Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taiwan.
J Agric Food Chem. 2010 Apr 28;58(8):4638-43. doi: 10.1021/jf100269g.
Cordycepin is a bioactive constituent of Cordyceps sinensis that has been shown to regulate homeostatic function. As an adenosine analogue, it is possible cordycepin goes through a similar metabolic pathway to that of adenosine. To investigate this hypothesis, a sensitive liquid chromatography with photodiode-array detector (HPLC-PDA) coupled to a microdialysis sampling system was developed to monitor cordycepin and adenosine in rat blood and liver. Other endogenous nucleosides were simultaneously measured to further understand the downstream metabolic pathway. The experiments were divided into six parallel groups for drug administration: (1) normal saline vehicle, (2) adenosine, (3) cordycepin, (4) normal saline + erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; a potent adenosine deaminase inhibitor), (5) adenosine + EHNA, and (6) cordycepin + EHNA. The pharmacokinetic results suggest that the levels of both adenosine and cordycepin decreased rapidly in blood around 30 min after drug administration. When adenosine was given, the concentrations of adenosine metabolites, hypoxanthinosine and hypoxanthine, increased in rat blood. This phenomenon was inhibited by EHNA pretreatment. An unidentified peak was observed in the blood and liver samples after cordycepin administration. The decline of this unidentified peak paralleled the decreased of the concentration of cordycepin, and it was not observed in the presence of the adenosine deaminase inhibitor. It is concluded that adenosine and cordycepin had short elimination half-lives and high rates of clearance and their biotransformation was suppressed by EHNA.
蛹虫草中的虫草素是一种具有生物活性的成分，已被证明可以调节体内稳态功能。作为一种腺嘌呤类似物，虫草素可能通过与腺嘌呤相似的代谢途径进行代谢。为了验证这一假设，我们开发了一种灵敏的液相色谱-光电二极管阵列检测（HPLC-PDA）与微透析采样系统相结合的方法，用于监测大鼠血液和肝脏中的虫草素和腺嘌呤。同时测量其他内源性核苷，以进一步了解下游代谢途径。实验分为 6 个平行组进行药物给药：（1）生理盐水载体，（2）腺嘌呤，（3）虫草素，（4）生理盐水+依诺肝素（一种有效的腺嘌呤脱氨酶抑制剂），（5）腺嘌呤+依诺肝素，和（6）虫草素+依诺肝素。药代动力学结果表明，给药后约 30 分钟，血液中腺嘌呤和虫草素的水平迅速下降。当给予腺嘌呤时，大鼠血液中腺嘌呤代谢物次黄苷和次黄嘌呤的浓度增加。EHNA 预处理可抑制这种现象。在给予虫草素后，在血液和肝脏样本中观察到一个未鉴定的峰。该未鉴定峰的下降与虫草素浓度的下降平行，并且在存在腺嘌呤脱氨酶抑制剂时未观察到该峰。综上所述，腺嘌呤和虫草素的消除半衰期短，清除率高，EHNA 可抑制其生物转化。
