A study by the Max Planck Institute has revealed that Silibinin from milk thistle seeds is an effective treatment strategy against Cushing Disease. Cushing disease is caused by a tumor or excess growth (hyperplasia) of the pituitary gland. The pituitary gland is located at the base of the brain. A type of pituitary tumor called an adenoma is the most common cause. With Cushing disease, the pituitary gland releases too much ACTH. ACTH stimulates production and release of cortisol, a stress hormone. Too much ACTH causes the adrenal glands to make too much cortisol. Symptoms of the disease include upper body obesity (above the waist) and thin arms and legs, round, red, full face (moon face), elevated blood pressure and slow growth rate in children.
Researchers have been seeking another solution besides surgery to alleviate the symptoms as patients are prone to osteoporosis, infections and may show cognitive dysfunction or even depression and inoperative cases prevent effective treatment.
Scientists from the Max Planck Institute of Psychiatry in Munich used cell cultures derived from human tumor cells and animal models to investigate the impact of the active ingredient of milk thistle called silibinin. “Silibinin is the major active constituent of milk thistle seeds. It has an outstanding safety profile in humans and is already used for the treatment of liver disease and poisoning,” said Marcelo Paez-Pereda, leading scientist of the current study. The research published in the journal Nature Medicine, revealed that after silibinin treatment, tumor cells resumed normal ACTH production, tumor growth slowed down and symptoms of Cushing Disease disappeared in mice.
The researchers determined that silibinin acts by binding to a specific protein called heat shock protein (HSP90). In normal amounts the proteins assists another protein to fold another protein called the glucocorticoid receptor which in turn inhibits the production of ACTH. In tumor cases there are too many HSP90 molecules which stick to the glucocorticoid receptor.
“We found that silibinin binds to HSP90 thus allowing glucocorticoid receptor molecules to dissolve from HSP90. With silibinin we might have discovered a non-invasive treatment strategy not only for the rare Cushing Disease but also for other conditions with the involvement of glucocorticoid receptors such as lung tumours, acute lymphoblastic leukaemia or multiple myeloma,” said Paez-Pereda.
Riebold M, Kozany C, Freiburger L, Sattler M, Buchfelder M, Hausch F, Stalla GK and Paez-Pereda M. A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease. Nature Medicine, 9 February 2015 doi:10.1038/nm.3776