Taming the storm: potential anti-inflammatory compounds targeting SARS-CoV-2 MPro.

In severe COVID-19 cases, an exacerbated inflammatory response triggers a cytokine storm that can worsen the prognosis. Compounds with both antiviral and anti-inflammatory activities show promise as candidates for COVID-19 therapy, as they potentially act against the SARS-CoV-2 infection regardless of the disease stage. One of the most attractive drug targets among coronaviruses is the main protease (MPro). This enzyme is crucial for cleaving polyproteins into non-structural proteins required for viral replication. The aim of this review was to identify SARS-CoV-2 MPro inhibitors with both antiviral and anti-inflammatory properties. The interactions of the compounds within the SARS-CoV-2 MPro binding site were analyzed through molecular docking when data from crystallographic structures were unavailable. 18 compounds were selected and classified into five different superclasses. Five of them exhibit high potency against MPro: GC-376, baicalein, naringenin, heparin, and carmofur, with IC50 values below 0.2 µM. The MPro inhibitors selected have the potential to alleviate lung edema and decrease cytokine release. These molecules mainly target three critical inflammatory pathways: NF-κB, JAK/STAT, and MAPK, all previously associated with COVID-19 pathogenesis. The structures of the compounds occupy the S1/S2 substrate binding subsite of the MPro. They interact with residues from the catalytic dyad (His41 and Cys145) and/or with the oxyanion hole (Gly143, Ser144, and Cys145), which are pivotal for substrate recognition. The MPro SARS-CoV-2 inhibitors with potential anti-inflammatory activities present here could be optimized for maximum efficacy and safety and be explored as potential treatment of both mild and severe COVID-19.

HDAC specificity and kinase off-targeting by purine-benzohydroxamate anti-hematological tumor agents.

A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC50 ≤ 50 nM) vs. hematological cells and displayed moderate activity in solid tumor models (EC50 = 9.3-21.7 µM). Compound 4d potently inhibited multiple kinase targets of interest for anticancer effects, including JAK2, JAK3, HDAC1, and HDAC6. Molecular dynamics simulations showed that 4d has stable interactions with HDAC and members of the JAK family, with differences in the hinge binding energy conferring selectivity for JAK3 and JAK2 over JAK1. The kinase inhibition profile of compounds 4d-f allows selective cytotoxicity, with minimal effects on non-tumorigenic cells. Moreover, these compounds have favorable pharmacokinetic profiles, with high stability in human liver microsomes (e.g., see t1/2: >120 min for 4f), low intrinsic clearance, and lack of significant inhibition of four major CYP450 isoforms.

Anti-inflammatory potential of lactic acid bacteria from southern Brazil by reducing TNF-α and increasing IL-10 synthesis: an in vitro study.

AIMS: To evaluate the adhesion capacity and anti-inflammatory activity of lactic acid bacteria (LAB) isolated from raw cow milk and artisan cheese in Southern Brazil, investigating their effect on the release of cytokines such as TNF-α and IL-10 and their influence on the activation of the p38/MAPK pathway. METHODS AND RESULTS: Lentilactobacillus parabuchneri ML4, Lacticaseibacillus paracasei ML33, Lactiplantibacillus pentosus ML82, Lactiplantibacillus plantarum CH131, and L. paracasei CH135 demonstrated high adhesion potential in an in vitro model of the intestinal epithelium, as well as anti-inflammatory activity. After a 4-hour treatment, the strains significantly increased TNF-α levels, while a 24-hour treatment led to a significant decrease in TNF-α release. Moreover, IL-10 levels significantly increased after 24-hour and 48-hour treatments with LAB. The inhibition of p38/MAPK phosphorylation was identified as one of the mechanisms by which the L. paracasei ML33 and L. plantarum CH131 strains suppressed the production and release of TNF-α. CONCLUSIONS: We identified LAB strains with potential anti-inflammatory properties that could adhere to the intestinal mucosa and alleviate the inflammatory response by reducing the production and release of TNF-α through the inhibition of the p38/MAPK pathway, while promoting the production of IL-10.

Antiulcerogenic Potential of the Ethanolic Extract of Ceiba speciosa (A. St.-Hil.) Ravenna Evaluated by In Vitro and In Vivo Studies.

Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.

Saccorhiza polyschides-A Source of Natural Active Ingredients for Greener Skincare Formulations.

The growing knowledge about the harmful effects caused by some synthetic ingredients present in skincare products has led to an extensive search for natural bioactives. Thus, this study aimed to investigate the dermatological potential of five fractions (F1-F5), obtained by a sequential extraction procedure, from the brown seaweed Saccorhiza polyschides. The antioxidant (DPPH, FRAP, ORAC and TPC), anti-enzymatic (collagenase, elastase, hyaluronidase and tyrosinase), antimicrobial (Staphylococcus epidermidis, Cutibacterium acnes and Malassezia furfur), anti-inflammatory (nitric oxide, tumor necrosis factor-α, interleukin-6 and interleukin-10) and photoprotective (reactive oxygen species) properties of all fractions were evaluated. The ethyl acetate fraction (F3) displayed the highest antioxidant and photoprotective capacity, reducing ROS levels in UVA/B-exposed 3T3 fibroblasts, and the highest anti-enzymatic capacity against tyrosinase (IC50 value: 89.1 µg/mL). The solid water-insoluble fraction (F5) revealed the greatest antimicrobial activity against C. acnes growth (IC50 value: 12.4 µg/mL). Furthermore, all fractions demonstrated anti-inflammatory potential, reducing TNF-α and IL-6 levels in RAW 264.7 macrophages induced with lipopolysaccharides. Chemical analysis of the S. polyschides fractions by NMR revealed the presence of different classes of compounds, including lipids, polyphenols and sugars. The results highlight the potential of S. polyschides to be incorporated into new nature-based skincare products.

The functional role of p38 MAPK pathway in malignant brain tumors.

Gliomas are extremely debilitating malignant brain tumors with very limited response to therapies. The initiation and progression of gliomas can be attributed to several molecular abnormalities, such as mutations in important regulatory networks. In this regard, the mitogen-activated protein kinases (MAPKs) arise as key signaling pathways involved in cell proliferation, survival, and differentiation. MAPK pathway has been altered in most glial tumors. In glioma cells, the activation of p38 MAPK contributes to tumor invasion and metastasis and is positively correlated with tumor grade, being considered a potential oncogenic factor contributing to brain tumorigenesis and chemotherapy resistance. Hence, a better understanding of glioma pathogenesis is essential to the advancement of therapies that provide extended life expectancy for glioma patients. This review aims to explore the role of the p38 MAPK pathway in the genesis and progression of malignant brain tumors.

Neuroprotective Effect of Luteolin-7-O-Glucoside against 6-OHDA-Induced Damage in Undifferentiated and RA-Differentiated SH-SY5Y Cells.

Luteolin is one of the most common flavonoids present in edible plants and its potential benefits to the central nervous system include decrease of microglia activation, neuronal damage and high antioxidant properties. The aim of this research was to evaluate the neuroprotective, antioxidant and anti-inflammatory activities of luteolin-7-O-glucoside (Lut7). Undifferentiated and retinoic acid (RA)-differentiated SH-SY5Y cells were pretreated with Lut7 and incubated with 6-hydroxydopamine (6-OHDA). Cytotoxic and neuroprotective effects were determined by MTT assay. Antioxidant capacity was determined by DPPH, FRAP, and ORAC assays. ROS production, mitochondrial membrane potential (ΔΨm), Caspase-3 activity, acetylcholinesterase inhibition (AChEI) and nuclear damage were also determined in SH-SY5Y cells. TNF-α, IL-6 and IL-10 release were evaluated in LPS-induced RAW264.7 cells by ELISA. In undifferentiated SH-SY5Y cells, Lut7 increased cell viability after 24 h, while in RA-differentiated SH-SY5Y cells, Lut7 increased cell viability after 24 and 48 h. Lut7 showed a high antioxidant activity when compared with synthetic antioxidants. In undifferentiated cells, Lut7 prevented mitochondrial membrane depolarization induced by 6-OHDA treatment, decreased Caspase-3 and AChE activity, and inhibited nuclear condensation and fragmentation. In LPS-stimulated RAW264.7 cells, Lut7 treatment reduced TNF-α levels and increased IL-10 levels after 3 and 24 h, respectively. In summary, the results suggest that Lut7 has neuroprotective effects, thus, further studies should be considered to validate its pharmacological potential in more complex models, aiming the treatment of neurodegenerative diseases.

A Special View of What Was Almost Forgotten: p38δ MAPK.

The p38δ mitogen-activated protein kinase is an important signal transduction enzyme. p38δ has recently emerged as a drug target due to its tissue-specific expression patterns and its critical roles in regulation of cellular processes related to cancer and inflammatory diseases, such as cell proliferation, cell migration, apoptosis, and inflammatory responses. However, potent and specific p38δ inhibitors have not been defined so far. Moreover, in cancer disease, p38δ appears to act as a tumor suppressor or tumor promoter according to cancer and cell type studied. In this review, we outline the current understanding of p38δ roles in each cancer type, to define whether it is possible to delineate new cancer therapies based on small-molecule p38δ inhibitors. We also highlight recent advances made in the design of molecules with potential to inhibit p38 isoforms and discuss structural approaches to guide the search for p38δ inhibitors.

Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius.

Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10-100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H2O2) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC50 range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells' viability decrease was accompanied by an increase on H2O2 production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H2O2 levels and downstream apoptosis.

A Highly Selective In Vitro JNK3 Inhibitor, FMU200, Restores Mitochondrial Membrane Potential and Reduces Oxidative Stress and Apoptosis in SH-SY5Y Cells.

Current treatments for neurodegenerative diseases (ND) are symptomatic and do not affect disease progression. Slowing this progression remains a crucial unmet need for patients and their families. c-Jun N-terminal kinase 3 (JNK3) are related to several ND hallmarks including apoptosis, oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation. JNK inhibitors can play an important role in addressing neuroprotection. This research aims to evaluate the neuroprotective, anti-inflammatory, and antioxidant effects of a synthetic compound (FMU200) with known JNK3 inhibitory activity in SH-SY5Y and RAW264.7 cell lines. SH-SY5Y cells were pretreated with FMU200 and cell damage was induced by 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2). Cell viability and neuroprotective effect were assessed with an MTT assay. Flow cytometric analysis was performed to evaluate cell apoptosis. The H2O2-induced reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm) were evaluated by DCFDA and JC-1 assays, respectively. The anti-inflammatory effect was determined in LPS-induced RAW264.7 cells by ELISA assay. In undifferentiated SH-SY5Y cells, FMU200 decreased neurotoxicity induced by 6-OHDA in approximately 20%. In RA-differentiated cells, FMU200 diminished cell death in approximately 40% and 90% after 24 and 48 h treatment, respectively. FMU200 reduced both early and late apoptotic cells, decreased ROS levels, restored mitochondrial membrane potential, and downregulated JNK phosphorylation after H2O2 exposure. In LPS-stimulated RAW264.7 cells, FMU200 reduced TNF-α levels after a 3 h treatment. FMU200 protects neuroblastoma SH-SY5Y cells against 6-OHDA- and H2O2-induced apoptosis, which may result from suppressing the JNK pathways. Our findings show that FMU200 can be a useful candidate for the treatment of neurodegenerative disorders.

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum.

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells' exposure to 6-OHDA in the presence of Loliolide led to an increase of cells' viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.

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.

Review of Trials Currently Testing Stem Cells for Treatment of Respiratory Diseases: Facts Known to Date and Possible Applications to COVID-19.

Therapeutic clinical and preclinical studies using cultured cells are on the rise, especially now that the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a "public health emergency of international concern", in January, 2020. Thus, this study aims to review the outcomes of ongoing clinical studies on stem cells in Severe Acute Respiratory Syndrome (SARS), Acute Respiratory Distress Syndrome (ARDS), and Middle East Respiratory Syndrome (MERS). The results will be associated with possible applications to COVID-19. Only three clinical trials related to stem cells are considered complete, whereby two are in Phase 1 and one is in Phase 2. Basically, the ongoing studies on coronavirus are using mesenchymal stem cells (MSCs) derived from bone marrow or the umbilical cord to demonstrate their feasibility, safety, and tolerability. The studies not related to coronavirus are all in ARDS conditions; four of them are in Phase 1 and three in Phase 2. With the COVID-19 boom, many clinical trials are being carried out using different sources with an emphasis on MSC-based therapy used to inhibit inflammation. One of the biggest challenges in the current treatment of COVID-19 is the cytokine storm, however MSCs can prevent or mitigate this cytokine storm through their immunomodulatory capacity. We look forward to the results of the ongoing clinical trials to find a treatment for the disease. Researchers around the world are joining forces to help fight COVID-19. Stem cells used in the current clinical studies are a new therapeutic promise for COVID-19 where pharmacological treatments seem insufficient.Graphical Abstract.

An evaluation of the effects of probiotics on tumoral necrosis factor (TNF-α) signaling and gene expression.

The search for functional foods containing probiotics has been growing due to numerous benefits they provide to health, such as modulation of the immune system and of the anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines, such as TNF-α. However, the mechanisms of actions of the probiotics responsible for this inhibition have not been completely explained so far. A better understanding of the interaction between probiotics and cell signaling pathways related to inflammatory processes shall help to prevent inflammatory bowel diseases. Therefore, the aim of this revision is to help understand the mechanisms of action of probiotics in cell signaling pathways that regulate TNF-α expression. Probiotics might act at different points of the MAPK pathway, on NF-kB, on proteasome activity, on Toll-like receptors, and on their regulators and stimuli. The present revision reaches the conclusion that probiotics act through multiple mechanisms, especially by inhibiting IkB phosphorylation and degradation, thus preventing the translocation of NF-kB. Effects are also shown to be strain-specific, and probiotics of the genus Lactobacillus are proved to play and essential role in anti-inflammatory activity.

Antimicrobial and antileukemic effects: in vitro activity of Calyptranthes grandifolia aqueous leaf extract.

Natural products are still a promising source of bioactive molecules. Food and Drug Administration data showed that approximately 49% of the approved molecules originate naturally or chemically-resemble these substances, of which more than 70% are being used in anticancer therapy. It is noteworthy that at present there are no scientific studies to prove the effectiveness and safety of a number of plants used in folk medicine such as in the case of Calyptranthes grandifolia O. Berg (Myrtaceae) originally from South America. The aim of the present study was to determine the biological potential and toxicological effects of the aqueous leaf extract of C. grandifolia. The main detected phytoconstituents were condensed tannins and flavonoids and a high quantity of polyphenols. Regarding the antimicrobial potential, the extract exerted inhibitory activity against Pseudomonas aeruginosa. The results also revealed the extract induced DNA damage in a concentration-dependent manner in RAW 264.7 cells. In addition, C. grandifolia produced cytotoxicity in leukemia cell lines (HL60 and Kasumi-1) without affecting isolated human lymphocytes but significantly inhibited JAK3 and p38α enzyme activity. Taken together, these findings add important information on the biological and toxicological effects of C. grandifolia, indicating that aqueous extract may be a source of natural antimicrobial and antileukemic constituents.

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.

Are peptides a solution for the treatment of hyperactivated JAK3 pathways?

While the inactivation mutations that eliminate JAK3 function lead to the immunological disorders such as severe combined immunodeficiency, activation mutations, causing constitutive JAK3 signaling, are known to trigger various types of cancer or are responsible for autoimmune diseases, such as rheumatoid arthritis, psoriasis, or inflammatory bowel diseases. Treatment of hyperactivated JAK3 is still an obstacle, due to different sensibility of mutation types to conventional drugs and unwanted side effects, because these drugs are not absolutely specific for JAK3, thus inhibiting other members of the JAK family, too. Lack of information, in which way sole inhibition of JAK3 is necessary for elimination of the disease, calls for the development of isoform-specific JAK3 inhibitors. Beside this strategy, up to date peptides are a rising alternative as chemo- or immunotherapeutics, but still sparsely represented in drug development and clinical trials. Beyond a possible direct inhibition function, crossing the cancer cell membrane and interfering in disease-causing pathways or triggering apoptosis, peptides could be used in future as adjunct remedies to potentialize traditional therapy and preserve non-affected cells. To discuss such feasible topics, this review deals with the knowledge about the structure-function of JAK3 and the actual state-of-the-art of isoform-specific inhibitor development, as well as the function of currently approved drugs or those currently being tested in clinical trials. Furthermore, several strategies for the application of peptide-based drugs for cancer therapy and the physicochemical and structural relations to peptide efficacy are discussed, and an overview of peptide sequences, which were qualified for clinical trials, is given.

In vitro activities of Ceiba speciosa (A.St.-Hil) Ravenna aqueous stem bark extract.

Several species of the genus Ceiba (Malvaceae) are ethnopharmacologically used. Thus, this study aimed to investigate the in vitro beneficial properties of the aqueous stem bark extract of Ceiba speciosa. The extract presented a great amount of phenolic compounds (117.4 ± 6.2 mg GAE/g). The antioxidant activity was assessed by DPPH (IC50 = 42.87 µg/mL), ORAC (2351.17 µmol TE/g) and FRAP (235.94 µM FeSO4/g) methods. In addition, the extract reduced MCF-7 cell viability as assessed by MTT. However, it prevented mitochondrial membrane depolarization and reduced caspase-9 activity induced by hydrogen peroxide. In conclusion, these findings indicate the extract is an excellent source of natural antioxidants and is able to protect ROS-induced cell death. Therefore, C. speciosa extract may possess beneficial properties for application in pharmaceutical industry as an antioxidant. However, further studies to better elucidate its mechanisms and to isolate its active compounds are required.

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.