Greater Celandine's Ups and Downs-21 Centuries of Medicinal Uses of Chelidonium majus From the Viewpoint of Today's Pharmacology.
ABSTRACT: As antique as Dioscorides era are the first records on using Chelidonium as a remedy to several sicknesses. Inspired by the "signatura rerum" principle and an apparent ancient folk tradition, various indications were given, such as anti-jaundice and cholagogue, pain-relieving, and quite often mentioned-ophthalmological problems. Central and Eastern European folk medicine has always been using this herb extensively. In this region, the plant is known under many unique vernacular names, especially in Slavonic languages, associated or not with old Greek relation to "chelidon"-the swallow. Typically for Papaveroidae subfamily, yellow-colored latex is produced in abundance and leaks intensely upon injury. Major pharmacologically relevant components, most of which were first isolated over a century ago, are isoquinoline alkaloids-berberine, chelerythrine, chelidonine, coptisine, sanguinarine. Modern pharmacology took interest in this herb but it has not ended up in gaining an officially approved and evidence-based herbal medicine status. On the contrary, the number of relevant studies and publications tended to drop. Recently, some controversial reports and sometimes insufficiently proven studies appeared, suggesting anticancer properties. Anticancer potential was in line with anecdotical knowledge spread in East European countries, however, in the absence of directly-acting cytostatic compounds, some other mechanisms might be involved. Other properties that could boost the interest in this herb are antimicrobial and antiviral activities. Being a common synanthropic weed or ruderal plant, C. majus spreads in all temperate Eurasia and acclimates well to North America. Little is known about the natural variation of bioactive metabolites, including several aforementioned isoquinoline alkaloids. In this review, we put together older and recent literature data on phytochemistry, pharmacology, and clinical studies on C. majus aiming at a critical evaluation of state-of-the-art from the viewpoint of historical and folk indications. The controversies around this herb, the safety and drug quality issues and a prospective role in phytotherapy are discussed as well.
Project description:Chelidonium majus (also known as celandine) contains pharmacologically active compounds such as isoquinoline alkaloids (e.g., chelidonine, sanguinarine), flavonoids, saponins, carotenoids, and organic acids. Due to the presence of isoquinoline alkaloids, Chelidonii herba extracts are widely used as an antibacterial, antifungal, antiviral (including HSV-1 and HIV-1), and anti-inflammatory agent in the treatment of various diseases, while chitosan is a biocompatible and biodegradable carrier with valuable properties for mucoadhesive formulations preparation. Our work aimed to prepare mucoadhesive vaginal drug delivery systems composed of Chelidonii herba lyophilized extract and chitosan as an effective way to treat vaginitis. The pharmacological safety of usage of isoquinoline alkaloids, based on MTT test, were evaluated for the maximum doses 36.34 ± 0.29 µg/mL and 0.89 ± 1.16 µg/mL for chelidonine and sanguinarine, respectively. Dissolution rate profiles and permeability through artificial membranes for chelidonine and sanguinarine after their introduction into the chitosan system were studied. The low permeability for used save doses of isoquinoline alkaloids and results of microbiological studies allow confirmation that system Chelidonii herba lyophilized extract chitosan 80/500 1:1 (w/w) is a promising strategy for vaginal use. Ex vivo studies of mucoadhesive properties and evaluation of tableting features demonstrated that the formulation containing Chelidonii herba lyophilized extract (120.0 mg) with chitosan (80/500-100.0 mg) and polymer content (HPMC-100.0 mg, microcrystalline cellulose-50.0 mg, lactose monohydrate-30.0 mg and magnesium stearate-4.0 mg) is a vaginal dosage form with prolonging dissolution profile and high mucoadhesion properties (up to 4 h).
Project description:Isoquinoline alkaloids are the main group of secondary metabolites present in Chelidonium majus extracts, and they are still the object of interest of many researchers. Therefore, the development of methods for the investigation and separation of the alkaloids is still an important task. In this work, the application potential of a silica-based monolithic column for the separation of alkaloids was assessed. The influence of the organic modifier, temperature, salt concentration, and pH of the eluent on basic chromatographic parameters such as retention, resolution between neighboring peaks, chromatographic plate numbers, and peak asymmetry were investigated. Based on the obtained results, a gradient elution program was developed and used to separate and quantitatively determine the main alkaloids in a Chelidonium majus root extract.
Project description:Chelidonium majus L. is a rich source of isoquinoline alkaloids with confirmed anti-inflammatory, choleretic, spasmolytic, antitumor, and antimicrobial activities. However, their chromatographic analysis is difficult because they may exist both in charged and uncharged forms and may result in the irregular peak shape and the decrease in chromatographic system efficacy. In the present work, the separation of main C. majus alkaloids was optimized using a new-generation XB-C18 endcapped core-shell column dedicated for analysis of alkaline compounds. The influence of organic modifier concentration, addition of salts, and pH of eluents on chromatographic parameters such as retention, resolution, chromatographic plate numbers, and peak asymmetry was investigated. The results were applied to elaborate the optimal chromatographic system for simultaneous quantification of seven alkaloids from the root, herb, and fruit of C. majus.
Project description:Isoquinoline alkaloids belong to the toxic secondary metabolites occurring in plants of many families. The high biological activity makes these compounds promising agents for use in medicine, particularly as anticancer drugs. The aim of our study was to evaluate the cytotoxicity and proapoptotic activity of sanguinarine, berberine, and extracts of Chelidonium majus L. and Berberis thunbergii DC. IC10, IC50, and IC90 doses were established toward hematopoietic cancer cell lines using trypan blue staining. Alterations in the expression of 18 apoptosis-related genes in cells exposed to IC10, IC50, and IC90 were evaluated using real-time PCR. Sanguinarine and Chelidonium majus L. extract exhibit significant cytotoxicity against all studied cell lines. Lower cytotoxic activity was demonstrated for berberine. Berberis thunbergii DC. extract had no influence on cell viability. Berberine, sanguinarine, and Chelidonium majus L. extract altered the expression of apoptosis-related genes in all tested cell lines, indicating the induction of apoptosis. The presented study confirmed the substantial cytotoxicity and proapoptotic activity of sanguinarine, berberine, and Chelidonium majus L. extract toward the studied hematopoietic cell lines, which indicates the utility of these substances in anticancer therapy.
Project description:Background: Plants are an important origin of natural substances that the raw material for various pharmaceutical and therapeutic applications due to the presence of phytochemicals, such as alkaloids. Alkaloids, which are found in different plant species, possess numerous biological activities. Some alkaloids have strong cytotoxic effects on various cancer cells. The search for new drugs to treat various cancers is one of the most important challenges of modern scientific research. Objective: This study aimed to investigate of cytotoxic activity of extracts that were obtained from Chelidonium Majus; Berberis sp.; Thalictrum foetidum containing various alkaloids on selected cancer cell lines. The aim was also the quantification of selected alkaloids in the investigated extracts by HPLC. Methods: The analysis of alkaloids contents were performed while using HPLC in reversed phase (RP) mode using Polar RP column and mobile phase containing acetonitrile, water, and ionic liquid. The cytotoxic effect of the tested plant extracts and respective alkaloids' standards were examined while using human pharyngeal squamous carcinoma cells (FaDu), human tongue squamous carcinoma cells (SCC-25), human breast adenocarcinoma cell line (MCF-7), and human triple-negative breast adenocarcinoma cell line (MDA-MB-231). Conclusion: All of the investigated plant extracts possess cytotoxic activity against cancer cell lines: FaDu, SCC-25, MCF-7, and MDA-MB-231. The highest cytotoxic activity against FaDu and MDA-MB-231 cells was observed for Chelidonium majus root extract, while the highest cytotoxic activity against SCC-25 and MCF-7 cells was estimated for the Thalictrum foetidum root extract. There obtained significant differences in the cytotoxic activity of extracts that were obtained from the roots and herbs of Chelidonium majus and Thalictrum foetidum. Based on these results, investigated plant extracts can be recommended for further investigations of anticancer activity.
Project description:Senna alata is a medicinal herb of Leguminosae family. It is distributed in the tropical and humid regions. The plant is traditionally used in the treatment of typhoid, diabetes, malaria, asthma, ringworms, tinea infections, scabies, blotch, herpes, and eczema. The review is aimed at unveiling the ethnobotanical description and pharmacological activities of S. alata. Different parts of the plant are reported in folk medicine as therapeutic substances for remediation of diverse diseases and infections. The extracts and isolated compounds displayed pronounced pharmacological activities. Display of antibacterial, antioxidant, antifungal, dermatophytic, anticancer, hepatoprotective, antilipogenic, anticonvulsant, antidiabetic, antihyperlipidemic, antimalarial, anthelmintic, and antiviral activities could be due to the array of secondary metabolites such as tannins, alkaloids, flavonoids, terpenes, anthraquinone, saponins, phenolics, cannabinoid alkaloids, 1,8-cineole, caryophyllene, limonene, ?-selinene, ?-caryophyllene, germacrene D, cinnamic acid, pyrazol-5-ol, methaqualone, isoquinoline, quinones, reducing sugars, steroids, and volatile oils present in different parts of the plant. The review divulges the ethnobotanical and pharmacological activities of the plant and also justifies the ethnomedical claims. The significant medicinal value of this plant necessitates a scientific adventure into the bioactive metabolites which constitute various extracts.
Project description:The greater celandine 'Chelidonium majus' and its main alkaloid chelidonine have previously been shown to exert high cytotoxicity against cancer cells. Furthermore, chelidonine is proposed to possess pro-apoptotic and anti-metastatic properties. Within the present study, the effects chelidonine on several HNSCC cell lines, as well as primary cells, were analyzed with respect to growth, migration, angiogenesis and apoptosis. Chelidonine suppressed the growth of all tested HNSCC cell lines, including a paclitaxel-resistant and P-glycoprotein (MDR1) overexpressing cell line, but not in a clear dose-dependent manner. Mucosal keratinocytes were also strongly affected by chelidonine, while fibroblasts proved to be much more resistant. Chelidonine failed to trigger apoptosis at physiological concentrations in HNSCC cell lines. Based on a spheroid invasion model chelidonine suppressed invasion of FaDu cells effectively on gelatin, fibronectin, collagen I, laminin and Matrigel®. However, invasion inhibition of the more aggressively invading cell line HLaC78 largely failed. Using the tube formation assay, chelidonine effectively inhibited angiogenesis. Expression analysis revealed an upregulation of the xenobiotic metabolism genes CYP1A1 and MDR1 by chelidonine. In summary, chelidonine appeared to exert only minor impact on head and neck cancer cells. Chelidonine did not produce clear dose-dependent and cell-type specific cytotoxicity nor did it trigger apoptosis strongly.
Project description:A novel annotated Chelidonium majus L. transcriptome database composed of 23,004 unique coding sequences allowed to significantly improve the sensitivity of proteomic C. majus assessments, which showed novel defense-related proteins characteristic to its latex. To date, the composition of Chelidonium majus L. milky sap and biosynthesis of its components are poorly characterized. We, therefore, performed de novo sequencing and assembly of C. majus transcriptome using Illumina technology. Approximately, 119 Mb of raw sequence data was obtained. Assembly resulted in 107,088 contigs, with N50 of 1913 bp and N90 of 450 bp. Among 34,965 unique coding sequences (CDS), 23,004 obtained CDS database served as a basis for further proteomic analyses. The database was then used for the identification of proteins from C. majus milky sap, and whole plant extracts analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) approach. Of about 334 different putative proteins were identified in C. majus milky sap and 1155 in C. majus whole plant extract. The quantitative comparative analysis confirmed that C. majus latex contains proteins connected with response to stress conditions and generation of precursor metabolites and energy. Notable proteins characteristic to latex include major latex protein (MLP, presumably belonging to Bet v1-like superfamily), polyphenol oxidase (PPO, which could be responsible for browning of the sap after exposure to air), and enzymes responsible for anthocyanidin, phenylpropanoid, and alkaloid biosynthesis.
Project description:A highly stereo- and regioselective synthesis of the core skeleton of hexahydrobenzo[c]phenanthridine-type alkaloids is reported herein for the first time. A wide range of substrate scope, excellent functional group tolerance, and good to excellent yields were observed. This protocol gives very concise and efficient access to the core skeleton of chelidonine alkaloids as compared to the earlier approaches.
Project description:Isoquinoline alkaloids, which are one of the most important types of alkaloids, are extensively distributed in herbal medicines. However, systematic and comprehensive investigations of the fragmentation behaviours of isoquinoline alkaloids have rarely been reported. Therefore, the goal of the present study is to simultaneously investigate the collision-induced dissociation patterns and the corresponding mechanism of isoquinoline alkaloids by mass spectrometry (MS) combined with computations. Nineteen types of isoquinoline alkaloids (66 compounds) were used as references to identify the characteristic fragmentation behaviours by quadrupole time-of-flight mass spectrometry (Q-TOF/MS) in positive electrospray ionization (ESI) mode. These types of isoquinoline alkaloids were divided into three categories primarily by the characteristic [M-NHR1R2]+ (R1 and R2 represent the substituent groups of the N-atom) fragment ions. High- and low-abundance [M-NHR1R2]+ ions were observed respectively for type I (1-13) and type II (14-29) alkaloids, respectively; however, the characteristic fragments were not detected for type III alkaloids (30-66) because of the existence of a p-? conjugated system. Each type of alkaloid was further classified by its characteristic fragmentation patterns and fragment ions. In addition, isoquinoline alkaloid with vicinal methoxy and hydroxy, vicinal methoxy, methylenedioxy, methoxy, and quaternary N-methyl groups could form the characteristic fragments by the loss of CH3OH, CH4, CH2O or CO, CH3 and CO, and CH3 moieties, respectively. The mechanisms of some interesting fragmentation behaviours, such as the formation of [M-NH3]+ and [M-CH3]+ fragment ions, were further demonstrated by computational chemistry. These characteristic fragmentation behaviours and fragment ions of isoquinoline alkaloids provide a solid foundation for the rapid and high-efficiency structural elucidation of similar metabolites in plant-derived medicines.