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中药复方理冲生髓饮对卵巢癌影响的多维谱效关系

Multi-Dimensional Spectrum-Effect Relationship of the Impact of Chinese Herbal Formula Lichong Shengsui Yin on Ovarian Cancer.

作者信息

Wang Yanhong, Li Yang, Zhang Yan, Feng Guan, Yang Zhixin, Guan Qingxia, Wang Rui, Han Fengjuan

机构信息

College of Pharmacy, Heilongjiang University of Traditional Medicine, Harbin 150040, China.

Disha Pharmaceutical Group, Qingdao 266100, China.

出版信息

Molecules. 2017 Jun 13;22(6):979. doi: 10.3390/molecules22060979.

Abstract

Lichong Shengsui Yin (LCSSY) is an effective and classic compound prescription of Traditional Chinese Medicines (TCMs) used for the treatment of ovarian cancer. To investigate its pharmacodynamic basis for treating ovarian cancer, the multi-dimensional spectrum-effect relationship was determined. Four compositions (I to IV) were obtained by extracting LCSSY successively with supercritical CO₂ fluid extraction, 75% ethanol reflux extraction, and the water extraction-ethanol precipitation method. Nine samples for pharmacological evaluation and fingerprint analysis were prepared by changing the content of the four compositions. The specific proportions of the four compositions were designed according to a four-factor, three-level L₉(3⁴) orthogonal test. The pharmacological evaluation included in vitro tumor inhibition experiments and the survival extension rate in tumor-bearing nude mice. The fingerprint analyzed by chromatographic condition I (high-performance liquid chromatography-photodiode array detec tor,HPLC-PDA) identified 19 common peaks. High-performance liquid chromatography-photodiode array detector-Evaporative Light-scattering Detector (HPLC-PDA-ELSD )hyphenated techniques were used to compensate for the use of a single detector, and the fingerprint analyzed by chromatographic condition II identified 28 common peaks in PDA and 23 common peaks in ELSD. Furthermore, multiple statistical analyses were utilized to calculate the relationships between the peaks and the pharmacological results. The union of the regression and the correlation analysis results were the peaks of X₅, X₉, X, X, X, X, Y₅, Y₈, Y, Y, Y, Z₄, Z₅, Z₆, and Z₈. The intersection of the regression and the correlation analysis results were the peaks of X, X, X, X, Y₅, Y, and Z₅. The correlated peaks were assigned by comparing the fingerprints with the negative control samples and reference standard samples, and identifying the structure using high-performance liquid chromatography-mass spectrometry detector(HPLC-MS). The results suggested that the pharmacodynamic basis of LCSSY on anti-ovarian cancer activities were germacrone, furandiene, β-elemene, calycosin-7-glucoside, ononin, epimedin B, icariin, ginsenoside Rc, astragaloside, ginsenoside Rd, astragaloside II, and some unknown components.

摘要

理冲生髓饮(LCSSY)是用于治疗卵巢癌的一种有效且经典的中药复方制剂。为研究其治疗卵巢癌的药效学基础,确定了多维谱效关系。通过超临界CO₂流体萃取、75%乙醇回流萃取以及水提醇沉法依次提取LCSSY,得到4种成分(I至IV)。通过改变这4种成分的含量制备了9个用于药理评价和指纹图谱分析的样品。根据四因素三水平L₉(3⁴)正交试验设计4种成分的具体比例。药理评价包括体外肿瘤抑制实验和荷瘤裸鼠的生存延长率。采用色谱条件I(高效液相色谱-光电二极管阵列检测器,HPLC-PDA)分析指纹图谱,鉴定出19个共有峰。采用高效液相色谱-光电二极管阵列检测器-蒸发光散射检测器(HPLC-PDA-ELSD)联用技术弥补单一检测器的不足,色谱条件II分析指纹图谱在PDA中鉴定出28个共有峰,在ELSD中鉴定出23个共有峰。此外,利用多种统计分析方法计算峰与药理结果之间的关系。回归分析和相关性分析结果的并集为X₅、X₉、X、X、X、X、Y₅、Y₈、Y、Y、Y、Z₄、Z₅、Z₆和Z₈峰。回归分析和相关性分析结果的交集为X、X、X、X、Y₅、Y和Z₅峰。通过将指纹图谱与阴性对照样品和对照品比较,并采用高效液相色谱-质谱检测器(HPLC-MS)鉴定结构,对相关峰进行了归属。结果表明,LCSSY抗卵巢癌活性的药效学基础为莪术酮、呋喃二烯、β-榄香烯、毛蕊花糖苷、芒柄花苷、朝藿定B、淫羊藿苷、人参皂苷Rc、黄芪甲苷、人参皂苷Rd、黄芪甲苷II以及一些未知成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c9/6152777/c1e1f82af269/molecules-22-00979-g001.jpg

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