Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China.
Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou, 510515, PR China.
J Ethnopharmacol. 2024 Dec 5;335:118622. doi: 10.1016/j.jep.2024.118622. Epub 2024 Jul 23.
ETHNO-PHARMACOLOGICAL RELEVANCE: Huangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear.
Following PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE).
To evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed.
In mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect.
Our findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment.
黄芪葛根汤（HGD）由黄芪（AR）和葛根（PR）组成，在中国被广泛用于治疗血栓。然而，其协同治疗血栓的机制尚不清楚。
PR 的主要成分在给药后，其血浆暴露水平较低。鉴于此，本研究考察了 AR 对 PR 抗血栓作用的影响，以及黄芪多糖（APS）对葛根素（PUE）口服递送的影响。
为了评估 HGD 的协同作用，通过腹腔注射角叉菜胶建立血栓形成小鼠模型。治疗后，进行组织病理学观察，并检测尾巴血栓长度比例以及血浆 APTT、PT、INR 和 FIB 水平。采用分子对接评估 PR 成分中能抑制 HMGB1/NF-κB/NLRP3 通路的成分。还比较了 PR 组和 HGD 组大鼠 PR 成分的药代动力学。此外，评估了 APS 对 PUE 溶解度、肠吸收和药代动力学的影响。还评估了 APS 对 PUE 抗血栓作用的影响。
在小鼠中，AR 增强了 PR 的抗血栓作用。这种改善的 PR 作用与异黄酮诱导的 HMGB1/NF-κB/NLRP3 通路下调有关。HGD 成分的协同作用主要是通过提高 PR 异黄酮的血浆暴露来实现的。具体而言，APS 通过形成自组装纳米粒子来提高 PUE 的水溶解度，从而增加其肠吸收和口服生物利用度，进而抑制 HMGB1/NF-κB/NLRP3 通路，从而提高其抗血栓作用。
我们的研究结果表明，APS 提高了 PUE 的血浆暴露，增强了其对 HMGB1/NF-κB/NLRP3 通路的抑制作用。这一机制是 HGD 配伍在血栓治疗中的协同作用的关键方面。
