State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, No.38 Xueyuan Road, Beijing, 100191, China.
Tibet University Medical College, Lasa, 850002, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118813. doi: 10.1016/j.jep.2024.118813. Epub 2024 Sep 12.
Astragali Radix-Saposhnikoviae Radix (AR-SR) is a well-known and effective herb pair. Although the compatibility of these two herbs has been widely applied in many traditional Chinese medicine formulas, its potential mechanism still needs to be investigated.
To evaluate the pharmacokinetic profiles of 10 bioactive compounds derived from AR when administrated alone and in combination with SR to rats, aiming to further reveal the impact of SR on AR.
Two groups of male Sprague-Dawley rats received oral administration of AR and AR-SR freeze-dried powder solutions, respectively. UHPLC-QTRAP-MS/MS technology was utilized to perform the pharmacokinetic studies of 10 compounds derived from AR in rat plasma samples.
A reliable UHPLC-QTRAP-MS/MS method was established to simultaneously determine the rat plasma concentrations of eight isoflavonoids, referring to calycosin (CAL), calycosin-7-O-β-D-glucoside (CAL-G), formononetin (FOR), formononetin-7-O-β-D-glucoside (FOR-G), astrapterocarpan (APC), astrapterocarpan-3-O-β-D-glucoside (APC-G), astraisoflavan-7-O-β-D-glucoside (AIF-G) and formononetin-7-O-β-D-glucuronide (FOR-GN), and two saponins, including astragaloside IV (AS IV) and cycloastragenol (CAG), originating from AR. Following the oral administration of AR, seven isoflavonoids were quickly absorbed but exhibited low plasma concentrations under 17.88 ng/mL except FOR-GN. The latter maintained higher plasma concentration level more than 15 ng/mL for at least 10 h. Besides, for the first time, AS IV was observed with an obvious double-peak phenomenon after administering AR extract, whereas the concentration of CAG was lower than LLOQ before 6 h. When AR and SR were administrated together, the double-peak phenomena of CAL, FOR, APC, AIF-G and FOR-GN were enhanced and there was a significant increase in their values of area under the concentration-time curve (AUC) and mean residence time (MRT) (P < 0.05) while the pharmacokinetic profiles of CAL-G, FOR-G, APC-G, AS IV and CAG stayed almost unchanged (P > 0.05). Moreover, the elimination half-time (t) values of CAL, FOR and APC were significantly elevated, and the clearance rate/bioavailability (CL) for CAL and FOR was reduced (P < 0.05).
SR has the potential to modulate the ADME process of five out of the eight isoflavonoids (CAL, FOR, APC, AIF-G and FOR-GN, except CAL-G, FOR-G and APC-G) originating from AR. This interaction is especially likely to affect the hepatic and intestinal drug disposition of these isoflavonoids, thereby extending the duration of their pharmacological effects, which may subsequently impact the therapeutic efficacy of AR.
黄芪-防风（AR-SR）是一种众所周知且有效的草药组合。尽管这两种草药的配伍已广泛应用于许多中药方剂中，但仍需要研究其潜在机制。
评估单独给予和同时给予 AR-SR 冻干粉末溶液后，10 种源自 AR 的生物活性化合物在大鼠体内的药代动力学特征，旨在进一步揭示 SR 对 AR 的影响。
两组雄性 Sprague-Dawley 大鼠分别给予 AR 和 AR-SR 冻干粉末溶液口服给药。采用 UHPLC-QTRAP-MS/MS 技术对大鼠血浆样品中源自 AR 的 10 种化合物进行药代动力学研究。
建立了一种可靠的 UHPLC-QTRAP-MS/MS 方法，可同时定量测定大鼠血浆中 8 种异黄酮（包括芒柄花素（CAL）、芒柄花素-7-O-β-D-葡萄糖苷（CAL-G）、黄豆黄素（FOR）、黄豆黄素-7-O-β-D-葡萄糖苷（FOR-G）、紫檀芪（APC）、紫檀芪-3-O-β-D-葡萄糖苷（APC-G）、阿魏异黄酮-7-O-β-D-葡萄糖苷（AIF-G）和黄豆黄素-7-O-β-D-葡萄糖醛酸苷（FOR-GN））和 2 种源自 AR 的皂苷（黄芪甲苷（AS IV）和环黄芪醇（CAG））的浓度。AR 口服给药后，7 种异黄酮迅速吸收，但除 FOR-GN 外，血浆浓度均较低，低于 17.88ng/mL。后者至少 10h 内保持高于 15ng/mL 的较高血浆浓度水平。此外，首次观察到给予 AR 提取物后 AS IV 出现明显的双峰现象，而 CAG 的浓度在 6h 前低于定量下限。当 AR 和 SR 一起给药时，CAL、FOR、APC、AIF-G 和 FOR-GN 的双峰现象增强，其 AUC 和 MRT 值显著增加（P<0.05），而 CAL-G、FOR-G、APC-G、AS IV 和 CAG 的药代动力学特征几乎保持不变（P>0.05）。此外，CAL、FOR 和 APC 的半衰期（t）值显著升高，CAL 和 FOR 的清除率/生物利用度（CL）降低（P<0.05）。
SR 有可能调节源自 AR 的 8 种异黄酮中的 5 种（除 CAL-G、FOR-G 和 APC-G 外的 CAL、FOR、APC、AIF-G 和 FOR-GN）的 ADME 过程。这种相互作用很可能影响这些异黄酮的肝肠药物处置，从而延长其药理作用的持续时间，这可能会影响 AR 的治疗效果。
