The complete genome sequence of a putative novel cytorhabdovirus identified in Chelidonium majus in China.

A new cytorhabdovirus, tentatively named "chelidonium yellow mottle associated virus" (CheYMaV), was identified in Chelidonium majus with yellow mottle symptoms by high-throughput sequencing and RT-PCR. Its genome is 12,121 nucleotides in length and contains eight open reading frames (ORFs) in the order 3'-N-P'-P-P3-M-G-P6-L-5'. Amino acid sequence comparisons between the putative proteins of CheYMaV and the corresponding proteins of other cytorhabdoviruses showed that it shares the highest sequence similarity with Trifolium pratense virus A (TpVA, MH982250) and Glehnia littoralis virus 1 (GllV1, BK014304), but with sequence identity values below the species demarcation threshold for cytorhabdoviruses (< 80%). Phylogenetic analysis showed that CheYMaV is most closely related to TpVA and GllV1. CheYMaV should therefore be considered a new member of the genus Cytorhabdovirus. This is the first report of a cytorhabdovirus identified in Chelidonium majus.

A Hidden Cause of Hypertransaminasemia: Liver Toxicity Caused by Chelidonium Majus L. : Report of Two Cases of Herb-Induced Liver Injury and Literature Review.

BACKGROUND: In instances where individuals manifest elevated transaminase levels without a clearly discernible cause, a comprehensive patient history proves invaluable in unveiling latent triggers. In this report, we present 2 cases of herb-induced liver injury (HILI) characterized by severe hypertransaminasemia attributed to the consumption of Chelidonium majus L . (also known as greater celandine [GC]), an agent considered an alternative therapeutic remedy. AREAS OF UNCERTAINTY: Exploring the occurrence and range of clinical manifestations in HILI linked to Chelidonium majus L ., while also investigating the potential triggers and predisposing factors for hepatotoxic reactions post Chelidonium majus L. usage, remains challenging due to the absence of definitive laboratory tests to identify the causative agent. DATA SOURCES: Two case reports were detailed, and a systematic literature review using PubMed was conducted including published literature till March 2023. Moreover, a manual search of reference lists of pertinent articles was performed to identify any additional relevant missed publications. RESULTS: In the first case, a 64-year-old woman presented with jaundice, revealing a 1-month history of using GC capsules to manage gallstones. Diagnostic assessment identified HILI, gallstones, and choledocolithiasis, with transaminase levels exceeding 1000 IU/L. After discontinuing GC and receiving intravenous therapy with amino acids and phospholipids, the patient's condition significantly improved. Subsequently, she underwent endoscopic common bile duct stone removal and cholecystectomy. In the second case, a 66-year-old woman presented with elevated liver function test results discovered incidentally during musculoskeletal pain evaluation. Upon further questioning, the patient disclosed regular consumption of GC tea for "health promotion." Following intravenous therapy using amino acids and phospholipids, her transaminase levels returned to normal. The literature review identified 38 cases of HILI associated with GC preparations, primarily in adult women aged 27-77 years, with a predominant reporting location in Germany. Various forms of GC were used, with treatment durations ranging from 1 week to a year. Discontinuation of GC generally led to recovery in these cases. CONCLUSION: Chelidonium majus L ., a potent herb often used in alternative medicine, has significant hepatotoxic potential, requiring physicians to be vigilant in cases of unexplained liver injury.

The Greater Celandine: Identification and Characterization of an Antimicrobial Peptide from Chelidonium majus.

Chelidonium majus, known as Greater Celandine, is a latex-bearing plant that has been leveraged for its anticancer and antimicrobial properties. Herein, C. majus aerial tissue is mined for the presence of antimicrobial peptides. A highly abundant cysteine-rich peptide with a length of 25 amino acids, deemed CM-AMP1, is characterized through multiple mass spectrometric approaches. Electron-activated dissociation is leveraged to differentiate between isoleucine and leucine residues and complement conventional collision-induced dissociation to gain full sequence coverage of the full-length peptide. CM-AMP1 shares little sequence similarity with any proteins in publicly available databases, highlighting the novelty of its cysteine landscape and core motif. The presence of three disulfide bonds in the native peptide confers proteolytic stability, and antimicrobial activity is greatly decreased upon the alkylation of the cysteine residues. Synthetic variants of CM-AMP1 are used to confirm the activity of the full-length sequence and the core motif. To assess the biological impact, E. coli was grown in a sublethal concentration of CM-AMP1 and quantitative proteomics was used to identify proteins produced by the bacteria under stress, ultimately suggesting a membrane lytic antimicrobial mechanism of action. This study integrates multiple analytical methods for molecular and biological characterization of a unique antimicrobial peptide identified from C. majus.

Novel Approaches for the Analysis and Isolation of Benzylisoquinoline Alkaloids in Chelidonium majus.

Benzylisoquinoline alkaloids are the major bioactive components in Chelidonium majus, a plant that has a long usage history for the treatment of gastrointestinal ailments in European and Asian phytomedicine. This study reports on the development and application of a supercritical fluid chromatography technique for the simultaneous qualitative and quantitative determination of seven benzylisoquinoline alkaloids in under six minutes using a Viridis BEH 2-EP column and a modifier comprising methanol with 30% acetonitrile and 20 mM ammonium formate. The method was fully validated according to ICH guidelines showing, e.g., excellent linearity (≥ 0.9997) and maximum deviations for intraday and inter-day precision of 2.99 and 2.76%, respectively. The new supercritical fluid chromatography assay was not only employed for the analysis of several C. majus samples but was also used for the subsequent development of a fast centrifugal partition chromatography technique, whereby five benzylisoquinoline alkaloids could be isolated within approximately 2.5 h, with only two of them, protopine and chelidonine, requiring an additional purification step. To achieve this, a solvent system composed of chloroform/methanol/0.3 M hydrochloric acid was used in descending mode. By injecting 500 mg of crude extract, stylopine (1.93 mg), sanguinarine (0.57 mg), chelidonine (1.29 mg), protopine (1.95 mg), and coptisine (7.13 mg) could be obtained. The purity of compounds was confirmed by supercritical fluid chromatography and MS.

Screening of Chelidonium majus isoquinoline alkaloids reveals berberine and chelidonine as selective ligands for the nuclear receptors RORß and HNF4α, respectively.

The nuclear receptors hepatocyte nuclear factor 4α (HNF4α) and retinoic acid receptor-related orphan receptor-ß (RORß) are ligand-regulated transcription factors and potential drug targets for metabolic disorders. However, there is a lack of small molecular, selective ligands to explore the therapeutic potential in further detail. Here, we report the discovery of greater celandine (Chelidonium majus) isoquinoline alkaloids as nuclear receptor modulators: Berberine is a selective RORß inverse agonist and modulated target genes involved in the circadian clock, photoreceptor cell development, and neuronal function. The structurally related chelidonine was identified as a ligand for the constitutively active HNF4α receptor, with nanomolar potency in a cellular reporter gene assay. In human liver cancer cells naturally expressing high levels of HNF4α, chelidonine acted as an inverse agonist and downregulated genes associated with gluconeogenesis and drug metabolism. Both berberine and chelidonine are promising tool compounds to further investigate their target nuclear receptors and for drug discovery.

Chemical characterization of three different extracts obtained from Chelidonium majus L. (Greater celandine) with insights into their in vitro, in silico and network pharmacological properties.

Plant species C. majus, which is a very rich source of secondary metabolites, was used to obtain extracts, using a conventional extraction technique. For the extraction of bioactive molecules, three solvents were used: ethyl acetate, methanol and water, which differ from each other based on their polarity. The obtained extracts were examined in terms of chemical composition, antioxidant, enzyme inhibitory activity, and cytotoxic effects. The research results indicate that methanol was a better and more efficient extractant in the process of isolating bioactive compounds than ethyl acetate and water. The chemical composition of this solvent, i.e. its polarity, contributed the most to the extraction of alkaloids and flavonoids. The high content of total phenolic compounds in the methanol extract, as well as individual alkaloids, caused a very strong antioxidant activity, as well as a strong inhibitory power when it comes to inhibiting the excessive activity of cholinesterase and tyrosinase. Methanol and ethyl acetate extracts achieved very good cytotoxic activity against cancerous cells HGC-27 and HT-29 and did not exert a toxic effect on non-cancerous cell lines (HEK293). Extracts of plant species C. majus, especially methanol extract could be characterized as a very good starting plant material for the formulation of products intended for various branches of the food and pharmaceutical industry.

Evaluation of the in vitro and in vivo antimicrobial activity of alkaloids prepared from Chelidonium majus L. using MRSA- infected C. elegans as a model host.

Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.

Antimalarial potential of homeopathic medicines against schizont maturation of Plasmodium berghei in short-term in vitro culture

In vitro assessment of antimalarial drug susceptibility of Plasmodium has been a major research success, which has paved the way for the understanding of parasite and rapid screening of antimalarial drugs for their effectiveness. In the present study a preliminary screening to check the antiplasmodial activity of mother tincture (ϕ) and various potencies (6C, 30C, 200C) of homeopathic medicines Cinchona officinalis/china (Chin.), Chelidonium majus (Chel.) and Arsenicum album (Ars.) were done by assessing the in vitro schizont maturation inhibition assay. A significant reduction in the growth of intraerythrocytic stages of P. berghei was observed with decreasing dilution of ϕ and various potencies of Chin., Chel. and Ars. exhibiting a dose dependent effect. Maximum schizont maturation inhibition was observed by Chin. ϕ (1:1), Chin. 30 (1:1, 1:2) and Chel. 30 (1:1) i.e. 80%. The standard drug CQ at 10 µM concentration exhibited 95.4±1.6% inhibition of schizont maturation. Ars. 30 (1:1) also have been found to possess strong antiplasmodial efficacy with 75.5±2.6% schizont inhibition. The presence of free merozoites in Ars. 200 with weak schizonticidal inhibition activity (40-45%) also pointed towards the ability of parasite to survive in the given drug pressure.

O estudo in vitro da susceptibilidade de Plasmodium a drogras antimaláricas representa um grande avanço nas pesquisas, abrindo novas rotas para o entendimento do parasite e da efetividade de drogas antiomaláricas. Nesse trabalho, realizamos um estudo preliminar da atividade antiplasmódica da tintura mãe (ϕ) e várias potências (6 cH, 30 cH, 200 cH) dos medicamentos homeopáticos China officinalis (Chin), Chelidonium majus (Chel) e Arsenicum album (Ars), através do estudo in vitro da inibição da maturação de esquizontes. Observamos uma redução significativa do crescimento do estágio intra-eritrócito do P. berghei conforme a tintura mãe e demais potências de Chin, Chel e Ars foram diluídas, observando-se um efeito dependente da dose. O máximo de inibição na maturação dos esquizontes (80%) foi observado com Chin ϕ (1:1), Chin 30 cH (1:1, 1:2) and Chel 30 cH (1:1). A droga Cloroquina (CQ), usada como controle, em uma concentração de 10µM, exibiu (95.4 ± 1.6) % de inibição. Ars 30cH (1:1) também apresentou uma forte eficácia antiplasmódica com (75.5 ± 2.6) % de inibição de esquizontes. A presence de merozoites livres com Ars 200 cH e uma fraca atividade inibidora (40-45%) indicam a habilidade do parasita em sobreviver na presença dessa droga.

Efeito do Chelidonium majus D3 sobre a hipercolesterolemia experimentalmente induzida em coelhos / Effect of Chelidonium majus D3 on the experimentally induced hypercholesterolemia in rabbits

Introdução: A dislipidemia é um dos maiores fatores de risco para doenças cardiovasculares. Chelidonium majus é uma planta que tem possíveis efeitos sobre a colerese. Objetivo: Verificar a ação do Chelidonium majus D3 sobre a hipercolesterolemia induzida em coelhos. Metodologia: Utilizaram-se 13 coelhos Nova Zelândia brancos em ambiente controlado, recebendo ração hipercolesterolemiante, divididos em dois grupos: tratado e placebo. O grupo tratado recebeu dose via oral de Chelidonium majus D3 diluído em solução hidroalcoólica 30%, duas vezes por dia durante 30 dias, verificando-se os níveis de colesterol total, HDL-colesterol, triglicerídios e relação colesterol total / HDL-colesterol em ambos os grupos. O grupo-placebo recebeu apenas solução hidroalcoólica 30%. Foi utilizado o teste Mann-Whitney para análise dos dados. Resultados: Relacionandose os resultados das diferenças das medianas da coleta intermediária com a basal entre os grupos, obtiveram-se os seguintes resultados: colesterol total: 0,073; HDL-colesterol: 0,628; relação colesterol total / HDL-colesterol: 0,181; triglicerídios: 0,445. Entre a coleta final e a basal, verificaram-se entre os grupos os seguintes resultados: colesterol total: 0,628; HDL-colesterol: 0,366; relação colesterol total / HDL-colesterol: 0,035 (p < 0,05); triglicerídios: 0,035 (p < 0,05). Conclusão: Na amostra estudada não se verificou ação do Chelidonium majus como redutor do colesterol total ou estímulo à elevação do HDLcolesterol. Observou-se, no entanto, ação significativa sobre a redução dos triglicerídios e na redução da relação entre colesterol total e HDL-colesterol (AU)

Introduction: Dyslipidemia is one of the biggest risk factors for cardiovascular disease. Chelidonium majus is a plant that has possible action on choleresis. Objective: Verify the action of Chelidonium majus D3 on the induced hypercholesterolemia in rabbits. Methodology: Were used 13 white rabbits New Zeland in controlled environment, receiving hypercholesterolemic feeding, divided in two groups: treated and placebo. The treated group received oral dose of Chelidonium majus D3 diluted in hydro alcoholic solution 30%, twice a day during 30 days, verifying the total cholesterol, HDL-cholesterol and triglycerides levels and relation total cholesterol / HDL-cholesterol in both groups. The placebo group receveid just hydro alcoholic solution 30%. The Mann-Whitney Test was used for analysis of the data. Results: Becoming related the results of the differences of medians from the intermediate collection with the basal one between groups, we got the following results: Total Cholesterol: 0,073; HDL-cholesterol: 0,628; Relation Total Cholesterol / HDL-cholesterol: 0,181; Triglycerides: 0,445. Between the final collection and the basal one, was verified the following results between groups: Total Cholesterol: 0,628; HDL-cholesterol: 0,366; Relation Total Cholesterol / HDL-cholesterol: 0,035 (p<0,05); Triglycerides: 0,035(p<0,05). Conclusion: In this sample, the action of Chelidonium majus D3 in reducing the total cholesterol or stimulating the rising of HDL-cholesterol was not verified. It was observed, however, significant action on the reduction of the triglycerides and in the reduction of the relation between Total Cholesterol and HDL-cholesterol (AU)

Plantas medicinales milenares que la homeopatia mantiene vigentes / Ancients medicinal plants that homeopathy mantains alive

Cada una de las plantas medicinales tiene una historia que es inreresante conocer. Con frecuencia, su nombre popular o cientifico ya nos revela parte de ella. Casi siempre tales antecedentes historicos son como la brujula que nos orienta hacia su investigacion, primordialmente en lo que respecta a lo fitoquimico y a lo terapeutico. Tales conocimientos son de gran valor para el hombre y es gratificante observar como el pasado y presente utilitario de una planta siempre hacepromisorio su futuro, lo que nos abliga a cuidarlas, conservarlas, estudiarlas y reproducirlas. Para apoyar lo aqui sugerido, hablaremos de cuatro plantas medicinales cuyo uso terapeutico ha sido conocido desde hace cientos de anos en diferentes latitudes de nuestro planeta y que la homeopatia (que apenas cueta con doscientos anos) las mantiene vigentes hasta nuestros dias y que seguramente de acuerdo con su metodo las conservara como medicamentos de uso permanente