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Cecropia is a genus of neotropical trees mainly distributed in Mexico and Central and South America. Currently, 63 species have been described, some of which have been used for centuries in traditional medicine to treat conditions such as diabetes, high blood pressure, and wound healing, among others. In recent times, modern phytochemical studies have succeeded in isolating individual compounds with potential specific medicinal applications. This review aims to examine the literature data regarding isolated terpenes and their correlation with pharmacological activities, with the goal of unveiling the future potential of the genus.
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This study aimed to analyze the composition of grape seed oil (GSO) derived from an alternative source after traditional fermentation processes and its potential anti-inflammatory effects using an in vivo model of carrageenan-induced inflammation in mice. Gas chromatography high-resolution electron ionization mass spectrometry (GC-HR-EIMS) analysis identified eight main components in the GSO extract, including myristic acid methyl ester, palmitoleic acid methyl ester, methyl isoheptadecanoate, cis-linoleic acid, oleic acid methyl ester, linoleic acid stereoisomer, linoleic acid ethyl ester, and methyl (6E, 9E, 12E, 15E)-docose-6,9,12,15-tetraenoate. No significant differences were observed in the main fatty acids between commercially available grape seed oil and GSO extract obtained from fermented grape seeds. In the carrageenan-induced inflammation model, treatment with GSO resulted in a significant reduction in paw edema at 180 min, as in the reduction observed with diclofenac treatment. Combined treatment with GSO and diclofenac showed enhanced anti-inflammatory effects. Additionally, GSO exhibited antioxidative effects by decreasing the levels of glutathione (GSH) and malondialdehyde (MDA) in the serum. Chronic treatment with GSO for ten days did not provide a protective effect on inflammation. These findings suggest that GSO could be used as an alternative raw material and could possess anti-inflammatory and antioxidative properties. Further studies are needed to explore its potential therapeutic applications.
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Some of the most effective anticancer compounds are still derived from plants since the chemical synthesis of chiral molecules is not economically efficient. Rapid discovery of lead compounds with pronounced biological activity is essential for the successful development of novel drug candidates. This work aims to present the chemical diversity of antitumor bioactive compounds and biotechnological approaches as alternative production and sustainable plant biodiversity conservation. Astragalus spp., (Fabaceae) and Gloriosa spp. (Liliaceae) are selected as research objects within this review because they are known for their anticancer activity, because they represent two of the largest families respectively in dicots and monocots, and also because many of the medicinally important plants are rare and endangered. We summarized the ethnobotanical data concerning their anticancer application, highlighted the diversity of their secondary metabolites possessing anticancer properties such as saponins, flavonoids, and alkaloids, and revealed the potential of the in vitro cultures as an alternative way of their production. Since the natural supply is limited, it is important to explore the possibility of employing plant cell or organ in vitro cultures for the biotechnological production of these compounds as an alternative.
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INTRODUCTION: Gloriosa superba L. is a promising antitumoural plant species as a source of colchicinoids. Ethnobotanical applications of G. superba are associated with different plant parts such as leaves, seeds, fruits, tuber and the whole plant. OBJECTIVES: A comparative phytochemical study of purified extracts from in vitro cultures and native tubers of G. superba was carried out by ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HR-MS) in combination with the mass defect filtering (MDF) technique. MATERIAL AND METHODS: The individual compounds were tentatively annotated using database correlations, retention time (Rt), accurate m/z data obtained by electrospray ionisation (ESI) (+)-HR-MS, proposed elemental composition, ring double bond equivalent (RDBeq) values and HR-MS/MS fragmentation patterns. Moreover, the identification was based on transforming the exact mass ratio (m/z) for the protonated molecular ions [Ð + Ð]+ of the observed metabolites in Kendrick nominal masses (NKMs) and calculation of the Kendrick mass defect (KMD), which made it possible to graphically present the ion peaks in Kendrick plots. RESULTS: Building Kendrick plots allows easy differentiation of small structural differences such as methylation or demethylation of compounds from the same homologous series. In this way, a wide range of tropolone alkaloids was characterised. A greater variety was observed in in vitro cultures, compared to native sources. CONCLUSION: This LC-MS analysis unambiguously demonstrated the presence of tropolone alkaloids in in vitro cultures of G. superba. This approach of LC-MS data interpretation can be used to understand complex mass spectra such as those of plant extracts.
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Alcaloides , Espectrometria de Massas em Tandem , Cefotaxima , Cromatografia Líquida , Extratos Vegetais , Espectrometria de Massas por Ionização por Electrospray , TropolonaRESUMO
Seven tetracyclic spiro-alkaloids, i.e. glucoerysodine (1), erysodine (2), epi-erythratidine (3), erysovine (4), erythratidine (5), erysotrine (6) and erythraline (7) were isolated from the seeds of Erythrina latissima by means of conventional separation methods and HPLC-DAD-SPE-NMR. Their structures were elucidated by spectroscopic means. This is the first report on the isolation of compounds 3, 5 and 6 from this plant. Antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and cytotoxicity against MRC-5 cells (human fetal lung fibroblast cells) was assessed in vitro. Erysodine (2) and erysovine (4) showed moderate activity (IC50 6.53 µM and 4.05 µM, respectively), compared with the standard chloroquine (IC50 = 0.14 µM). No cytotoxicity was observed in a concentration up to 64.0 µM.
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Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antimaláricos/isolamento & purificação , Erythrina/química , Extratos Vegetais/química , Alcaloides/química , Antimaláricos/química , Linhagem Celular , Cloroquina/farmacologia , Cromatografia Líquida de Alta Pressão , Di-Hidro-beta-Eritroidina/análogos & derivados , Resistência a Medicamentos , Humanos , Alcaloides Indólicos , Espectroscopia de Ressonância Magnética , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Sementes/químicaRESUMO
Stem bark of Erythrina latissima E. Mey (Leguminosae) contains a wide range of prenylated flavonoids able to counteract the genotoxic properties of aflatoxin B1 (AFB1). Thus, the hypothesis was raised that E. latissima stem bark extracts (ELBE) may counteract the in vivo hepatotoxic effects of aflatoxins, contaminants in food and feed. An HPLC-DAD method was developed and validated to determine the level of flavonoid aglycones (11.82%) and glycosides (16.17%). ADME, pharmacokinetic and drug-likeness assessment of major flavonoids of ELBE, using the web tool SwissADME, showed good oral bioavailability. The protective effect of ELBE against AFB1 induced genotoxicity in the Vitotox assay after metabolic activation was confirmed (IC50 of 44.32⯵g/ml), followed by evaluation of its inhibitory effect on hepatotoxicity in rats induced by the same agent. Male Wistar rats were orally treated with ELBE (20â¯mg/kg, 50â¯mg/kg and 100â¯mg/kg) or curcumin (500â¯mg/kg) combined with piperine (20â¯mg/kg) - positive control, for 8 days prior to AFB1 exposure (1â¯mg/kg). The ELBE group showed a decreased activity of ALP and γ-GT compared to the AFB1 group. Histopathological examination of the liver demonstrated ameliorative effects of ELBE. Thus, ELBE could have a protective effect against hepatotoxins such as AFB1.
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Aflatoxina B1/toxicidade , Antimutagênicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Erythrina/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Animais , Antimutagênicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Simulação por Computador , Flavonoides/análise , Masculino , Extratos Vegetais/química , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
The aim of the current study was to evaluate the effect of a defatted extract (EAS) and three flavonoids, isolated from Astragalus spruneri Boiss. (Fabaceae) using in vitro/in vivo models of liver injury. The EAS was characterized by HPLC and flavonoids (14â¯mg/g dw) and saponins (8â¯mg/g dw) were proved. The flavonoids (ASF1, ASF3 and ASF5) were isolated from the same extract and partially identified by LC-MS. In in vitro models of non-enzyme induced (Fe2+/AA) lipid peroxidation in isolated liver microsomes and CCl4-induced metabolic bioactivation and t-BuOOH-induced oxidative stress in isolated rat hepatocytes, both EAS and the flavonoids exerted similar to silybin (positive control) an antioxidant and cytoprotective activity, discerned by decreased MDA production in the microsomes and by preserved cell viability and GSH levels as well as by decreased LDH activity and MDA quantity in isolated rat hepatocytes. The antioxidant and hepatoprotective effect of EAS has been confirmed in vivo against CCl4-induced liver injury in rats. EAS restored the GSH levels and the activity of the antioxidant enzymes CAT and SOD, affected by CCl4 administration, as well as decreased the production of MDA. The effect of EAS was commensurable with those of silymarin.
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Antioxidantes/administração & dosagem , Astrágalo/química , Flavonoides/administração & dosagem , Hepatopatias/prevenção & controle , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatias/metabolismo , Masculino , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Ratos , Ratos WistarRESUMO
Species from the genus Gypsophila are known for their medicinal, industrial and decorative applications. G. trichotoma Wend. is an endangered plant species for the Bulgarian flora according to the Red Data Book. Δ7-Sterols, which are unusual and rare in the plant kingdom, are present in the roots of this species. In previous studies different in vitro cultures were established from aerial parts of the species. The objective of this study was to explore the possibility for production of Δ7-sterols from in vitro cultured roots of G. trichotoma. The root cultures were grown on six modified MS media and the quantity of sterols was analyzed. These findings will serve to solve the important matter of the role of nutrients on sterols biosynthesis.
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Caryophyllaceae/metabolismo , Fitosteróis/biossíntese , Raízes de Plantas/metabolismo , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: Diabetes and hypertension are diseases that often coexist, which increases the risk of chronic organ damages and cardiovascular complications. PURPOSE: To evaluate the effects of saponarin, isolated from Gypsophila trichotoma Wend, on blood pressure, glycemia, body weight, and liver biochemical parameters related to oxidative stress in diabetic normotensive Wistar Kyoto rats (NTR) and spontaneously hypertensive rats (SHR). METHODS: Diabetes was induced by administration of streptozotocin (40 mg/kg, i.p.). The following biochemical parameters: reduced glutathione (GSH), malondialdehyde (MDA), total cytochrome P450, aniline hydroxylase (AH) activity, as well as the activities of antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were measured in the livers of euthanized rats. RESULTS: Saponarin exerted slight antihypertensive activity in non-diabetic SHR, judged by 19% (p<0.05) decrease of the initial blood pressure. However, such effect was not observed in streptozotocin-induced diabetic SHR (SHR-D). Streptozotocin-induced diabetes was evidenced by 78% (p<0.05) and by 171% (p<0.05) increase in blood glucose level in NTR and SHR, respectively. In non-diabetic SHR the initial MDA quantity was by 36% (p<0.05) higher and the initial GSH levels were by 28% (p<0.05) lower in comparison to non-diabetic NTR. Significant decrease in the activities of GPx, GR, and GST was measured in the livers of all diabetic rats. Treatment with saponarin ameliorated the above mentioned liver parameters in both diabetic strains, however its effects were less pronounced in the diabetic SHR group. CONCLUSION: Taken together our data indicate that diabetes and hypertension in combination are more difficult to be modulated by saponarin.
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Antioxidantes/farmacologia , Apigenina/farmacologia , Caryophyllaceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Glucosídeos/farmacologia , Hipertensão/tratamento farmacológico , Hipoglicemiantes/farmacologia , Animais , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , EstreptozocinaRESUMO
The Linum thracicum ssp. thracicum cell lines developed in this study are a feasible source for the sustainable production of podophyllotoxin, a lignan with an aryltetralin skeleton that is used for the manufacture of the chemotherapeutic drugs etopophos and teniposide. We used mass spectrometry to confirm the presence of the aryltetralin lignan in the thracian flax cell cultures. Next, we explored how changes in the culture medium influenced the podophyllotoxin content. Out of six developed cell lines, four were selected for further experiments and challenged with elicitors. The selected cell lines clustered into two groups: developed in full strength medium (Li) vs developed in half strength medium (HS). While podophyllotoxin production in the Li cell lines was boosted by 80% upon administration of the elicitor methyl jasmonate, the HS lines produced high amounts of the target metabolite triggered by reduced concentration of nutrients and were only slightly influenced by the elicitor.
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Acetatos/metabolismo , Meios de Cultura , Ciclopentanos/metabolismo , Linho/metabolismo , Oxilipinas/metabolismo , Podofilotoxina/biossíntese , Linhagem Celular , Linho/efeitos dos fármacos , Sais/administração & dosagem , Sacarose/administração & dosagemRESUMO
BACKGROUND: Arylnaphthalene lignan Justicidin B is a lead compound in the management of bone cancer and osteoclastogenesis. The compound is the main cytotoxic principle of rare medicinal plant Linum narbonense L. (Linaceae). However, there have been no reports on the bioreactor production of justicidin B. OBJECTIVE: to develop cost-effective biotechnology for production of this anticancer metabolite. MATERIALS AND METHODS: The genetic transformation in hairy roots induced by Agrobacterium rhizogenes strain ATCC 15834, was proven by PCR analysis. The control of bioreactor was synthesized by gradient method. The optimal values of the controlling parameters were estimated with presence of technological limitation. The general structure of control system was based on "Hardware in the Loop" (HIL). RESULTS: Hairy roots produced five-fold higher yields of justicidin B (7.78mg/g DW) compared to callus. A rapidly growing root line was selected for cultivation in 2-L stirred tank bioreactor. After optimization, maximum biomass of 22.5 g.l(-1) dry wt was harvested from the bioreactor culture vessel (recording about 8 times increase over initial inoculum), with 1.42 % ± 0.12 Justicidine B, greater than contents from flasks were obtained. The extracts were tested in a panel of human tumor cell lines, using the MTT-dye reduction assay, exert inhibitory effects against malignant cells. CONCLUSION: Our findings are the first work on large cultivation of L. narbonense hairy roots and bioreactor production of plant anticancer agent Justicidin B. To extend the research to human clinical studies, we have found a reliable biotechnological supply of plant material, produced this target compound.
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Crinum zeylanicum is used in folk medicine as a rubefacient in rheumatism, a treatment for malaria or as a poison. Complex alkaloid profiles in C. zeylanicum plant organs were revealed by GC-MS analysis, including several bioactive compounds. Crinine, lycorine, 11-O-acetoxyambelline, ambelline, 6-hydroxybuphanidrine and 6-ethoxybuphanidrine (an artefact of the isolation procedure) were isolated. Crinine, 6-hydroxybuphanidrine and 6-ethoxybuphanidrine showed antiproliferative effects against human tumor cell lines, crinine being the most active (IC50 14.04 µM against HL-60/Dox). The latter compound induced apoptosis in a dose-dependent manner in HL-60 and MDA-MB-231 cell lines. Structure-activity relationships in the studied molecules indicated that the hydrogenation of the double bond at C1-C2 leads to a loss of activity, whereas substitutions at C6, C8 and C11 affect their cytotoxicity.
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Alcaloides de Amaryllidaceae/farmacologia , Apoptose/efeitos dos fármacos , Crinum/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Células HL-60/efeitos dos fármacos , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Lignans in eighteen samples of Linum species ( L. tauricum ssp. tauricum, serbicum, bulgaricum and linearifolium; L. elegans; L. flavum ssp. sparsiflorum, L. capitatum var. laxiflorum), all members of the section Syllinum occurring in Bulgaria, were analysed by HPLC-ESI/MS and HPLC-UV/DAD. The ESI/MS fragmentation pathways recently established for aryltetralin lignans are now extended to ester and glycoside derivatives. In total, 22 different lignans, mainly of the aryltetralin type, were identified. 6-Methoxypodophyllotoxin and its glucoside were present as major constituents in all samples. Differences between the investigated taxa were observed especially with respect to the accumulation of 6-deoxy-7-hydroxy-aryltetralins such as podophyllotoxin and of 6-hydroxy-7-deoxy-aryltetralin lignans of the peltatin type. The distribution of aryltetralin lignans with different oxygenation patterns in the various samples, and correlations between the chemical data and the molecular phylogeny based on an analysis of ITS sequences of the investigated species are discussed.
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Linho/química , Lignanas/análise , Bulgária , Linho/genética , Linho/metabolismo , Variação Genética , Lignanas/química , Lignanas/metabolismo , Estrutura Molecular , FilogeniaRESUMO
Deoxypodophyllotoxin is stereoselectively converted into epipodophyllotoxin by recombinant human cytochrome P450 3A4 (CYP3A4). Further kinetic analysis revealed that the Michaelis-Menten K(m) and V(max) for hydroxylation of deoxypodophyllotoxin by CYP3A4 at C7 position were 1.93 microM and 1.48 nmol/min/nmol, respectively. Deoxypodophyllotoxin was subjected to automated docking analysis in order to get better knowledge of the interaction between the CYP3A4 enzyme and the substrate, using the PatchDock algorithm with distance constraints. Automated docking showed that the beta-hydrogen atom at C7 position is in the most appropriate binding orientation at the site of oxidation. The docking results are consistent with the experimental data for the bioconversion of deoxypodophyllotoxin into epipodophyllotoxin by CYP3A4. In addition, the effects of five lignans, deoxypodophyllotoxin, epipodophyllotoxin, podophyllotoxin, demethylenedeoxypodophyllotoxin, and demethylenepodophyllotoxin, on CYP3A4 were compared in order to investigate the influence of the methylenedioxy group on the biotransformation process, to give insight into the mode of metabolization and to explain inhibitory activity of lignans.
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Citocromo P-450 CYP3A/metabolismo , Podofilotoxina/análogos & derivados , Algoritmos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Humanos , Modelos Moleculares , Podofilotoxina/metabolismo , Proteínas Recombinantes/metabolismoRESUMO
Callus and hairy root cultures of Linum leonii were established. The genetic transformation in hairy roots was proven by PCR analysis, which showed integration of rol A and rol C genes into the plant genome. Calli and hairy roots accumulate the arylnaphthalene lignan justicidin B as a major constituent. Hairy roots produce 5-fold higher yields of justicidin B (10.8 mg g(-1) DW) compared to calli. Justicidin B shows strong cytotoxicity on the chronic myeloid leukemia LAMA-8 and K-562 cell lines and on the chronic lymphoid leukemia SKW-3 cell line with IC(50) values of 1.11, 6.08, and 1.62 microM, respectively. Apoptotic properties of justicidin B are reported for the first time.
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Antineoplásicos Fitogênicos/farmacologia , Dioxolanos/farmacologia , Linho/química , Linho/genética , Lignanas/farmacologia , Plantas Geneticamente Modificadas/química , Plantas Geneticamente Modificadas/genética , Plantas Medicinais/química , Plantas Medicinais/genética , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Dioxolanos/química , Dioxolanos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , França , Concentração Inibidora 50 , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Raízes de Plantas/químicaRESUMO
Biotransformation of deoxypodophyllotoxin to epipodophyllotoxin by three major human hepatic enzymes, CYP1A2, CYP2C9 and CYP3A4, heterologously expressed in E. coli DH5alpha, was investigated. It was shown that CYP3A4 catalysed the hydroxylation of deoxypodophyllotoxin into epipodophyllotoxin in yields up to 90%. The structure of the metabolite was determined using HPLC-MS and HPLC-SPE-NMR techniques. There was no detectable production of epipodophyllotoxin or podophyllotoxin by CYP1A2 and CYP2C9 enzymes. The CYP3A4 enzyme shows a distinctly different reactivity to deoxypodophyllotoxin compared to the semi-synthetic derivatives etoposide and teniposide, which are degraded by 3-O-demethylation. These findings demonstrate a novel system for the production of 2,7'-cyclolignans, starting from the easily accessible deoxypodophyllotoxin.