Author: Nguyen, Huyen Thu Thi ; Huynh, Thi Anh Huynh ; Nguyen, Sil Thanh ; Ma, Trinh To Huynh ; Do, Tho Vinh Minh Chau ; Lu, Phuc Thien ; Dang, Thu Huynh ; Nguyen, Duyen Cam Thi

Lotus (Nelumbo nucifera Gaertn.) is widely utilized in traditional medicine and cuisine throughout Asia, with its leaves containing valuable bioactive alkaloids and flavonoids. However, Lotus leaves are often considered as by-products, urging the need for methods to analyze these components and enhance biological and economic value. In this study, a novel, rapid, and reliable UPLC-MS/MS method was developed to evaluate the quality of Folium Nelumbinis by establishing the first chromatographic fingerprint of simultaneously determination of bioactive alkaloids (nuciferine, O-nornuciferine, N-nornuciferine) and flavonoids (kaempferol, quercetin, isoquercitrin, quercetin-3-O-glucuronide). The method was validated according to the Association of Official Analytical Chemists and European Commission Decision 2021/808/EC guidelines, demonstrating high sensitivity, specificity, and reproducibility, with detection and quantification limits below 0.48 ng/mL and 1.50 ng/mL, respectively. When the procedure was applied to 49 Lotus leaf samples collected across various regions and growth stages in Vietnam, revealing significant regional and developmental variations in alkaloid and flavonoid content. Nuciferine and quercetin-3-O-glucuronide were the most abundant compounds, with the highest alkaloid concentration found in Hanoi and the highest flavonoid content in Lam Dong. Besides, this study contributes not only to the quality control of Lotus leaves but also to the understanding of geographical and developmental impacts on their bioactive composition. The chromatographic fingerprinting initiative described here highlights the application of the approach as a potential standard for the quality and regularity of traditional herbal medicines and hence the sustainable and optimal utilization of Lotus leaves in pharmaceutical and nutraceutical applications.

01 Jun 2025·Neurochemistry International

Illustrating the distribution and metabolic regulatory effects of nuciferine by mass spectrometry imaging and spatial metabolomics

Article

Author: Wang, Qian ; Liu, Guangyuan ; Wu, Yiying ; Kong, Dezhi ; Pan, Liangyu ; Zhang, Yuyu ; Zhang, Wei ; Zhang, Panpan ; Yan, Jingwen

Nuciferine has been widely used in traditional Chinese medicine compound preparations and natural edible resources. Most current studies have concentrated on its lipid-lowering and weight-loss effects, while relatively few have explored its impact on central nervous system disorders. To investigate the effects of nuciferine on the nervous system and its potential pharmacological mechanisms, we mapped the distribution of nuciferine and its key metabolites in brain microregions and major organs of mice using air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). Nuciferine was found to be distributed throughout the brain, particularly in the prefrontal cortex and hippocampus. Additionally, nuciferine was detected in several peripheral organs, including the heart, liver, kidneys, and spleen. We also identified the distribution of a major demethylated metabolite (M1), which correlated with the localization of the CYP1A2 enzyme. Metabolomic analysis revealed that nuciferine significantly alters purine metabolism, specifically increasing adenosine levels while decreasing xanthine and hypoxanthine. This metabolic shift suggests a potential enhancement of neuroinhibitory effects, contributing to nuciferine's sedative, hypnotic, and analgesic properties. These findings provide novel insights into the neuropharmacological mechanisms of nuciferine.

18 Apr 2025·ACS Chemical Biology

Formation of the i-motif Structures by Human Telomeric c-Rich Sequences d(CCCTAA)n and Its Recognition by Bisbenzylisoquinoline Alkaloids

Article

Author: Lin, Zexuan ; Cui, Xiaojie ; Luo, Feixian ; Tang, Huining ; Yang, Jishun ; Tang, Yi ; Huang, Junliu ; Wang, Wenshu ; Yang, Yang

The human telomeric repeat CCCTAA has been reported to form a higher-order structure called an intercalated motif (i-motif) that plays important roles in telomere function and telomerase activity regulation, and small molecule ligands targeting human telomeric i-motif (hTelo-iM) is a promising therapeutic strategy for cancer treatment, yet the i-motif folding pattern of long CCCTAA repeats and the hTelo-iM ligand screening have not been studied extensively. In this study, we systematically investigated the i-motif structures formed by four and eight telomeric C-rich repeats d(CCCTAA)₄ (hTeloC-24mer) and d(CCCTAA)₈ (hTeloC-48mer) under varied conditions and found that the long hTeloC-48mer probably forms unstacked tandem i-motif consisting of two hTeloC-24mer i-motif monomers under near physiological conditions. Moreover, natural bisbenzylisoquinoline (BBI) alkaloids, isofangchinoline, fangchinoline, cepharanthine, and tetrandrine, were screened from 33 natural small molecules to effectively disrupt and destabilize the hTelo-iM structures mainly through major groove hydrogen bonding and van der Waals interactions. Further, telomerase repeated amplification protocol (TRAP) assay suggested that the selected BBI alkaloids can inhibit the telomere extension by telomerase. These findings provide a theoretical basis for further telomere structure research as well as a novel class of natural small molecule compounds regulating the hTelo-iM structure and telomerase activity, which may contribute to the anticancer drug design and strategy development taking the hTelo-iM as a target.

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Indication	Highest Phase	Country/Location	Organization	Date
Central Nervous System Diseases	Preclinical	United States	City University of New York	22 Jul 2024

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