Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Pharmaceutical College, Harbin University of Commerce, Harbin 150086, China.
Molecules. 2017 Oct 26;22(11):1826. doi: 10.3390/molecules22111826.
Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were detected by fingerprint similarity evaluation software. Among them, 15 peaks were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Pharmacodynamics experiments were conducted in collagen-induced arthritis (CIA) mice to obtain the anti-inflammatory effects of different batches of CRM with four pro-inflammation cytokines (TNF-α, IL-β, IL-6, and IL-17) as indicators. These cytokines were suppressed at different levels according to the different batches of CRM treatment. The spectrum-effect relationships between chemical fingerprints and the pro-inflammation effects of CRM were established by multiple linear regression (MLR) and gray relational analysis (GRA). The spectrum-effect relationships revealed that the alkaloids (-methylcytisine, magnoflorine), saponins (leiyemudanoside C, leiyemudanoside D, leiyemudanoside G, leiyemudanoside B, cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C, and cauloside A), sapogenins (oleanolic acid), β-sitosterols, and unknown compounds (X3, X17) together showed anti-inflammatory efficacy. The results also showed that the correlation between saponins and inflammatory factors was significantly closer than that of alkaloids, and saponins linked with less sugar may have higher inhibition effect on pro-inflammatory cytokines in CIA mice. This work provided a general model of the combination of HPLC and anti-inflammatory effects to study the spectrum-effect relationships of CRM, which can be used to discover the active substance and to control the quality of this treatment.
脉泰（CRM）是一种具有显著治疗类风湿关节炎（RA）效果的中药。本研究旨在探讨高效液相色谱（HPLC）指纹图谱与 CRM 抗炎作用的谱效关系。指纹相似度评价软件检测到 17 个共有峰，其中 15 个峰通过液相色谱-质谱联用（LC-MS）进行鉴定。在胶原诱导关节炎（CIA）小鼠中进行药效学实验，以四种促炎细胞因子（TNF-α、IL-β、IL-6 和 IL-17）为指标，获得不同批次 CRM 的抗炎作用。根据不同批次的 CRM 治疗，这些细胞因子受到不同程度的抑制。采用多元线性回归（MLR）和灰色关联分析（GRA）建立化学指纹图谱与 CRM 促炎作用的谱效关系。谱效关系揭示，生物碱（-甲基胞啶、木兰碱）、皂苷（莱叶绵马糖 C、莱叶绵马糖 D、莱叶绵马糖 G、莱叶绵马糖 B、长春甙 H、莱菔子苷 D、长春甙 G、长春甙 D、长春甙 B、长春甙 C 和长春甙 A）、甾体皂苷（齐墩果酸）、β-谷甾醇和未知化合物（X3、X17）共同表现出抗炎功效。结果还表明，皂苷与炎症因子的相关性明显比生物碱更密切，且与较少糖结合的皂苷可能对 CIA 小鼠的促炎细胞因子具有更高的抑制作用。该工作为采用 HPLC 和抗炎作用相结合的方法研究 CRM 的谱效关系提供了一个通用模型，可用于发现活性物质和控制该治疗的质量。
