative stress in colonic tissues that is induced by sepsis, which will improve inflammation and Apoptosis in colonic tissues.

Keywords

Autophagy; CLP; Colonic injury; Monotropein; NRF2/PINK axis.

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