Cushing in a Leaf: Endocrine Disruption From a Natural Remedy.

BACKGROUND: Information regarding the safety of herbal drugs is often not reported. We describe the case of a 65-year-old woman referred to us for a iatrogenic hypercortisolism, who denied any previous steroid consumption. She reported only a chronic application of a phytocosmetic cream, containing ethanol extract of the Cardiospermum halicacabum (CH) plant. Adrenal insufficiency occurred after the cream application was stopped. CH is used in traditional and Western medicine for its documented anti-inflammatory properties. Once the presence of synthetic glucocorticoids was ruled out in the phytocosmetic product, we investigated whether and how its chronic application could have caused the iatrogenic hypercortisolism. METHODS: Liquid chromatography high-resolution mass spectrometry (LC-HRMS) was performed to exclude the presence of known glucocorticoids in the cream. ELISA assay and Western blot analysis were employed to assess ACTH secretion and the glucocorticoid receptor expression respectively in murine ACTH-secreting pituitary adenoma cells AtT-20/D16v-F2, treated with dexamethasone, CH tincture, and mifepristone alone or in combination. To detect specific interaction of CH extract with the glucocorticoid receptor, we performed a dual-luciferase reporter assay in HEK293 cells. RESULTS: In AtT-20/D16v-F2 cells, CH extract showed to significantly reduce basal and CRH-induced ACTH secretion and the glucocorticoid receptor expression, similarly to dexamethasone; these effects were counteracted by mifepristone. In HEK293 cells, dexamethasone significantly induced luciferase activity after 24- and 36-hour treatment and CH tincture only after 36 hours; these effects were antagonized by mifepristone. CONCLUSIONS: CH extract displays a glucocorticoid-like activity, by means of a direct binding to the glucocorticoid receptor.

Effect of administration of aqueous extract of hippobromus pauciflorus leaves in male Wistar rats.

The effect of administration of aqueous extract of Hippobromus pauciflorus (L.f.) Radlk (Sapindaceae) leaves at 50, 100 and 200 mg/kg body weight for 14 days on some biochemical parameters in male Wistar rats was investigated. The extract at all the doses tested did not significantly (P>0.05) alter the levels of white blood cells, red blood cells, mean corpuscular volume, platelets, neutrophils, monocytes, lymphocytes and large unstained cells. While the levels of haemoglobin, packed cell volume and basophils increased significantly (P<0.05) at specific doses, the mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and eosinophils decreased significantly (P<0.05). Again, the extract did not significantly (P<0.05) alter the computed liver- and kidney-body weight ratios, sodium, chloride and total protein, though, the levels of potassium, inorganic phosphorus, globulin, urea, total and conjugated bilirubin increased significantly (P<0.05) at certain doses. In contrast, the levels of albumin and creatinine also decreased significantly (P<0.05) at specific doses. While the activities of alkaline phosphatase, gamma glutamyl transferase and alanine aminotransferase remained significantly (P<0.05) unaltered in the serum, aspartate aminotransferase activity increased only at 200 mg/kg body weight. The atherogenic index as well as the concentrations of cholesterol, high- and low-density lipoprotein cholesterol in the serum of the animals were not significantly (P>0.05) altered. However, the extract significantly (P<0.05) increased the concentration of triacylglycerol. The results suggest that the extract has mild and dose specific haemato-, hepato- and nephrotoxic effects and may not be completely safe as oral remedy at the doses investigated.