Researchers from Harbin Medical University in China found that the naturally occurring flavonoid kaempferol could have a protective role in pulmonary arterial hypertension (PAH), as published in the Journal of Pharmaceutical and Biomedical Analysis.

“We found that kaempferol reversed pulmonary hemodynamic changes induced by [monocrotaline], including an abnormal decrease in PAAT [pulmonary artery acceleration time], PAVTI [pulmonary arterial velocity time integral] and increase in RVSP [right ventricle systolic pressure], while right ventricular function was significantly improved, and pulmonary vascular remodeling was also alleviated,” they said.

Intragastric administration of kaempferol at a dose of 150 mg/kg for 21 consecutive days increased PAAT and PAVTI and decreased RVSP. Moreover, it reversed the increase in intima-to-media ratio in monocrotaline-treated rats. The protective effects of kaempferol on PAH were mediated, at least in part, by autophagy.


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Treatment with kaempferol could reverse the abnormal expression of autophagy maker proteins, such as beclin-1, sequestosome 1, the microtubule-associated protein light chain LC3B-II, and the autophagy-related proteins ATG5 and ATG7.

In addition, the researchers showed that kaempferol induced metabolic changes in PAH rats, including in arachidonic acid metabolism. It also partially reversed the disorder of amino acid metabolism observed in PAH
rats.

The researchers identified 247 plasma biomarkers associated with the preventive effects of kaempferol. These included 3,4-dihydroxyphenylpropionic acid, rosmarinic acid, and 3-methyl-2-oxobutanoic acid, which were upregulated in the kaempferol-treated group, and spermidine, pyridoxamine, and 5-methylcytosine, which were downregulated in the kaempferol-treated group.

Future studies will help understand the mechanisms underlying kaempferol-mediated regulation of endogenous metabolic disorders in PAH.

Despite the promising results, the low bioavailability of kaempferol may make its translation into clinical practice difficult, the authors said. Therefore, efforts should be made to improve the bioavailability of kaempferol in tissues.

Reference

Yi J, Wang X, Song K, et al. Integrated metabolomics and mechanism to reveal the protective effect of kaempferol on pulmonary arterial hypertension. J Pharm Biomed Anal. Published online February 15, 2022. doi:10.1016/j.jpba.2022.114662