RESUMO
Owing to the lack of selection and limited intelligence in mechanical picking, some immature tomatoes that contain alkaloids are thrown away. Tomatine alkaloids are steroidal alkaloids naturally present in Solanaceae plants, which are distributed in small amounts in immature tomato fruits and decrease as the fruits ripen. Tomato glycoalkaloids are harmful to human health. However, in small quantities, there is some evidence that these compounds might be beneficial, as other non-antioxidant bioactivities. This article considers recent research on the biological effects of tomato glycoalkaloids in immature tomatoes, providing reference value for the potential development of these compounds.
Assuntos
Alcaloides , Solanaceae , Solanum lycopersicum , Humanos , Tomatina/toxicidade , Alcaloides/toxicidade , Extratos Vegetais/farmacologiaRESUMO
The Amaryllidaceae family is widely distributed in the tropics, presenting biological activity attributed mostly to alkaloids, such as an important inhibitory activity of acetylcholinesterase (AChE), antifungal, antibacterial, and cytotoxic activities. The present study aims to review the spectrum of action of the main biological activities and toxicity of secondary metabolites found in Amaryllidaceae through a literature review, using Prisma and the descriptors "Pharmacological effects of Amaryllidaceae" and "Amaryllidaceae family" and "Pharmacological actions of Amaryllidaceae", used in English and Portuguese. The literature search was done in March and May 2023. Original works published from 2012 to 2023, available in full, and presenting experimental and clinical studies were included. After the selection considering the inclusion and exclusion criteria, 60 articles fulfilled the defined criteria. From a pharmacological point of view, the highlight is due to the alkaloid galantamine, which has the potential- and is already used - for treating Alzheimer's. The toxicological aspect must be considered and evaluated carefully, as alkaloids have been associated with adverse effects such as nausea, vomiting, diarrhea, abdominal pain, and cardiovascular, neurological, and respiratory changes. Furthermore, some studies indicate that consuming these plants in significant quantities can lead to hepatic and renal toxicity. Therefore, the therapeutical use of this family's plant drugs and derivatives requires further studies to elucidate its effects and point out metabolites with therapeutic potential.
Assuntos
Alcaloides , Amaryllidaceae , Extratos Vegetais , Alcaloides/farmacologia , Alcaloides/toxicidade , Amaryllidaceae/química , Inibidores da Colinesterase/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidadeRESUMO
Tripterygium wilfordii (TW), a well-known traditional Chinese medicine, was widely used in the treatment of autoimmune disorders and inflammatory diseases. However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity. Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW.
Assuntos
Alcaloides , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Espectrometria de Massas em Tandem , Tripterygium/química , Metabolômica , Biomarcadores , Alcaloides/toxicidade , Aminoácidos/metabolismoRESUMO
Undoubtedly, it is important to remain vigilant and manage invasive grasses to prevent their spread and mitigate their negative impact on the environment. However, these aggressive plants can also play a beneficial role in certain contexts. For example, several invasive grasses provide valuable forage for livestock and have disease control potential. Therefore, a research experiment was conducted to explore the pros and cons of this approach, not only for surrounding vegetation but also for human and animal disease control. The study is primarily focused on developing livestock feed, plant-derived herbicides, and an understanding of the phytotoxic effects of invasive species. All plant parts of Cenchrus ciliaris L., Polypogon monspeliansis L., and Dicanthium annulatum (Forssk.) Stapf, were tested for their phyto-chemical screening, proximate, and toxicity analysis which was caused by the methanolic extract of these grass species. Qualitative phytochemical screening tests were performed for proximate composition analysis and toxicity assessment essays. The phytochemical analysis revealed the positive results for alkaloids, flavonoids, coumarins, phenols, saponins, and glycosides, while negative for tannins. Comparison of proximate analysis intimated maximum moisture (10.8%) and crude fat (4.1%) in P. monspeliensis, whereas maximum dry matter (84.1%), crude protein (13.95%), crude fiber (11%), and ash (7.2%) in D. annulatum. Five (10, 100, 500, 100, 10,000 ppm) and three (10, 1000, 10,000 ppm) different concentrations of methanolic extract prepared from C. ciliaris, P. monspeliansis, and D. annulatum were used respectively for root inhibition and seed germination essay. Furthermore, three different concentrations (10, 30, 50 mg) of plant fine powder were used for sandwich method test. There was a significant decline in the growth rate of experimental model radish seeds (P > 0.005), and results from sandwich method tests showed suppressed growth of root hairs, inhibiting the anchoring of the radish seed. In comparison, results manifest that; P. monspeliansis indicated an upsurge of inhibition (66.58% at 10,000 ppm), D. annulatum revealed soar germination (75.86% in controlled conditions), and C. ciliaris exhibited dramatic shoot up of inhibition because of sandwich method test (14.02% at 50 mg). In conclusion, although grasses are toxic, it is important to consider the beneficiary account.
Assuntos
Alcaloides , Extratos Vegetais , Humanos , Animais , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Poaceae , Espécies Introduzidas , Taninos/análise , Alcaloides/toxicidade , Alcaloides/análise , Compostos Fitoquímicos/toxicidadeRESUMO
OBJECTIVE: The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products. METHODS: The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products. RESULTS: Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity. CONCLUSION: Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.
Assuntos
Alcaloides , Diterpenos , Humanos , Aconitina/toxicidade , Aconitina/química , Cardiotoxicidade , Areia , Alcaloides/toxicidade , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Diterpenos/toxicidadeRESUMO
Some snail species pose a serious threat for human health, economy, and the environment due to their widespread distribution and the transmission of dangerous parasites causing, among others, schistosomiasis and fascioliasis. Scientists from around the world have been studying the effects of plant extracts on snails for many years in order to find an alternative to molluscicides of synthetic origin. The main purpose of this study was to collect the results obtained so far on the effect of plant alkaloids on snails in the context of their molluscicidal properties. This work presents the results of publications on the effect of plant alkaloids on snails, which were published in the years 1974-2021. The Solanaceae, Papaveraceae, and Asteraceae are the plant families most frequently cited for containing alkaloids with molluscicidal activity. The alkaloids identified as molluscicidal belonged to various groups, of which the most numerous were pseudoalkaloids and tyrosine-derived alkaloids. Most of the tested alkaloids were characterized by a high mortality rate among the studied groups of snails. Based on the collected research results, it was found that plant alkaloids can be extremely useful in the fight against problematic species of snails and cause much lower harm to the environment than synthetic molluscicides.
Assuntos
Alcaloides , Moluscocidas , Esquistossomose , Humanos , Extratos Vegetais/toxicidade , Alcaloides/toxicidade , Esquistossomose/prevenção & controle , Moluscocidas/toxicidadeRESUMO
Despite their advantages, biotechnological and omic techniques have not been applied often to characterize phytotoxicity in depth. Here, we show the distribution of phytotoxicity and glycoalkaloid content in a diploid potato population and try to clarify the source of variability of phytotoxicity among plants whose leaf extracts have a high glycoalkaloid content against the test plant species, mustard. Six glycoalkaloids were recognized in the potato leaf extracts: solasonine, solamargine, α-solanine, α-chaconine, leptinine I, and leptine II. The glycoalkaloid profiles of the progeny of the group with high phytotoxicity differed from those of the progeny of the group with low phytotoxicity, which stimulated mustard growth. RNA sequencing analysis revealed that the upregulated flavonol synthase/flavonone 3-hydroxylase-like gene was expressed in the progeny of the low phytotoxicity group, stimulating plant growth. We concluded that the metabolic shift among potato progeny may be a source of different physiological responses in mustard. The composition of glycoalkaloids, rather than the total glycoalkaloid content itself, in potato leaf extracts, may be a driving force of phytotoxicity. We suggest that, in addition to glycoalkaloids, other metabolites may shape phytotoxicity, and we assume that these metabolites may be flavonoids.
Assuntos
Flavonoides , Extratos Vegetais , Solanum tuberosum , Alcaloides/análise , Alcaloides/toxicidade , Diploide , Flavonoides/análise , Flavonoides/toxicidade , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Extratos Vegetais/toxicidade , Folhas de Planta/químicaRESUMO
Isoquinoline alkaloids constitute one of the most common classes of alkaloids that have shown a pronounced role in curing various diseases. Finding ways to reduce the toxicity of these molecules and to increase their therapeutic margin is an urgent matter. Here, a one-step method for the synthesis of a series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines was performed in 85-98% yield by the Pictet-Spengler reaction. This was accomplished using the reaction between 3,4-dimethoxyphenylethylamine and substituted benzaldehydes boiling in trifluoroacetic acid. Furthermore, 1-(3'-amino-, 4'-aminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were obtained in 94% and 97% yield by reduction in 1-(3'-nitro-, 4'-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines with SnCl2 × 2H2O. The structures of the substances obtained were confirmed by infrared (IR) and nuclear magnetic resonance (1H and 13C NMR) spectra. ADMET/TOPKAT in silico study concluded that the synthesized compounds exhibited acceptable pharmacodynamic and pharmacokinetic properties without carcinogenic or mutagenic potential but with variable hepatotoxicity. The acute toxicity and structure-toxicity relationship (STR) in the series of 20 derivatives of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines (3a-r, 4a, b) was studied via determination of acute toxicity and resorptive action in white mice employing intragastric step-by-step administration. The first compound, 1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3a), showed the highest toxicity with LD50 of 280 mg/kg in contrast to 1-(3'-bromo -4'-hydroxyphenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3e) which proved to be the safest of the compounds studied. Its toxicity was 13.75 times lower than that of the parent compound 3a. All compounds investigated showed high local anesthetic activity on rabbit eyes in the concentrations studied. Only 3r, 3n, and 4a caused eye irritation and redness. All investigated derivatives (except 4b) in 1% concentration were more active than lidocaine, providing longer duration of complete anesthesia. Therefore, based on the obtained results of in silico tests, local anesthesia, and acute toxicity, a conclusion can be drawn that the experimental compounds need further extensive future investigations and possible modifications so that they can act as promising drug candidates.
Assuntos
Alcaloides , Tetra-Hidroisoquinolinas , Camundongos , Animais , Coelhos , Anestésicos Locais , Anestesia Local , Tetra-Hidroisoquinolinas/toxicidade , Tetra-Hidroisoquinolinas/química , Alcaloides/toxicidade , Dose Letal MedianaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Euodiae Fructus (EF) has been used to treat stomachache, belching, and emesis for more than a thousand years. Ancient records and modern research have shown that EF has mild toxicity, which needs to be processed with licorice juice to reduce its toxicity. Research suggested that the toxicity of EF can be caused by in vivo metabolism, but whether its metabolites are related to hepatotoxicity and whether licorice can affect the metabolism of EF have not been reported, which needed an effective strategy to clarify the correlation between metabolites and toxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: The poisonous substances and metabolic pathways were clarified by comparing the mechanism in vivo process of the main alkaloids of EF in normal rats and rats treated with dexamethasone (DXMS), ketoconazole (KTC), and EF processed with licorice (EFP). MATERIALS AND METHODS: Rats were given EF and EFP by oral administration, respectively. The EF + DXMS and EF + KTC groups were pretreated with DXMS and KTC, respectively, by i. p. for seven days, and their toxicity differences were compared. The comprehensive strategy based on UPLC-Q-Exactive-MS and Orthogonal Partial Least Squares Discriminant Analysis was developed to compare the types and contents of metabolites and clarify the metabolic pathways of alkaloids among EF, EFP, EF + KTC, and EF + DXMS groups. RESULTS: EF + DXMS group significantly increased the hepatotoxicity, whereas the EF + KTC and EFP groups reduced the hepatotoxicity compared with the EF group. One hundred and thirty-five metabolites were detected, and the metabolic pathways of the main alkaloid components related to toxicity were inferred in the plasma, urine, feces, and bile of rats. KTC and licorice similarly inhibited the production of toxic metabolites, changed metabolism in vivo, and produced many new II and a few phases I metabolites, while the contents of toxic metabolites increased in the DXMS group. CONCLUSION: Licorice and KTC could inhibit the production of metabolites of EF related to toxicity, increase the production of other metabolites and promote the excretion of alkaloids, which may be why licorice and KTC can minimize EF toxicity.
Assuntos
Alcaloides , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Glycyrrhiza , Ratos , Animais , Inibidores do Citocromo P-450 CYP3A , Indutores do Citocromo P-450 CYP3A , Alcaloides/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Cetoconazol , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cromatografia Líquida de Alta PressãoRESUMO
OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.
Assuntos
Humanos , Aconitina/química , Cardiotoxicidade , Areia , Alcaloides/toxicidade , Arritmias Cardíacas/tratamento farmacológico , Diterpenos/toxicidadeRESUMO
Dysphania ambrosioides (L.) Mosyakin and Clemants is a medicinal plant that has traditionally been used to cure a range of diseases. There has been no thorough investigation of the potential toxicity of this plant. The objective of this study is to assess the acute and subacute toxicity of D. ambrosioides hydroethanolic extract (DAHE), as well as it alkaloids composition, utilizing LC-MS/MS analysis. An in silico approach was applied to determine pharmacokinetic parameters and to predict the toxicity of D. ambrosioides identified alkaloids. A 14-day treatment with a single oral dose of 1-7 g/kg was carried out to investigate acute toxicity. DAHE was given orally at dosages of 5, 50, and 500 mg/kg for 15 days in the subacute toxicity investigation, and body weight and biochemical parameters were evaluated. Livers, kidneys, lungs, and heart were examined histologically. Chromatographic investigation revealed the existence of nine alkaloids, with N-formylnorgalanthamine being the most prevalent. The oral LD50 value of DAHE was found to be 5000 mg/kg in an acute toxicity study. No variations were observed with respect to food intake, water consumption, mortality, or body and organ weight in the subacute toxicity study. On the other hand, DAHE (500 mg/kg) significantly enhanced alanineaminotransferase, aspartate aminotransferase, and urea. Liver and kidney histological examinations revealed modest infiltration of hepatocyte trabeculae by inflammatory cells in the liver and slight alteration in the kidney histoarchitecture. According to our findings, DAHE exhibits low to moderate toxicity.
Assuntos
Alcaloides , Espectrometria de Massas em Tandem , Alcaloides/análise , Alcaloides/toxicidade , Cromatografia Líquida , Flores/química , Extratos Vegetais/química , Testes de Toxicidade AgudaRESUMO
Croton linearis is a shrub that grows in Caribbean regions, which is rich in metabolites such as alkaloids. The main aim of this study was to evaluate the antiplasmodial effect of alkaloids from this species. Three isoquinoline alkaloids, i.e. reticuline (1), laudanidine (2) and 8,14-dihydrosalutaridine (3), were isolated from the leaves of C. linearis by flash chromatography and semi-preparative HPLC-DAD-MS. Their structures were elucidated by spectroscopic techniques. Antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and cytotoxicity against MRC-5 cells (human fetal lung fibroblast cells) were assessed in vitro. Reticuline, laudanidine and 8,14-dihydrosalutaridine showed moderate antiplasmodial activity with IC50 values of 46.8 ± 0.6, 17.7 ± 0.6 and 16.0 ± 0.5 µM, respectively, but no cytotoxicity was observed in a concentration up to 64.0 µM. This is the first report on the antiplasmodial activity of laudanidine and 8,14-dihydrosalutaridine.
Assuntos
Alcaloides , Antimaláricos , Croton , Alcaloides/química , Alcaloides/toxicidade , Antimaláricos/química , Antimaláricos/toxicidade , Humanos , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta/química , Plasmodium falciparumRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Approximately 60 species of the genus Stephania (Menispermaceae) are distributed worldwide. Among these, 39 species are located in South and Southwest China; in particular, these plants are rich in alkaloids and were used in traditional Chinese medicine (TCM) against numerous ailments. AIM OF THIS REVIEW: The purpose of this study was to provide organized information on the ethnopharmacological uses as well as the phytochemical, pharmacological, and toxicological evaluation of the alkaloids derived from plant species included in the genus Stephania. In addition, we aimed to provide comprehensive basic knowledge on the medicinal properties of these plants and establish meaningful guidelines for further research. MATERIALS AND METHODS: Information related to the Stephania genus was collected from scientific databases, such as Web of Science, PubMed, Baidu Scholar, and China Academic Journals (CNKI), within the last 20 years on phytochemistry, pharmacology, and toxicology of the plants in genus Stephania. Furthermore, information was obtained from the Pharmacopoeia of the People's Republic of China. Chinese Pharmacopoeia and Flora of China. RESULTS: Plant species belonging to the genus Stephania have been mentioned as traditional remedies and various alkaloidal compounds have been identified and isolated, including aporphine, proaporphine, morphinane, hasubanane, protoberberine, benzylisoquinoline, and bisbenzylisoquinoline and among others. The isolated alkaloidal compounds reportedly exhibited promising pharmacological properties, such as antimicrobial, antiviral, antitumor, antioxidant, antihyperglycemic, anti-inflammatory, antinociceptive, anti-multidrug resistance, neuroprotective, and cardioprotective activities. CONCLUSIONS: The genus Stephania is widely used in TCM. The ethnopharmacological uses, phytochemistry, and pharmacology of the Stephania sp. Described in this review demonstrated that these plants contain numerous alkaloids and active constituents and display myriad pharmacological activities. Typically, research on the plants' pharmacological activity focuses on parts of the plants and the associated compounds. However, many Stephania species have rarely been studied, and the ethnomedicinal potential of those discovered has not been scientifically evaluated and needs to be further elucidated. Furthermore, quality control and toxicology studies are warranted in the future.
Assuntos
Alcaloides , Menispermaceae , Stephania , Alcaloides/toxicidade , Etnofarmacologia , Humanos , Medicina Tradicional , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Fitoterapia , Extratos Vegetais/farmacologiaRESUMO
Plants are the cradle of the traditional medicine system, assuaging human or animal diseases, and promoting health for thousands of years. However, many plant-derived medicines contain toxic alkaloids of varying degrees of toxicity that pose a direct or indirect threat to human and animal health through accidental ingestion, misuse of plant materials, or through the food chain. Thus, rapid, easy, and sensitive methods are needed to effectively screen these toxic alkaloids to guarantee the safety of plant-derived medicines. Antibodies, due to their inherent specificity and high affinity, have been used as a variety of analytical tools and techniques. This review describes the antigen synthesis and antibody preparation of the common toxic alkaloids in plant-derived medicines and discusses the advances of antibody-based immunoassays in the screening and detection of toxic alkaloids in plants or other related matrices. Finally, the limitations and prospects of immunoassays for toxic alkaloids are discussed.
Assuntos
Alcaloides , Alcaloides/toxicidade , Animais , Imunoensaio , Medicina Tradicional , Plantas TóxicasRESUMO
Six diterpenoids including three ent-kauranes (1-2, 4) and three cleistanthanes (3, 5-6) were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels. Of them, (16S)-ent-16,17,18-tri-hydroxy-19-nor-kaur-4-en-3-one (1), phyllanthone A (2), and 6-hydroxycleistanthol (3) are new compounds, while the ent-kaurane diterpenoids were reported from the titled plant for the first time. Their structures were elucidated on the basis of the extensive spectroscopic analyses. Compounds 2 and 4-6 displayed cytotoxic potential with IC50 values ranging from 1.96 to 29.15 µM. They also showed moderate anti-inflammatory activities (IC50 = 6.30-12.05 µM). Particularly, the new ent-kaurane 2 displayed cytotoxic potential against HL-60 (IC50 = 2.00 µM) and MCF-7 (IC50 = 3.55 µM) cells, and anti-inflammatory activity (IC50 = 6.47 µM).
Assuntos
Diterpenos do Tipo Caurano/toxicidade , Diterpenos/toxicidade , Phyllanthus/química , Extratos Vegetais/toxicidade , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos do Tipo Caurano/química , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/síntese química , Raízes de Plantas/química , Caules de Planta/químicaRESUMO
Yunaconitine (YAC), crassicauline A (CCA), 8-deacetylyunaconitine (DYA), and 8-deacetylcrassicauline A (DCA), as hidden toxic Aconitum alkaloids, are detected in some products of processed Aconitum carmichaelii lateral root and poisoning cases. The distribution and toxicity of these four components in Aconitum herbs should be further systematically studied for medication safety. This study developed a new UHPLC-QQQ-MS/MS method to determine ten Aconitum alkaloids, including aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, YAC, CCA, DYA, and DCA, for Aconitum herbs simultaneously. YAC and CCA were founded in some samples of unprocessed A. carmichaelii lateral root (7.04%), A. carmichaelii root (9.43%), A. brachypodum root (6.00%), and A. ouvrardianum root (100%). Four hidden toxic Aconitum alkaloids were detected in processed A. carmichaelii lateral root (2.56%) and A. vilmorinianum root (100%). Four hidden toxic Aconitum alkaloids played significant roles in the classification of Aconitum herbs by OPLS-DA analysis. The acute toxicity test was performed by up-and-down procedure (UDP). The oral administration of the half lethal dose (LD50) of YAC, CCA, DYA, and DCA to female ICR mice was 2.37 mg/kg, 5.60 mg/kg, 60.0 mg/kg, and 753 mg/kg, respectively. The LD50 by intravenous injection was 0.200 mg/kg, 0.980 mg/kg, 7.60 mg/kg, and 34.0 mg/kg, respectively. The LD50 of unprocessed A. carmichaelii lateral root, A. vilmorinianum root, and A. brachypodum root to mice orally was 1.89 g/kg, 0.950 g/kg, and 0.380 g/kg, respectively. Symptoms of Aconitum alkaloid poisoning in mice were decreased activity, fur erect, palpebral edema, vomiting, polypnea, and convulsions. The main change of organs was flatulence. No poisoning or death occurred in mice at the maximum dosage (27.0 g/kg) of A. ouvrardianum root orally. To better control the quality and safety of Aconitum herbs, this study provides favorable support for improving the existing standards to strengthen the supervision of the four hidden toxic Aconitum alkaloids.
Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Aconitina/toxicidade , Alcaloides/toxicidade , Animais , Medicamentos de Ervas Chinesas/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Raízes de Plantas , Espectrometria de Massas em TandemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum komarovii Al. Iljinski is a ethnomedicinal herb and this ethno-medicine is used mainly to treat arthritis, toothache, reducing phlegm, relieving cough. Total alkaloids of Cynanchum komarovii Al. Iljinski (TACKI) is the main active compound of Cynanchum komarovii Al. Iljinski. Previous investigations have revealed that TACKI can significantly inhibit rat foot swelling caused by carrageenan; it has a significant inhibitory effect on granulation tissue proliferation. Pharmacology study showed that Cynanchum komarovii Al. Iljinski has analgesia, anti-inflammatory, antibacterial, anti-tumor, relieving cough and relieving asthma. However, there is no any investigation on the mechanism of analgesia and anti-inflammation. AIM OF THE STUDY: To clarify the analgesic effect and material basis of Cynanchum komarovii Al. Iljinski, determine the analgesic effect of TACKI, and provide experimental data support for its traditional application in the treatment of various pains. MATERIALS AND METHODS: TACKI were prepared by the traditional acid extraction and alkaline precipitation method, and TACKI was analyzed through classic animal models of acute antinociceptive animal models and chronic antinociceptive. Evaluation of analgesic effects, and preliminary discussion of the mechanism of its analgesic effects were performed in this work. RESULTS: Acute toxicity experiments showed that the LD50 of TACKI mice was 2960.88 mg/kg, and symptoms of poisoning appeared. Patholog of liver and kidney studies have shown that TACKI reduces eosinophils and increases basophils in kidney glomeruli. In the study of analgesic effects, TACKI had analgesic activity through the PWL, formalin test, and acetic acid writhing test. In the chronic inflammatory antinociceptive study, the latency of the withdrawal reflex in the TACKI group was prolonged, and the mechanical withdrawal reflex threshold was significantly increased. The protein expression of NMDA, GFAP and Iba-1 in rat brain tissue can be reduced significantly byTACKI. Meanwhile, the content of TNF-α and IL-6 in rat brain tissue is reduced. CONCLUSION: TACKI has a significant analgesic activities. It may be related to inhibiting the activation of astrocytes and reducing the content of inflammatory mediators.
Assuntos
Alcaloides/farmacologia , Analgésicos/farmacologia , Cynanchum/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/toxicidade , Analgésicos/química , Analgésicos/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Dose Letal Mediana , Fígado/efeitos dos fármacos , Masculino , Medicina Tradicional , Camundongos , Camundongos Endogâmicos ICR , Dor/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Ratos , Fatores de TempoRESUMO
Phytochemical investigation of Sophora secundiflora alkaloid fraction led to isolation of one new quinolizidine alkaloid (1) 13-methoxyanagyrine together with six known ones (2-7). The insecticidal activity of 70% methanol extract of leaves of S. secundiflora, S. tomentosa and the isolated alkaloids were assessed against 3rd instar larvae of Culex pipiens (Diptera: Culicidae) using different concentrations and mortality rate was recorded. Sophora tomentosa extract showed highest mortality rate with median lethal concentration LC50 3.11 ppm after 24 h and 0.66 ppm after 48 h and anagyrine (6) exhibited remarkably insecticidal activity with LC50 value of 3.42 ppm after 24 h of exposure. Additionally, cytotoxic activity of alkaloid fraction of S. secundiflora, S. tomentosa and isolated alkaloids was also studied using crystal violet assay against MCF-7 and HEPG-2 cell lines. Anagyrine (6) exhibited IC50 values of 27.3 ± 0.7 and 30.2 ± 0.9 µg/mL against MCF-7 and HEPG-2 cancer cells, respectively.
Assuntos
Alcaloides , Antineoplásicos , Culex , Culicidae , Inseticidas , Quinolizidinas , Sophora , Alcaloides/toxicidade , Animais , Antineoplásicos/farmacologia , Inseticidas/farmacologia , Larva , Extratos Vegetais/farmacologia , Sophora/químicaRESUMO
Euodiae Fructus (EF), the dried unripe scented fruit of Euodia rutaecarpa (Juss.) Benth., was reported to show anti-hypertensive, antitumor, and anti-obesity effects. The main alkaloids of EF were reported as the reason for toxicity of EF by metabolic activation majority through CYP3A. Up till the present moment, the cytotoxicity mechanisms of EF have not yet to be fully clarified. For the purposes of this article, the influence of CYP3A inducer and inhibitor on cytotoxicity of EF and metabolism in L02 cells of five alkaloids related to toxicity of EF were evaluated. The results indicated that CYP3A inducer aggravated the toxicity and CYP3A inhibitor alleviated the toxicity. UPLC-Q-Exactive-MS was used for the identification of five alkaloids of EF in L02 cells. A total of 13 metabolites were detected in L02 cells. In general, five alkaloids were widely metabolized in L02 cells such as oxygenation, demethylation, dehydrogenation, and etc. In addition, oxygenation was the main metabolic pathway. It was inferred that the toxicity of EF was closely related to the CYP3A and the metabolic intermediate might be one of the reasons for the toxicity of EF. Hence, the choice of optimal dose might be critical to avoid the adverse reactions owing to combination of EF and CYP3A inducer.
Assuntos
Alcaloides/química , Inibidores do Citocromo P-450 CYP3A/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Evodia/toxicidade , Fígado/efeitos dos fármacos , Alcaloides/metabolismo , Alcaloides/toxicidade , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/química , Inibidores do Citocromo P-450 CYP3A/metabolismo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Evodia/química , Evodia/metabolismo , Frutas/química , Frutas/metabolismo , Frutas/toxicidade , Humanos , Fígado/enzimologia , Espectrometria de MassasRESUMO
This study investigated the acute and subacute toxicity of the ethanolic extract (EE) and alkaloid fraction (FA) from A. nitidum. The EE was obtained from trunk bark with ethanol, FA was obtained from the fractionation of EE. To test the acute toxicity, mice were divided into four groups, and the negative controls received water or aqueous solution of dimethyl sulfoxide, whereas the others received EE or FA (2000 mg/kg, orally, single dose). The same controls were used in the subacute trial. However, the animals were treated for 28 days, and the dose used was 1000 mg/kg per day of EE and FA. Daily clinical evaluations of the animals were performed. At the end of the experiment, hematological, biochemical, and histopathological assessments (liver, lung, heart, and kidney) were performed. In the acute and subacute toxicity studies, mice treated with EE and FA did not show any clinical changes, there were no changes in weight gain, hematological and biochemical parameters compared to the control groups (p > 0.05). In the histopathological examination, there was no abnormality in the organs of the treated animals. Therefore, EE and FA did not produce toxic effects in mice after acute and subacute treatment.