Search Results (14)

Fritillaria thunbergii Miq., a medicinal plant rich in steroidal alkaloids, produces bulbs that clear heat, resolve phlegm, and detoxify. However, excessive yield-oriented cultivation has reduced the number of F. thunbergii plants that meet commercial standards. This study explored the effects of potassium application and shading on the bulb biomass and medicinal substance content of F. thunbergii. Shading increased the active ingredient content in bulbs by approximately 20.71% but reduced biomass by approximately 17.24%. Fertilization with different potassium concentrations under shading (K1S–K3S) alleviated shading-induced biomass reduction and increased active ingredient accumulation, with the K2S and K3S groups yielding significantly better results than the K1S group. Pharmacological experiments showed that the K2S group exerted the best antitussive, expectorant, and anti-inflammatory effects. Metabolome analysis showed that compared with those in the controls, peiminine, peimine, imperialine, solasodine, and cyclopamine were the most abundant steroidal alkaloids under K2S treatment. Transcriptome analysis identified key genes and biosynthetic pathways for major steroidal alkaloids, namely, farnesyl pyrophosphate synthase (FtFPS) involved in steroidal alkaloid biosynthesis. Transcription factor analysis revealed that nine transcription factors predominantly expressed under the K2S treatment might regulate steroidal alkaloid biosynthesis. Furthermore, FtFPS was identified as a hub gene in the co-expression network and was verified to catalyze the biosynthesis of farnesyl pyrophosphate. The interaction between FtFPS and FtAP2/ERF was verified through yeast two-hybrid experiments. These findings offer new insights into the steroidal alkaloid biosynthesis mechanism triggered in F. thunbergii by potassium application and shading, supporting ecological strategies to enhance steroidal alkaloid levels in this species. Full article

Globally, lung cancer is the primary cause of deaths associated with cancer; however, current therapies are costly and toxic, highlighting the need for novel treatments. Peiminine (Verticinone), a key bioactive compound derived from Fritillaria ussuriensis Maxim., has demonstrated diverse biological activities. However, the precise pharmacological mechanisms underlying its anti-lung cancer effects remain unclear. The objective of this study was to quantify the content of peiminine in Fritillaria ussuriensis Maxim. from different geographical regions using UHPLC-MS/MS and to elucidate the anti-lung cancer mechanisms of peiminine through network pharmacology, bioinformatics, and in vitro experiments. The content of peiminine in Fritillaria ussuriensis Maxim. from various regions was determined using UHPLC-MS/MS. Potential target genes associated with peiminine and lung cancer were systematically screened from multiple databases. To identify core genes, we set up a PPI (protein–protein interaction) network, followed by in-depth analyses of their corresponding target proteins. Survival analysis, molecular docking, and dynamics simulations were used to explore potential anti-cancer mechanisms. In vitro experiments on human H1299 NSCLC cells assessed peiminine’s anti-tumor activity and measured key gene transcription levels. UHPLC-MS/MS analysis revealed that Fritillaria ussuriensis Maxim. from Mudanjiang (Heilongjiang Province) exhibited the highest peiminine content. Network pharmacological analysis identified PIK3CG, SRC, JAK3, AKT2, and PRKCA as key potential targets of peiminine in lung cancer treatment. Molecular docking results demonstrated strong binding affinities between peiminine and PIK3CG, SRC, and JAK3; these results were further confirmed using molecular dynamics simulations. Survival analysis indicated that a high AKT2 and PRKCA expression correlated with bad prognosis in lung cancer patients. In vitro, peiminine inhibited H1299 cell viability and regulated genes involved in the PI3K–Akt pathway (PI3K, AKT, and PTEN) and apoptosis (Bcl-2, Bax), suggesting that it may induce its effects via PI3K–Akt pathway inhibition. Peiminine from Fritillaria ussuriensis Maxim. exhibits significant anti-lung cancer potential by targeting key genes such as PIK3CG, SRC, and JAK3, as well as by modulating the PI3K-Akt signaling pathway and apoptosis-related genes. These results lay a foundation for further investigations into peiminine as a potentially effective therapeutic option for treating lung cancer. Additionally, the identified targets (PIK3CG, SRC, JAK3, AKT2, and PRKCA) may function as possible biomarkers for predicting lung cancer prognosis and guiding personalized therapy. Full article

Background/Objectives: Fritillaria taipaiensis P.Y. Li is a valuable traditional Chinese medicinal herb that utilizes bulbs as medicine, which contain multiple alkaloids. Biomass, as a sustainable resource, has promising applications in energy, environmental, and biomedical fields. Recently, the biosynthesis and regulatory mechanisms of the main biomass components of biomass have become a prominent research topic. Methods: In this article, we explored the differences in the heterosteroidal alkaloid components of F. taipaiensis biomass using liquid chromatography–mass spectrometry and high-throughput transcriptome sequencing. Results: The experimental results demonstrated significant differences in the eight types of heterosteroidal alkaloid components among the biomass of F. taipaiensis, including peimisine, imperialine, peimine, peiminine, ebeinone, ebeiedine, ebeiedinone, and forticine. Transcriptomic analysis revealed substantial significant differences in gene expression patterns in the various samples. Three catalytic enzyme-coding genes, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and terpene synthase (TPS), were speculated to contribute to the regulation of the differential accumulation of alkaloid synthesis in F. taipaiensis bulbs. A strong positive correlation was observed between the transcriptional level of the TPS gene and the alkaloid content of F. taipaiensis biomass, suggesting that TPS may be a key gene in the biosynthesis pathway of alkaloids. This finding can be used for subsequent gene function verification and molecular regulatory network analysis. Conclusions: This work provides fundamental data and novel insights for the subsequent research on alkaloid biosynthesis in F. taipaiensis. Full article

Fritillariae thunbergii Bulbus (FTB), a member of the Liliaceae family, has a long history of use in many herbal formulations for traditional and modern clinical applications to treat various infections and inflammation. To understand FTB’s diverse physiochemical properties, it is important to determine the pharmacokinetic properties of its active constituents, the steroidal alkaloids. The aim of the present study was to investigate the pharmacokinetic alterations of the alkaloids, the active components of FTB, in the presence of colitis. A single oral dose of FTB (1 g/kg) was treated to a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis rat model to assess whether the colitis condition could influence the pharmacokinetics of the major alkaloids present in FTB. Among the four major alkaloids, peimisine exhibited a significantly increased systemic exposure, approximately five times higher, under the colitis condition compared with the normal state. Meanwhile, peimine, peiminine, and sipeimine exhibited shorter half-lives in the DNBS group without significant changes in systemic absorption. As herbal medicine may contain active substances with different or opposing efficacies, careful consideration of pharmacokinetic changes in individual components due to diseases is necessary. Further experiments on peimisine are required to ensure the effectiveness and safety of FTB’s clinical application in the presence of colitis. Full article

Peiminine is the main natural alkaloid compound extracted from the Chinese herb Fritillaria. Although peiminine is known for its antioxidant and anti-inflammatory effects in conditions such as mastitis and arthritis, its impact on inflammation induced by Cutibacterisum acnes (C. acnes) has not been explored. The aim of this study was to investigate the effect of peiminine on C. acnes-induced inflammatory responses in the skin and to identify the underlying mechanism involved. We discovered that peiminine inhibits the C. acnes-induced expression of inflammatory mediators such as pro-interleukin-1β (pro-IL-1β), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in mouse bone marrow-derived macrophages (BMDMs). Peiminine suppressed the activation of nuclear factor-kappa B (NF-κB) without affecting the activation of mitogen-activated protein kinase (MAPK) pathways such as JNK, ERK, and p38 MAPK. In addition, we found that peiminine suppressed inflammatory cytokine expression and ameliorated histological symptoms in C. acnes-induced mouse skin. Our study is the first to provide evidence that peiminine has an inhibitory effect on acne, and it points toward the potential of incorporating peiminine into cosmetic and pharmaceutical formulations for acne treatment. Full article

Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid 11-β dehydrogenase 1 like gene (HSD11B1L) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment. Full article

Fritillariae thunbergii bulbus has been widely used to treat symptoms of coughs and airway congestion in the chest due to pathological colds and damp phlegm in traditional Chinese medicine. Despite its long history of traditional use, its pharmacological activities on osteoclastogenesis and osteoporosis have not been evaluated. This study investigated the effects of the water extract of Fritillariae thunbergii bulbus (WEFT) on osteoclast differentiation in bone marrow-derived macrophage cells and on ovariectomy (OVX)-induced osteoporosis in mice. We found that WEFT significantly inhibited osteoclastogenesis by downregulating the receptor activator of the NF-κB ligand (RANKL) signaling-induced nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression. In an OVX-induced osteoporosis model, WEFT significantly prevented the OVX-induced trabecular loss of femurs, accompanied by a reduction in fat accumulation in the bone marrow and liver. In addition, WEFT significantly prevented weight gain and gonadal fat gain without recovering uterine atrophy. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, seven alkaloids (peimisine glucoside, yibeissine, peiminoside, sipeimine-glucoside, peimisine, peimine, and peiminine) were identified in WEFT. The results of this study suggest that WEFT can be a potential pharmacological candidate to reduce menopausal osteoporosis and menopause-related symptoms, such as fat accumulation. Full article

Parkinson’s disease (PD) is a degenerative disease that can cause motor, cognitive, and behavioral disorders. The treatment strategies being developed are based on the typical pathologic features of PD, including the death of dopaminergic (DA) neurons in the substantia nigra of the midbrain and the accumulation of α-synuclein in neurons. Peiminine (PMN) is an extract of Fritillaria thunbergii Miq that has antioxidant and anti-neuroinflammatory effects. We used Caenorhabditis elegans and SH-SY5Y cell models of PD to evaluate the neuroprotective potential of PMN and address its corresponding mechanism of action. We found that pretreatment with PMN reduced reactive oxygen species production and DA neuron degeneration caused by exposure to 6-hydroxydopamine (6-OHDA), and therefore significantly improved the DA-mediated food-sensing behavior of 6-OHDA-exposed worms and prolonged their lifespan. PMN also diminished the accumulation of α-synuclein in transgenic worms and transfected cells. In our study of the mechanism of action, we found that PMN lessened ARTS-mediated degradation of X-linked inhibitor of apoptosis (XIAP) by enhancing the expression of PINK1/parkin. This led to reduced 6-OHDA-induced apoptosis, enhanced activity of the ubiquitin–proteasome system, and increased autophagy, which diminished the accumulation of α-synuclein. The use of small interfering RNA to down-regulate parkin reversed the benefits of PMN in the PD models. Our findings suggest PMN as a candidate compound worthy of further evaluation for the treatment of PD. Full article

Investigations were carried out to study the effects of light-emitting diode (LED) lights on growth and development of isosteroidal alkaloids in embryogenic calli of Fritillaria cirrhosa D. Don, an important traditional Chinese medicine herb. Calli were cultured in glass bottles, each containing 100 mL of Murashige and Skoog’s basal medium supplemented with 2% sucrose and 0.4% gellan gum powder, a gelling agent. These bottles were incubated in a specially designed plant growth chamber equipped with eight different LED lights consisting of single or combinations of four different light spectra emitting blue (450 nm), green (525 nm), red (660 nm), and far-red (730 nm) light. After three months of incubation, morphological changes in embryogenic calli were recorded, and LC-MS/MS analysis of cultures was carried out for peimisine, sipeimine, peiminine, and peimine. The highest number of somatic embryos and the maximum fresh weight was recorded in calli incubated under red (9R), infrared (9IR), and a combination of red+blue+infrared (3R3B3IR), respectively, in decreasing order. The highest contents of peimisine, peiminine, and peimine were recorded under red (9R) and infrared (9IR) lights, respectively. Eight LED lights had significant effects on the morphogenesis of embryogenic calli of F. cirrhosa D. Don and contents of isosteroidal alkaloids. Full article

Peiminine, an alkaloid extracted from Fritillaria plants, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effect of peiminine on a mouse lipopolysaccharide (LPS)-induced mastitis model remains to be elucidated. The purpose of this experiment was to investigate the effect of peiminine on LPS-induced mastitis in mice. LPS was injected through the canals of the mammary gland to generate the mouse LPS-induced mastitis model. Peiminine was administered intraperitoneally 1 h before and 12 h after the LPS injection. In vitro, mouse mammary epithelial cells (mMECs) were pretreated with different concentrations of peiminine for 1 h and were then stimulated with LPS. The mechanism of peiminine on mastitis was studied by hematoxylin-eosin staining (H&E) staining, western blotting, and enzyme-linked immunosorbent assay (ELISA). The results showed that peiminine significantly decreased the histopathological impairment of the mammary gland in vivo and reduced the production of pro-inflammatory mediators in vivo and in vitro. Furthermore, peiminine inhibited the phosphorylation of the protein kinase B (AKT)/ nuclear factor-κB (NF-κB), extracellular regulated protein kinase (ERK1/2), and p38 signaling pathways both in vivo and in vitro. All the results suggested that peiminine exerted potent anti-inflammatory effects on LPS-induced mastitis in mice. Therefore, peiminine might be a potential therapeutic agent for mastitis. Full article

A simple and high sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of peimine and peiminine in beagle dog plasma after the oral administration of Fritillariae ussuriensis Maxim and Fritillariae thunbergii Miq powder. Chromatographic separation was achieved on an ACQUIT UPLC^® BEH C₁₈ column (1.7 μm, 2.1 × 100 mm) in a gradient elution way with a mobile phase consisting of acetonitrile and water containing 0.1% formic acid at a flow rate of 0.4 mL/min. The plasma samples were prepared by a liquid–liquid extraction (LLE) method with ethyl acetate. The analytes were detected with a triple quadrupole tandem mass spectrometry (MS) in multiple reaction monitoring (MRM) mode and a positive ion electrospray ionization (ESI) of the transitions at m/z 432.4→414.4 for peimine and m/z 430.3→412.3 for peiminine. The method was linear for two analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The lower limit of quantification (LLOQ) was 0.988 ng/mL for peimine and 0.980 ng/mL for peiminine. The mean extraction recoveries of peimine and peiminine at three quality control samples (QC) levels were ranged from 82.56 to 88.71%, and matrix effects ranged from 92.06 to 101.2%. The intra-day and inter-day precision and accuracy were within the acceptable limits at LLOQ and QC levels. The method was effectively and successfully applied to the pharmacokinetics of peimine and peiminine after oral administration of powder to beagle dogs. The obtained results may be help to guide the clinical application of Fritillaria ussuriensis Maxim and Fritillaria thunbergii Miq. Full article

Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson’s disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation. We evaluated the effects of peiminine on behavioural dysfunction, microglial activation and the loss of dopaminergic neurons in a rat model of lipopolysaccharide (LPS)-induced PD. BV-2 cells were pretreated with peiminine for 1 h and then stimulated with LPS for different times. Then, inflammatory responses and the related signalling pathways were analysed. Peiminine markedly attenuated behavioural dysfunction and inhibited the loss of dopaminergic neurons and microglial activation in the LPS-induced PD rat model. In BV-2 cells, peiminine significantly decreased LPS-induced expression of the pro-inflammatory mediators TNF-α, IL-6 and IL-1β, COX-2 and iNOS by inhibiting the phosphorylation of ERK1/2, AKT and NF-κB p65. Based on these results demonstrated that peiminine has a role in protecting dopaminergic neurons in the LPS-induced PD rat model by inhibiting neuroinflammation. Full article

Rapid, non-destructive, and accurate quantitative determination of the effective components in traditional Chinese medicine (TCM) is required by industries, planters, and regulators. In this study, near-infrared hyperspectral imaging was applied for determining the peimine and peiminine content in Fritillaria thunbergii bulbi under sulfur fumigation. Spectral data were extracted from the hyperspectral images. High-performance liquid chromatography (HPLC) was conducted to determine the reference peimine and peiminine content. The successive projection algorithm (SPA), weighted regression coefficient (Bw), competitive adaptive reweighted sampling (CARS), and random frog (RF) were used to select optimal wavelengths, while the partial least squares (PLS), least-square support vector machine (LS–SVM) and extreme learning machine (ELM) were used to build regression models. Regression models using the full spectra and optimal wavelengths obtained satisfactory results with the correlation coefficient of calibration (r_c), cross-validation (r_cv) and prediction (r_p) of most models being over 0.8. Prediction maps of peimine and peiminine content in Fritillaria thunbergii bulbi were formed by applying regression models to the hyperspectral images. The overall results indicated that hyperspectral imaging combined with regression models and optimal wavelength selection methods were effective in determining peimine and peiminine content in Fritillaria thunbergii bulbi, which will help in the development of an online detection system for real-world quality control of Fritillaria thunbergii bulbi under sulfur fumigation. Full article

Supercritical fluid extraction (SFE) was used to extract total alkaloids, peimisine, peimine and peiminine from the bulb of Fritillaria thunbergii Miq. The antioxidant capacity of the extracts was evaluated by DPPH radical scavenging activity (DPPH-RSA), ABTS radical scavenging activity (ABTS-RSA) and ferric reducing capacity (FRAP) assay. A central composite design (CCD) with four variables and five levels was employed for optimization of process parameters, and response surface plots were constructed in accordance with a second order polynomial model. Under optimal conditions of 3.0 h, 60.4 °C, 26.5 MPa and 89.3% ethanol, the highest yields were predicted to be 3.8 mg/g for total alkaloids, 0.5 mg/g for peimisine, 1.3 mg/g for peimine and 1.3 mg/g for peiminine, and the antioxidant capacity of extracts displayed EC_{50, DPPH} value of 5.5 mg/mL, EC_{50, ABTS} value of 0.3 mg/mL and FRAP value of 118.2 mg ascorbic acid equivalent (AAE)/100 g. Full article