2. Academic Validation
  3. Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathway

Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathway

  • J Pharm Pharmacol. 2023 May 9;rgad045. doi: 10.1093/jpp/rgad045.
Qin Yin 1,  Sen Wang 2,  Jie Yang 1,  Cunyu Fan 1,  Yihan Yu 1,  Juan Li 3,  Feng Mei 3,  Shiwei Zhang 4,  Rengang Xi 5,  Xiuyun Zhang 6
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China.
  • 2 Department of Forensic Medicine, Guangxi Medical University, Nanning, Guangxi, China.
  • 3 The First Clinical College of Hubei University of Chinese Medicine, Wuhan, China.
  • 4 Department of Pathology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China.
  • 5 Department of Radiology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China.
  • 6 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
PMID: 37158759 DOI: 10.1093/jpp/rgad045
Abstract

Objectives: Nobiletin is a flavonoid found in the peel of Citrus sinensis (oranges). The purpose of this study is to investigate whether Nobiletin can alleviate the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and explore the underlying mechanisms.

Methods: The PAH rat model was replicated by subcutaneous injection of MCT. Nobiletin (1, 5 and 10 mg/kg) was administered by gavage from day 1 to day 21. After 21 days of MCT injection, the mean pulmonary artery pressure, pulmonary vascular resistance, Fulton Index, pulmonary artery remodelling, blood routine parameters, liver and kidney functions was measured. The level of inflammatory cytokines and PI3K/Akt/STAT3 were detected by qPCR, ELISA and western blot, the proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by CCK-8.

Key findings: Nobiletin (10 mg/kg) inhibited the MCT-induced increase in mean pulmonary artery pressure and pulmonary vascular resistance, right ventricular hypertrophy and pulmonary artery remodelling in rats. Nobiletin decreased the levels of inflammatory cytokines and phosphorylation level of PI3K/Akt/STAT3 in lungs of MCT-treated rats. Nobiletin inhibited the proliferation and lowered the inflammatory cytokines level induced by PDGF-BB in PASMCs.

Conclusion: Nobiletin attenuates MCT-induced PAH, and the potential mechanism is to inhibit inflammation through PI3K/Akt/STAT3 pathway.

Keywords

Nobiletin; PI3K/Akt/STAT3 pathway; inflammation; pulmonary arterial hypertension.

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