Seed extract of mahogany trees eases vessel remodeling in PH mice
New research into a traditional medicine in treating pulmonary hypertension
Treatment with swietenine — extracted from the seeds of Swietenia macrophylla, a tree commonly called mahogany — eased the remodeling of lung blood vessels in a mouse model of pulmonary hypertension (PH).
Researchers in China found that swietenine worked against this disease hallmark by inhibiting the growth of smooth muscle cells (PASMCs) that line the walls of pulmonary arteries.
“Our findings provide novel insights into the therapeutic potential of Swi [swietenine] in the molecular pathogenesis [development] of vascular remodeling in the experimental PH,” the researchers wrote.
The study, “Swietenine Alleviates Vascular Remodeling by Enhancing Mitophagy of Pulmonary Arterial Smooth Muscle Cells in Experimental Pulmonary Hypertension,” was published in the Canadian Journal of Cardiology.
Swietenine, the seed extract, was given to mice in PH model for four weeks
PH is characterized by high blood pressure in the pulmonary arteries that transport blood to the lungs, due to a progressive increase in vascular resistance to blood flow. This is the result of pulmonary vascular remodeling, in which smooth muscle cells grow uncontrollably, progressively thickening the arterial walls.
Problems in the workings of mitochondria, tiny structures inside the cells that produce energy, are known contribute to smooth muscle cell overgrowth. Some studies suggest that insufficient removal of dysfunctional mitochondria from these cells, a process called mitophagy, might be linked to vascular remodeling in PH.
Seeds of the Swietenia macrophylla tree, a traditional medicine in tropical areas, have been reported to effectively treat cardiovascular diseases. Swietenine, extracted from these seeds, also has shown benefits against diabetes and heart failure.
“The pharmacological activities of Swi include anti-oxidant, anti-inflammation, and cardiovascular protection,” the researchers wrote.
After previous work found swietenine could reverse damaging changes in heart muscle, scientists led by those at Nanjing Medical University sought to test it as a PH treatment.
They used a mouse model of PH induced by the combination of SU5416, a blocker of the growth of new blood vessels, and hypoxia — low oxygen levels — for four weeks. These mice showed a decrease in the diameter of the pulmonary valve, which controls blood flow from the heart to the lungs.
Swietenine, at a dose of 10 mg/kg, was given daily to the mice by under-the-skin injections across the four weeks of SU5416 and hypoxia exposure. Its use, results showed, allowed for a lesser decrease in the pulmonary valves’ diameter and a normal muscularization of pulmonary blood vessels — a key early event of pulmonary vascular remodeling.
“Together, these data indicate the protective effects of Swi on [SU5416 and hypoxia]-induced pulmonary vascular remodeling in mice,” the researchers wrote.
Considering that PASMC growth is crucial for PH, the researchers grew these pulmonary artery smooth muscle cells in the lab and exposed them to hypoxia. Hypoxia led to their growth and migration, an effect that was significantly inhibited by swietenine.
Hypoxia also significantly increased the number of mitochondria and caused damaging changes in mitochondrial structure, effects that again were reversed by swietenine. Treatment also appeared to restore mitophagy in hypoxia-exposed PASMCs, as suggested by partial normalization of the levels of protein markers Pink1 and Lc3 II.
“We found that mitophagy inhibition of PASMCs [that] occurs under hypoxia condition could be ameliorated by Swi via affecting the mitophagy proteins,” the researchers wrote.
Swietenine’s benefits in terms of mitochondrial numbers and Pink1 levels were confirmed in the mouse model.
“In summary, we demonstrated that Swi exerts a preventive effect on the experimental PH vascular remodeling by reversing the inhibition of mitophagy of PASMCs,” the researchers concluded.
Further studies are needed to explore the potential effects of swietenine on other cell types involved in PH, they added.
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