Potential plants for inflammatory dysfunction in the SARS-CoV-2 infection.

The inflammatory process is a biological response of the organism to remove injurious stimuli and initiate homeostasis. It has been recognized as a key player in the most severe forms of SARS-CoV-2, characterized by significantly increased pro-inflammatory cytokine levels, the so-called "cytokine storm" that appears to play a pivotal role in this disease. Therefore, the aim of this systematic review was to select clinical trials with anti-inflammatory plants and relate the activity of these plants to inflammatory markers of SARS-CoV-2 infection. PRISMA guidelines are followed, and studies of interest are indexed in PubMed and ClinicalTrials.gov databases. As a result, 32 clinical trials encompassing 22 plants were selected. The main anti-inflammatory mechanisms described in the studies are the inhibition of inflammatory cytokines, such as IL-6, TNF-a, IFN-γ, and IL-1; decreased CRP and oxidative marker levels; increased endogenous antioxidant levels; modulation of cardiovascular risk markers. The data found are not directly related to SARS-CoV-2 infection. However, they provide possibilities for new studies as plants have a wide array of phytochemicals, and detecting which ones are responsible for anti-inflammatory effects can provide invaluable contribution to studies aiming to evaluate efficacy in scenarios of SARS-CoV-2 infection.

In vitro and in vivo anti-inflammatory and anticoagulant activities of Myrciaria plinioides D. Legrand ethanol leaf extract.

Myrciaria plinioides D. Legrand (Myrtaceae) is a native plant of Southern Brazil, which have potential in the food industry due to its edible fruits. Many plants belonging to this genus have been used for a variety of illnesses, including inflammatory disorders due to antioxidant properties. However, therapeutic uses of M. plinioides have been poorly studied. The aim of study was to assess the anti-inflammatory and anticoagulant activities of the ethanol leaf extract of M. plinioides. In M. plinioides extract-treated RAW 264.7 cells, assessments of cell viability, TNF-α release and p38 MAPK pathway-dependent protein expression were detected. In addition, rat paw edema models were used to analyze the anti-inflammatory effect of the extract. Macrophages cell line treated with M. plinioides extract showed a slight decrease in cell viability. In LPS-stimulated macrophages treated with different concentrations of the extract for 24 h, TNF-α release was inhibited, while modulation of p38 signaling pathway and inhibition of NF-κB p65 protein expression were dose-dependent. In rats, the extract inhibited the formation of paw edema, while an inhibitory effect on trypsin-like enzymes derived from mast cells was seen. Furthermore, the extract presented anticoagulant activity via extrinsic pathway, being able to block specifically factor Xa and thrombin. The study suggests that extract possess potent anti-inflammatory and anticoagulant effects. M. plinioides present great biological potential as a source for the development of anti-inflammatory and anticoagulant drugs. Additional studies can be proposed to better elucidate the mechanism by which M. plinioides exerts its effects.

Traditional plants with antioxidant properties in clinical trials-A systematic review.

There is a trend toward the use of natural substances present in plants and vegetables. In general, foods rich in antioxidants are complex matrices; therefore, understanding its absorption effects is extremely relevant to know its bioactive potential. Thus, this systematic review focused on clinical trials involving plants (or compounds) registered on the National List of Medicinal Plants of Interest to the Unified Health System (RENISUS) with antioxidant properties. Following the reporting guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyzes studies of interest indexed in the PubMed and ClinicalTrials.gov databases were analyzed. Of the 59 clinical trials found, Allium sativum and Curcuma longa are the plant species with the highest percentage of clinical research. Prevention/attenuation of oxidative stress was one of the main antioxidant mechanisms indicated in the studies. The most tested compounds of the RENISUS plants in clinical trials were curcumin and soy isoflavone. In this review, we selected studies in advanced stages that highlight plants' value in optimizing antioxidant status; however, even with high-quality studies, it is not prudent to overstate the clinical efficacy of these plants.

Clinical trials with plants in diabetes mellitus therapy: a systematic review.

INTRODUCTION: The chronic metabolic disorder diabetes mellitus is a fast-growing global problem with huge social, health, and economic consequences, having one of the highest morbidities and mortality rates. Prolonged use of many available medications can produce undesirable side effects. Thus, plants appear as an important source of bioactive resources for the discovery of new treatments for diabetes. AREAS COVERED: In this sense, this systematic review focused on clinical trials involving plants of National List of Medicinal Plants of Interest to the Unified Health System (RENISUS) (or compounds) with antidiabetic properties. We analyzed indexed studies in PubMed following the reporting guidelines of PRISMA. EXPERT OPINION: Of the 51 clinical trials found, Curcuma longa, Glycine max, Zingiber officinale, Punica granatum, Aloe vera, Momordica charantia are the species with the greatest amount of clinical trials and the attenuation of insulin resistance, decreased fasting blood glucose and glycosylated hemoglobin levels are some of the main mechanisms by which these plants exert hypoglycemic effects. Thus, we speculate that the Clinical Pharmacology should explore the field of plant-based compounds that will keep concentrating the attention of researchers, and therefore, we gathered studies in advanced stages that highlight the role of plants in the diabetes therapy.

Plant species used in Brazil and Asia regions with toxic properties.

Many efforts are being made to find biomolecules extracted from plants to be useful therapeutic agents to replace the drugs traditionally used in clinical medicine with known side effects and high financial investment, thus offering greater safety and less risk to the population. However, the presence of toxic substances such as alkaloids, amino acids, amides, glycosides, saponins, and tannins are the main reasons for the poisonous activity of some medicinal plants. In this sense, understanding plants constituents and lethal doses can be important source in managing several diseases in human life. This review aimed to present extracts, fractions, and/or compounds of plants of Brazil and Asia regions that have reported toxicity to in vitro and in vivo models. The results presented here contribute to warning the population about the toxicological characterization of some plants, however, further high-quality studies are needed to firmly establish the clinical efficacy of the plants (or compounds).

Compounds of plants with activity against SARS-CoV-2 targets.

INTRODUCTION: The COVID-19 global pandemic is a public health emergency due to its high virulence and mortality. Many vaccine development studies at clinical trials are currently conducted to combat SARS-CoV-2. Plants are a rich source of phytochemicals with different biological activities, including antiviral activities, which are the focus of many studies. AREAS COVERED: This review shows compounds of traditional plants listed on RENISUS list have therapeutic properties against SARS-CoV-2 targets. EXPERT OPINION: The rise of new variants, more pathogenic and virulent, impacts in the increase of mortality from SARS-CoV-2 infection, and thus, the control of the outbreaks of disease remains a global challenge. Other's drug and vaccines development is an essential element in controlling SARS-COV-2. Therefore, it is imperative that approach to tackle this pandemic has to be solidly evidence-informed. It should be noticed that the immune system does play critical roles in fighting viruses. Studies show that T cells levels decreased continuously as the disease progressed. T cell-mediated cellular immune response, probably by immunological memory, is essential for direct virus eradication after infection whilst B cells functions in producing antibodies that neutralize virus.But, have distinct patterns of T cell response exist in different patients, suggesting the possibility of distinct clinical approaches. Efforts are concentrated to elucidate the underlying immunological mechanisms in SARS-CoV-2 pathogenesis and progression for better design of diagnostic, therapeutic and preventive strategies. We seek to identify biomolecules with the potential to act in biomarkers that predict how severe the disease can get. But it is important to warn that the plants that produce the compounds mentioned here should not be used without a physician prescription. Finally, we speculate that these compounds may eventually attract the attention of physicians and researchers to perform tests in specific contexts of SARS-CoV-2 infection, and if they show positive results, be tested in Clinical trials.

RENISUS Plants and Their Potential Antitumor Effects in Clinical Trials and Registered Patents.

Cancer is a significant cause of morbidity and mortality. Scientific advances, coupled with potential flaws in current treatments, are driving research into the discovery of new bioactive molecules. This systematic review focused on scientific studies with clinical trials and patents registered on the National Relation of Medicinal Plants of Interest to the Unified Health System (RENISUS) plants (or derivative compounds) with antitumor potential. Studies with 19 different forms of cancer were found, the prostate being the organ with the highest research incidence and the species Glycine max, Curcuma longa, and Zingiber officinale, beside the phytochemicals curcumin and soy isoflavone were the most tested in clinical trials/patents.

Neuroprotective potential of Myrciaria plinioides D. Legrand extract in an in vitro human neuroblastoma model.

Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system affecting approximately 30 million individuals worldwide. Mitochondrial dysfunction and oxidative stress have also been implicated in causing neurodegeneration. As life expectancy is increasing, neurodegenerative disorders are becoming a major social issue. None of the drugs currently available for treatment are capable of healing the patient. This means that new molecules should be explored. Plants have been used for treatment of countless medical conditions and extensive research is being carried out on species of the Myrtaceae family, widely used in traditional medicine. To date, Myrciaria plinioides D. Legrand has not been studied for its therapeutic use. To evaluate the neuroprotective effect of aqueous and ethanol extracts of this plant, we investigated the protective effects in human neuroblastoma cells (SH-SY5Y). High-performance liquid chromatography fingerprinting of extracts revealed the presence of phenolic compounds and flavonoids. Extracts showed antioxidant activity in the ORAC, DPPH, FRAP and GAE methods. Ethanol extract presented a strong inhibitory activity toward p38 and JNK3 MAPKs and AChE activity and also toward TNF-α release in human whole blood. None of the extracts significantly affected cell viability; the ethanol extract, however, reversed 6-OHDA-induced toxicity. Particularly the ethanol extract suggests neuroprotective effects by preventing membrane depolarization and by significantly decreasing H2O2 production and caspase-3 activity. The present results indicate that the ethanol extract protects SH-SY5Y cells against oxidative damage and apoptosis, as shown by the antioxidative activity of the extract as well as by the inhibition of important proteins such as caspase-3, p38 and JNK3 and the cytokine TNF-α.

The healing properties of medicinal plants used in the Brazilian public health system: a systematic review.

OBJECTIVE: The aim of this study was to conduct a systematic review of the healing potential of medicinal plants belonging to the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS). METHOD: PubMed and ScienceDirect databases were searched for relevant articles, regardless of the language, from 2010 to June 2016. Two reviewers independently assessed study eligibility. Articles were included if they presented evidence of healing potential of medicinal plants. Only those available as full and open access texts were considered. RESULTS: A total of 1381 articles met the inclusion criteria. Of these, 156 studies were considered eligible and were reviewed as full text. Following full analysis, 64 studies were included in this review. The studies covered 27 of the 71 plants belonging to RENISUS, nine of which are native to Brazil. In addition, two species are currently available in the Brazilian public health system as herbal medicine. CONCLUSION: This review may encourage and contribute to the appropriate use of medicinal plants in the public health system in Brazil.

Medicinal plants used in Brazil Public Health System with neuroprotective potential: a systematic review / Plantas medicinales utilizadas en el Sistema de Salud Pública de Brasil con potencial neuroprotector: una revisión sistemática

Current pharmacological therapies to treat neurological diseases are at best palliative and manage only the symptoms. Unfortunately, few therapies can affect diseases outcomes and alternative strategies such as stem cell therapy, neurotransplantation and deep brain stimulation are still in progress. Diseases such as Alzheimer's and Parkinson's disease become major public health challenge worldwide. In this way, the interest in the development of neuroprotective drugs of natural origin grows. Hence, this systematic review has quantified the studies that refer neuroprotective potential of plants listed in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS). Searches were performed in two scientific databases (PubMed and Science Direct) from 2010 to 2016. A total of 4.532 articles met the inclusion criteria. 445 studies were considered eligible and were reviewed as full text. Following full analysis, 63 studies were included in this review. The studies covered 12 of the 71 plants belonging to RENISUS. In addition, two species are currently available in the Brazilian public health system as herbal medicine. This review may encourage and contribute to the proper use of medicinal plants in public health system.

Las terapias farmacológicas actuales para tratar enfermedades neurológicas son, en el mejor de los casos, paliativas y sólo controlan los síntomas. Desafortunadamente, pocas terapias pueden afectar los avances de las enfermedades y las estrategias alternativas tales como terapia con células madre, neurotransplantate y la estimulación profunda del cerebro están todavía en curso. Enfermedades como el Alzheimer y la enfermedad de Parkinson se convierten en un reto importante para la salud pública en todo el mundo. De esta manera, crece el interés en el desarrollo de fármacos neuroprotectores de origen natural. Por lo tanto, esta revisión sistemática ha cuantificado los estudios que hacen referencia al potencial neuroprotector de las plantas incluidas en la Lista Nacional Brasileña de Plantas Medicinales de Interés para el Sistema Único de Salud (RENISUS). Las búsquedas se realizaron en dos bases de datos científicas (PubMed y Science Direct) de 2010 a 2016. Un total de 4,532 artículos cumplieron los criterios de inclusión. 445 estudios se consideraron elegibles y se revisaron como texto completo. Después del análisis completo, se incluyeron 63 estudios en esta revisión. Los estudios abarcaron 12 de las 71 plantas pertenecientes a RENISUS. Además, actualmente hay dos especies disponibles en el sistema de salud pública brasileño como medicina herbaria. Esta revisión puede alentar y contribuir al uso adecuado de las plantas medicinales en el sistema de salud pública.

Revisão sistemática das plantas de Interesse ao Sistema Único de Saúde com potencial terapêutico cardiovascular / Revisión sistemática de las plantas de interés para el Sistema de Salud con potencial terapéutico cardiovascular / Systematic review of the plants of interest to the National Health System with cardiovascular therapeutic potential

Introdução: doenças cardiovasculares constituem uma das principais causas de mortalidade, pois muitos são os fatores de risco associados ao seu desenvolvimento. Estudos vêm demonstrando que moléculas extraídas de plantas medicinais podem reduzir o risco de doenças crônicas. Assim, o Ministério da Saúde, publicou em fevereiro de 2009, a Relação Nacional de Plantas Medicinais de Interesse ao SUS. Objetivos: quantificar os estudos clínicos que referem potencial terapêutico sobre doenças cardiovasculares a partir da utilização de Plantas da Medicinais de Interesse ao SUS, publicados entre 2010 e fevereiro de 2013 em três bases de dados científicas (SciELO, Science Direct e Springer). Métodos: os descritores utilizados na busca inicial foram o nome científico das 71 plantas da Relação Nacional de Plantas Medicinais de Interesse ao SUS. Considerou-se todos os artigos científicos gratuitos, disponibilizados sob forma de texto completo nas bases de pesquisa, independente do idioma. A busca inicial resultou na seleção de 21,357 artigos encontrados nas bases de dados. A análise foi realizada inicialmente a partir da leitura do título da publicação. Os artigos selecionados foram avaliados através da leitura do Abstratc. Por fim, foi lido integralmente o texto dos artigos selecionados após a avaliação do Abstract, tendo sido selecionados estudos pré-clínicos e clínicos, in vitro e in vivo, que comprovam potencial terapêutico sobre doenças cardiovasculares. Resultados: esta seleção resultou em 34 artigos de interesse, dos quais, 17 estudos foram realizados com a planta Curcuma longa. Infarto do miocárdio, isquemia cerebral e hipertensão arterial foram as morbidades com a maior quantidade de estudos terapêuticos. Conclusões: os resultados deste estudo fornecem subsídios teóricos para discussões na Saúde Pública sobre tratamentos alternativos para doenças cardiovasculares(AU)

Introducción: las enfermedades cardiovasculares constituyen una de las principales causas de mortalidad, al existir muchos factores de riesgo asociados a su aparición. Hay estudios que demuestran que moléculas extraídas de plantas medicinales pueden reducir el riesgo de enfermedades crónicas. De esta forma, el Ministerio de Salud, publicó en febrero de 2009, la Lista Nacional de Plantas Medicinales de Interés para el SUS. Objetivos: cuantificar los estudios clínicos que refieren potencial terapéutico sobre las enfermedades cardiovasculares a partir de la utilización de Plantas da Medicinais de Interesse ao SUS, publicados entre 2010 y febrero de 2013 en tres bases de datos científicas (SciELO, Science Direct y Springer). Métodos: los descriptores utilizados en la búsqueda inicial fueron el nombre científico de 71 plantas de Plantas da Medicinais de Interesse ao SUS. Se consideraron todos los artículos científicos gratuitos, disponibles en texto completo en las bases de investigación, independiente del idioma. Primero se seleccionaron 21,357 artículos encontrados en las bases de datos. El análisis fue realizado a partir de la lectura del título de publicación. Los artículos seleccionados fueron evaluados a través de la lectura del Abstract. Por último, fueron leídos de forma íntegra el texto de los artículos seleccionados después de la evaluación del Abstract, fueron seleccionados estudios pre-clínicos y clínicos in vitro e in vivo, que comprueban el potencial terapéutico sobre las enfermedades cardiovasculares. Resultados: esta selección resultó de 34 artículos de interés, de los cuales, 17 estudios fueron realizados con la planta Curcuma longa. Infarto de miocardio, isquemia cerebral e hipertensión arterial fueron las comorbilidades con la mayor cantidad de estudios terapéuticos. Conclusiones: los resultados de este estudio ofrecen subsidios teóricos para discusiones en Salud Pública sobre tratamientos alternativos para las enfermedades cardiovasculares(AU)

Introduction: cardiovascular diseases are a major cause of mortality, because there are many risk factors associated with its development. Studies have shown that molecules extracted from medicinal plants can reduce the risk of chronic diseases. Thus, the Ministry of Health, published in February 2009, the National List of Medicinal Plants of Interest to SUS. Objective: to quantify the clinical studies that relate therapeutic potential of cardiovascular disease from the use of the National List of Medicinal Plants of Interest to SUS, published between 2010 and February 2013 in three scientific databases (SciELO, Science Direct and Springer). Methods: the descriptors used in the initial search were the scientific name of the 71 plants from the National List of Medicinal Plants of Interest to SUS. It considered all free papers made available in the form of full text search in databases, regardless of the language. The initial search resulted in the selection of 21 357 articles found in databases. The analysis was initially performed from reading the title of the publication. The articles were evaluated by reading the Abstratc. Finally, it was fully read the text of the articles selected after evaluation of the Abstract and was selected pre-clinical and clinical studies, in vitro and in vivo, that show therapeutic potential for cardiovascular disease. Results: this selection resulted in 34 articles of interest, of which 17 studies were conducted with the Curcuma longa plant. Myocardial infarction, cerebral ischemia and hypertension were morbidities with the greatest amount of therapeutic studies. Conclusions: the results of this study provide theoretical basis for discussions at the Public Health on alternative treatments for cardiovascular disease(AU)

Plantas com potencial antibacteriano da relação nacional de plantas medicinais de interesse do sistema único de saúde: revisão sistemática / Plants with potential antibacterial of national list medical plants of health system only interest: systematic review

Espécies de bactérias podem apresentar a capacidade genética de adquirir e transmitir resistência contra agentes antibacterianos, tornando-se multi-resistentes aos medicamentos disponíveis. Esta revisão sistemática objetivou quantificar os estudos clínicos que referem potencial terapêutico sobre doenças antibacterianas a partir do estudo de plantas constantes na Relação Nacional de Plantas Medicinais de Interesse ao Sistema Único de Saúde publicados entre 2010 e fevereiro de 2013 em três bases de dados científicas (SciELO, Science Direct e Springer). Dos 21.357 artigos encontrados nas bases de dados, tal análise resultou na seleção de 19 estudos de interesse, com diferentes plantas da relação. Os resultados encontrados neste estudo contribuem para que sejam tratadas novas discussões sobre alternativas terapêuticas aos tratamentos convencionais de doenças bacterianas, empregando plantas como um adjuvante.

Bacterial species may have the genetic ability to acquire and convey resistance to antibacterial agents, becoming multi-drug resistant available. This systematic review aimed to quantify the clinical studies which reported on antibacterial therapeutic potential diseases from the study of the plants in RENISUS, published between 2010 and February 2013 in three scientific databases (SciELO, Science Direct and Springer). Of the 21 357 articles found in databases such analysis resulted in selection of 19 studies of interest with different plants RENISUS. The results of this study contribute to be treated further discussions on alternative therapies with conventional treatments of bacterial diseases, using plants as an adjuvant.

Plantas medicinais da RENISUS com potencial anti-inflamatório: revisão sistemática em três bases de dados científicas / Medicinal plants RENISUS with potential anti-inflammatory: systematic review in three scientific databases

A inflamação é uma resposta aguda à lesão do tecido responsável por produzir sintomas característicos que levam a alterações na homeostase do tecido e no fluxo sanguíneo, sendo um mecanismo de defesa do sistema imune. No entanto, a inflamação crônica é a causa de inúmeras doenças como câncer, arteriosclerose, diabetes e doenças neurodegenerativas. Grande parte dos fármacos anti-inflamatórios exercem inúmeros efeitos colaterais que podem restringir seu uso. Uma alternativa a tais medicamentos são as plantas medicinais, que oferecem uma importante perspectiva na identificação de compostos bioativos. Esta revisão sistemática objetivou quantificar os estudos clínicos que referem potencial terapêutico sobre doenças inflamatórias a partir do estudo de plantas da RENISUS, publicados entre 2010 e fevereiro de 2013 em três bases de dados científicas (SciELO, Science Direct e Springer). Dos 21.357 artigos encontrados nas bases de dados, a análise dos artigos foi realizada inicialmente a partir da leitura do título do periódico, os artigos elegidos foram posteriormente avaliados quanto ao Abstract. Por fim, com os artigos escolhidos nesta etapa, foi analisado o texto completo. Tal análise resultou na seleção de 44 estudos de interesse, que tratavam de 20 plantas diferentes da RENISUS.(AU)

The inflammation is a response to acute tissue injury responsible for producing characteristic symptoms that lead to changes in tissue homeostasis and blood flow, as a defense mechanism of the immune system. However, chronic inflammation is a cause of many diseases like cancer, arteriosclerosis, diabetes and neurodegenerative diseases. Most anti-inflammatory drugs exert significant side effects that may limit their use. An alternative to such drugs are the medicinal plants, which provide an important approach for the identification of bioactive compounds. This systematic review aimed to quantify the clinical studies that relate therapeutic potential for inflammatory diseases from the study of plants RENISUS, published between 2010 and February 2013 in three scientific databases (SciELO, Science Direct and Springer). Of the 21 357 articles found in databases, analysis of articles was originally made from the title of journal reading, the chosen articles were subsequently assessed for Abstract. Finally, Articles chosen at this stage, the full text was analyzed. This analysis resulted in the selection of 44 studies of interest, which dealt with 20 different plants RENISUS.(AU)