Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China; State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
J Ethnopharmacol. 2019 Mar 1;231:394-402. doi: 10.1016/j.jep.2018.10.025. Epub 2018 Oct 23.
In traditional Chinese medicine (TCM), Rehmanniae Radix (RR, derived from the root of Rehmannia glutinosa (Gaertn.) DC.) is commonly used as natural medicine for thousands of years, two types including the dried and rice-wine processed RR were used for different clinical purposes respectively, which were the typical case that pharmaceutical effect changed by processing in TCM.
The goal of this study was to investigate the differences in the antithrombosis and hematopoietic effects of extracts of dried and processed RR (DRR and PRR) in vivo, and to explore the chemical basis underlying changes of medicinal properties caused by processing.
The aqueous extracts of DRR and PRR were prepared. Protective effect of varying doses of different extracts were investigated in type-I carrageenan induced mice tail thrombosis and cyclophosphamide induced myelosuppression model. The chemical composition of DRR and PRR extracts were determined by High Performance Liquid Chromatography coupled with tandem quadrupole time-of-flight Mass Spectrometry (HPLC/Q-TOF-MS).
In antithrombosis activity tests, PRR possessed less ameliorated effects than DRR in the model mouse on body temperature, tail thrombus length and blood flow. Both DRR and PRR had no significant influence on prothrombin time (PT) and activated partial thromboplastin time (APTT), only high dose DRR could decrease the content of fibrinogen (FIB) in plasma. Histological examination of lung tissue suggested that thrombosis was significantly improved in DRR-H group. For myelosuppression model, only PRR could improve peripheral hemogram, both DRR and PRR had hematopoietic effects as demonstrated by their abilities to ameliorate the bone marrow nucleated cells (BMNC) and pathology of bone marrow tissue. The hematopoietic effects of PRR were significantly more potent than that of DRR at the concentration of 9 g/kg. By comparing the chemical composition, we found that iridoid glycosides were decreased and furfural derivatives increased in DRR after processing which may be the chemical mechanism contribute to the differences in efficacy.
According to the results of this research, processing with rice wine for nine cycles significantly reduced antithrombotic effects and enhanced the hematopoietic effects of DRR as demonstrated in model mice. It can scientifically explain the different effect among two types of RR in clinical through the diverse method of processing and usage. Meanwhile, the predicted activity compounds from two types of RR can be potential candidates for the treatment of thrombosis and anemia.
在中药(TCM)中,地黄(RR,源自地黄(Rehmannia glutinosa(Gaertn.)DC.)的根)已被广泛用作天然药物数千年,两种类型的 RR 分别是干地黄和酒地黄,用于不同的临床用途,这是 TCM 中通过炮制改变药物作用的典型案例。
本研究旨在探讨干地黄和酒地黄提取物(DRR 和 PRR)在体内抗血栓形成和造血作用的差异,并探讨炮制引起药物性质变化的化学基础。
制备 DRR 和 PRR 的水提取物。在 I 型角叉菜胶诱导的小鼠尾血栓形成和环磷酰胺诱导的骨髓抑制模型中,考察了不同剂量不同提取物的保护作用。采用高效液相色谱-串联四极杆飞行时间质谱联用(HPLC/Q-TOF-MS)法测定 DRR 和 PRR 提取物的化学成分。
在抗血栓形成活性试验中,PRR 在模型小鼠的体温、尾血栓长度和血流方面的改善作用均低于 DRR。DRR 和 PRR 均对凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)无显著影响,仅高剂量 DRR 可降低血浆纤维蛋白原(FIB)含量。肺组织组织学检查表明,DRR-H 组血栓明显改善。对于骨髓抑制模型,仅 PRR 可改善外周血象,DRR 和 PRR 均具有造血作用,表现为改善骨髓有核细胞(BMNC)和骨髓组织病理学。PRR 的造血作用在 9g/kg 浓度下明显强于 DRR。通过比较化学成分,我们发现 DRR 经炮制后,其环烯醚萜苷类减少,糠醛衍生物增加,这可能是其疗效差异的化学机制。
根据本研究结果,酒九蒸炮制显著降低了 DRR 的抗血栓形成作用,增强了其造血作用。这可以通过不同的炮制方法和用途,从科学上解释临床中两种 RR 的不同作用。同时,两种 RR 的预测活性化合物可以成为治疗血栓形成和贫血的潜在候选药物。