Celastrol has promise as preventive BPD-PH treatment in rat study
Herbal compound may reduce inflammation, protect lung tissue from damage
Celastrol, a herbal compound used in traditional Chinese medicine, may help prevent pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) by reducing inflammation and protecting lung tissue from damage, a study in rats and lab-grown cells suggests.
While these preclinical findings are promising, the compound is still experimental and more research is needed to test it in BPD, a common complication of preterm birth that results when a baby’s lungs aren’t fully developed.
“Celastrol is a promising preventive treatment for BPD-PH,” researchers wrote in “Celastrol has benepulmonaryhypertensionnews.com/pulmonary-hypertension-overviewficial effects on pulmonary hypertension associated with bronchopulmonary dysplasia: Preclinical study outcomes,” which was published in Biomedicine & Pharmacotherapy.
In BPD, treatments like oxygen and breathing support can damage the lungs and its blood vessels, even though they are necessary, and can cause high blood pressure in the lungs, putting pressure on the heart to pump more blood. Because there’s no standardized diagnosis, BPD-PH is often diagnosed late. Treatments are mainly to help with breathing and available medications don’t reduce inflammation or remodel damaged lung tissue. Such medications also lack testing in newborns. Better treatments with new approaches are needed.
Celastrol is a natural compound isolated from Tripterygium wilfordii, a vine used in traditional Chinese medicine. It works as an anti-inflammatory and as an antioxidant that counteracts oxidative stress, an imbalance between reactive oxygen species and the body’s ability to neutralize them.
Testing celastrol in newborn rats
Here, researchers turned to a preclinical model where newborn rats are exposed to high levels of oxygen for two weeks, causing BPD. A control group of newborn rats grew under normal oxygen levels. In each group, half the rats were given daily injections of celastrol while the other half received a control solution.
The proportion of rats that remained alive after two weeks of exposure to high oxygen was significantly lower compared with that of rats exposed to normal oxygen. However, daily celastrol — given intraperitoneally, or into the abdominal space, at either 0.5 or 1 mg/kg — helped prevent death in those rats.
Rats under high oxygen developed high blood pressure in the blood vessels that supply the lungs, with enlarged hearts and thicker blood vessels. Celastrol, at a daily dose as low as 0.1 mg/kg reduced right ventricle enlargement. At a dose of 1 mg/kg, it fully restored pulmonary blood flow. Celastrol also prevented thickening of the blood vessels.
In BPD-PH, immune cells called macrophages can contribute to damage by releasing molecules that signal inflammation. The lung tissue of rats exposed to high oxygen had significantly more macrophages, but daily treatment with celastrol (1 mg/kg) prevented this increase, with no effect in rats exposed to normal levels of oxygen.
Also, celastrol prevented hyperreactivity of blood vessels exposed to high oxygen to a molecule called endothelin-1, which makes them contract.
Celastrol also reduced levels of inflammatory molecules in the lungs of newborn rats and lab-grown cells, suggesting it may help reduce inflammation. Another effect of celastrol was in increasing heme oxygenase-1 (HO-1), an enzyme that helps protect cells from oxidative stress. High oxygen naturally increased HO-1, but celastrol increased it even more.
“The present study demonstrates, for the first time, that celastrol administered from birth had a beneficial effect on the main hallmarks of PH,” the researchers wrote. “Celastrol thus appears to be a new promising preventive treatment for BPD-PH.”
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