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基于多成分定量分析结合体外生物测定法的 苷片质量综合评价。

Comprehensive Evaluation of the Quality of Glycosides Tablets Based on Multi-Component Quantification Combined with an In Vitro Biological Assay.

机构信息

National Institutes for Food and Drug Control, Beijing 102629, China.

Traditional Chinese Medicine Processing Technology Innovation Center of Hebei Province, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.

出版信息

Molecules. 2022 Aug 10;27(16):5102. doi: 10.3390/molecules27165102.

Abstract

glycosides tablets (TGTs) are widely used in clinical practice to treat rheumatoid arthritis and other autoimmune diseases, with significant beneficial effects but also high toxicity, necessitating rigorous quality evaluation and control. In current study, a rapid resolution liquid chromatography tandem electrospray ionization triple quadrupole mass spectrometry (RRLC-ESI-MS/MS) method was developed and validated for the quantitative analysis of 14 components of ten batches of TGTs produced by different manufacturers, including four diterpenoids, three triterpenoids, and seven sesquiterpene alkaloids. Meanwhile, the NO inhibition effects of these TGTs were evaluated in LPS-induced RAW264.7 cells for their downstream anti-inflammatory activities, as well as their cytotoxicity. The results indicate that the TGTs from different manufacturers showed poor quality consistency, as evidenced by large variations in chemical profiles and biological effects, which may increase the risks associated with clinical use. To improve the quality status of TGTs, it is crucial to identify indicator components whose characterization can accurately reflect the efficacy and toxicity of TGTs from which they were derived. Our study reveals that triptolide, triptoquinone B, celastrol, and demethylzelaysteral considerably contributed to the anti-inflammatory activity and/or cytotoxicity of TGTs, implying that they should be further investigated as candidate indicator components for TGT quality control.

摘要

糖苷片(TGTs)广泛应用于临床治疗类风湿关节炎和其他自身免疫性疾病,具有显著的疗效,但也有很高的毒性,因此需要严格的质量评估和控制。在本研究中,建立并验证了一种快速分辨液相色谱串联电喷雾电离三重四极杆质谱(RRLC-ESI-MS/MS)法,用于定量分析来自不同制造商的十批 TGTs 中的 14 种成分,包括四种二萜、三种三萜和七种倍半萜生物碱。同时,评估了这些 TGTs 在 LPS 诱导的 RAW264.7 细胞中的 NO 抑制作用,以评估其下游抗炎活性及其细胞毒性。结果表明,不同制造商生产的 TGTs 质量一致性较差,表现在化学成分和生物效应方面存在较大差异,这可能会增加临床应用的风险。为了提高 TGTs 的质量状况,识别能够准确反映其来源的 TGTs 疗效和毒性的指标成分至关重要。我们的研究表明,雷公藤红素、雷公藤酮 B、昆明山海棠碱和去甲基泽拉木醛对 TGTs 的抗炎活性和/或细胞毒性有很大贡献,这意味着它们应该作为 TGT 质量控制的候选指标成分进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3538/9416487/37fc1aed9f2d/molecules-27-05102-g001.jpg

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