a Department of Pharmacy , The Affiliated Hospital of Qingdao University , Qingdao , People's Republic of China.
b Beijing Key Laboratory of Drug Target Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , People's Republic of China.
Pharm Biol. 2018 Dec;56(1):399-406. doi: 10.1080/13880209.2018.1491998.
Salvianolic acid A (Sal A) is a hydrophilic bioactive compound isolated from Salvia miltiorrhiza Bunge (Lamiaceae). It exerts beneficial effects after oral administration on diabetic complications.
To systematically study the absorption, distribution and excretion of Sal A after single-dose oral administration.
Animal experiments were conducted in Sprague-Dawley rats. Plasma was sampled at designated times after oral doses of 5, 10 and 20 mg/kg, and an intravenous dose of 50 μg/kg. Tissues were harvested at 10, 60 and 120 min postdosing. Bile, urine and feces were collected at specified intervals before and after dosing. Absorption and distribution characteristics were analyzed by LC-MS, and excretion characteristics were analyzed by UPLC-MS/MS. The Caco-2 cell model was applied to investigate potential mechanisms.
The C (5 mg/kg: 31.53 μg/L; 10 mg/kg: 57.39 μg/L; 20 mg/kg: 111.91 μg/L) of Sal A increased linearly with doses (r> 0.99). The calculated absolute bioavailability was 0.39-0.52%. Transport experiment showed poor permeability and the ratio of P to P was 3.13-3.97. The highest concentration of Sal A was achieved in stomach followed by small intestine and liver, and it could also be detected in brain homogenate. Approximately 0.775% of its administered dose was excreted via feces, followed by bile (0.00373%) and urine (0.00252%).
These results support the future development of Sal A as an oral drug for the treatment of diabetic complications. Future research should be conducted to investigate the reason for its poor bioavailability and improve this situation.
丹酚酸 A（Sal A）是从丹参（唇形科）中分离得到的一种亲水性生物活性化合物。它经口服给药后对糖尿病并发症有有益作用。
系统研究单次口服给药后 Sal A 的吸收、分布和排泄。
在 Sprague-Dawley 大鼠中进行动物实验。口服 5、10 和 20mg/kg 及静脉注射 50μg/kg 后，在指定时间采集血浆。给药后 10、60 和 120min 时采集组织。在给药前后的指定时间间隔采集胆汁、尿液和粪便。通过 LC-MS 分析吸收和分布特征，通过 UPLC-MS/MS 分析排泄特征。应用 Caco-2 细胞模型研究潜在机制。
Sal A 的 C（5mg/kg：31.53μg/L；10mg/kg：57.39μg/L；20mg/kg：111.91μg/L）随剂量呈线性增加（r>0.99）。计算的绝对生物利用度为 0.39-0.52%。转运实验表明其渗透性差，P 与 P 的比值为 3.13-3.97。Sal A 的最高浓度出现在胃，其次是小肠和肝脏，也可以在脑匀浆中检测到。约 0.775%的给药剂量通过粪便排泄，其次是胆汁（0.00373%）和尿液（0.00252%）。
这些结果支持将 Sal A 开发为治疗糖尿病并发症的口服药物。未来应开展研究以探究其生物利用度差的原因并加以改善。
