National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China.
Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China.
Molecules. 2023 Jul 13;28(14):5382. doi: 10.3390/molecules28145382.
Nardosinone, a predominant bioactive product from DC, is well-known for its promising therapeutic applications, such as being used as a drug on anti-inflammatory, antidepressant, cardioprotective, anti-neuroinflammatory, anti-arrhythmic, anti-periodontitis, etc. However, its stability under varying environmental conditions and its degradation products remain unclear. In this study, four main degradation products, including two previously undescribed compounds [2-deoxokanshone M (64.23%) and 2-deoxokanshone L (1.10%)] and two known compounds [desoxo-narchinol A (2.17%) and isonardosinone (3.44%)], were firstly afforded from the refluxed products of nardosinone in boiling water; their structures were identified using an analysis of the extensive NMR and X-ray diffraction data and the simulation and comparison of electronic circular dichroism spectra. Compared with nardosinone, 2-deoxokanshone M exhibited potent vasodilatory activity without any of the significant anti-neuroinflammatory activity that nardosinone contains. Secondly, UPLC-PDA and UHPLC-DAD/Q-TOF MS analyses on the degradation patterns of nardosinone revealed that nardosinone degraded more easily under high temperatures and in simulated gastric fluid compared with the simulated intestinal fluid. A plausible degradation pathway of nardosinone was finally proposed using nardosinonediol as the initial intermediate and involved multiple chemical reactions, including peroxy ring-opening, keto-enol tautomerization, oxidation, isopropyl cleavage, and pinacol rearrangement. Our findings may supply certain guidance and scientific evidence for the quality control and reasonable application of nardosinone-related products.
冬凌草甲素是 DC 的主要生物活性产物，以其在抗炎、抗抑郁、心脏保护、抗神经炎症、抗心律失常、抗牙周炎等方面的有前途的治疗应用而闻名。然而，其在不同环境条件下的稳定性及其降解产物仍不清楚。在这项研究中，从冬凌草甲素在沸水中回流的产物中首次获得了四个主要的降解产物，包括两个以前未描述的化合物[2-去氧卡酮 M（64.23%）和 2-去氧卡酮 L（1.10%）]和两个已知的化合物[去氧-那可醇 A（2.17%）和异冬凌草甲素（3.44%）]；它们的结构是通过广泛的 NMR 和 X 射线衍射数据以及电子圆二色谱的模拟和比较来确定的。与冬凌草甲素相比，2-去氧卡酮 M 表现出强大的血管扩张活性，而不含有冬凌草甲素的显著抗神经炎症活性。其次，对冬凌草甲素的降解模式进行 UPLC-PDA 和 UHPLC-DAD/Q-TOF MS 分析表明，与模拟肠液相比，冬凌草甲素在高温和模拟胃液中更容易降解。最后，使用冬凌草甲二醇作为初始中间体，提出了冬凌草甲素的可能降解途径，涉及多个化学反应，包括过氧基开环、酮-烯醇互变异构、氧化、异丙基裂解和邻二醇重排。我们的发现可能为冬凌草甲素相关产品的质量控制和合理应用提供一定的指导和科学依据。
