Comparative analysis of the main medicinal substances and applications of Echium vulgare L. and Echium plantagineum L.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Echium vulgare L. and Echium plantagineum L. originated in the Mediterranean, and were later domesticated in Africa, America, Asia, Europe and Oceania, where they were widely used to treat many diseases including cough, urinary tract infection, fever, inflammation and muscle strain. AIM OF THE STUDY: The purpose of this review is to provide scientific literature on the traditional uses, bioactive chemical components and pharmacological activities of two species of Echium, and to critically analyze the information provided, so as to understand the current work on these two species and explore the possible prospect of this plant in pharmaceutical research. METHODS: Systematic review and meta-analysis were conducted according to Prisma guidelines, and the related literatures searched on Google Academic, Science Direct, Baidu Scholars and China National Knowledge Infrastructure (CNKI) up to June 2021 were reviewed. The key words used are: Echium, E.vulgare, E.plantagineum, plant components, chemical components, pharmacological activities, pharmaceutical products and applications. Thereafter all eligible studies are analyzed and summarized in this review. The selection of manuscripts is based on the following inclusion criteria: the article has years of research or publication, is published in English, Portuguese or Spanish and Chinese, and there are keywords in the title, abstract, keywords or full text of the article. For the selection of manuscripts, first, select articles according to titles, then summarize them, and finally, analyze the full text of the publication. Elimination criteria: 1. Duplicate reports; 2. There are research design defects and poor quality; 3. Incomplete data and unclear ending effect; 4. The statistical method is wrong and cannot be corrected. RESULTS: The pharmacological characteristics of E.vulgare and E.plantagineum can basically support their traditional use, but the medicinal substances contained in them are quite different in composition and content, and the development and application of corresponding products are also different. CONCLUSIONS: At present, there is little clinical data about drugs related to the two species, and more research is needed in the future, especially human experiments and clinical trials, to evaluate the cellular and molecular mechanisms based on pharmacological, biological activity and safety studies, and to provide more powerful scientific basis for their traditional medicinal properties. In addition, the further application and development of the medicinal products of E.vulgare and E.plantagineum still need to be precise and identified, so as to give full play to their medicinal potential.

Oxidative stability of Echium plantagineum oil / Estabilidade Oxidativa do óleo de echium plantagineum

The evidences about the cardioprotective effects of omega-3 fatty acids (n-3 FA), especially EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), have increased the consumption of these fatty acids. Echium plantagineum is a plant from Boragenacea family, known as potential source of non-marine omega-3 fatty acids (n-3 FA). Echium seeds presents 12-16% of stearidonic acid (SDA), that can be converted to EPA and DHA at a more elevated rate than the conversion obtained from α-linolenic acid (ALA), present in several other vegetable oils. However, echium oil is highly susceptible to oxidation because it has a high proportion of polyunsaturated fatty acids. Thus, the objective of this study was to combine three natural strategies to inhibit the oxidative damage in echium oil. In the first step, a mixture containing hydrophilic (HM: synaptic + ascorbic + citric acids) or lipophilic (LM: α-tocopherol + ascorbyl palmitate + citric acid) antioxidants was applied in the flaxseed oil, kept at 40oC/ 15 days. The oxidative markers were compared with the oil added of TBHQ (120 ppm) and EDTA (75 ppm), both artificial compounds. The results showed that LM and HM had an oxidative protection similar to the artificial antioxidants and that, HM promoted a better protection than LM. Based on this result, HM was selected as a strategy to be applied in the next step. In the second part of this study, Echium oil was obtained by two process: continuous screew pressing (PRESS) and extraction using hexane (SOLV). Both samples were added of HM combined with a high oleic sunflower oil and kept at different temperatures during storage. Two conditions were analyzed: 6 months into sealed flasks and 30 days into opened flasks. Oxidation reaction was followed by measuring the concentration of hydroperoxide, malondialdehyde, tocopherol and volatile compounds. In general, results showed that temperature reduction was enough to keep the oils stability during storage. Thus, the focus of the strategy's combination was directed toward samples after exposition to oxygen. In this context, better results were obtained by blending 20% of high oleic sunflower oil and the hydrophilic antioxidant mixture (500 ppm of synaptic acid, 250 ppm of ascorbic acid and 150 ppm of citric acid). In this condition it was observed 37-41% reduction in the hydroperoxide values and 40-75% in the malondialdehyde concentration in the samples prepared according to the optimized condition, when compared with the standard conditions by which the oil is currently extracted and processed

As evidências do efeito cardioprotetor dos ácidos graxos ômega 3 (AG n-3), principalmente do ácido eicosapentenoico (EPA) e docosahexaenoico (DHA), tem aumentado o consumo desses ácidos graxos. Echium plantagineum é uma planta da família Boragenacea, conhecida como uma fonte potencial AG n-3 de origem não marinha. As sementes de Echium apresentam 12-16% de ácido estearidônico (SDA), que pode ser convertido em EPA e DHA a uma maior taxa que a obtida através do consumo do ácido alfa linolênico (ALA), presente em diversos óleos vegetais. Porém, o óleo de echium é extremamente suscetível à oxidação, por ter um alto teor de ácidos graxos poli-insaturados. Portanto, o objetivo desse estudo foi combinar três estratégias naturais para inibir a oxidação no óleo de echium. Na primeira parte do estudo, misturas contendo antioxidantes hidrofílicos (HM: ácido sinápico + ácido ascórbico + ácido cítrico) ou lipofílicos (LM: alfa-tocoferol + palmitado de ascobila + ácido cítrico) foram aplicados no óleo de linhaça, e mantidos a 40oC por 15 dias. Os marcadores de oxidação foram comparados com óleo de linhaça no qual foram adicionados compostos artificiais: TBHQ (120 ppm) e EDTA (75 ppm). Os resultados mostraram que LM e HM apresentaram uma proteção antioxidante similar ao efeito apresentado pelos compostos artificiais, e que a mistura HM promoveu uma melhor proteção antioxidante que a mistura LM. A partir desse resultado, a mistura HM foi selecionada como estratégia a ser aplicada na etapa seguinte. Assim, na segunda parte do estudo, o óleo de echium foi obtido por dois processos de extração: prensagem mecânica continua (PRESS) e extração usando hexano (SOLV). A mistura HM e o óleo de girassol alto oleico foram selecionados como estratégias antioxidantes, além da redução de temperatura de estocagem. Duas condições foram analisadas: 6 meses em frascos fechados e 30 dias em frascos abertos. A oxidação foi quantificada através da determinação das concentrações de hidroperóxido, malonaldeído, tocoferol e compostos voláteis. No geral, os resultados mostraram que a redução de temperatura foi suficiente para manter a estabilidade do óleo durante o estoque. Portanto, objetivou-se combinar estratégias para aumentar a estabilidade oxidativa das amostras expostas ao oxigênio. Neste contexto, os melhores resultados foram obtidos quando 20% de óleo de girassol alto oleico foi combinado com a mistura hidrofílica de antioxidantes naturais (500 ppm de ácido sinápico, 250 ppm de ácido ascórbico e 150 ppm de ácido cítrico). Nessa condição, foi observada uma redução de 37-41% nos valores de hidroperóxidos e 40-75% na concentração de malonaldeído, quando comparado com a condição padrão

Bioactivity and quantitative analysis of isohexenylnaphthazarins in root periderm of two Echium spp.: E. plantagineum and E. gaditanum.

Isohexenylnaphthazarins are commonly found in the root periderm of several Boraginaceous plants and are known for their broad range of biological activities. The work described herein concerns the biological activity of compounds from the roots of Echium plantagineum L. and Echium gaditanum Boiss (Boraginaceae) collected from field sites in southern Spain and Australia. Bioactivity was assessed using etiolated wheat coleoptile bioassay and in vitro growth inhibitory activity in HeLa and IGROV-1 cells. The quantification of four isohexenylnaphthazarins (shikonin/alkannin, deoxyshikonin/deoxyalkannin, acetylshikonin/acetylalkannin and dimethylacrylshikonin/dimethylacrylalkannin) was performed by LC-MS/MS using juglone as internal standard. Correlation coefficient values for the activities and concentrations of these four analytes were in the linear range and were greater than 0.99. Acetylshikonin/acetylalkannin and dimethylacrylshikonin/dimethylacrylalkannin were present in the highest concentrations in extracts of both species. The results reveal that greatest overall inhibition was observed in both bioassays with E. gaditanum extracts. Strong correlations between time of collection, sampling location and bioactivity were identified.

Ecology and genetics affect relative invasion success of two Echium species in southern Australia.

Echium plantagineum and E. vulgare are congeneric exotics first introduced to Australia in the early 1800 s. There, E. plantagineum is now highly invasive, whereas E. vulgare has a limited distribution. Studies were conducted to evaluate distribution, ecology, genetics and secondary chemistry to shed light on factors associated with their respective invasive success. When sampled across geographically diverse locales, E. plantagineum was widespread and exhibited a small genome size (1 C = 0.34 pg), an annual life cycle, and greater genetic diversity as assessed by DNA sequence analysis. It was found frequently in areas with temperature extremes and low rainfall. In contrast, E. vulgare exhibited a larger genome size (1 C = 0.43 pg), a perennial lifecycle, less chloroplast genetic diversity, and occurred in areas with lower temperatures and higher rainfall. Twelve chloroplast haplotypes of E. plantagineum were evident and incidence aligned well with reported historical introduction events. In contrast, E. vulgare exhibited two haplotypes and was found only sporadically at higher elevations. Echium plantagineum possessed significantly higher levels of numerous pyrrolizidine alkaloids involved in plant defence. We conclude that elevated genetic diversity, tolerance to environmental stress and capacity for producing defensive secondary metabolites have contributed to the successful invasion of E. plantagineum in Australia.

Aplicação de planejamento fatorial na oxidação de óleos contendo diferentes tipos de ácidos graxos ômega 3 / The use of factorial design to evaluate the oxidation of oils containing differents types of omega 3 fatty acids

Óleos contendo alta proporção de ácidos graxos ômega-3 (n-3 FA) têm sido aplicados na formulação de alimentos ou comercializados como suplementos, com a finalidade de reduzir o risco cardiovascular, principalmente devido aos seus efeitos hipotriglicêmicos e anti-inflamatórios. No entanto, a susceptibilidade à oxidação dos n-3 FA é elevada, levando à formação de vários produtos secundários, incluindo alguns tóxicos e potencialmente aterogênicos. Por esta razão, compostos naturais com propriedades antioxidantes têm sido investigados com o objetivo de melhorar a estabilidade oxidativa dos óleos com alta proporção de n-3 FA. Neste estudo, avaliou-se a capacidade antioxidante de dois compostos naturais (ácido sinápico e hidrato de rutina) utilizando-se um modelo acelerado para oxidar os óleos. Foram combinados cinco indutores (Temperatura; Ferro- Fe2+; 2,2'-Azobis dicloridrato de 2-amidinopropano - AAPH; ascorbil palmitato - AP e 2,2'-azobis -2,4-dimetilvaleronitrilo - AMVN) em um delineamento fatorial (25-1) com ½ fração de "resolução V" para acelerar a oxidação de três óleos (linhaça, Echium e peixe) contendo diferentes fontes de n-3 FA: ácido α-linolênico (ALA), ácido estearidônico (SDA) e ácido eicosapentaenóico (EPA) + ácido docosahexaenóico (DHA), respectivamente. Não houve diferença entre os marcadores de oxidação (LOOH e TBARS) estimados pelos modelos e os valores observados experimentalmente. Os indutores AMVN e Fe2+ foram os principais fatores responsáveis pelo aumento da concentração de TBARS. Os valores dos marcadores oxidativos obtidos 48 h após a indução foram semelhantes ou superiores àqueles observados nas amostras oxidadas a 60°C por 15 dias, sendo ambos maiores que os valores observados nas amostras de óleo frescas. Entre os compostos voláteis formados pela oxidação de diferentes fontes de n-3 FA, (E, E) 2,4 -heptadienal, (E, E) 2,4-decadienal, decanal, undecanal e (E) -2-undecenal foram identificados em todas as amostras, podendo ser utilizados como marcadores oxidativos mais específicos. Utilizando o modelo de oxidação acelerada, o hidrato de rutina melhorou a estabilidade oxidativa do óleo de peixe, provavelmente devido à presença de grupos catecol em sua estrutura química. Este estudo contribuiu para que ensaios mais rápidos fossem realizados na avaliação do efeito antioxidante de novas moléculas aplicadas em óleos funcionais comestíveis

Oils containing a high proportion of omega-3 fatty acids (n-3 FA) have been used in the formulation of foods or sold as supplements, aiming to reduce cardio-vascular risks, mainly due to their hypotriglycemic and anti-inflammatory effects. However, n-3 FA are highey susceptible to oxidation, leading to the formation of several products, including some toxic and potentially atherogenic. For this reason, natural products with antioxidant properties have been investigated to improve the oxidative stability of oils with a high proportion of n-3 FA. This study evaluated the antioxidant capacity of two natural compounds (sinapic acid and rutin hydrate), using an accelerated model to oxidize the oils. Five inducers were combined (Temperature, Iron-Fe2+, 2,2'-Azobis (2-amidinopropane) dihydrochloride-AAPH, Ascorbyl palmitate-AP and 2,2'-azobis-2,4-dimethylvaleronitrile-AMVN) in a factorial design (25-1) ½ fraction of "resolution V" to accelerate the oxidation of three oils (flaxseed, Echium and fish) containing different sources of n-3 FA: α-linolenic acid (ALA), stearidonic acid (SDA) and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), respectively. There was no difference between the oxidation markers (LOOH and TBARS) estimated by the regression models and the values experimentally observed. The inducers AMVN and Fe2+ were the main factors responsible for the increase of TBARS concentration. The values of the oxidation markers obtained 48h after the induction were similar to or higher than those obtained when the samples were oxidized at 60°C for 15 days, both being more elevated than the values observed in the fresh oils. Among the volatile compounds formed by the oxidation of different sources of n-3 FA, (E, E) 2,4-heptadienal, (E, E) 2,4-decadienal, decanal, undecanal and (E)-2-undecenal were identified in all samples, and could be used as more specific oxidation markers. Using the accelerated model, rutin hydrate improved the oxidative stability of fish oil, probably due to the presence of catechol groups in its chemical structure. This study showed that faster anays could be performed to evaluate the antioxidant effect of new molecules applied on edible functional oils

Delta6-desaturase sequence evidence for explosive Pliocene radiations within the adaptive radiation of Macaronesian Echium (Boraginaceae).

The oceanic islands of Macaronesia provide an ideal temporal and spatial context to test hypotheses of plant evolution using a novel set of phylogenetic markers, Delta(6)-desaturase sequences. In contrast to the limited resolution of standard molecular markers (nrDNA and plastid sequences), the Delta(6)-desaturase sequence phylogeny of Echium unequivocally reconstructs its active colonization across islands and archipelagos (Madeira, the Canary Islands, and Cape Verde), as well as its subsequent geographical and ecological speciation. Molecular-clock estimates using penalized likelihood and Bayesian inference reveal two radiation processes coincident with two dramatic climatic changes recorded in the region: the advent of the cold Canarian sea current (ca. 4 Ma) and the establishment of a strong seasonality in the Pleistocene (1.8 Ma). Though Echium had available all the diversity of present-day Macaronesian environments (xeric and mesic scrub, laurisilva, pine forest, and subalpine habitats) in the Miocene, evolutionary divergence appears to have been triggered by an extension of fluctuating xeric and mesic habitats with the advent of Pliocene conditions. These Echium radiations not only fulfill traditional predictions of adaptive radiation (i.e., common ancestry, rapid speciation, and phenotype-environment correlation), but also, uniquely among Macaronesian species, trait utility of woodiness. A Pliocene transition from annuality to a bush or tree-like condition occurred in early Echium lineages. Maintenance of woodiness in major lineages, and reversal to an herbaceous condition by three independent events, is reported for the first time in plants of oceanic islands.

Substrate specificity of acyl-Delta(6)-desaturases from Continental versus Macaronesian Echium species.

Echium (Boraginaceae) species from the Macaronesian islands exhibit an unusually high level of gamma-linolenic acid (18:3n-6; GLA) and relatively low content of octadecatetraenoic acid (18:4n-3; OTA) in the seed, while the amounts of both fatty acids in their Continental (European) relatives are rather similar. We have tested the hypothesis of whether a different specificity of the acyl-Delta(6)-desaturases (D6DES) towards their respective usual substrates, linoleic acid (18:2n-6; LA) for GLA and alpha-linolenic acid (18:3n-3; ALA) for OTA, was partly responsible for this composition pattern. To this aim we have expressed in yeast the coding sequences of the D6DES genes for the Continental species Echium sabulicola, and the Macaronesian Echium gentianoides. When the yeast cultures are supplemented with the two fatty acid substrates (LA and ALA), a similar utilization of both compounds was found for the D6DES of E. sabulicola, while a preference for LA over ALA was observed for the enzyme of E. gentianoides. This substrate preference must contribute to the increased accumulation of GLA in the seeds of the Macaronesian Echium species. Comparison among the amino acid sequences of these desaturases and other related enzymes, allowed us the discussion about the possible involvement of some specific positions in the determination of substrate specificity.