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1.
J Ethnopharmacol ; 248: 112329, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31672526

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mesenchymal stem cells (MSCs) are multipotent stem cells possessing regenerative potential. Symphytum officinale (SO) is a medicinal plant and in homoeopathic literature, believed to accelerate bone healing. AIM OF THE STUDY: This study aimed to determine if homoeopathic doses of SO could augment osteogenesis in MSCs as they differentiate into osteoblasts in vitro. MATERIALS AND METHODS: Bone marrow samples were obtained from patients who underwent bone grafting procedures (n = 15). MSCs were isolated, expanded and characterized by flow cytometry (CD90, CD105). Cytotoxicity of SO was evaluated by MTT assay. Osteogenic differentiation was induced in MSCs with ß-glycerophosphate, ascorbic acid and dexamethasone over 2 weeks. Different homoeopathic doses of SO (MT, 3C, 6C, 12C and 30C) were added to the basic differentiation medium (BDM) and efficiency of MSCs differentiating into osteoblasts were measured by evaluating expression of Osteocalcin using flow cytometry, and alkaline phosphatase activity using ELISA. Gene expression analyses for osteoblast markers (Runx-2, Osteopontin and Osteocalcin) were evaluated in differentiated osteoblasts using qPCR. RESULTS: Flow cytometry (CD90, CD105) detected MSCs isolated from bone marrow (93-98%). MTT assay showed that the selected doses of SO did not induce any cytotoxicity in MSCs (24 hours). The efficiency of osteogenic differentiation (2 weeks) for different doses of Symphytum officinale was determined by flow cytometry (n = 10) for osteoblast marker, Osteocalcin, and most doses of Symphytum officinale enhanced osteogenesis. Interestingly, gene expression analysis for Runx-2 (n = 10), Osteopontin (n = 10), Osteocalcin (n = 10) and alkaline phosphatase activity (n = 8) also showed increased osteogenesis with the addition of Symphytum officinale to BDM, specially mother tincture. CONCLUSIONS: Our findings suggest that homoeopathic dose (specially mother tincture) of Symphytum officinale has the potential to enhance osteogenesis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Diferenciação Celular/efeitos dos fármacos , Confrei , Homeopatia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fosfatase Alcalina/metabolismo , Conservadores da Densidade Óssea/isolamento & purificação , Diferenciação Celular/genética , Linhagem Celular , Confrei/química , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/genética , Osteopontina/metabolismo , Fenótipo , Extratos Vegetais/isolamento & purificação
2.
Planta Med ; 85(14-15): 1177-1186, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31450245

RESUMO

Comfrey is a medicinal plant, extracts of which are traditionally used for the treatment of painful inflammatory muscle and joint problems, because the plant contains allantoin and rosmarinic acid. However, its medicinal use is limited because of its toxic pyrrolizidine alkaloid (PA) content. PAs encompass more than 400 different compounds that have been identified from various plant lineages. To date, only the first pathway-specific enzyme, homospermidine synthase (HSS), has been characterized. HSS catalyzes the formation of homospermidine, which is exclusively incorporated into PAs. HSS has been recruited several times independently in various plant lineages during evolution by duplication of the gene encoding deoxyhypusine synthase (DHS), an enzyme of primary metabolism. Here, we describe the establishment of RNAi knockdown hairy root mutants of HSS in Symphytum officinale. A knockdown of HSS by 60 - 80% resulted in a significant reduction of homospermidine by ~ 86% and of the major PA components 7-acetylintermedine N-oxide and 3-acetylmyoscorpine N-oxide by approximately 60%. The correlation of reduced transcript levels of HSS with reduced levels of homospermidine and PAs provides in planta support for HSS being the central enzyme in PA biosynthesis. Furthermore, the generation of PA-depleted hairy roots might be a cost-efficient way for reducing toxic by-products that limit the medicinal applicability of S. officinale extracts.


Assuntos
Alquil e Aril Transferases/genética , Confrei/química , Regulação da Expressão Gênica de Plantas , Alcaloides de Pirrolizidina/metabolismo , Alquil e Aril Transferases/metabolismo , Confrei/genética , Mutação , Raízes de Plantas/química , Raízes de Plantas/genética , Plantas Medicinais , Alcaloides de Pirrolizidina/toxicidade , Interferência de RNA
3.
Bioresour Technol ; 274: 73-82, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30500766

RESUMO

Symphytum officinale L., as a hyperaccumulator, was pyrolyzed into biochar at 350, 550, and 750 °C, respectively. PTEs could be enriched in biochars except Cd volatilized greatly at 750 °C. In order to evaluate the environmental acceptability of biochars, a series of sequential and single extractions and biochar oxidation procedures were performed for simulating different environmental conditions. There was a sharp decline in PTEs release under various conditions when the temperature above 550 °C, indicating PTEs might transform into more stable forms at higher temperature. Thus, increasing the pyrolysis temperature is helpful for reducing biochar phytotoxicity, suppressing biochar leaching and improving biochar environmental safety. Moreover, the economic feasibility analysis of the biochar confirmed the practicability of it. Findings from this work illustrated that biochars pyrolyzed from Symphytum officinale L. at the temperature higher than 550 °C might be environmental acceptable, which is beneficial for biochar application.


Assuntos
Biodegradação Ambiental , Carvão Vegetal/metabolismo , Confrei/metabolismo , Temperatura Alta
4.
J Chem Ecol ; 45(2): 128-135, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30054770

RESUMO

Pyrrolizidine alkaloids (PAs) are a typical class of plant secondary metabolites that are constitutively produced as part of the plant's chemical defense. While roots are a well-established site of pyrrolizidine alkaloid biosynthesis, comfrey plants (Symphytum officinale; Boraginaceae) have been shown to additionally activate alkaloid production in specialized leaves and accumulate PAs in flowers during a short developmental stage in inflorescence development. To gain a better understanding of the accumulation and role of PAs in comfrey flowers and fruits, we have dissected and analyzed their tissues for PA content and patterns. PAs are almost exclusively accumulated in the ovaries, while petals, sepals, and pollen hardly contain PAs. High levels of PAs are detectable in the fruit, but the elaiosome was shown to be PA free. The absence of 7-acetyllycopsamine in floral parts while present in leaves and roots suggests that the additional site of PA biosynthesis provides the pool of PAs for translocation to floral structures. Our data suggest that PA accumulation has to be understood as a highly dynamic system resulting from a combination of efficient transport and additional sites of synthesis that are only temporarily active. Our findings are further discussed in the context of the ecological roles of PAs in comfrey flowers.


Assuntos
Confrei/química , Alcaloides de Pirrolizidina/química , Cromatografia Líquida de Alta Pressão , Confrei/metabolismo , Flores/química , Flores/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Alcaloides de Pirrolizidina/isolamento & purificação , Alcaloides de Pirrolizidina/metabolismo , Extração em Fase Sólida
5.
Int J Biol Macromol ; 115: 876-882, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29727640

RESUMO

The effects of extraction techniques on the physicochemical properties, antioxidant activity and antihyperglycemic activity of comfrey polysaccharides (CPs) were evaluated. Four techniques were used to extract CPs: hot water extraction (HW), ultrasonic-assisted extraction (UA), enzyme-assisted extraction (EA) and enzyme-ultrasonic-assisted extraction (EUA). Experimental results indicated that CPs extracted by the UA (UA-CPs) and EUA methods (EUA-CPs) had higher extraction yields. The four CPs showed the same monosaccharide composition but a significant difference in monosaccharide content. CPs showed antioxidant activities and antihyperglycemic activities in a concentration-dependent manner. UA-CPs exhibited better antioxidant capacity, which might have been related to its smaller molecular weight and higher uronic acid content. In addition, UA-CPs showed notable α-glucosidase inhibition activity. These results suggested that ultrasonic-assisted extraction technology was more beneficial to enhance the extraction yields of the polysaccharides, and obtain higher bioactive polysaccharides from comfrey.


Assuntos
Fracionamento Químico/métodos , Fenômenos Químicos , Confrei/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Benzotiazóis/química , Compostos de Bifenilo/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Peso Molecular , Monossacarídeos/análise , Picratos/química , Polissacarídeos/farmacologia , Ácidos Sulfônicos/química , Ondas Ultrassônicas , Água/química , alfa-Amilases/antagonistas & inibidores
6.
Int J Biol Macromol ; 112: 889-899, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29428386

RESUMO

This study was designed to investigate the extraction conditions of polysaccharides from comfrey (Symphytum officinale L.) root (CRPs) using response surface methodology (RSM). The effects of three variables including liquid-solid ratio, extraction time and extraction temperature on the extraction yield of CRPs were taken into consideration. Moreover, the effects of drying methods including hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the physicochemical properties and antioxidant activities of CRPs were evaluated. The optimal conditions to extract the polysaccharides were as follows: liquid-solid ratio (15mL/g), extraction time (74min), and extraction temperature (95°C), allowed a maximum polysaccharides yield of 22.87%. Different drying methods had significant effects on the physicochemical properties of CRPs such as the chemical composition (contents of total polysaccharides and uronic acid), relative viscosity, solubility and molecular weight. CRPs drying with FD method showed stronger reducing power and radical scavenging capacities against DPPH and ABTS radicals compared with CRPs drying with HD and VD methods. Therefore, freeze drying served as a good method for keeping the antioxidant activities of polysaccharides from comfrey root.


Assuntos
Antioxidantes/farmacologia , Fenômenos Químicos , Confrei/química , Dessecação/métodos , Raízes de Plantas/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Benzotiazóis/química , Compostos de Bifenilo/química , Cromatografia Líquida de Alta Pressão , Vermelho Congo/química , Depuradores de Radicais Livres/química , Umidade , Concentração de Íons de Hidrogênio , Peso Molecular , Monossacarídeos/análise , Oxirredução , Picratos/química , Análise de Regressão , Solubilidade , Ácidos Sulfônicos/química , Temperatura , Fatores de Tempo , Viscosidade
7.
Food Chem Toxicol ; 112: 178-187, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29288756

RESUMO

Comfrey root preparations are used for the external treatment of joint distortions and myalgia, due to its analgesic and anti-inflammatory properties. Up to date, key activity-determining constituents of comfrey root extracts have not been completely elucidated. Therefore, we applied different approaches to further characterize a comfrey root extract (65% ethanol). The phenolic profile of comfrey root sample was characterized by HPLC-DAD-QTOF-MS/MS. Rosmarinic acid was identified as main phenolic constituent (7.55 mg/g extract). Moreover, trimers and tetramers of caffeic acid (isomers of salvianolic acid A, B and C) were identified and quantified for the first time in comfrey root. In addition, pyrrolizidine alkaloids were evaluated by HPLC-QQQ-MS/MS and acetylintermedine, acetyllycopsamine and their N-oxides were determined as major pyrrolizidine alkaloids in the comfrey root sample. Lastly, the antioxidant activity was determined using four assays: DPPH and ABTS radicals scavenging assays, reducing power assay and 15-lipoxygenase inhibition assay. Comfrey root extract exhibited significant antioxidant activities when compared to known antioxidants. Thus, comfrey root is an important source of phenolic compounds endowed with antioxidant activity which may contribute to the overall bioactivity of Symphytum preparations.


Assuntos
Alcenos/análise , Antioxidantes/análise , Confrei/química , Raízes de Plantas/química , Polifenóis/análise , Alcaloides de Pirrolizidina/química , Alcaloides de Pirrolizidina/toxicidade , Alcenos/farmacologia , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Polifenóis/farmacologia , Espectrometria de Massas em Tandem/métodos
9.
Nat Prod Res ; 32(5): 605-609, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28490191

RESUMO

The root of Symphytum officinale L. is commonly used in folk medicine to promote the wound healing, reduce the inflammation and in the treatment of broken bones. The objective of our investigation was to analyse the extract from S. officinale in term of its antioxidant activity and the effect on cell viability and proliferation of human skin fibroblast (HSF). Moreover, the quantification of main phenolics and allantoin was conducted using HPLC-DAD method. Five compounds were found: rosmarinic, p-hydroxybenzoic, caffeic, chlorogenic and p-coumaric acid. DPPH, FRAP and TPC assay showed the high antioxidant activity of the extract. MTT test proved the stimulatory effect on cell metabolism and viability of HSF cells. Moreover, no changes in cytoskeleton structure and cells shape were observed. The obtained results indicate that non-toxic extract from S. officinale root has strong antioxidant potential and a beneficial effect on human skin fibroblasts.


Assuntos
Antioxidantes/farmacologia , Confrei/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Alantoína/análise , Antioxidantes/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Fibroblastos/efeitos dos fármacos , Humanos , Fenóis/análise , Raízes de Plantas/química , Pele/citologia , Cicatrização/efeitos dos fármacos
10.
J Diet Suppl ; 15(4): 556-581, 2018 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28981366

RESUMO

A current listing of potentially life-threatening, cancer-related dietary supplements (DSs; includes herbs) based on PubMed case reports was summarized in online tables that can now be updated continually to forewarn United States consumers, clinicians, and DS companies. Documented PubMed case reports were used to create a "Toxic Table" related to cancer (1966 to April 2016, and cross-referencing). Keywords included "herb" or "dietary supplement" combined with "cancer" as well as the specific herb "name" combined with "cancer" and sometimes "toxicity." Excluded were herb combinations (some exceptions), Chinese herb mixtures, teas of mixed herb contents, fungi (mycotoxins from molds and mushrooms), poisonous plants, self-harm, excessive doses (except vitamins/minerals), legal or illegal drugs, drug-herb interactions, and confounders of drugs or diseases related to cancer. Also included were a few foods related to cancer. Over the past 50+ years, PubMed case reports revealed an increased risk of cancer related to approximately one herb (guang fang ji), no dietary supplements (except those containing guang fang ji or aristolochic acid), and two foods (bracken fern, which is sometimes sold as an herbal supplement, and hot maté). This online "Toxic Table" can now be continually updated to assist researchers and clinicians in preventing serious adverse events from DSs related to cancer.


Assuntos
Suplementos Nutricionais/toxicidade , Neoplasias/induzido quimicamente , Preparações de Plantas/toxicidade , Aloe/toxicidade , Animais , Ácidos Aristolóquicos/toxicidade , Confrei/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Interações Ervas-Drogas , Humanos , Extratos Vegetais/toxicidade , Fatores de Risco , Estados Unidos
11.
Georgian Med News ; (267): 119-124, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28726668

RESUMO

Application of phytofilms based on biosolublepolymers is considered as a prospectivemethod for burn treatment . Herbal remedies contain biologically active substances, that are relatively less toxic, do not cause skin irritation or allergic reactions and, importantly, affectstrains of the microorganisms and viruses resistant to antibiotics and synthetic drugs. Nowadays, the advantages are given to such burn healing drugs, which along with high specific efficacy, have analgesic, anti-inflammatory and antimicrobial effects, and don't irritate the tissues. The mentioned peculiarities are characteristic for a new herbal phenolic biopolymer poly[3-(3,4-dihydroxyphenyl) glyceric acid](PDGA), isolated from the roots and stems of different comfrey species . The aim of the study was the development of the formulation and technology of biosoluble films for burn treatment on the basis of PDGA. The optimal content of phytofilm for burn healing was selected on the basis of the biopharmaceutical study results. The impact of the film-former on the quality, adhesion and moisture absorption of the phytofilmhas been studied. The optimal degree of the phytofilm moisture, determining its high adhesive properties,was established. The film prepared on the basis of sodium alginate, with 30.4% humidity, demonstrated the greatest adhesion strength. After investigation of the PDGA release it was found, that the hydrophilic bases such as: sodium carboxymethyl-cellulose (69.2%) andsodium alginate (78,65%) appeared to be optimal among the others. At the same time, taking into consideration the disadvantages of sodium carboxymethyl-cellulose (tautening effect on burnt surface, relatively low stability), a film based on sodium alginate has been chosen. The manufacturing technology for obtaining PDGA-containing phytofilm by casting is proposed. Theshelf-lifeofproposedPDGA-containingphytofilmis 2 years.


Assuntos
Queimaduras/terapia , Confrei/química , Ácidos Glicéricos/química , Materiais Biocompatíveis/química , Biopolímeros/química , Raízes de Plantas/química , Caules de Planta/química , Cicatrização
12.
Clin Toxicol (Phila) ; 55(7): 670-673, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28463019

RESUMO

CONTEXT: Accidental ingestion of foxglove (Digitalis purpurea) can cause significant cardiac toxicity. We report a patient who ingested foxglove mistaking it for comfrey and developed refractory ventricular arrhythmias. The patient died despite treatment with digoxin-specific antibody fragments (DSFab) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). CASE DETAILS: A 55-year-old woman presented to the emergency department with nausea, vomiting and generalized weakness eight hours after drinking "comfrey" tea. She had bradycardia (54 beats/min) and hyperkalemia (7.6 mEq/L). Electrocardiogram revealed a first-degree atrioventricular conduction block with premature atrial contractions, followed by polymorphic ventricular tachycardia three hours after arrival. A serum digoxin level was 151.2 ng/mL. The patient developed ventricular fibrillation while waiting for Digibind infusion. Resuscitation was performed and an emergent VA-ECMO was set up. A total of eight vials of Digibind were given over the next 16 hours. She temporarily regained consciousness, but remained hemodynamically unstable and subsequently developed lower limb ischemia and multiple organ failure, and she expired on hospital day seven. A botanist confirmed that the plant was foxglove. CONCLUSIONS: The diagnosis of cardiac glycoside plant poisoning can be difficult in the absence of an accurate exposure history. In facilities where DSFab is unavailable or insufficient, early VA-ECMO might be considered in severely cardiotoxic patients unresponsive to conventional therapy.


Assuntos
Acidentes , Glicosídeos Cardíacos/envenenamento , Confrei , Digitalis/envenenamento , Cardiopatias/induzido quimicamente , Intoxicação por Plantas/etiologia , Cardiotoxicidade , Eletrocardiografia , Oxigenação por Membrana Extracorpórea , Evolução Fatal , Feminino , Cardiopatias/diagnóstico , Cardiopatias/terapia , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Pessoa de Meia-Idade , Intoxicação por Plantas/diagnóstico , Intoxicação por Plantas/terapia , Valor Preditivo dos Testes , Ressuscitação , Fatores de Tempo , Resultado do Tratamento
13.
Plant Physiol ; 174(1): 47-55, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28275146

RESUMO

Pyrrolizidine alkaloids (PAs) are toxic secondary metabolites that are found in several distantly related families of the angiosperms. The first specific step in PA biosynthesis is catalyzed by homospermidine synthase (HSS), which has been recruited several times independently by duplication of the gene encoding deoxyhypusine synthase, an enzyme involved in the posttranslational activation of the eukaryotic initiation factor 5A. HSS shows highly diverse spatiotemporal gene expression in various PA-producing species. In comfrey (Symphytum officinale; Boraginaceae), PAs are reported to be synthesized in the roots, with HSS being localized in cells of the root endodermis. Here, we show that comfrey plants activate a second site of HSS expression when inflorescences start to develop. HSS has been localized in the bundle sheath cells of specific leaves. Tracer feeding experiments have confirmed that these young leaves express not only HSS but the whole PA biosynthetic route. This second site of PA biosynthesis results in drastically increased PA levels within the inflorescences. The boost of PA biosynthesis is proposed to guarantee optimal protection especially of the reproductive structures.


Assuntos
Confrei/genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Folhas de Planta/genética , Alcaloides de Pirrolizidina/metabolismo , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Confrei/metabolismo , Flores/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
14.
Georgian Med News ; (262): 92-98, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28252436

RESUMO

One of the most actual problems of pharmacy is the development of medication forms for external application with complex effects on (gel, emplastro, aerosol, etc.) skin wounds, burns and inflammatory factors. The centuries-old practice of using phyto-preparations (herbal remedies) proved that they have fewer side effects in comparison with synthetic drugs. Despite the wide application of herbal preparations, in the literature there is a little information about their application in development of wound and burn healing modern dosage forms. Among the medicinal plants with the mentioned pharmacological actions, comfrey (Symphytum L.) should be distinguished. Phenolic polymer poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDGA) or poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene], amounting approximately 25% of polysaccharides and 1.5-2.5% of dry plant material, were isolated from the roots and stems of Caucasian comfrey species (S. asperum, S. caucasicum). Contrary to polysaccharides this phenolic polymer of Comfrey appeared to have a high immunomodulatory (anticomplement), antioxidative, antilipoperoxidantive, anti-inflammatory and wound-healing efficacy/activities. The aim of the study was development of the composition and technology of PDGA-containing gel. According to the results of complex biopharmaceutical studies PDGA gel optimal composition has been proved. The technological scheme for preparation of PDGA gel has been developed. PDGA gel stability under normal conditions of storage at +40С was studied. The gel has a shelf life (determined expiration date) of 2 year.


Assuntos
Ácidos Glicéricos/química , Confrei/química , Liberação Controlada de Fármacos , Excipientes , Géis , Ácidos Glicéricos/isolamento & purificação , Osmose
15.
Regul Toxicol Pharmacol ; 83: 1-4, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27840092

RESUMO

Mutagenic and teratogenic pyrrolizidine alkaloids (PAs) have been identified in several plant species. The industrially most important PA-containing plant is Symphytum officinale (common comfrey). The application of its root is restricted in several countries due to its PA content. In medicines, the daily alkaloid quantity and duration of treatment may be limited even in case of topical application. Due to the confirmed good absorption of PAs from the gastrointestinal tract, the prohibition of oral use is justified, however the limitation of external application is not supported by relevant data. Penetration experiments on human skin are not available to be a rational basis for limitation. The aim of our work was to carry out pharmacokinetic studies on the diffusion and penetration of lycopsamine (a main PA of comfrey) from a Symphytum product through a synthetic membrane and human skin. Investigations were carried out on vertical Franz diffusion cell and lycopsamine was quantified by a validated LC-MS method. The amount of lycopsamine diffused through a synthetic membrane varied between 0.11% and 0.72% (within 24 h). On human epidermis, the rate of penetration was lower (0.04-0.22%). Our results may contribute to the more realistic toxicological assessment of externally applied PA-containing products.


Assuntos
Confrei/química , Epiderme/metabolismo , Extratos Vegetais/metabolismo , Alcaloides de Pirrolizidina/metabolismo , Absorção Cutânea , Administração Cutânea , Adulto , Cromatografia Líquida de Alta Pressão , Difusão , Humanos , Cinética , Masculino , Membranas Artificiais , Modelos Biológicos , Pomadas , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Raízes de Plantas , Plantas Medicinais , Alcaloides de Pirrolizidina/administração & dosagem , Alcaloides de Pirrolizidina/isolamento & purificação , Alcaloides de Pirrolizidina/toxicidade , Medição de Risco , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Toxicocinética
16.
BMJ Case Rep ; 20162016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27908913

RESUMO

A previously well woman aged 63 years presents to the emergency department with vomiting, palpitations and 3 presyncopal episodes. She had no previous medical or cardiac history, with the patient stating that she tried a herbal remedy of boiled comfrey leaves for insomnia 18 hours before arrival to the department. Her ECG showed multiple abnormalities, including bradycardia, second-degree atrioventricular node block, Mobitz Type 2, a shortened QT interval, downsloping ST depression and presence of U waves. After viewing the images of comfrey and foxglove, it highlighted the possibility of mistaken ingestion of Digitalis, containing the organic forms of cardiac glycosides, such as digoxin and digitoxin. Raised serum digoxin levels confirmed this. The patient was haemodynamically stable, and given digoxin-binding antibodies. After 5 days of cardiac monitoring, her ECG returned to normal rhythm, and she was discharged home.


Assuntos
Acidentes , Anticorpos Heterófilos/uso terapêutico , Bloqueio Atrioventricular/induzido quimicamente , Confrei , Digitalis/envenenamento , Digoxina/envenenamento , Intoxicação por Plantas/diagnóstico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Anticorpos Heterófilos/imunologia , Bradicardia/etiologia , Digitalis/imunologia , Digoxina/imunologia , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Folhas de Planta/envenenamento , Intoxicação por Plantas/complicações , Intoxicação por Plantas/tratamento farmacológico , Plantas Medicinais , Resultado do Tratamento , Vômito/etiologia
18.
Homeopathy ; 105(1): 92-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26828003

RESUMO

METHODS: Ninety-six cobb race chickens were equally divided in 4 groups and randomly assigned to receive a standard treatment feed + homeopathic concentrations of Symphytum (S.) officinalis (9CH), or standard treatment feed + homeopathic concentrations of Tricalcarea (4CH), or standard treatment feed + homeopathic concentrations of Calcarea (C.) carbonica (30CH) or a placebo (the same feed but without any homeopathic compound) in order to assess the ability of the homeopathic compounds to increase the concentration of calcium hydroxyapatite in the sternal spongy bone tissue. We measured the concentration of calcium hydroxyapatite in the sternal spongy bone tissue of all chickens by means of a computed tomography (CT). RESULTS: 30%, 36% and 63% increase of sternum spongy-bone mineralization was observed after a 2 years period in the treatment groups with S. officinalis (9CH), Tricalcarea (4CH) (*P < 0.05) and C. carbonica (30CH) (***P < 0.001) respectively. CONCLUSION: Bone mineralization is usually low in battery chickens reared in commercial poultry-sheds, creating a weakness of the whole animal supporting apparatus. Homeopathic preparations with bone-tissue tropism may improve their health quality.


Assuntos
Densidade Óssea/efeitos dos fármacos , Homeopatia/métodos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/veterinária , Ração Animal/efeitos adversos , Animais , Galinhas , Confrei , Durapatita/análise , Minerais/uso terapêutico
19.
J Appl Toxicol ; 36(5): 716-25, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26177929

RESUMO

Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a tisane or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52 and 1.04 mmol lycopsamine, intermedine or reduced comfrey extract per kg bodyweight (BW) for 10 days. After another 7 days chicks were euthanized. Based on clinical signs of poisoning, serum biochemistry, and histopathological analysis the reduced comfrey extract was more toxic than lycopsamine and intermedine. This work suggests a greater than additive effect of the individual alkaloids and/or a more potent toxicity of the acetylated derivatives in the reduced comfrey extract. It also suggests that safety recommendations based on purified compounds may underestimate the potential toxicity of comfrey.


Assuntos
Confrei/toxicidade , Extratos Vegetais/toxicidade , Alcaloides de Pirrolizidina/toxicidade , Animais , Aspartato Aminotransferases/sangue , Ácidos e Sais Biliares/sangue , Galinhas , Colesterol/sangue , Confrei/química , Creatina Quinase/sangue , L-Iditol 2-Desidrogenase/sangue , L-Lactato Desidrogenase/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Alcaloides de Pirrolizidina/química , Triglicerídeos/sangue , gama-Glutamiltransferase/sangue
20.
Artigo em Inglês | MEDLINE | ID: mdl-26482059

RESUMO

Pyrrolizidine alkaloids (PAs) are a class of naturally occurring compounds produced by many flowering plants around the World. Their presence as contaminants in food systems has become a significant concern in recent years. For example, PAs are often found as contaminants in honey through pollen transfer. A validated method was developed for the quantification of four pyrrolizidine alkaloids and one pyrrolizidine alkaloid N-oxide in plants and honey grown and produced in British Columbia. The method was optimised for extraction efficiency from the plant materials and then subjected to a single-laboratory validation to assess repeatability, accuracy, selectivity, LOD, LOQ and method linearity. The PA content in plants ranged from1.0 to 307.8 µg/g with repeatability precision between 3.8 and 20.8% RSD. HorRat values were within acceptable limits and ranged from 0.62 to 1.63 for plant material and 0.56-1.82 for honey samples. Method accuracy was determined through spike studies with recoveries ranging from 84.6 to 108.2% from the raw material negative control and from 82.1-106.0 % for the pyrrolizidine alkaloids in corn syrup. Based on the findings in this single-laboratory validation, this method is suitable for the quantitation of lycopsamine, senecionine, senecionine N-oxide, heliosupine and echimidine in common comfrey (Symphytum officinale), tansy ragwort (Senecio jacobaea), blueweed (Echium vulgare) and hound's tongue (Cynoglossum officinale) and for PA quantitation in honey and found that PA contaminants were present at low levels in BC honey.


Assuntos
Poluentes Ambientais/isolamento & purificação , Mel/análise , Extratos Vegetais/química , Alcaloides de Pirrolizidina/isolamento & purificação , Boraginaceae/química , Colúmbia Britânica , Calibragem , Cromatografia Líquida , Confrei/química , Echium/química , Contaminação de Alimentos/análise , Xarope de Milho Rico em Frutose/química , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Senécio/química , Espectrometria de Massas em Tandem , Zea mays/química
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