Pharmacokinetic assessment and phytochemical triterpene control from Cecropia angustifolia using plant biotechnology.

INTRODUCTION: Cecropia angustifolia Trécul. is a native Andean plant containing high levels of pentacyclic triterpenes (PTs), including several isobaric molecules that serve as chemical markers. Preclinical studies suggest that PTs positively modulate metabolic and vascular diseases. However, their low oral absorption reduces their bioactive effects. OBJECTIVE: The objective of this study was (1) to improve the absorption of PTs from C. angustifolia and (2) to establish a platform to produce biomass or botanical reference material using a strategy for their accumulation. METHODS: MALDI-TOF and UPLC-MS were used to characterize and quantify PTs in different matrices. An in vitro platform for PT production was established. Chemical profiles of triterpenes were also evaluated from wild and in vitro herbal material using TLC coupled with mass spectrometry. RESULTS: To overcome the low absorption of PTs, a premier raw material was used, which increased their bioavailability to 9.2%. Active ingredients in herbal material can vary, and there is an urgent need for standardized extracts using pharmacokinetics as an effective tool to reveal the dynamics of active ingredients in vivo. A temporary immersion system was produced as a promising platform with a total PT accumulation exceeding 50% of the content in the dry fraction, indicating it is a feasible mechanism to produce biomass or botanical reference material. CONCLUSIONS: Plant tissue culture is a promising eco-friendly technology for phytochemical production and a modern strategy to protect biodiversity in natural assets. Alternative and modern, yet environmentally friendly production methods are needed to meet the large demand for herbal products.

Sambucus nigra: A traditional medicine effective in reducing inflammation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sambucus nigra L. is a plant of European origin and popularly known as elder, elderberry, black elder, European elder, European elderberry, and European black elderberry, being described in pharmacopoeia of several countries. Its flowers and berries have been used in folk medicine to treat feverish conditions, coughing, nasal congestion, and influenza besides its popular use as anti-inflammatory, analgesic, and diuretic agent. AIM OF THE STUDY: The aim of this investigation was to elucidate the anti-inflammatory and the relaxant effect of the lyophilized aqueous extract obtained from S. nigra's flowers on in vivo and in vitro inflammation assays and on the isolated rat vascular and airway smooth muscle tissue. MATERIAL AND METHODS: The anti-inflammatory activity of the extract was investigated using carrageenan-induced inflammation model in the subcutaneous tissue of male Swiss mice orally treated with S. nigra extract (30, 100, 300 or 600 mg/kg). Leukocyte influx and the secretion of chemical mediators were quantified in the inflamed exudate. Additionally, histological analysis of the pouches was performed. N-Formyl-methionine-leucine-phenylalanine-induced chemotaxis, lipopolysaccharide-induced TNF, IL-6, IL-1ß, IL-10 and NO production, and adhesion molecule expression (CD62L, CD49d and CD18, flow cytometry) were analyzed in vitro using oyster glycogen-recruited peritoneal neutrophils or macrophages (RAW 264.7) stimulated with LPS and treated with the extract (1, 10 or 100 µg/mL). The resolution of inflammation was accessed by efferocytosis assay, and the antinociceptive activity was investigated using carrageenan-induced mechanical hypersensitivity. Finally, the effect of the extract was evaluated in isolated rat aorta and trachea rings. RESULTS: The oral treatment with S. nigra promoted reduction in the neutrophil migration as well as the decrease of TNF, IL-1ß and IL-6 levels in the inflamed exudate. In vitro treatment with S. nigra decreased NO2-, TNF, IL-1ß and IL-6 and promoted increase of IL-10 in LPS-stimulated neutrophils. Similarly, the extract reduced the NO2-, TNF and IL-6 in LPS-stimulated macrophages. Rutin, the major constituent of S. nigra extract reduced NO2-, TNF, IL-1ß, and IL-6 and promoted the increase of IL-10 in LPS-stimulated neutrophils supernatant. The extract also shed CD62L and CD18 expressions. The extract was able to increase the efferocytosis of apoptotic neutrophils by increasing the IL-10 and decreasing the TNF levels. Additionally, the extract reduced the hypersensitivity induced by carrageenan and promoted a relaxant effect in isolated vascular and non-vascular rat tissue. CONCLUSIONS: S. nigra flowers extract presents anti-inflammatory effect by modulating macrophage and neutrophil functions including the production of inflammatory mediators and cell migration, by promoting efferocytosis and consequently the resolution of acute inflammation, besides exerting antinociceptive effects, scientifically proving its popular use as medicinal plant. Allied to the relaxant effect in both vascular and non-vascular smooth muscle tissue, S. nigra extract represents an important tool for the management of acute inflammation.

Global market for veterinary herbal products during the 2018-2019 period / Mercado mundial de produtos fitoterápicos veterinários durante o período 2018-2019

The industrial manufacturing of natural products for veterinary use represents a major weakness in the veterinary sector despite increased interest and the traditional ancestral knowledge that supports them. A cross-sectional, descriptive observational study was conducted to characterize the veterinary herbal products marketed worldwide during 2018 and 2019. A comprehensive thematic search limited to the 2018-2019 period was performed in the ScienceDirect, Scopus, PubMed, Web of Science, ResearchGate, and Academic Search Complete databases. The investigation identified 487 products registered in the global market manufactured by 54 companies, led by India, The Netherlands, and the United Kingdom. The market segments of animal production and phytomedicines were dominant with 73.7% and 53.0% of products, respectively. Cattle (22.2%), sheep-goats (16.2%), and canines (16.2%) were the most favored species. The most represented therapeutic indications were those intended to treat gastrointestinal disorders (30.47%), antimicrobials (16.66%), and antiparasitic agents (10.47%). The families Fabaceae, Lamiaceae, Asteraceae, Apiaceae, Malvaceae, and Rutaceae stood out because of their frequent use, encompassing 35.0% of the 137 declared species. Andrographis paniculata (Burm.f.) Nees and Withania somnifera (Lin) Dunal were the most important species. Oral formulations for internal use (72%) and liquids (51%) in 100 mL, 500 mL, and 1 L presentations showed the highest prevalence on the market. The global market for veterinary herbal products during the 2018-2019 period was relevant in the productive and medical animal sector. No differences were found between medicinal plant species used to formulate herbal products for human and animal use.(AU)

A fabricação industrial de produtos naturais para uso animal é uma das grandes fragilidades do setor veterinário, apesar de um crescente interesse e do suporte dado pelos conhecimentos tradicionais ancestrais. Foi realizado um estudo observacional descritivo transversal para caracterizar os fitoterápicos veterinários comercializados mundialmente no período de 2018-2019 através de uma busca temática exaustiva nas bases de dados ScienceDirect, Scopus, PubMed, Web of Science, ResearchGate e Academic Search Complete. O estudo mostrou a existência de 487 produtos registrados no mercado mundial, fabricados por 54 empresas, lideradas pela Índia, Holanda e Reino Unido. Os segmentos Danimal produtivo e fitomedicamentos dominam o mercado com 73,7% e 53,0% dos produtos, respectivamente. Bovinos (22,2%), ovinos-cabras (16,2%) e caninos (16,2%) foram as espécies mais favorecidas. As indicações terapêuticas mais representadas foram aquelas destinadas à correção de distúrbios gastrointestinais (30,47%), antimicrobianos (16,66%) e antiparasitários (10,47%). Devido à alta frequência de uso, destacam-se as famílias Fabaceae, Lamiaceae, Asteraceae, Apiaceae, Malvaceae e Rutaceae, que compreendem 35,0% das 137 espécies declaradas a saber, Andrographis paniculata(Burm.f.) Nees e Withania somnífera (Lin) Dunal, são as mais importantes. Constatou-se que as formulações para uso interno via oral (72%) e líquida (51%) em embalagens de 100, 500 e 1000 mL são as que prevalecem no mercado. O mercado global de produtos fitoterápicos durante o período de 2018-2019 foi relevante para animais produtivos e o setor médico. Não foram encontradas diferenças entre as espécies de plantas medicinais utilizadas em formulações de produtos fitoterápicos para uso humano e animal.(AU)

Global market for veterinary herbal products during the 2018-2019 period / Mercado mundial de produtos fitoterápicos veterinários durante o período 2018-2019

The industrial manufacturing of natural products for veterinary use represents a major weakness in the veterinary sector despite increased interest and the traditional ancestral knowledge that supports them. A cross-sectional, descriptive observational study was conducted to characterize the veterinary herbal products marketed worldwide during 2018 and 2019. A comprehensive thematic search limited to the 2018-2019 period was performed in the ScienceDirect, Scopus, PubMed, Web of Science, ResearchGate, and Academic Search Complete databases. The investigation identified 487 products registered in the global market manufactured by 54 companies, led by India, The Netherlands, and the United Kingdom. The market segments of animal production and phytomedicines were dominant with 73.7% and 53.0% of products, respectively. Cattle (22.2%), sheep-goats (16.2%), and canines (16.2%) were the most favored species. The most represented therapeutic indications were those intended to treat gastrointestinal disorders (30.47%), antimicrobials (16.66%), and antiparasitic agents (10.47%). The families Fabaceae, Lamiaceae, Asteraceae, Apiaceae, Malvaceae, and Rutaceae stood out because of their frequent use, encompassing 35.0% of the 137 declared species. Andrographis paniculata (Burm.f.) Nees and Withania somnifera (Lin) Dunal were the most important species. Oral formulations for internal use (72%) and liquids (51%) in 100 mL, 500 mL, and 1 L presentations showed the highest prevalence on the market. The global market for veterinary herbal products during the 2018-2019 period was relevant in the productive and medical animal sector. No differences were found between medicinal plant species used to formulate herbal products for human and animal use.(AU)

A fabricação industrial de produtos naturais para uso animal é uma das grandes fragilidades do setor veterinário, apesar de um crescente interesse e do suporte dado pelos conhecimentos tradicionais ancestrais. Foi realizado um estudo observacional descritivo transversal para caracterizar os fitoterápicos veterinários comercializados mundialmente no período de 2018-2019 através de uma busca temática exaustiva nas bases de dados ScienceDirect, Scopus, PubMed, Web of Science, ResearchGate e Academic Search Complete. O estudo mostrou a existência de 487 produtos registrados no mercado mundial, fabricados por 54 empresas, lideradas pela Índia, Holanda e Reino Unido. Os segmentos Danimal produtivo e fitomedicamentos dominam o mercado com 73,7% e 53,0% dos produtos, respectivamente. Bovinos (22,2%), ovinos-cabras (16,2%) e caninos (16,2%) foram as espécies mais favorecidas. As indicações terapêuticas mais representadas foram aquelas destinadas à correção de distúrbios gastrointestinais (30,47%), antimicrobianos (16,66%) e antiparasitários (10,47%). Devido à alta frequência de uso, destacam-se as famílias Fabaceae, Lamiaceae, Asteraceae, Apiaceae, Malvaceae e Rutaceae, que compreendem 35,0% das 137 espécies declaradas a saber, Andrographis paniculata(Burm.f.) Nees e Withania somnífera (Lin) Dunal, são as mais importantes. Constatou-se que as formulações para uso interno via oral (72%) e líquida (51%) em embalagens de 100, 500 e 1000 mL são as que prevalecem no mercado. O mercado global de produtos fitoterápicos durante o período de 2018-2019 foi relevante para animais produtivos e o setor médico. Não foram encontradas diferenças entre as espécies de plantas medicinais utilizadas em formulações de produtos fitoterápicos para uso humano e animal.(AU)

Effects of Eugenia umbelliflora O. Berg (Myrtaceae)-leaf extract on inflammation and hypersensitivity.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Eugenia species are widely used in popular medicine to treat several diseases, such as arthritis, rheumatism and diabetes. Eugenia umbelliflora O. Berg is popularly known in Brazil as "baguaçu", name also conferred to Eugenia jambolana probably due to their apparent similarity. Although the popular use scientifically proved of E. jambolana as anti-diabetes and also as anti-inflammatory, there are only two scientific studies demonstrating anti-ulcer and bactericide activities of E. umbelliflora leaves extract, without reference to its possible anti-inflammatory activity. AIM OF THE STUDY: The aim of this study was to show the anti-oxidant and anti-inflammatory activity of the methanol extract obtained from E. umbelliflora leaves (EuL) using in vitro and in vivo protocols. MATERIALS AND METHODS: The total phenolic content was evaluated using the folin-Ciocalteu colorimetric method and phloroglucinols content by HPLC. The anti-oxidant activity was evaluated by ORAC, ABTS•+, DPPH, and metal chelation methods. The anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally pre-treated with the EuL (0.3, 1 or 3 mg/kg). The leukocyte influx (optical microscopy) and secretion of chemical mediators (TNF, IL-6, IL-1ß and CXCL1, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. Histological analysis of the pouches was also performed. The anti-hypersensitive activity was investigated using carrageenan-induced mechanical hypersensitivity and mice were then evaluated using the von Frey filaments. The Open Field test was used to evaluate possible interference of adverse effect of EuL on locomotor activity that could lead to misinterpretation of the hypersensitivity evaluation. RESULTS: The EuL demonstrated important and moderate reducing capacity on ABTS•+ and DPPH assays, respectively, but with slight activity in ORAC test. It reflects low protection against cell damage. The EuL also presented 30% of phenolic compounds. The phloroglucinols content of EuL was 25.9 mg/g, 18.4 mg/g and 16.6 mg/g of eugenial C, eugenial D and eugenial E, respectively. The in vivo analysis of the inflammatory exudate of EuL-treated mice demonstrated reduction in the polymorphonuclear cells (PMN) migration to the inflamed tissue, as well as the reduction of the pro-inflammatory cytokine IL-1ß. Histologically, it was observed evident decrease in the oedema, formed essentially by non-haemorrhagic fibrin exudate, as well as PMN infiltrate, when compared with control mice injected with carrageenan. Furthermore, the extract also presented effective reduction of the mechanical hypersensitivity induced by carrageenan without any interference in animal's locomotor and exploratory activity. CONCLUSIONS: Together, the results herein obtained show that EuL presented anti-inflammatory activity by decreasing the influx of PMN to the inflamed tissue, as well as the cytokine IL-1ß level. This anti-inflammatory activity was also accompanied by significant anti-hypersensitive effect. The effects presented by EuL seem not to be correlated with an antioxidant activity. However other extract chemical compounds could be responsible for its important anti-inflammatory effects.

Hepatotoxicidade de um fitoterápico contendoChenopodium ambrosioides, Mentha piperita e Rheumpalmatum em camundongos Swiss / Hepatotoxicity of an herbal product containing Chenopodiumambrosioides, Mentha piperita and Rheum palmatum in Swiss mice

Introdução: Entre as diversas plantas que possuem efeito antiparasitário,as espécies Chenopodium ambrosioides, Mentha piperitae Rheum palmatum vem sendo empregadas em associação comoproduto fitoterápico antiparasitário. Porém, esse tipo de preparo éutilizado de forma indiscriminada e abusiva, o que pode levar aosurgimento de danos à saúde.Objetivo: Avaliar a função hepática de camundongos Swiss submetidosa tratamento com um produto fitoterápico contento Chenopodiumambrosioides, Mentha piperita e Rheum palmatum, usadopopularmente como antiparasitário.Métodos: Foram utilizados 20 camundongos, distribuídos em doisgrupos: grupo tratamento, submetidos à terapia com fitoterápicopor via orogástrica por 9 dias, e grupo controle negativo, tratadoscom solução salina estéril pela mesma via, diariamente, durante omesmo período. Após tratamento, foram realizadas dosagens plasmáticasdas enzimas alanina aminotrasnferase (ALT) e aspartatoaminotransferase (AST) por metodologia cinético-UV em duplicata...

Introduction: Among the various plants having antiparasitic effect,the species Chenopodium ambrosioides, Mentha piperita andRheum palmatum has been used in combination as a herbal productantiparasitic . However, this type of preparation is used indiscriminatelyand improperly which can lead to the emergence ofhealth damage.Objective: Assess liver function of Swiss mice undergoing treatmentwith an herbal product containing Chenopodium ambrosioides,Mentha piperita and Rheum palmatum, popularly used as aantiparasitic.Methods: Were used 20 mice, distributed into two groups: treatmentgroup, underwent to herbal therapy by orogastric route for9 days, and a negative control group, treated with sterile saline bythe same route, daily, during the same period. After treatment, weremade plasmatic dosages of the enzymes alanine aminotransferase(ALT) and aspartate aminotransferase (AST) in duplicate. Resultsand conclusion: Was observed significant elevation of ALT, anddecreasing of AST (no significant), which means that the studiedproduct have may cause mild hepatocellular damage in animals...