Abstract
Pre-clinical safety evaluation of traditional medicines is imperative because of the universality of drug-induced adverse reactions. Psoralen and isopsoralen are the major active molecules and quality-control components of a traditional herbal medicine which is popularly used in Asia, Fructus Psoraleae. The purpose of this study is to assess the long-term effects of psoralen and isopsoralen with low levels on the biochemical parameters and metabolic profiles of rats. Three doses (14, 28, and 56 mg/kg) of psoralen and one dose (28 mg/kg) of isopsoralen were administered to rats over 12 weeks. Blood and selected tissue samples were collected and analyzed for hematology, serum biochemistry, and histopathology. Metabolic changes in serum samples were detected via proton nuclear magnetic resonance (1H-NMR) spectroscopy. We found that psoralen significantly changed the visceral coefficients, blood biochemical parameters, and histopathology, and isopsoralen extra influenced the hematological index. Moreover, psoralen induced remarkable elevations of forvaline, isoleucine, isobutyrate, alanine, acetone, pyruvate, glutamine, citrate, unsaturated lipids, choline, creatine, phenylalanine, and 4-hydroxybenzoate, and significant reductions of ethanol and dimethyl sulfone. Isopsoralen only induced a few remarkable changes of metabolites. These results suggest that chronic exposure to low-level of psoralen causes a disturbance in alanine metabolism, glutamate metabolism, urea cycle, glucose-alanine cycle, ammonia recycling, glycine, and serine metabolism pathways. Psoralen and isopsoralen showed different toxicity characteristics to the rats.
Highlights
Fructus Psoraleae (F.P.), the seed of Psoralea corylifolia L. (Leguminosae), has been widely used inAsian countries as a traditional medicine with the effects of warming kidney [1], activating “yang,”promoting inspiration [2], and checking diarrhea [3]
The administration of psoralen or isopsoralen for 12 weeks did not induce any behavioral modification at any time point in treated rats compared to their respective control group
Clinical application of F.P., the concerns have risen about the safe medication of F.P. and the toxicity with the continuously expanded clinical application of F.P., the concerns have risen about the safe induced hasofattracted increasing attention
Summary
Fructus Psoraleae (F.P.), the seed of Psoralea corylifolia L. (Leguminosae), has been widely used inAsian countries as a traditional medicine with the effects of warming kidney [1], activating “yang,”promoting inspiration [2], and checking diarrhea [3]. Fructus Psoraleae (F.P.), the seed of Psoralea corylifolia L. Asian countries as a traditional medicine with the effects of warming kidney [1], activating “yang,”. Promoting inspiration [2], and checking diarrhea [3]. There are more than 40 prescriptions containing. With the continuously expanded clinical application of F.P., toxicity problems have been concerned by researchers and doctors. Oral administration of the F.P. aqueous extract (25 g/kg) induced significantly liver and kidney injuries in Wistar rats, and the biomarkers related to glycerol phospholipids metabolism, amino acid metabolism, and energy metabolism, were largely changed [5]. Psoralen (P) and isopsoralen (IP) are the major active molecules and quality-control components of Metabolites 2019, 9, 263; doi:10.3390/metabo9110263 www.mdpi.com/journal/metabolites
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