The Mitragyna speciosa (Kratom) Genome: a resource for data-mining potent pharmaceuticals that impact human health.

Mitragyna speciosa (kratom) produces numerous compounds with pharmaceutical properties including the production of bioactive monoterpene indole and oxindole alkaloids. Using a linked-read approach, a 1,122,519,462 bp draft assembly of M. speciosa "Rifat" was generated with an N50 scaffold size of 1,020,971 bp and an N50 contig size of 70,448 bp that encodes 55,746 genes. Chromosome counting revealed that "Rifat" is a tetraploid with a base chromosome number of 11, which was further corroborated by orthology and syntenic analysis of the genome. Analysis of genes and clusters involved in specialized metabolism revealed genes putatively involved in alkaloid biosynthesis. Access to the genome of M. speciosa will facilitate an improved understanding of alkaloid biosynthesis and accelerate the production of bioactive alkaloids in heterologous hosts.

Breaks of macrosynteny and collinearity among moth bean (Vigna aconitifolia), cowpea (V. unguiculata), and common bean (Phaseolus vulgaris).

Comparative cytogenetic mapping is a powerful approach to gain insights into genome organization of orphan crops, lacking a whole sequenced genome. To investigate the cytogenomic evolution of important Vigna and Phaseolus beans, we built a BAC-FISH (fluorescent in situ hybridization of bacterial artificial chromosome) map of Vigna aconitifolia (Vac, subgenus Ceratotropis), species with no sequenced genome, and compared with V. unguiculata (Vu, subgenus Vigna) and Phaseolus vulgaris (Pv) maps. Seventeen Pv BACs, eight Vu BACs, and 5S and 35S rDNA probes were hybridized in situ on the 11 Vac chromosome pairs. Five Vac chromosomes (Vac6, Vac7, Vac9, Vac10, and Vac11) showed conserved macrosynteny and collinearity between V. unguiculata and P. vulgaris. On the other hand, we observed collinearity breaks, identified by pericentric inversions involving Vac2 (Vu2), Vac4 (Vu4), and Vac3 (Pv3). We also detected macrosynteny breaks of translocation type involving chromosomes 1 and 8 of V. aconitifolia and P. vulgaris; 2 and 3 of V. aconitifolia and P. vulgaris; and 1 and 5 of V. aconitifolia and V. unguiculata. Considering our data and previous BAC-FISH studies, six chromosomes (1, 2, 3, 4, 5, and 8) are involved in major karyotype divergences between genera and five (1, 2, 3, 4, and 5) between Vigna subgenera, including mechanisms such as duplications, inversions, and translocations. Macrosynteny breaks between Vigna and Phaseolus suggest that the major chromosomal rearrangements have occurred within the Vigna clade. Our cytogenomic comparisons bring new light on the degree of shared macrosynteny and mechanisms of karyotype diversification during Vigna and Phaseolus evolution.

Flavonóides: constituição química, ações medicinais e potencial tóxico / Flavonoids: Chemical composition, medical actions and toxicity

Os flavonóides são um grupo de substâncias naturais com estrutura fenólica variável, e portanto, de considerável interesse científico e terapêutico. Assim, teve-se por objetivo realizar uma revisão bibliográfica, de forma extensa porém objetiva, sobre as principais ações terapêuticas e a toxicidade das principais classes de flavonóides. A partir desta revisão da literatura, verificou-se, em ensaios pré-clínicos, que estes compostos tem o potencial de modificar a biossíntese de eicosanoides (resposta anti-prostanoide e antiinflamatoria); de proteger o colesterol-LDL da oxidacão (inibindo formação de placa aterosclerotica); de prevenir a agregacão plaquetária tendo efeitos anti-trombóticos; de promover o efeito anti-hipertensivo e anti-isquêmico; de regenerar antioxidantes primários, como a vitamina C, no organismo; de ter efeito antipromocionais na carcinogênese de alguns tipos de câncer; de amenizar os sintomas da menopausa; de aumentar a lipólise; de desacelerar o processo degenerativo em bainhas de mielina; de aumentar a secreção de insulina; de aumentar a expressão de genes responsáveis pela produção de proteínas sinápticas; de estimular os linfócitos B a produzirem anticorpos e de possuir atividade leishmanicida. Quanto a toxicidade dos flavonóides, estudos demostram que em altas doses e em utilização crônica, estes compostos desencadeiam reações alérgicas em humanos; modificam as membranas de hepatócitos causando necrose e morte celular em ratos; causam mutagenicidade e clastogenicidade em medula óssea de camundongos; interferem de forma significativa no funcionamento da tireóide e inibe a ação de citocromos P450 causando alterações drásticas no funcionamento do fígado de roedores. Dessa forma, pode-se verificar que os flavonóides tem uma grande capacidade terapêutica quando bem utilizado, devendo-se sempre levar em consideração doses e tempo de exposição aos organismos aos quais são administrados. Essas considerações são importantes por servirão de base para o estabelecimento de doses seguras e eficazes de utilização dos flavonóides para a população.

Flavonoids are a group of natural substances with variable phenolic structure and therefore, considerable scientific interest and therapeutic. Thus, the objective was to conduct a literature review of but objective extensively on major therapeutic actions and on the toxicity of flavonoids class. In this literature review, it was found that, in preclinical studies, these compounds have the potential to modify the biosynthesis of eicosanoids; protect LDL cholesterol from oxidation; prevent platelet aggregation with antithrombotic effects; promote the antihypertensive and anti-ischemic effect; regenerate primary antioxidants like vitamin C in the body; not to promote some carcinogenic effects on certain types of cancer; alleviate menopausal symptoms; increase lipolysis; slow down degenerative process in myelin sheaths; increase insulin secretion; increase the expression of genes responsible for the production of synaptic proteins; stimulate lymphocytes B to produces antibodies and have leishmanicydal activity. About the toxicity of flavonoids, studies show that, at high doses and in chronic use, these compounds trigger allergic reactions in humans; modify the membranes of hepatocytes, causing necrosis and cell death, in rats; cause mutagenicity and clastogenicity in mouse bone marrow, interfere significantly on thyroid function and inhibit the action of cytochrome P450, causing drastic changes in the function of the liver in rodents. Thus, it can be seen that the flavonoids have a wide therapeutic capacity when properly used, taking into account doses and exposure times to whom they are administered. These considerations are important because they set the bases for the establishment of safe and effective doses of flavonoids on the population.

Flavonóides: constituiþÒo química, aþ§es medicinais e potencial tóxico / Flavonoids: Chemical composition, medical actions and toxicity

Os flavonóides sÒo um grupo de substÔncias naturais com estrutura fenólica variável, e portanto, de considerável interesse científico e terapÛutico. Assim, teve-se por objetivo realizar uma revisÒo bibliográfica, de forma extensa porém objetiva, sobre as principais aþ§es terapÛuticas e a toxicidade das principais classes de flavonóides. A partir desta revisÒo da literatura, verificou-se, em ensaios pré-clínicos, que estes compostos tem o potencial de modificar a biossíntese de eicosanoides (resposta anti-prostanoide e antiinflamatoria); de proteger o colesterol-LDL da oxidacÒo (inibindo formaþÒo de placa aterosclerotica); de prevenir a agregacÒo plaquetária tendo efeitos anti-trombóticos; de promover o efeito anti-hipertensivo e anti-isquÛmico; de regenerar antioxidantes primários, como a vitamina C, no organismo; de ter efeito antipromocionais na carcinogÛnese de alguns tipos de cÔncer; de amenizar os sintomas da menopausa; de aumentar a lipólise; de desacelerar o processo degenerativo em bainhas de mielina; de aumentar a secreþÒo de insulina; de aumentar a expressÒo de genes responsáveis pela produþÒo de proteínas sinápticas; de estimular os linfócitos B a produzirem anticorpos e de possuir atividade leishmanicida. Quanto a toxicidade dos flavonóides, estudos demostram que em altas doses e em utilizaþÒo cr¶nica, estes compostos desencadeiam reaþ§es alérgicas em humanos; modificam as membranas de hepatócitos causando necrose e morte celular em ratos; causam mutagenicidade e clastogenicidade em medula óssea de camundongos; interferem de forma significativa no funcionamento da tireóide e inibe a aþÒo de citocromos P450 causando alteraþ§es drásticas no funcionamento do fígado de roedores. Dessa forma, pode-se verificar que os flavonóides tem uma grande capacidade terapÛutica quando bem utilizado, devendo-se sempre levar em consideraþÒo doses e tempo de exposiþÒo aos organismos aos quais sÒo administrados. Essas consideraþ§es sÒo importantes por servirÒo de base para o estabelecimento de doses seguras e eficazes de utilizaþÒo dos flavonóides para a populaþÒo.(AU)

Flavonoids are a group of natural substances with variable phenolic structure and therefore, considerable scientific interest and therapeutic. Thus, the objective was to conduct a literature review of but objective extensively on major therapeutic actions and on the toxicity of flavonoids class. In this literature review, it was found that, in preclinical studies, these compounds have the potential to modify the biosynthesis of eicosanoids; protect LDL cholesterol from oxidation; prevent platelet aggregation with antithrombotic effects; promote the antihypertensive and anti-ischemic effect; regenerate primary antioxidants like vitamin C in the body; not to promote some carcinogenic effects on certain types of cancer; alleviate menopausal symptoms; increase lipolysis; slow down degenerative process in myelin sheaths; increase insulin secretion; increase the expression of genes responsible for the production of synaptic proteins; stimulate lymphocytes B to produces antibodies and have leishmanicydal activity. About the toxicity of flavonoids, studies show that, at high doses and in chronic use, these compounds trigger allergic reactions in humans; modify the membranes of hepatocytes, causing necrosis and cell death, in rats; cause mutagenicity and clastogenicity in mouse bone marrow, interfere significantly on thyroid function and inhibit the action of cytochrome P450, causing drastic changes in the function of the liver in rodents. Thus, it can be seen that the flavonoids have a wide therapeutic capacity when properly used, taking into account doses and exposure times to whom they are administered. These considerations are important because they set the bases for the establishment of safe and effective doses of flavonoids on the population.(AU)