ABSTRACT
Aristolochic acid analogues (AAAs), naturally existing in herbal Aristolochia and Asarum genera, were once widely used in traditional pharmacopeias because of their anti-inflammatory properties, but lately they were identified as potential nephrotoxins and mutagens. A method for rapid characterization of AAAs in serum was developed using ion mobility spectrometry coupled with mass spectrometry (IMS-MS). Five AAAs, containing four aristolochic acids and one aristolactam, were separated and identified within milliseconds. AAAs were separated in gas phase based on the difference of their ion mobility (K0), and then identified based on their K0 values, m/z, and product ions from MS/MS. Quantitative analysis of AAAs was performed using an internal standard with a satisfactory sensitivity. Limits of detection (signal-to-noise = 3) and quantification (signal-to-noise = 10) were 1-5 ng/mL and 3-8 ng/mL, respectively. The method was validated and successfully applied to the pharmacokinetics study of AAAs in rats, offering a promising way for fast screening and evaluation of AAAs in biological samples.
Subject(s)
Aristolochic Acids/blood , Animals , Aristolochia/chemistry , Aristolochic Acids/chemistry , Asarum/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Ion Mobility Spectrometry/economics , Ion Mobility Spectrometry/methods , Limit of Detection , Male , Mutagens/chemistry , Mutagens/pharmacokinetics , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To test the effect of asarinin, the extract of Herba Asari, on the acute heart transplantation rejection and the expression of adhesion molecule. METHOD: Asarinin was extracted from herba asari. 64 SD rats undergone heart transplantation were divided into four groups: group A (control group), group B (Cyclosporine A treated), group C (Asarinin treated), and group D (1/2 CsA and 1/2 Asarinin). Some rats were used to examine survival time (n = 8) and the others were used to observe the pathological injury and the expression level of interrellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-I (VCAM-1) by using immunohistochemistry. RESULT: Asarinin could prolong the survival time of allografts, which was similar to CsA group (P > 0.05). Asarinin could relieve the damage of cardiomyocytes of the transplanted. Asarinin could also decrease the level of ICAM-1 and VCAM-1 in the allografts. CONCLUSION: Asarinin may play important roles in suppressing the immune rejection, prolong the allografts survival time and protect the donor organ, which was similar to CsA. The expression level of ICAM-1 and VCAM-1 is increased in suppressing the course of acute rejection and asarinin can inhibit their expression level. Asarinin can decrease the dosage of CsA.