3种不同基源豨莶作同一药材使用合理性的再评价

The property of multi-origin (multi-based source) is common in many Chinese medicines (CMs), which may lead to problems related to consumption safety, clinical efficacy and quality controllability. Systemic investigations of the chemical compositions and pharmacological activities/mechanisms of the Chinese medicinal herb with different origins are critical for the standardization and modernization of the traditional Chinese medicine (TCM). Siegesbeckiae Herba is one of the widely used CM for treating chronic diseases such as arthritis, numbness of limbs and hemiplegia. In the Chinese Pharmacopeia (2010), three species of the plants are recorded to be used as Siegesbeckiae Herba. Among them, only Siegesbeckia pubescens Makino has been traditionally used for hundreds of years. Other two species, S. orientalis L. and S. glabrescens Makino are new species which were added in the Chinese Pharmacopeia after 1977. However, our preliminary studies indicated that the chemical compositions and pharmacological activities of these three species of Siegesbeckiae Herba showed significantly differences, which were consistent with the previous publications. In this proposed project, we will systemically investigate the specific effective components in each individual species of Siegesbeckiae Herba and elucidate their mechanisms of action on anti-inflammation. We will combine instrumental analysis and metabolomics study to investigate the chemical compositions, the pharmacokinetics and pharmacodynamics of these 3 species and compare their clinical efficacies. The results in this study will provide scientific evidences to suggest a feasibility to prescribe these three difference species as Siegesbeckiae Herba. Moreover, the obtained results will also lay a solid scientific foundation to further improve the standardization and quality control of Siegesbeckiae Herba.

中药材品种的多基源性导致了药材品种混杂，质量难以控制等诸多问题。在辨明正异的科学基础上"正本清源"，逐步解决中药材长期存在的同名多基源问题，保证临床用药的安全性、有效性和可控性，是中药标准化和现代化的必然趋势。豨莶草为临床常用抗风湿中药之一，中国药典中共收载3个基源植物。其中腺梗豨莶（Siegesbeckia pubescens Makino）与历史沿用品种一致，豨莶（S. orientalis L.）和毛梗豨莶（S. glabrescens Makino）为77版药典后增品种。我们研究发现这3个基源的豨莶所含的化学组分和药理活性存在显著差异，与文献报道一致。本研究将结合化学、药代动力学和药效学的评价方法，从化学组成和代谢组学等方面探讨3种基源豨莶各自的药效物质基础和作用机制，为豨莶草药材"正本清源"。研究的结果也将为豨莶草药材质量标准的进一步完善，提供实验的研究基础和理论依据。

豨莶草是临床常用抗风湿中药之一。《中国药典》收载豨莶草的植物来源包括菊科植物豨莶（SO）、腺梗豨莶（SP）和毛梗豨莶（SG），其质量评价以奇壬醇为单一指标。.本课题综合了分析化学、植物化学、药理学、药效学、药物代谢动力学等多学科的研究方法，从化学物质基础、药理作用机制以及药代动力学/药效学等多个方面，对豨莶草3种基源植物（SO、SP和SG）进行系统的研究、分析和比较，探讨3者在化学物质基础和药理药效等方面的相似性和差异性，旨在为进一步完善豨莶草药材的质量标准提供试验数据和研究依据。.整体化学的研究表明， SP所含的化学成分与SO和SG存在显著的差异，而SO和SG则有一定的相似性；进一步考察分离优化得到的7个主要抗炎活性化合物（奇壬醇，SP6/SG9 (C1)；16-邻乙酰基豨莶苷，SO10 (C2)；3,7-dimetoxi-5,3',4'-tri-hidroxifavona，SO13/SP9 (C3)；3-邻-甲基槲皮素，SG12 (C4)；Leocarpinolide B，SG15 (C5)；SG16 (C6)和豨莶苷 (C7)）在3种豨莶植物中的分布特征，化合物C1、C3 和C4为3种豨莶植物共有，化合物C2 和C7主要分布在SO中，化合物C5则为SG所特有。细胞药理的研究表明，3种豨莶植物均能通过下调NF-κB和MAPKs活化的iNOS和COX-2表达升高，从而有效抑制细胞炎症反应。药代动力学研究表明，4个成分（C1、C4、C5和C7）能透过MDCK单细胞层转运被吸收；其中C1 （奇壬醇）在大鼠多剂量口服给药时可能存在肝-肠循环。动物药效的研究表明，3种豨莶提取物均能不同程度地调节和改善胶原蛋白诱导关节炎大鼠的免疫功能，平衡血液循环系统及病灶部位炎症相关细胞因子的表达水平，进而改善大鼠的关节病变。此外，SP提取物对Pam3CSK4诱导细胞炎症也具有较好的抑制效果；SO提取物则对动物手术后认知功能障碍、全身炎症以及神经炎症的发生与发展具有较好的改善和预防效果。.综上所述，豨莶草3种基源植物在抗炎的药效和分子机制上具有一定程度的相似性，但在抗炎的化学物质基础上存在较大的差别。其中，优化得到豨莶草中的7个主要活性成分，可作为完善豨莶草质量标准中，指标性成分的备选化合物。