Safety and efficacy of a feed additive consisting of Macleaya cordata (Willd.) R. Br. extract and leaves (Sangrovit® Extra) for suckling and weaned piglets and other growing Suidae (Phytobiotics Futterzusatzstoffe GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Macleaya cordata (Willd.) R. Br. extract and leaves (Sangrovit® Extra) as a zootechnical feed additive for suckling and weaned piglets and other growing Suidae. The additive is standardised to contain a concentration of the sum of the four alkaloids sanguinarine, chelerythrine, protopine and allocryptopine of 1.25%, with 0.5% sanguinarine. Owing to the presence of the DNA intercalators sanguinarine and chelerythrine, a concern for genotoxicity was identified. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) had no safety concerns for the target species when the additive is used at the recommended level of 0.750 mg sanguinarine/kg complete feed for suckling and weaned piglets and other growing Suidae. Since in all consumer categories the exposure to sanguinarine and chelerythrine via the use of Sangrovit® Extra exceeds the threshold of toxicological concern of 0.0025 µg/kg bw per day for DNA reactive mutagens and/or carcinogens, the FEEDAP Panel could not conclude on the safety for the consumers. The additive was shown to be irritant to the eyes but not irritant to skin or a skin sensitiser. The FEEDAP Panel could not exclude the potential of the additive to be a respiratory sensitiser. When handling the additive, exposure of unprotected users to sanguinarine and chelerythrine may occur. Therefore, to reduce the risk, the exposure of users should be reduced. The use of Sangrovit® Extra as a feed additive under the proposed conditions of use was considered safe for the environment. The additive Sangrovit® Extra had the potential to be efficacious in improving performance of weaned piglets at 0.600 mg sanguinarine/kg complete feed. This conclusion was extended to suckling piglets and extrapolated to other growing Suidae.

Safety and efficacy of a feed additive consisting of Macleaya cordata (Willd.) R. Br. extract and leaves (Sangrovit® extra) for all poultry species (excluding laying and breeding birds) (Phytobiotics Futterzusatzstoffe GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Macleaya cordata (Willd.) R. Br. extract and leaves (Sangrovit® Extra) when used as a zootechnical feed additive (functional group: other zootechnical additives) for all poultry species (excluding laying and breeding birds). The additive is standardised to contain a concentration of the sum of the four alkaloids sanguinarine, chelerythrine, protopine and allocryptopine of 1.25%, with 0.5% sanguinarine. Owing to the presence of the DNA intercalators sanguinarine and chelerythrine, a concern for genotoxicity was identified. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) had no safety concerns when the additive is used at the recommended level of 150 mg/kg complete feed (corresponding to 0.750 mg sanguinarine/kg complete feed) for chickens for fattening and other poultry species for fattening. No conclusion can be drawn for poultry reared for laying/breeding. The use of Sangrovit® Extra in poultry species for fattening at the maximum recommended level was considered of low concern for consumers. The additive was shown to be irritant to the eyes but not irritant to skin or a skin sensitiser. The FEEDAP Panel could not exclude the potential of the additive to be a respiratory sensitiser. When handling the additive, exposure of unprotected users to sanguinarine and chelerythrine may occur. Therefore, to reduce the risk, the exposure of users should be reduced. The use of Sangrovit® Extra as a feed additive under the proposed conditions of use was considered safe for the environment. The additive Sangrovit® Extra had the potential to be efficacious in improving performance of chickens for fattening at 45 mg/kg complete feed. This conclusion was extended to chickens reared for laying/breeding and extrapolated to all poultry species for fattening or reared for laying/breeding.

Impacts of Macleaya cordata on Productive Performance, Expression of Growth-Related Genes, Hematological, and Biochemical Parameters in Turkey.

Macleaya cordata (M. cordata) is a herbal plant that has abundant amounts of sanguinarine, which has many biomedical properties. The effects of M. cordata dietary supplementation on the productive performance, some blood constituents, and growth-related genes' expression were evaluated in turkey. M. cordata extract was dietary supplemented to turkey at levels of 25, 50, and 100 ppm and a control group. Growth performance measurements (FBW, ADG, and FCR) and production efficiency factor for turkey (BPEF) were similar (p > 0.05) in all supplemented groups. M. cordata has no adverse effects (p > 0.05) on the birds' health regarding hematological (Hb, RBCs, WBCs, and PCV) and blood biochemical indices evaluating liver function, kidney function, and lipid profile. Moreover, the mRNA expression of growth-related genes, such as growth hormone receptor (GHR), insulin-like growth factor 1 (IGF-1), cyclooxygenase 3 (COX-3), adenine nucleotide translocase (ANT), and uncoupling protein 3 (UCP-3) were upregulated (p < 0.001) in M. cordata treatments with the highest value for SG50 compared with the control group. We concluded that exogenous M. cordata dietary supplementation upregulated the expression of growth-related genes in turkey at a level of 50 ppm without adverse effects on their health status regarding hematological and biochemical indices.

Identification of the Impurities in Bopu Powder® and Sangrovit® by LC-MS Combined with a Screening Method.

Bopu powder® and Sangrovit® were developed from Macleayacordata and are widely used in agriculture and animal husbandry, but their impurities have been rarely reported in the literature. Impurity analysis is of great importance to the quality and safety of veterinary drugs. In this study, high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with a screening method was used to screen and characterize the impurities in Bopu powder® and Sangrovit®. A total of 58 impurities were screened from Bopu powder® and Sangrovit® using the screening strategies, of which 39 were identified by their accurate m/z value, characteristic MS/MS data, and fragmentation pathways of references. This established method was used for impurity analysis for the first time and proved to be a useful and rapid tool to screen and identify the impurities of Bopu powder® and Sangrovit®, especially for those at trace levels in a complex sample. In addition, this study marks the first comprehensive research into impurities in these two products and has great significance for the systematic detection of impurities in other plant-derived drugs.

Location, distribution, and quantification of myenteric plexus neurons of the jejunum of quails fed with different levels of commercial Macleaya cordata extract / Localização, distribuição e quantificação dos neurônios do plexo mioentérico do jejuno de codornas de postura alimentadas com diferentes inclusões do extrato comercial de Macleaya cordata

ABSTRACT: Coturniculture has been promising, progressing from a subsistence to a technical activity due to its quick production, low breeding investment, and rapid economic return. After the restriction of antimicrobials as growth promoters, some studies aimed to evaluate alternative products that would make the farming of healthy birds viable without impacting their performance, with commercial Macleaya cordata extract being one of these substitutes. The functions of the gastrointestinal tract are coordinated mainly by the enteric nervous system, and the myenteric plexus is responsible for the reflex control of contractile activities of the external muscles. Thus, this study located and demonstrated the distribution of the myenteric plexus, quantifing the total population of myenteric neurons (Giemsa+) and the subpopulation of myenteric nitrergic neurons (NADPH-d+), and evaluated the effects of commercial Macleaya cordata extract on these populations of quail jejunum neurons. A total of 240 one-day-old female laying quails were distributed into four treatments, with four repetitions of 15 birds each. The test groups (T1, T2, and T3) were treated with commercial Macleaya cordata extract throughout the experimental period using the following doses: T1 - test group, basal diet added with 150 ppm of the extract in the feed; T2- test group, basal diet added with100 ppm of the extract in the feed; T3 - test group, basal diet added with 50 ppm of the extract in the feed; and T4 - control group, basal diet with no added extract. The study included histological analysis, Giemsa+, and NADPH-d+ myenteric neuron staining. The results showed that the myenteric plexus is located between longitudinal layer fibers and in the transition region between the longitudinal and circular layers of the muscular tunic, with the myenteric population organized into ganglia and isolated in the region of neuronal fiber bundles. The commercial Macleaya cordata extract showed no quantitative changes in the myenteric Giemsa+ population and myenteric NADPH-d+ subpopulation, however, the groups that consumed the extract showed greater NADPH-d+ neuron activity compared to the control group, implying that the food remained longer in the intestinal lumen, therefore, enabling greater nutrient use and resulting in increased productive performance.

RESUMO: A coturnicultura tem apresentado características promissoras, deixando de ser uma atividade de subsistência e ocupando patamares tecnificados devido a sua precocidade produtiva, baixo investimento de criação e rápido retorno econômico. A partir da restrição da utilização de antimicrobianos como promotores de crescimento, estudos foram direcionados com o objetivo de se avaliar produtos alternativos que viabilizassem a criação de aves saudáveis, sem comprometer seu desempenho, sendo o extrato comercial da Macleaya cordata um destes substitutos. As funções do trato gastrintestinal são coordenadas principalmente pelo sistema nervoso entérico, sendo o plexo mioentérico responsável pelo controle reflexo das atividades contráteis da musculatura externa. Desta forma, o presente trabalho teve como objetivo localizar e demonstrar a distribuição do plexo mioentérico, quantificar a população total de neurônios mioentéricos (Giemsa+), e a subpopulação de neurônios mioentéricos nitrérgicos (NADPH-d+), além de avaliar os efeitos do extrato comercial da Macleaya cordata sobre estas populações de neurônios do jejuno de codornas. Foram alojadas 240 codornas de postura, fêmeas, com um dia de idade, distribuídas aleatoriamente em quatro tratamentos, com quatro repetições de 15 aves cada. Os grupos testes (T1, T2 e T3) foram tratados com extrato comercial de Macleaya cordata durante todo o período experimental conforme as doses indicadas, sendo: T1 - grupo teste, com dieta basal adicionada de 150 ppm do extrato na ração; T2 - grupo teste, com dieta basal adicionada de 100 ppm do extrato na ração; T3 - grupo teste, com dieta basal adicionada de 50 ppm do extrato na ração, e T4 - grupo controle, com dieta basal isenta do extrato. Foram realizadas análise histológica e a marcação dos neurônios mioentéricos Giemsa+ e NADPH-d+. Os resultados demonstraram que o plexo mioentérico está localizado entre as fibras do estrato longitudinal, e na região de transição entre os estratos longitudinal e circular da túnica muscular, estando a população mioentérica organizada em gânglios, e também isoladamente na região dos feixes das fibras neuronais. O extrato comercial da Macleaya cordata não alterou quantitativamente os neurônios da população mioentérica Giemsa+ e da subpopulação mioentérica NADPH-d+, mas os grupos que consumiram o extrato apresentaram maior atividade dos neurônios NADPH-d+ em relação ao grupo controle, permitindo inferir que o alimento permaneceu maior tempo no lúmen intestinal e, portanto, possibilitou um maior aproveitamento dos nutrientes, podendo refletir em melhor desempenho produtivo.