Identification and characterization of major alkaloid from Sinomenium acutum stem and their metabolites after oral administration in rat plasma, urine, bile and feces based on UPLC-Q-TOF/MS

Wang, Yuefei; Gao, Xia; Wang, Jiajia; Tang, Ming; Yu, Boyang; Wang, Zhenzhong; Cao, Lei; Chen, Xialin; Qian, Mengyu; Wang, Shan‐Li; Xiao, Wei

doi:10.1016/j.jpba.2022.115005

Cited by 8 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The choice of animal model is crucial. We chose rats animal model to study the arctigenin metabolites referring to many literatures ( Wu et al, 2021 ; Mengmeng et al, 2022 ; Wang Y. et al, 2022 ), and it was also used in the published papers of our team ( Cui et al, 2022 ; Jing et al, 2022 ; Wang H. et al, 2022 ). There are undeniably multiple differences between human and rats.…”

Section: Discussionmentioning

confidence: 99%

Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis

Lan

Wang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Arctigenin is a phenylpropanoid dibenzylbutyro lactone lignan compound with multiple biological functions. Previous studies have shown that arctigenin have neuroprotective effects in Alzheimer’s disease (AD) models both in vivo and in vitro; however, its metabolism in vivo has not been studied. Most traditional analytical methods only partially characterize drug metabolite prototypes, so there is an urgent need for a research strategy that can fully characterize drug metabolites. In the present study, ions fishing with a serial five-membered lactone ring as a fishhook strategy based on ultrahigh-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilised to characterise the metabolism of arctigenin, and the establishment of this strategy also solved the challenge of creating a comprehensive metabolic profile of neolignan. Based on the proposed strategy, a total of 105 metabolites were detected and characterised, 76 metabolites of which were found in rats and 49 metabolites in liver microsomes. These metabolites were postulated to be produced through oxidation, reduction, hydrolysis, and complex reactions. Subsequently, network pharmacology was utilized to elucidate the mechanism of arctigenin and its main metabolites against Alzheimer’s disease, screening 381 potential targets and 20 major signaling pathways. The study on the comprehensive metabolism of arctigenin provides a holistic metabolic profile, which will help to better understand the mechanism of arctigenin in the treatment of Alzheimer’s disease (AD) and also provide a basis for the safe administration of arctigenin.

show abstract

Section: Discussionmentioning

confidence: 99%

Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis

Lan

Wang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…For the bleeding assay, one hour after the last administration, mice were anaesthetized, and the tail bleeding assay was performed as previously described [34]. The phytochemical components of Sinomenium acutum were identified as depicted above [16,17] and compared with the reference retention time and mass spectrum. The latter included higenamine, gelsemine, magnoflorine, scopoletin, columbamine, jatrorrhizine, palmatine, syringin, and eleutheroside E, which were purchased from TargetMol (Wellesley Hills, MA, USA).…”

Section: Fecl 3 -Induced In Vivo Thrombosis and Tail Bleeding Timementioning

confidence: 99%

Sinomenium acutum Modulates Platelet Aggregation and Thrombus Formation by Regulating the Glycoprotein VI-Mediated Signalosome in Mice

Kim,

Lee

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

Sinomenium acutum (SA) has long been used as a traditional medicine in China, Japan, and Korea to treat a wide range of diseases. It has been traditionally used to ameliorate inflammation and improve blood circulation. However, its role in platelet activation has not been thoroughly investigated. Hence, we conducted this study to assess the potential inhibitory effect of SA on platelet aggregation and thrombus formation. The antiplatelet activities of SA were evaluated by assessing platelet aggregation, granular secretion, intracellular Ca2+ mobilization, and the Glycoprotein (GP) VI-mediated signalosome. The thrombosis and bleeding time assays were used to investigate the effect of SA (orally administered at 50 and 100 mg/kg for seven days) in mice. SA treatment at concentrations of 50, 100, and 200 μg/mL significantly reduced GPVI-mediated platelet aggregation, granular secretion, and intracellular Ca2+ mobilization. Further biochemical studies revealed that SA inhibited spleen tyrosine kinase, phospholipase Cγ2, phosphatidylinositol 3-kinase, and AKT phosphorylation. Interestingly, oral administration of SA efficiently ameliorated FeCl3-induced arterial thrombus formation without prolonging the tail bleeding time. These findings suggest that SA has beneficial effects in thrombosis and hemostasis. Therefore, SA holds promise as an effective therapeutic agent for the treatment of thrombotic diseases.

show abstract

“…With the help of chromatography separation and mass spectrometry detection techniques, screening the chemical information of the wide-range polarity or the trace constituents, which might be considered as the effective components, can be realized [5]. Gas chromatography-mass spectrometry (GC-MS) united with a comprehensive and trustworthy database with standard mass spectra is helpful for identifying volatile chemical compositions [6,7], whilst ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight MS (UHPLC/QTOF-MS) technique combined with UNIFI has been evolved into an effective method for the separation and characterization of the trace polarity ingredients due to its high resolution and good efficiency [8][9][10]. A combination of the above-mentioned technologies can largely explain the different polarity, content, and structural characteristics of the ingredients, especially the TCM which is composed of different sources.…”

Section: Introductionmentioning

confidence: 99%

Chemical components characterization and in vivo metabolites profiling of Lingbao Huxin Dan by gas chromatography‐mass spectrometry and ultra‐high‐performance liquid chromatography‐tandem quadrupole time‐of‐flight mass spectrometry

Huang,

Wang,

Wang

et al. 2023

J of Separation Science

View full text Add to dashboard Cite

Lingbao Huxin Dan (LBHX) is an effective prescription for treating various cardiovascular diseases. However, its systematic chemical composition analysis and important marker components remain unclear, which hinders the development of standards or guidelines for quality evaluation. Herein, a high‐resolution and efficient method was established to comprehensively investigate the chemical ingredients and metabolites of LBHX by using gas chromatography‐tandem mass spectrometry and ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry. AutoDock Vina was applied to conduct visual screening for identifying potential active compounds targeting two important sick sinus syndrome‐associated proteins. As a result, 53 volatile compounds, as well as 191 non‐volatile chemical components, including bufadienolides, diterpenoids, bile acids, phenolic acids, and triterpenoid saponins, were unambiguously characterized or tentatively identified. Fifty prototypes and 62 metabolites were identified in the plasma of rats, whilst metabolism reactions included phase I reactions (hydrolysis, oxidation, and hydroxylation) and phase II reactions (glucuronidation and methylation). Eleven compounds with good binding affinity have been observed by docking with key proteins. It is the first systematic study on the pharmacodynamic material basis of LBHX and the result consolidates the foundation for further study regarding the mechanism in treating cardiovascular diseases.

show abstract

Identification and characterization of major alkaloid from Sinomenium acutum stem and their metabolites after oral administration in rat plasma, urine, bile and feces based on UPLC-Q-TOF/MS

Cited by 8 publications

References 5 publications

Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis

Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis

Sinomenium acutum Modulates Platelet Aggregation and Thrombus Formation by Regulating the Glycoprotein VI-Mediated Signalosome in Mice

Chemical components characterization and in vivo metabolites profiling of Lingbao Huxin Dan by gas chromatography‐mass spectrometry and ultra‐high‐performance liquid chromatography‐tandem quadrupole time‐of‐flight mass spectrometry

Contact Info

Product

Resources

About