不同基原芍药制备的黄芩汤治疗溃疡性结肠炎药效对比研究

Pharmacological effects of Huangqin Decoction prepared from roots of multi-originated peony on ulcerative colitis in mice:a comparative study

黄芩汤为《伤寒论》中经典治痢名方,现代临床主要用于治疗溃疡性结肠炎(ulcerative colitis, UC)。黄芩汤中以芍药记载,未明确白芍或赤芍,临床上两者均有应用。虽白芍和赤芍基原相近,主成分类似,但两者药性与功效不同,是否能引起黄芩汤治疗UC药效差异未见系统比较研究。该研究以不同芍药(白芍、北赤芍和川赤芍)分别制备黄芩汤,采用葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎模型,从动物行为学、病理切片和细胞因子表达水平同步评价和比较不同芍药对经方黄芩汤整体药效的影响,从而来确定黄芩汤中芍药的确切基原。结果表明不同芍药制备的黄芩汤均能改善葡聚糖硫酸钠诱导的UC小鼠相关症状,与黄芩汤(白芍)相比,黄芩汤(北赤芍)和黄芩汤(川赤芍)在UC小鼠体质量降低率、结肠长度、病理损伤评分上均有显著差异,但黄芩汤(北赤芍)和黄芩汤(川赤芍)间无明显差异。而黄芩汤(川赤芍)小鼠结肠组织病理形态改善最为明显,黏膜缺损情况较黄芩汤(北赤芍)和黄芩汤(白芍)均有显著改善。结合前期成分表征及含量配比比较结果,认为黄芩汤中芍药在治疗UC上以川赤芍最佳,可能与川赤芍中含有大量芍药单萜苷和没食子鞣酸类成分有关。该研究可为黄芩汤中芍药基原的准确确定及临床的精准用药提供科学依据。

Huangqin Decoction(HQD) is a classic prescription for treating dysentery in the Treatise on Cold Damage and now is mainly used for the treatment of ulcerative colitis(UC). Since there are no requirements on specific Paeonia species, both Paeoniae Radix Alba(white peony root, WPR) and Paeoniae Radix Rubra(red peony root, RPR) are clinically used in HQD now. Although the two types of peony roots are close in origin and similar in primary components, the medicinal properties and efficacies are different. Furthermore, the systematic comparative analysis on the efficacy differences in treating UC of HQD with the roots of multi-originated peony has been seldom reported. This study compared and evaluated the pharmacological effects of HQD prepared from the roots of multi-originated peony, including WPR, RPR-l(derived from P. lactiflora), and RPR-v(derived from P. veitchii) based on the mouse model of UC induced by dextran sodium sulfate(DSS) by animal behaviors, pathological section(colon), and cytokine expression(IL-1β and IL-6), aiming to provide evidence for the identification of the original resource of peony root in HQD. The results indicated that all HQD samples prepared from WPR, RPR-l, and RPR-v could improve the symptoms of UC. Compared with the HQD-WPR, HQD-RPR-l and HQD-RPR-v were significantly different in weight loss, colon length, and disease activity index(DAI) score, but there was no significant difference between HQD-RPR-l and HQD-RPR-v. Moreover, HQD-RPR-v exhibited the most significant improvement in the pathological morphology of colonic tissue and mucosal defects. According to the previous comparative analysis of chemical profiling and content distribution of HQD prepared from the roots of multi-originated peony, RPR-v in HQD was potent in protecting against UC, which was presumedly attributed to a large number of monoterpene glycosides and galloyl glucoses. This study provided a scientific basis for the determination of peony root in HQD and its clinical medication.