Nobiletin has been found to attenuate monocrotaline-induced pulmonary arterial hypertension (PAH) conditions in rat models; these results indicate that it may inhibit PAH-related inflammation through the PI3K/AKT/STAT3 pathway, according to a study published in the Journal of Pharmacy and Pharmacology. 

A growing number of studies have implicated inflammation as a key driver of PAH pathology. Scientists have used inflammatory cytokines as biomarkers for the clinical evaluation of PAH in rat models. Currently, none of the available drugs for PAH are curative; they can only extend survival. 

Nobiletin is a flavonoid that is obtained from the peel of citrus fruits; it has become the subject of numerous studies due to its supposed antioxidant and anti-inflammatory properties. However, there have been no studies conducted on the use of nobiletin in alleviating PAH symptoms. Thus, the authors sought to investigate if nobiletin could be used to reduce inflammation in PAH. 

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For this study, the researchers used rat models, most of which had been injected with monocrotaline to induce PAH-like conditions. They divided the rat models into 5 groups: the control (rats who were not injected with monocrotaline), the model (rats injected with monocrotaline only), and 3 groups injected with monocrotaline and treated with sildenafil, low-dose nobiletin, and high-dose nobiletin respectively. The rats were sacrificed after 3 weeks for further assessment. 

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The researchers reported that nobiletin at a dose of 10 mg/kg attenuated PAH changes in the monocrotaline-treated rat models; most significantly, it managed to alleviate right ventricular hypertrophy and pulmonary artery remodeling in those rats. In addition, nobiletin was found to inhibit inflammatory cytokines expressed in monocrotaline-treated rats, suggesting that it may play a role in inhibiting inflammation in PAH. 

“In general, nobiletin has the potential to treat PAH and deserves attention for further development,” the authors concluded. 


Yin Q, Wang S, Yang J, et al. Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathwayJ Pharm Pharmacol. Published online May 9, 2023. doi:10.1093/jpp/rgad045