Degradation Profiling of Nardosinone at High Temperature and in Simulated Gastric and Intestinal Fluids

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-07, Vol.28 (14), p.5382
• Main Authors: Xue, Bian-Xia, Yang, Tian-Tian, He, Ru-Shang, Gao, Wen-Ke, Lai, Jia-Xin, Liu, Si-Xia, Duan, Cong-Yan, Wang, Shao-Xia, Yu, Hui-Juan, Yang, Wen-Zhi, Zhang, Li-Hua, Wang, Qi-Long, Wu, Hong-Hua
• Format: Article
• Language: English
• Subjects: 2–deoxokanshone M; Anti-arrhythmia drugs; Antidepressants; Chromatography; degradation; Health aspects; High temperature; Instrument industry; Ions; Mass spectrometry; nardosinone; Nardostachys jatamansi DC; NMR; Nuclear magnetic resonance; Pharmacokinetics; Scientific imaging; simulated gastric fluid; simulated intestinal fluid
• ISSN: 1420-3049; 1420-3049
• 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.