Search Results (9)

Breast cancer represents a persistent global health burden, marked by extensive molecular heterogeneity and frequent therapeutic resistance in aggressive subtypes, particularly triple-negative breast cancer (TNBC). These clinical challenges underscore the urgency for alternative therapeutic strategies. Bioactive alkaloids isolated from Nelumbo nucifera, especially the bisbenzylisoquinoline compounds liensinine (LIE), isoliensinine (ISO), and neferine (NEF), have emerged as promising candidates due to their ability to disrupt oncogenic signaling pathways and inhibit malignant cellular transformation. The present study conducted a systematic investigation of LIE, ISO, and NEF across multiple breast cancer cell lines, including highly aggressive TNBC models. Results revealed potent growth-inhibitory effects mediated through apoptosis induction and cell cycle arrest at both the G1 and G2/M phases. Furthermore, transcriptomic profiling and molecular analysis identified LIE as a principal effector, driving extensive transcriptional reprogramming and targeting the MAPK and mTOR pathways as core regulators of its anti-cancer efficacy. Collectively, these findings define a mechanistic framework for the anti-cancer potential of N. nucifera-derived alkaloids and provide a compelling foundation for their development as therapeutic candidates for advanced breast cancer. Full article

Lotus seed embryos, a key component in traditional Chinese medicine, have attracted growing scientific interest due to their wide-ranging therapeutic potential. Among the bioactive compounds found in lotus seed embryos, three bisbenzylisoquinoline alkaloids—liensinine, isoliensinine, and neferine—stand out for their diverse pharmacological activities. These alkaloids are known to exhibit significant antitumor, anti-inflammatory, antihypertensive, neuroprotective, and antifibrotic effects, which make them promising candidates for the treatment of various chronic and acute diseases. Recent studies have highlighted their ability to modulate key signaling pathways involved in cancer progression, inflammation, fibrosis, and neurodegeneration. The precise mechanisms underlying their actions include modulation of oxidative stress, inhibition of pro-inflammatory cytokines, regulation of apoptosis, and modulation of cellular metabolism. This review aims to provide an in-depth overview of the pharmacological relevance of these alkaloids, focusing on their mechanisms of action and their therapeutic potential across different disease models. By synthesizing current evidence from preclinical studies, this review also lays a solid scientific foundation for future research, supporting the rational design and development of lotus-derived compounds for clinical application. Full article

Nelumbo nucifera (lotus) has long been used in traditional medicine across Asia, and its bioactive alkaloids have recently garnered attention for their neuroprotective properties. This review summarizes the current research on the mechanisms by which lotus-derived alkaloids, particularly neferine, nuciferine, liensinine, and isoliensinine, protect neural tissues. These compounds exhibit a wide range of pharmacological activities, including antioxidant and anti-inflammatory effects, regulation of calcium signaling and ion channels, promotion of neurogenesis, and modulation of key neurotransmitter systems, such as dopaminergic, cholinergic, and GABAergic pathways. Notably, they attenuate tau hyperphosphorylation, reduce oxidative stress-induced neuronal apoptosis, and enhance neurotrophic signaling via BDNF-related pathways. While antioxidant and anti-inflammatory actions are the most extensively studied, emerging evidence also highlights their roles in autophagy modulation and mitochondrial protection. Together, these findings suggest that lotus alkaloids are promising candidates for the prevention and treatment of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Further investigation is warranted to explore the synergistic mechanisms and potential clinical applications of these compounds. Full article

Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. To investigate the “homologous plants with different effects” phenomenon in traditional Chinese medicine, this study established a Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) method. This study employed immature lotus seeds as the experimental material, diverging from the mature seeds conventionally used. Conductive double-sided tape was employed for sample preparation, and complete longitudinal sections of the seeds were obtained, followed by MALDI-MSI analysis to identify and visualize the spatial distribution of characteristic secondary metabolites within the entire seeds. The results unveiled the diversity of metabolites in lotus seeds and their differential distribution across tissues, with pronounced distinctions in the plumule. A total of 152 metabolites spanning 13 categories were identified in lotus seeds, with 134, 89, 51, and 98 metabolites discerned in the pericarp, seed coat, cotyledon, and plumule, respectively. Strikingly, young lotus seeds were devoid of liensinine/isoliensinine and neferine, the dominant alkaloids of mature lotus seed plumule, revealing an early-stage alkaloid profile that sharply contrasts with the well-documented abundance found in mature seeds and has rarely been reported. We further propose a biosynthetic pathway to explain the presence of the detected benzylisoquinoline and the absence of the undetected bisbenzylisoquinoline alkaloids in this study. These findings present the first comprehensive metabolic atlas of immature lotus seeds, systematically exposing the pronounced chemical divergence from their mature counterparts, and thus lays a metabolomic foundation for dissecting the spatiotemporal mechanisms underlying the nutritional and medicinal value of lotus seeds. Full article

Myocardial infarction (MI) is characterized by the sudden reduction in myocardial blood flow and remains the leading cause of death worldwide. Because MI causes irreversible damage to the heart, discovering drugs that can limit the extent of ischemic damage is crucial. Liensinine (LSN) is a natural alkaloid that has exhibited beneficial effects in various cardiovascular diseases, including MI; however, its molecular mechanisms of action remain largely unelucidated. In this study, we constructed murine models of MI to examine the potential beneficial effects and mechanisms of LSN in myocardial ischemic injury. Murine models of MI in wild-type and cardiomyocyte-specific β-catenin knockout mice were used to explore the role of LSN and Wnt/β-catenin signaling in MI-induced cardiac injuries and inflammatory responses. The administration of LSN markedly improved cardiac function and decreased the extent of ischemic damage and infarct size following MI. LSN not only prevented excessive inflammatory responses but also inhibited the aberrant activation of Wnt/β-catenin signaling, two factors that are critically involved in the exacerbation of MI-induced injury. Our findings provide important new mechanistic insight into the beneficial effect of LSN in MI-induced cardiac injury and suggest the therapeutic potential of LSN as a novel drug in the treatment of MI. Full article

Liensinine is a bisbenzylisoquinoline alkaloid found in various parts of the lotus (Nelumbo nucifera Gaertn.) including seeds. In this study, we explored the preventive activity of liensinine on vascular inflammation via attenuation of inflammatory mediators in macrophage and targeting the proliferation and migration of human vascular smooth muscle cells (VSMC). Anti-oxidative activity was evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay method and measuring the peroxidation of serum lipid. Inflammatory markers were studied by evaluating the release of nitric oxide (NO) and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in macrophage cells (RAW264.7) and interleukin (IL)-6 production in VSMC. Similarly, anti-proliferative activity in VSMC was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The enzymatic activity of matrix metalloproteinase (MMP)-9 in VSMC was evaluated by gelatin zymography. Liensinine possesses significant anti-oxidative activity as revealed by the DPPH assay and inhibition of serum lipid peroxidation. Likewise, liensinine decreased NO generation in RAW 264.7 cells. In VSMC, liensinine suppressed platelet-derived growth factor stimulated proliferation and tumor necrosis factor-α (TNF-α) induced MMP-9 enzymatic activity as well as IL-6 expression. Our results revealed the potential preventive effect of liensinine on vascular inflammation, suggesting it as a promising compound for the prevention of vascular inflammation. Full article

Promoting white-to-beige adipocyte transition is a promising approach for obesity treatment. Although Liensinine (Lie), a kind of isoquinoline alkaloid, has been reported to affect white-to-beige adipocyte transition, its effects on inhibiting beige adipocytes recovering to white adipocytes and maintaining the characteristics of beige adipocyte remain unclear. Therefore, we explored the effects and underlying mechanism of Lie on beige adipocyte maintenance in vitro and in vivo. Here, we first demonstrated that after white adipocytes turned to beige adipocytes by rosiglitazone (Rosi) stimuli, beige adipocytes gradually lost their characteristics and returned to white adipocytes again once Rosi was withdrawn. We found that Lie retained high levels of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation complex I, II, III, IV and V (COX I–V), oxygen consumption rate (OCR) after Rosi withdrawal. In addition, after Rosi withdrawal, the beige-to-white adipocyte transition was coupled to mitophagy, while Lie inhibited mitophagy flux by promoting the accumulation of pro-cathepsin B (pro-CTSB), pro-cathepsin D (pro-CTSD) and pro-cathepsin L (pro-CTSL), ultimately maintaining the beige adipocytes characteristics in vitro. Moreover, through blocking mitophagy flux, Lie significantly retained the molecular characteristics of beige adipocyte, reduced body weight gain rate and enhanced energy expenditure after stimuli withdrawal in vivo. Together, our data showed that Lie inhibited lysosomal cathepsin activity by promoting the accumulation of pro-CTSB, pro-CTSD and pro-CTSL, which subsequently inhibited mitophagy flux, and ultimately inhibited the beige adipocytes recovering to white adipocytes and maintained the characteristics of beige adipocyte after stimuli withdrawal. In conclusion, by blocking lysosome-mediated mitophagy, Lie inhibits beige adipocytes recovering to white adipocytes and may be a potential candidate for preventing high fat diet induced obesity. Full article

Due to drug-induced potential congestive heart failure and irreversible dilated cardiomyopathies, preclinical evaluation of cardiac dysfunction is important to assess the safety of traditional or novel treatments. The embryos of Nelumbo nucifera Gaertner seeds are a homology of traditional Chinese medicine and food. In this study, we applied the real time cellular analysis (RTCA) Cardio system, which can real-time monitor the contractility of cardiomyocytes (CMs), to evaluate drug safety in rat neonatal CMs and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). This study showed detailed biomechanical CM contractility in vitro, and provided insights into the cardiac dysfunctions associated with liensinine and neferine treatment. These effects exhibited dose and time-dependent recovery. Neferine showed stronger blocking effect in rat neonatal CMs than liensinine. In addition, the effects of liensinine and neferine were further evaluated on hiPS-CMs. Our study also indicated that both liensinine and neferine can cause disruption of calcium homeostasis. For the first time, we demonstrated the potential cardiac side effects of liensinine or neferine. While the same inhibition was observed on hiPS-CMs, more importantly, this study introduced an efficient and effective approach to evaluate the cardiotoxicity of the existing and novel drug candidates. Full article

This study was conducted to investigate the effect of Nelumbinis Plumula total alkaloid (NPA) and its main alkaloid components on oxidative stress induced by tert-butyl hydroperoxide (t-BHP) in the human hepatocellular HepG2 cell line. According to HPLC analysis, several major alkaloid compounds such as liensinine, isoliensinine and neferine were present in NPA. The cytotoxic effects in 0.55 mM t-BHP-induced HepG2 cells were significantly inhibited by NPA and the major compound in NPA, neferine, showed the strongest activities. The protective effect of neferine against oxidative stress induced by t-BHP may be associated with decreased ROS formation, TBARS generation, LDH release and increased GSH levels, suggesting their involvement of the cytoprotective on oxidative stress. The effects were comparable with quercetin, which was used as positive control. Overall, total alkaloid and alkaloid compounds from Nelumbinis Plumula displayed a significant cytoprotective effect against oxidative stress. Further study is needed to elucidate the relationship between the chemical structures of the components in NPA and their protective effect on oxidative stress. Full article