Effects of light regulation on the synthesis of secondary metabolites in medicinal plants / 药学实践杂志

Secondary metabolites of medicinal plants are extremely important to human health because of their special pharmacological activities or efficacy. They are the main source of drugs, health care products, and cosmetics. As human beings continue to pursue health and longevity, the demand in the pharmaceutical market continues to grow. It becomes especially important to improve the production and quality of secondary metabolites of medicinal plants. Plant secondary metabolites are a kind of adaptation of plants to their environment and are the result of the interaction between plants and biotic and abiotic factors during the long-term evolution process. The production and accumulation of secondary metabolites in medicinal plants are mainly affected by plant genetic factors and environmental factors. Among them, light environment is extremely important for their synthesis. Therefore, light regulation has long been a research focus for many scholars in China and abroad. In this article, we the recent research progress on the effects of light regulation on the secondary metabolites of medicinal plants were reviewed, mainly focusing on the effects of light quality, light intensity and photoperiod, in order to provide theoretical basis and practical guidance for the efficient production of secondary metabolites with important pharmacological activities.

Seasonal effect on phenolic content and antioxidant activity of young, mature and senescent leaves from Anredera cordifolia (Ten. ) Steenis (Basellaceae) / Efeito sazonal no conteúdo de fenólicos e ação antioxidante de folhas jovens, maduras e senescentes de Anredera cordifolia (Ten. ) Steenis (Basellaceae)

Anredera cordifolia (Ten.) Steenis is a vine species native to Brazil that is considered an unconventional food plant and a medicinal species whose phenolic compounds exert antioxidant activity. Since the production of metabolites is determined by environmental factors and leaf maturity, it is important to track these changes in order to determine the best time to harvest. This study aimed to verify whether leaf phenology and seasonality cause variations in the amount of phenolic compounds and in the antioxidant activity of this species. The leaves were collected in different seasons between September 2018 and April 2019, and separated according to maturity: young, mature, and senescent. Daily atmospheric temperature and rainfall data were used to characterize the collection period. The total phenolic content (TPC), determined by Folin-Ciocalteu method, was significantly higher in the young leaves collected in winter, a season of lower temperatures. These leaves showed 54.4 mg of gallic acid equivalents per 100 g of dry matter (mg GAE 100 g-1DM). Other results averaged 25.6 mg GAE 100 g-1DM. The highest antioxidant activity, assessed via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, regardless of leaf phenology, was observed in leaves harvested in autumn (73.7%) and winter (71.1%), seasons with lower rainfall. Leaves harvested in summer and spring had lower antioxidant action rates (54.3 e 37.5%, respectively). There was no significant correlation between the total phenolic content and antioxidant activity. Thus, the phenolic composition of A. cordifolia, and consequently its activity on free radicals, varies seasonally in response to temperature and rainfall, and may or may not interact with the age of the leaves.

Anredera cordifolia (Ten.) Steenis é uma trepadeira nativa do Brasil considerada uma planta alimentícia não convencional e uma espécie medicinal, cujos compostos fenólicos exercem ação antioxidante. Como a produção de metabólitos é determinada por fatores ambientais e pela maturidade das folhas, é importante acompanhar essas mudanças a fim de determinar a época de colheita. Neste estudo objetivou-se verificar se a fenologia foliar e a sazonalidade ocasionam variação na quantidade de compostos fenólicos e na ação antioxidante dessa espécie. As folhas foram coletadas em diferentes estações, entre setembro de 2018 e abril de 2019, e separadas conforme a maturidade: jovens, maduras e senescentes. Os dados diários de temperatura atmosférica e pluviosidade foram usados para caracterizar o período de coleta. O conteúdo de fenólicos totais (TPC), determinado pelo método Folin-Ciocalteu, foi significativamente maior nas folhas jovens coletadas no inverno, período caracterizado por temperaturas mais baixas. Estas folhas apresentaram 54,4 mg equivalentes de ácido gálico por 100 g de matéria seca (mg GAE 100 g-1DM) . A média dos outros resultados foi de 25,6 mg GAE 100 g-1DM. A maior ação antioxidante, avaliada pelo método do radical livre 2,2-difenil-1-picrilhidrazil (DPPH), foi observada em folhas colhidas no outono (73,7%) e inverno (71,1%), independentemente da fenologia foliar. Nestes períodos a pluviosidade foi menor. Folhas colhidas no verão e na primavera apresentaram menores percentuais de ação antioxidante (54,3 e 37,5%, respectivamente). Não houve correlação significativa entre o conteúdo de fenólicos totais e a atividade antioxidante. Conclui-se que a composição fenólica de A. cordifolia e, consequentemente, sua ação sobre radicais livres, varia sazonalmente em resposta à temperatura e pluviosidade, podendo ou não interagir com a idade das folhas.

Analysis of Differences in Secondary Metabolites from Dendrobium nobile Stems Cultivated on Epiphytic Rocks in Different Growth Years Based on Metabolomics / 中国实验方剂学杂志

ObjectiveTo study the changing characteristics of secondary metabolic compounds accumulated in Dendrobium nobile stems at different growth years， a simulated wild stone plant， in order to provide a theoretical basis for rational planning of the harvesting period of D. nobile. MethodUltra-high performance liquid chromatography-mass spectrometry（UPLC-MS/MS） was used to detect and analyze the secondary metabolites in the stems of 1-year-old， 2-year-old， and 3-year-old D. nobile. The mass spectrometry data were processed using Analyst 1.6.3 software， and all samples were subjected to principal component analysis（PCA）， cluster heat map analysis， partial least squares-discriminant analysis（PLS-DA）， and differential secondary metabolites were screened based on variable importance in projection（VIP） values>1， fold change（FC）≥2 and FC≤0.5. Then differential secondary metabolites were identified based on relative molecular weight， fragmentation ions and mass spectrometry database， and enriched pathways were identified based on the Kyoto Encyclopedia of Genes and Genomes（KEGG） database. ResultA total of 1 317 secondary metabolites were identified in the stems of D. nobile at three growth stages， with flavonoids， phenolic acids， alkaloids and terpenoids accounting for 76.55% of the total. Compared with the 1-year-old stems of D. nobile， 289 differential secondary metabolites were identified in the 2-year-old stems， of which 255 were up-regulated and 34 were down-regulated， 682 differential secondary metabolites were identified in the 3-year-old stems， of which 502 were up-regulated and 180 were down-regulated. Compared to the 2-year-old stems， the 3-year-old stems had 602 differential secondary metabolites， with 405 up-regulated and 197 down-regulated. As the growth stage of D. nobile increased， the top 10 up-regulated differential metabolites mainly included flavonoids， phenolic acids， phenylpropanoids and terpenoids， such as kaempferol derivatives， asperulosidic acid， apigenin derivatives， chrysoeriol derivatives， isorhamnetin derivatives， taxifolin derivatives， quercetin derivatives. KEGG enrichment analysis showed significant enrichment of secondary metabolites in the flavonoid biosynthesis， flavone， and flavonol biosynthesis， secondary metabolite biosynthesis， and phenylpropanoid biosynthesis pathways with the increase of growth years. ConclusionWith the increase of the growth years， the levels of secondary metabolites such as flavonoids， phenolic acids， phenylpropanoids and terpenoids in the wild-grown D. nobile have been significantly enhanced. In practical production， grading based on different growth years can be carried out to improve the medicinal and economic values of D. nobile.

Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreatic OL cells into pancreatic β cells / 中国药理学通报

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Relationship between metabolites of peripheral tryptophan-kynurenine metabolic pathway and clinical symptoms in patients with schizophrenia / 四川精神卫生

BackgroundSchizophrenia is a common severe mental disorder with complex pathogenesis. There are few studies on the correlation between kynurenine metabolites in peripheral serum and urine in schizophrenia. ObjectiveTo investigate the concentration of tryptophan-kynurenine metabolites and interleukin-6 （IL-6） in serum and urine in patients with schizophrenia， and their correlation with clinical symptoms， so as to explore potential biological characteristics related to schizophrenia. MethodsA total of 38 patients with schizophrenia who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and were hospitalized or attended outpatient clinic at Hangzhou Seventh People's Hospital from December 2021 to December 2022 were included in the study. Additionally， 26 healthy individuals were concurrently recruited from the community of Hangzhou to serve as a control group. All participants were requested to complete the Positive and Negative Symptom Scale （PANSS）. The levels of tryptophan （TRP）， kynurenine （KYN）， kynurenic acid （KYNA）， quinolinic acid （QUIN）， picolinic acid （PIC）， xanthurenate and 5-hydroxytryptamine （5-HT） in both serum and urine were measured using ultra-high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry. Serum and urine IL-6 were measured using enzyme-linked immunosorbent assay. Pearson correlation analysis was conducted to examine the correlation between serum and urinary KYN metabolites， as well as the correlation between metabolite levels and clinical symptoms in the patient group. ResultsPatients with schizophrenia had significantly higher level of IL-6 in serum （U=798.500， P<0.01） and lower level of PIC in urine （U=253.000， P=0.013） compared with the control group. Additionally， level of serum KYN was positively correlated with QUIN/KYNA ratio and QUIN/PIC ratio （r=0.562， 0.438， P<0.05） in patients with schizophrenia. 5-HT/KYN ratio in serum was positively correlated with PANSS total score and negative symptom subscale score （r=0.458， 0.455， P<0.01） in patients with schizophrenia. ConclusionSerum TRP-KYN pathway metabolite levels in patients with schizophrenia were associated with neurotoxic metabolite ratios in urine and the severity of negative symptoms. ［Funded by Zhejiang Medical and Health Science and Technology Program Exploratory （number， 2022KY990）］

Seasonal effect on phenolic content and antioxidant activity of young, mature and senescent leaves from Anredera cordifolia (Ten.) Steenis (Basellaceae)

Abstract Anredera cordifolia (Ten.) Steenis is a vine species native to Brazil that is considered an unconventional food plant and a medicinal species whose phenolic compounds exert antioxidant activity. Since the production of metabolites is determined by environmental factors and leaf maturity, it is important to track these changes in order to determine the best time to harvest. This study aimed to verify whether leaf phenology and seasonality cause variations in the amount of phenolic compounds and in the antioxidant activity of this species. The leaves were collected in different seasons between September 2018 and April 2019, and separated according to maturity: young, mature, and senescent. Daily atmospheric temperature and rainfall data were used to characterize the collection period. The total phenolic content (TPC), determined by Folin-Ciocalteu method, was significantly higher in the young leaves collected in winter, a season of lower temperatures. These leaves showed 54.4 mg of gallic acid equivalents per 100 g of dry matter (mg GAE 100 g-1DM). Other results averaged 25.6 mg GAE 100 g-1DM. The highest antioxidant activity, assessed via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, regardless of leaf phenology, was observed in leaves harvested in autumn (73.7%) and winter (71.1%), seasons with lower rainfall. Leaves harvested in summer and spring had lower antioxidant action rates (54.3 e 37.5%, respectively). There was no significant correlation between the total phenolic content and antioxidant activity. Thus, the phenolic composition of A. cordifolia, and consequently its activity on free radicals, varies seasonally in response to temperature and rainfall, and may or may not interact with the age of the leaves.

Resumo Anredera cordifolia (Ten.) Steenis é uma trepadeira nativa do Brasil considerada uma planta alimentícia não convencional e uma espécie medicinal, cujos compostos fenólicos exercem ação antioxidante. Como a produção de metabólitos é determinada por fatores ambientais e pela maturidade das folhas, é importante acompanhar essas mudanças a fim de determinar a época de colheita. Neste estudo objetivou-se verificar se a fenologia foliar e a sazonalidade ocasionam variação na quantidade de compostos fenólicos e na ação antioxidante dessa espécie. As folhas foram coletadas em diferentes estações, entre setembro de 2018 e abril de 2019, e separadas conforme a maturidade: jovens, maduras e senescentes. Os dados diários de temperatura atmosférica e pluviosidade foram usados para caracterizar o período de coleta. O conteúdo de fenólicos totais (TPC), determinado pelo método Folin-Ciocalteu, foi significativamente maior nas folhas jovens coletadas no inverno, período caracterizado por temperaturas mais baixas. Estas folhas apresentaram 54,4 mg equivalentes de ácido gálico por 100 g de matéria seca (mg GAE 100 g-1DM) . A média dos outros resultados foi de 25,6 mg GAE 100 g-1DM. A maior ação antioxidante, avaliada pelo método do radical livre 2,2-difenil-1-picrilhidrazil (DPPH), foi observada em folhas colhidas no outono (73,7%) e inverno (71,1%), independentemente da fenologia foliar. Nestes períodos a pluviosidade foi menor. Folhas colhidas no verão e na primavera apresentaram menores percentuais de ação antioxidante (54,3 e 37,5%, respectivamente). Não houve correlação significativa entre o conteúdo de fenólicos totais e a atividade antioxidante. Conclui-se que a composição fenólica de A. cordifolia e, consequentemente, sua ação sobre radicais livres, varia sazonalmente em resposta à temperatura e pluviosidade, podendo ou não interagir com a idade das folhas.

Trichoderma spp., una alternativa para la agricultura sostenible: una revisión

En la actualidad uno de los retos a los que se enfrentan los agricultores es producir alimentos bajo las inclemencias climáticas. Para el 2050, se estima un aumento en la demanda en producción de alimentos básicos a causa del incremento demográfico, aumentando con ello el detrimento de los recursos naturales. Dentro de las alternativas biológicas está el uso de insumos a base de microorganismos benéficos, como el género Trichoderma. Los cuales se han utilizado en los campos agrícolas para el control biológico contra un gran número de fitopatógenos. Sin embargo, aún son poco conocidas otras propiedades benéficas de este género para las plantas que coloniza y el ecosistema. Se realizó una búsqueda de artículos científicos en Academic Search Ultimate, BioOne, Acsess, Esmerald, Fuente Académica, ScienceDirect y Springer, entre 2015 y 2023, con dos excepciones de años anteriores. Se utilizó la palabra clave "Trichoderma" y aquellas relacionadas con interacciones microbianas y su aplicación agrícola. Esta revisión resume los hallazgos bibliográficos actuales de este género que muestran su alta capacidad hacia el desarrollo sostenible de los agroecosistemas. Varias investigaciones reportan su capacidad de inducir la defensa vegetal, la promoción del crecimiento y desarrollo radicular, así como la estimulación y síntesis de sustancias que contribuyen a fortalecer la fertilidad del suelo. Con ello mejora los rendimientos de los cultivos a los que se encuentra asociado. En definitiva, la aplicación de Trichoderma puede coadyuvar a disminuir los efectos negativos ocasionados por el uso de agroquímicos y fertilizantes sintéticos, contribuyendo a una producción más sostenible.

Currently, one of the most critical challenges facing farmers is the production of food under adverse weather conditions. By 2050, an increase in the production of staple foods is estimated due to demographics, thereby increasing the depletion of natural resources. Among the biological alternatives is the use of inputs based on beneficial microorganisms such as the Trichoderma genus, which have been used in agricultural fields for biological control against a large number of phytopathogens. However, other beneficial properties of this genus for the plants it colonizes, and the ecosystem are still little known. Therefore, a search for scientific articles was carried out in Academic Search Ultimate, BioOne, Acsess, Esmerald, Fuente Academic, ScienceDirect and Springer, between 2015 and 2023, with two exceptions from previous years. The keyword "Trichoderma" was used and those related to microbial interactions and their agricultural application. Therefore, this review summarizes the current bibliographic findings of this genus, that shows its high capacity towards the sustainable development of agroecosystems. Several investigations report its ability to induce plant defense, promote growth and root development, and stimulate and synthesize substances that help strengthen soil fertility. This improves the yields of the crops to which they are associated. With this, the application of Trichoderma can reduce the negative effects caused by the use of agrochemicals and synthetic fertilizers, contributing to a more sustainable production.

Reserve mobilization and secondary metabolites during seed germination and seedling establishment of the tree Erythrina velutina (Fabaceae) / Movilización de reservas y metabolitos secundarios durante la germinación de semillas y el establecimiento de plántulas del árbol Erythrina velutina (Fabaceae)

Introduction: The lack of knowledge on seed germination and seedling establishment is a main constraint for the restoration of degraded areas, including the tropical dry forest known as Caatinga. Objective: To assess reserve and secondary metabolite mobilization during seed germination and seedling establishment in Erythina velutina. Methods: We scarified, disinfected, imbibed, sown between towel paper, and incubated seeds under controlled conditions. We hydroponically cultivated seedlings in a greenhouse. We harvested cotyledons at seed imbibition, radicle protrusion, hypocotyl emergence, apical hook formation and expansion of cordiform leaves, first trifoliate leaf, and second trifoliate leaf. Results: Seeds contained approximately 20 % starch, 14.5 % storage proteins, 11.6 % neutral lipids, and 5.7 % non-reducing sugars on a dry weight basis. Soluble sugars were mainly consumed from hypocotyl emergence to apical hook formation, while major reserves were mobilized from apical hook formation to expansion of first trifoliate leaf. Enzymatic activity increased from mid to late seedling establishment, causing the mobilization of starch, oils, and proteins. Terpenoid-derivatives, flavonoids, phenolic acids, and alkaloids were detected. Flavonoids and phenolic acids were present at almost all stages and terpenoid-derivatives disappeared at expansion of cordiform leaves. Conclusion: Soluble sugars support early seedling growth, while starch, oils and proteins are simultaneously mobilized from mid to late establishment by amylases, lipases, and acid proteases. The cotyledons contain secondary metabolites, which may act in seedling defense. High content of reserves and presence of secondary metabolites in the cotyledons could enable E. velutina seedlings endure stress, validating their use in the restoration of degraded areas.

Introducción: La falta de conocimiento sobre la germinación de semillas y el establecimiento de plántulas es una de las principales limitaciones para la restauración de áreas degradadas, incluido el bosque seco tropical conocido como Caatinga. Objetivo: Evaluar la movilización de reservas y metabolitos secundarios durante estas etapas de desarrollo en Erythina velutina. Métodos: Las semillas fueron escarificadas, desinfectadas, embebidas, sembradas entre toallas de papel e incubadas bajo condiciones controladas. Cultivamos las plántulas hidropónicamente en un invernadero. Recolectamos los cotiledones en la imbibición de la semilla, la protrusión de la radícula, la emergencia del hipocótilo, la formación del gancho apical y la expansión de las hojas cordiformes, la primera y segunda hoja trifoliada. Resultados: Las semillas contenían 20 % de almidón, 14.5 % de proteínas de almacenamiento, 11.6 % de lípidos neutros y 5.7 % de azúcares no reductores en peso seco. Los azúcares solubles se consumieron desde la emergencia del hipocótilo hasta la formación del gancho apical. Las principales reservas se movilizaron desde la formación del gancho apical hasta la expansión de la primera hoja trifoliada. La actividad enzimática aumentó desde la mitad hasta el final del establecimiento de las plántulas, movilizando almidón, aceites y proteínas. Se detectaron derivados de terpenoides, flavonoides, ácidos fenólicos y alcaloides. Los flavonoides y los ácidos fenólicos estuvieron en casi todas las etapas y los derivados terpenoides desaparecieron en la expansión de las hojas cordiformes. Conclusión: Los azúcares solubles apoyan el crecimiento temprano de las plántulas; el almidón, los aceites y las proteínas se movilizan simultáneamente desde el establecimiento medio hasta el final por amilasas, lipasas y proteasas ácidas. Los cotiledones contienen metabolitos secundarios, que pueden actuar en la defensa de las plántulas. El alto contenido de reservas y los metabolitos secundarios en los cotiledones podría permitir que las plántulas de E. velutina toleren estrés, validando su uso en la restauración de áreas degradadas.

Traditional medicinal uses and biological activities of species of the genus Desmodium: a literature review / Usos medicinales tradicionales y actividades biológicas de las especies del género Desmodium: una revisión de la literatura

The genus Desmodium includes about 350 species, distributed in tropical and subtropical regions around the world. The objective of this review wa s to associate the traditional medicinal uses of the genus Desmodium with its biological activities reported in the scientific literature. Traditional medicinal uses and biological activities were described in 56 species. More than 100 traditional medicina l uses have been reported in 43 countries, highlighting the use in inflammatory, gastrointestinal and infectious processes, muscular pain, rheumatic, renal and hepatic affections. Among the 45 biological activities experimentally evaluated, antioxidant, an timicrobial, anti - inflammatory, hepatoprotective and antinociceptive were the most reported. The species with the highest number of studies were D. gangeticum, D. adscendens and D. styracifolium. In conclusion, several traditional medicinal uses have been experimentally supported, demonstrating the pharmacological potential of this genus.

El género Desmodium incluye alrededor de 350 especie s, distribuidas en regiones tropicales y subtropicales alrededor del mundo. El objetivo de esta revisión fue asociar los usos medicinales tradicionales del género Desmodium con sus actividades biológicas reportadas en la literatura científica. Los usos med icinales tradicionales y las actividades biológicas fueron descritos en 56 especies. Más de 100 usos medicinales tradicionales han sido reportados en 43 países, destacándose el uso en procesos inflamatorios, gastrointestinales e infecciosos, dolores muscul ares, reumáticos, afecciones renales y hepáticas. Dentro de las 45 actividades biológicas evaluadas experimentalmente, las más reportadas fueron la antioxidante, antimicrobiana, antiinflamatoria, hepatoprotectora y antinociceptiva. Las especies con mayor n úmero de estudios fueron D. gangeticum, D. adscendens y D. styracifolium. En conclusión, varios usos medicinales tradicionales han sido experimentalmente respaldados, demostrando el potencial farmacológico de este género.

A comparative study on surgical outcomes of trabeculectomy with and without anti-metabolites in juvenile open-angle glaucoma

Purpose: To compare the surgical outcomes of trabeculectomy with and without anti?metabolites in patients with juvenile open?angle glaucoma (JOAG). Methods: This retrospective comparative case series included 98 eyes of 66 patients with JOAG who underwent either trabeculectomy without anti?metabolites (group A, n = 53 eyes) or with anti?metabolites (group B, n = 45 eyes) with a minimum of 2 years follow?up. The main outcome measures were intra?ocular pressure (IOP), number of glaucoma medications, visual acuity, additional surgical interventions, surgical complications, and risk factors for failure. Surgical failure was defined as IOP >18 mmHg or failure to reduce IOP by <30% from the baseline value or IOP ?5 mmHg or re?operation for refractory glaucoma or a complication or loss of light perception vision. Results: The mean post?operative IOP reduced significantly from baseline at all post?operative visits until 6 months and thereafter. The cumulative probability of failure at 2 years was 28.7% in group A [95% confidence interval (CI) = 17.6–44.8%] and 29.1% in group B (95% CI = 17.1–46.7%) (P = 0.78). Surgical complications occurred in 18 eyes (34%) in group A and 19 eyes (42%) in group B. Re?operations for glaucoma or complications were performed in two eyes (3.8%) in group A and two eyes (4.4%) in group B. Cox?hazard regression model revealed male gender (HR = 0.29; P = 0.008), baseline high IOP (HR = 0.95; P = 0.002), and an increased number of pre?operative glaucoma medications (HR = 2.08; P = 0.010) as significant factors associated with failure. Conclusion: Our study results on trabeculectomy in JOAG revealed a success of 71% in both groups at 2 years follow?up. There was no significant difference in success or failure rates between the two groups. The risk factors for poor surgical outcome in JOAG were male gender, baseline high IOP, and an increased number of glaucoma medications

Phytochemical Characterization and Systemic Exposure of Bioactive Metabolites of the Aqueous Extracts of Ficus thonningii Blume (Moraceae) on Albino Wistar Rats

Ficus thonningii (Blume) is considered as a herbal plant with well documented biological activity in the management of several diseases in the tropics. However, there is a gap of information on its safety and proof of efficacy in evidence-based medicine. The objective of this study was to characterize the bioactive metabolites of the hydro-ethanolic extract of the stem bark of Ficus. thonningii and in vivo evaluation of the systemic exposure of the bioactive metabolite. Phytochemical screening was done using standard extraction techniques, and test according to methods adopted from Sofowora and collaborators. Quantitative analysis was done using spectrophotometer of plant extract with different reference standards. Analysis of the animals' plasma following administration of the extract was used to investigate systemic exposure to confirmed the presence of absence of metabolites in systemic circulation. This work shows that F. thonningii (Blume) stem bark hydro-ethanolic extract contains polyphenols, saponins, alkaloids, flavonoids, catechic tannins, gallic tannins, coumarins, quinones, phlobatannins. This study shows that the hydro-ethanolic extract of F. thonningii contains total phenolic content of 192,27 ± 3,40 mgEQ/MS g gallic acid and total flavonoid content of 103,59 ± 15,72 mgEQ/MS quercetin. This study shows that the secondary metabolites in the hydro-ethanolic extract of the stem bark of F. thonningii (Blume) were not detected in plasma and not bioavailable.

Potencial antiinflamatorio del plátano Musa spp. ABB para la elaboración de fitofármacos

Los plátanos pertenecientes al género Musa spp. ABB han sido utilizados para el tratamiento de la inflamación y el dolor. La búsqueda de antiinflamatorios de origen natural, más que una alternativa, constituye una terapia complementaria del tratamiento de la inflamación, ya que los antiinflamatorios no esteroideos son los más utilizados para enfermedades inflamatorias agudas o crónicas, pero a la vez presentan efectos secundarios gastrointestinales, cardiovasculares y renales, por lo que no es recomendable su uso prolongado. En este trabajo se ofrece información actualizada sobre los efectos farmacológicos y los metabolitos secundarios del grupo Musa spp. ABB, para su uso en la elaboración de un medicamento antiinflamatorio. Los procedimientos realizados incluyen el análisis documental y bibliográfico -en bases de datos- de artículos científicos, tesis doctorales y comunicaciones científicas; el registro de la información, y la elaboración del artículo científico, teniendo en cuenta la actualización de la información y los sitios donde se promueve la misma. Se han comprobado, a partir de extractos acuosos y alcohólicos de la planta, efectos farmacológicos tales como antiinflamatorio, antioxidante, analgésico, gastroprotector, inmunomodulador, antidiabético, anticancerígeno, antibacteriano, antiviral, hipolipemiante, antidiarreico, antihipertensivo, hepatoprotector, cicatrizante, antiulceroso y antifúngico. Los efectos antiinflamatorios y antioxidantes están relacionados con la presencia de fenoles, ácidos fenólicos, flavonoides, fitoesteroles y carotenos. Es muy limitado el empleo de extractos del grupo Musa spp. ABB en medicamentos, de ahí la propuesta de desarrollar una crema antiinflamatoria como alternativa o complemento para el tratamiento de múltiples enfermedades inflamatorias.

Plantains belonging to the genus Musa spp. ABB have been used for the treatment of infection and pain. The search for anti-inflammatories of natural origins, more than an alternative, is a complementary therapy for the treatment of inflammation, since non-steroidal anti-inflammatories are the most used for acute or chronic inflammatory diseases, but at the same time they present gastrointestinal, cardiovascular and renal side effects, so their prolonged use is not recommended. In this paper, updated information is provided on the pharmacological effects and secondary metabolites of the Musa ssp. ABB group, for its use in elaborating an anti-inflammatory drug. The procedures carried out include documental and bibliographic analysis -in databases-of scientific articles, doctoral theses and scientific communications; the information record and preparation of the article taking into account the information updating and the sites where it is supported. From aqueous and alcoholic extracts of the plant, the following effects were proven: anti-inflammatory, antioxidant, analgesic, gastro-protective, inmuno-modulator, antidiabetic, anticancer, antibacterial, antiviral, lipid-lowering, antidiarrheal, antihypertensive, hepatoprotective, healing, anti-ulcerative and antifungal. The anti-inflammatory and antioxidant effects are related to the presence of phenols, phenolic acids, flavonoids, phytosterols and carotenes. The use of Musa spp. ABB group in drugs is very limited, therefore the proposal of developing an anti-inflammatory cream to treat multiple inflammatory diseases.

Atividade in vitro de extratos e frações de Copernicia prunifera (Arecaceae) contra bactérias de importância clínica em saúde pública / In vitro activity of extracts and fractions of Copernicia prunifera (Arecaceae) against bacteria of clinical importance in public health / Actividad in vitro de extractos y fracciones de Copernicia prunifera (Arecaceae) frente a bacterias de importancia clínica en salud pública

Introdução: O aumento contínuo da resistência bacteriana aos antibióticos convencionais é um problema de importância global. Encontrar produtos como alternativas terapêuticas naturais é essencial. As plantas medicinais possuem uma composição química muito rica, que podem ser estruturalmente otimizadas e processadas em novos antimicrobianos. Objetivo: Avaliar o potencial antibacteriano frente a microrganismos humanos potencialmente patogênicos do extrato etanólico e frações de Copernicia prunifera. Metodologia: A triagem fitoquímica de plantas foi realizada usando métodos de precipitação e coloração e a atividade antibacteriana utilizando o método de difusão em disco e microdiluição em caldo contra cepas padronizadas de Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa e Staphylococcus aureus. Resultados: A triagem fitoquímica revela a presença de taninos, flavonoides, esteroides, triterpernóides, saponinas e alcaloides. Os extratos etanólico e frações da casca do caule e folhas tiveram atividade inibitória contra S. aureus e K. pneumonie com zona de inibição que variou de 7,0±1,73 a 9,33±0,58 mm pelo método de difusão em disco. Pelo método de microdiluição em caldo os extratos foram satisfatórios somente contra K. pneumoniae (CIM = 125 a 1000 µg/mL) S. aureus, P. aeruginosa e E. coli se mostraram resistentes aos testes (CIM > 1000 µg/mL). Conclusão: Esses resultados fornecem uma base para futuras investigações em modelos in vivo, para que os compostos de C. prunifera possam ser aplicados no desenvolvimento de novos agentes antimicrobianos contra K. pneumoniae.

Introduction: The continuous increase in bacterial resistance to conventional antibiotics is a problem of global importance. Finding products as natural therapeutic alternatives is essential. Medicinal plants have a very rich chemical composition, which can be structurally optimized and processed into novel antimicrobials. Objective: To evaluate the antibacterial potential against potentially pathogenic human microorganisms of the ethanolic extract and fractions of Copernicia prunifera. Methodology: Phytochemical screening of plants was performed using precipitation and staining methods and antibacterial activity using the disk diffusion and broth microdilution method against standardized strains of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Results: Phytochemical screening reveals the presence of tannins, flavonoids, steroids, triterpernoids, saponins and alkaloids. The ethanolic extracts and fractions of stem bark and leaves had inhibitory activity against S. aureus and K. pneumonie with zone of inhibition ranging from 7.0±1.73 to 9.33±0.58 mm by disc diffusion method. By broth microdilution method the extracts were satisfactory only against K. pneumoniae (MIC = 125 to 1000 µg/mL) S. aureus, P. aeruginosa and E. coli were resistant to the tests (MIC > 1000 µg/mL). Conclusion: These results provide a basis for further investigation in in vivo models, so that compounds from C. prunifera can be applied in the development of new antimicrobial agents against K. pneumoniae.

Introducción: El continuo aumento de la resistencia bacteriana a los antibióticos convencionales es un problema de importancia mundial. Es esencial encontrar productos como alternativas terapéuticas naturales. Las plantas medicinales tienen una composición química muy rica, que puede optimizarse estructuralmente y transformarse en nuevos antimicrobianos. Objetivo: Evaluar el potencial antibacteriano frente a microorganismos humanos potencialmente patógenos del extracto etanólico y fracciones de Copernicia prunifera. Metodología: Se realizó el cribado fitoquímico de las plantas mediante los métodos de precipitación y tinción y la actividad antibacteriana mediante el método de difusión en disco y microdilución en caldo frente a cepas estandarizadas de Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa y Staphylococcus aureus. Resultados: El cribado fitoquímico revela la presencia de taninos, flavonoides, esteroides, triterpernoides, saponinas y alcaloides. Los extractos etanólicos y las fracciones de la corteza del tallo y las hojas presentaron actividad inhibitoria contra S. aureus y K. pneumonie con una zona de inhibición que osciló entre 7,0±1,73 y 9,33±0,58 mm por el método de difusión en disco. Por el método de microdilución en caldo, los extractos sólo fueron satisfactorios frente a K. pneumoniae (CMI = 125 a 1000 µg/mL). S. aureus, P. aeruginosa y E. coli fueron resistentes a las pruebas (CMI > 1000 µg/mL). Conclusiones: Estos resultados proporcionan una base para futuras investigaciones en modelos in vivo, de modo que los compuestos de C. prunifera puedan aplicarse en el desarrollo de nuevos agentes antimicrobianos contra K. pneumoniae.

Insecticidal potential of organic extracts of Calotropis procera to Spodoptera frugiperda

This study evaluated the toxic effects of organic extracts of Calotropis proceraleaves on the survival, development, and reproduction of Spodoptera frugiperda. Solutions of crude methanol extract and hexane and methanol fractions of C. proceraleaves were added at 1.15% and 2.14% concentrations to the artificial diet of S. frugiperda. The mortality and duration of larval and pupal phases, weights of female and male pupae, deformations of pupae and adults, the reduction of adults able to reproduce, pre-oviposition and oviposition periods, the number of postures per female, and the fecundity and fertility of S. frugiperdafemales were also evaluated. The extracts harmed the survival, development, and reproduction of S. frugiperda. The ingestion of extracts and fractions by caterpillars affected adults by decreasing the oviposition period, the number of postures, fecundity, and fertility. The crude MeOH extract at a2.14% concentration harmed the evaluated parameters of the insect, except for pupal mortality, female pupae weight, and pre-oviposition period. The MeOH fraction at 2.14% caused a 50.0% mortality of caterpillars and 16.0% deformation in pupae and 33.0% inadults, reducing by 72.0% the population able to reproduce. The MeOH fraction at the 2.14% concentration caused 25.0% and 38.0% of pupal mortality and deformation, respectively. Calotropis procerahas promising insecticidal properties for a biological insecticide, a convenient and sustainable strategy for protecting plants against S. frugiperda.

Metabolic study of trimetazidine using ultra-high performance liquid chromatography-tandem mass spectrometry

Abstract In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known-as well as hitherto unknown-trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0-4 h, 4-8 h, 8-12 h, and 12-24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS / 法医学杂志

OBJECTIVES@#To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*METHODS@#The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.@*RESULTS@#The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.@*CONCLUSIONS@#This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active components identification / 中国天然药物

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.

Comparative chemical characters of Pseudostellaria heterophylla from geographical origins of China / 中草药·英文版

OBJECTIVE@#Pseudostellaria heterophylla has been paid more attention in recent years, mainly as a medicine food homology plant. The content determination of P. heterophylla is not specified in the Chinese Pharmacopoeia (version 2020). The environmental conditions in different production areas could exert an influence on the quality of P. heterophylla. The purpose of this study is to discriminate P. heterophylla collected from different geographical origins of China.@*METHODS@#In this study, the content of polysaccharide in 28 batches of P. heterophylla was determined using phenol-sulfuric acid. HPLC fingerprints were established under optimised HPLC-PDA methods. Subsequently, the similarity analysis (SA) and the quantification of heterophyllin B were analyzed. The metabolites of P. heterophylla were identified and evaluated using UHPLC-Q Exactive HF orbitrap MS system. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA) and orthogonal PLS-DA (OPLS-DA) were performed based on all peak areas.@*RESULTS@#The polysaccharide content in Guizhou and Jiangsu was higher than that of other production areas, which varied significant from different origins. While the content of heterophyllin B in Anhui and Jiangsu was high. The correlation coefficients of HPLC fingerprints for 28 batches samples ranged from 0.877 to 0.990, and the characteristic map can be used to identify and evaluate the quality of P. heterophylla. The samples from Fujian, Guizhou, Jiangsu provinces can be relatively separated using multivariate statistical analysis including PCA, PLS-DA, HCA, OPLS-DA, indicating that their metabolic compositions were significantly different. Ultimately, a total of 15 metabolites which were filtrated by a VIP-value > 1 and a P-value < 0.05 associated with the separation of different origins were identified.@*CONCLUSION@#HPLC fingerprint was established to evaluate the quality and authenticity of P. heterophylla. The present work showed that the difference of geographic distributions had an influence on the internal chemical compositions. A sensitive and rapid untargeted metabolomics approach by UHPLC-Q Exactive HF orbitrap MS was utilized to evaluate P. heterophylla from different origins in China for the first time. Overall, this study provides insights to metabolomics of P. heterophylla and supplies important reference values for the development of functional foods.