Phytotherapeutic alternatives for neurodegenerative dementias: Scientific review, discussion and therapeutic proposal.

The incidence and prevalence of age-related neurodegenerative dementias have been increasing. There is no curative therapy and conventional drug treatment can cause problems for patients. Medicinal plants traditionally used for problems associated with ageing are emerging as a therapeutic resource. The main aim is to give a proposal for use and future research based on scientific knowledge and tradition. A literature search was conducted in several searchable databases. The keywords used were related to neurodegenerative dementias, ageing and medicinal plants. Boolean operators and filters were used to focus the search. As a result, there is current clinical and preclinical scientific information on 49 species used in traditional medicine for ageing-related problems, including neurodegenerative dementias. There are preclinical and clinical scientific evidences on their properties against protein aggregates in the central nervous system and their effects on neuroinflammation, apoptosis dysregulation, mitochondrial dysfunction, gabaergic, glutamatergic and dopaminergic systems alterations, monoamine oxidase alterations, serotonin depletion and oestrogenic protection. In conclusion, the potential therapeutic effect of the different medicinal plants depends on the type of neurodegenerative dementia and its stage of development, but more clinical and preclinical research is needed to find better, safer and more effective treatments.

Phenolics as GABAA Receptor Ligands: An Updated Review.

Natural products can act as potential GABA modulators, avoiding the undesirable effects of traditional pharmacology used for the inhibition of the central nervous system such as benzodiazepines (BZD). Phenolics, especially flavonoids and phlorotannins, have been considered as modulators of the BZD-site of GABAA receptors (GABAARs), with sedative, anxiolytic or anticonvulsant effects. However, the wide chemical structural variability of flavonoids shows their potential action at more than one additional binding site on GABAARs, which may act either negatively, positively, by neutralizing GABAARs, or directly as allosteric agonists. Therefore, the aim of the present review is to compile and discuss an update of the role of phenolics, namely as pharmacological targets involving dysfunctions of the GABA system, analyzing both their different compounds and their mechanism as GABAergic modulators. We focus this review on articles written in English since the year 2010 until the present. Of course, although more research would be necessary to fully establish the type specificity of phenolics and their pharmacological activity, the evidence supports their potential as GABAAR modulators, thereby favoring their inclusion in the development of new therapeutic targets based on natural products. Specifically, the data compiled in this review allows for the directing of future research towards ortho-dihydroxy diterpene galdosol, the flavonoids isoliquiritigenin (chalcone), rhusflavone and agathisflavone (biflavonoids), as well as the phlorotannins, dieckol and triphlorethol A. Clinically, flavonoids are the most interesting phenolics due to their potential as anticonvulsant and anxiolytic drugs, and phlorotannins are also of interest as sedative agents.

Antioxidant Activity of Natural Hydroquinones.

Secondary metabolites derived from hydroquinone are quite rare in nature despite the original simplicity of its structure, especially when compared to other derivatives with which it shares biosynthetic pathways. However, its presence in a prenylated form is somewhat relevant, especially in the marine environment, where it is found in different algae and invertebrates. Sometimes, more complex molecules have also been identified, as in the case of polycyclic diterpenes, such as those possessing an abietane skeleton. In every case, the presence of the dihydroxy group in the para position gives them antioxidant capacity, through its transformation into para-quinones.This review focuses on natural hydroquinones with antioxidant properties referenced in the last fifteen years. This activity, which has been generally demonstrated in vitro, should lead to relevant pharmacological properties, through its interaction with enzymes, transcription factors and other proteins, which may be particularly relevant for the prevention of degenerative diseases of the central nervous system, or also in cancer and metabolic or immune diseases. As a conclusion, this review has updated the pharmacological potential of hydroquinone derivatives, despite the fact that only a small number of molecules are known as active principles in established medicinal plants. The highlights of the present review are as follows: (a) sesquiterpenoid zonarol and analogs, whose activity is based on the stimulation of the Nrf2/ARE pathway, have a neuroprotective effect; (b) the research on pestalotioquinol and analogs (aromatic ene-ynes) in the pharmacology of atherosclerosis is of great value, due to their agonistic interaction with LXRα; and (c) prenylhydroquinones with a selective effect on tyrosine nitration or protein carbonylation may be of interest in the control of post-translational protein modifications, which usually appear in chronic inflammatory diseases.

Medicinal Plants in the Treatment of Depression. II: Evidence from Clinical Trials.

Depression is a syndrome characterized by deep sadness and the inhibition of psychic functions, sometimes accompanied by neurovegetative disorders, with symptoms of anxiety almost always present. The disease produces alterations in a variety of neural networks and neurotransmission systems, along with a dysfunction of the hypothalamic-pituitary-adrenal axis, which leads to concomitant alterations in the immunological response. Generally, there is a parallel increase in proinflammatory mediators as well as oxidative and nitrosative damage caused by a reduction of antioxidant defenses. In a previous review, we compiled and examined studies of medicinal plants that had been evaluated in preclinical assays, including existing data on 155 species studied and reported as antidepressants or as sources of active principles for treating this condition. This review will thus limit its focus to the 95 clinical trials found in PubMed among the 670 articles on antidepressant-like medicinal plants. To this end, we have reviewed the publications cited in the Cochrane Database of Systematic Reviews, PubMed, and the Science Citation Index from 2000 to 2020. Our review emphasizes those species that have demonstrated the greatest pharmacological potential when studied for their antidepressant properties in humans through clinical trials. Saffron, turmeric, St. John's wort, ginkgo, kava, and golden root are the most relevant plants that have provided important evidence for the treatment of depression in clinical trials.

Salvia miltiorrhiza: una revisión de sus posibilidades terapéuticas / Salvia miltiorrhiza: uma revisão das suas possibilidades terapêuticas / Salvia miltiorrhiza: a review of its therapeutic possibilities

La salvia roja o salvia china, Salvia miltiorrhiza Bunge (Lamiáceas), es una planta perenne originaria de China, conocida como danshen (inglés) o dānshēn (chino). Su raíz, ampliamente utilizada en la medicina oriental, contiene componentes lipofílicos diterpénicos como las tanshinonas, e hidrofílicos, de tipo fenólico, como los ácidos salvianólicos, salviánico A (danshensu), litospérmico y otros. Sus propiedades farmacológicas han sido evaluadas in vivo, in vitro, y en ensayos clínicos, principalmente con extractos, aunque también se ha estudiado el efecto de constituyentes o mezclas concretas de ellos, como el “salvianolato”, que contiene diferentes principios hidrosolubles de la raíz. Uno de los principales problemas en la evaluación del potencial terapéutico de la salvia china es que la mayor parte de estudios clínicos se han realizado con combinaciones de sus preparados o constituyentes con preparados de otros drogas vegetales o incluso fármacos sintéticos. Un elevado número de estudios arrojan resultados prometedores, destacando sus efectos beneficiosos en la enfermedad cardiovascular, infarto de miocardio, angina y aterosclerosis. Además, cabe señalar sus propiedades antiosteoporóticas, antidiabéticas, neuroprotectoras y antitumorales, aunque algunas de ellas solo tienen evidencias preclínicas. Sería deseable incrementar los estudios clínicos con protocolos más acordes con la medicina occidental: el empleo de una única especie botánica, ensayos aleatorizados, doble ciego y controlados con placebo, multicéntricos, y con un mayor número de pacientes. De esta forma, la salvia china podría alcanzar para la fitoterapia europea una consideración similar a la que posee para medicina oriental. (AU)

A salva vermelha ou salva chinesa, Salvia miltiorrhiza Bunge (Lamiáceas), é uma planta perene originária da China, conhecida como dānshēn (inglês) ou dānshēn (chinês). A sua raiz, amplamente utilizada na medicina oriental, contém componentes diterpénicos lipofílicos, como as tanshinonas, e hidrofílicos, do tipo fenólico, como os ácidos salvianólicos, salviánico A (danshensu), litospérmico e outros. As suas propriedades farmacológicas foram avaliadas in vivo, in vitro e em ensaios clínicos, principalmente com extratos, embora também tenha sido estudado o efeito de constituintes específicos ou misturas deles, como o "salvianolato", que contem diferentes princípios hidrossolúveis da raiz. Um dos principais problemas na avaliação do potencial terapêutico da salva chinesa é que a maioria dos estudos clínicos tem sido realizada com associações de preparações ou constituintes de salva com preparações de outros fármacos vegetais ou mesmo fármacos sintéticos. Um grande número de estudos mostra resultados promissores, destacando os seus efeitos benéficos em doenças cardiovasculares, enfarte do miocárdio, angina e aterosclerose. Além disso, destacam-se também propriedades antiosteoporóticas, antidiabéticas, neuroprotectoras e antitumorais, embora algumas delas tenham apenas evidências pré-clínicas. Seria desejável aumentar os estudos com protocolos mais condizentes com a medicina ocidental: o uso de uma única espécie botânica, ensaios randomizados, duplamente-cegos, controlados por placebo, multicêntricos e com maior número de pacientes. Desse modo, a salva chinesa poderia alcançar na fitoterapia europeia uma reputação semelhante à que tem na medicina oriental. (AU)

Danshen, Salvia miltiorrhiza Bunge (Lamiaceae), is a perennial plant native to China, also known as dānshēn in Chinese. Its root, widely used in oriental medicine, contains lipophilic diterpenic constituents such as tanshinones, and hydrophilic constituents, of phenolic type, such as salvianolic acids, as well as salvianic A (danshensu), lithospermic acids and others. Its pharmacological properties have been evaluated in vivo, in vitro, and in clinical trials, mainly with extracts, although the effect of specific constituents or mixtures of them, such as "salvianolate", containing different watersoluble principles of the root, has also been studied. One of the main problems in evaluating the therapeutic potential of danshen is that most clinical studies were carried out with combinations of its preparations or constituents with preparations of other herbal drugs or even synthetic drugs. A large number of studies display promising results, showing beneficial effects in cardiovascular disease, myocardial infarction, angina and atherosclerosis. In addition, it should be noted anti-osteoporotic, antidiabetic, neuroprotective and antitumor properties, although some of them have only preclinical evidence. It would be desirable to perform additional clinical trials with protocols more aligned with Western medicine: using a single botanical species, randomized, double-blinded, placebo-controlled, multicenter, and with a larger number of patients. In this way, danshen could achieve a similar consideration for European herbal medicine as it has for oriental medicine. (AU)

Intraparenchymal Meningioma.

Meningiomas have been described as the most frequent extra-axial tumor in the brain. Most are benign and correspond to World Health Organization (WHO) grade I; however, there are some reports of cases that shows atypical locations, like subcortical intra-axial meningiomas. This represents a challenge in radiological diagnosis because it could be taken as a metastasis tumor or vascular malformations. The authors bring a case report of a previously healthy patient who presents a traumatic brain injury with no traumatic lesions. A computed tomography (CT) evidenced a left frontal rounded subcortical lesion surrounded by large vasogenic edema. The first diagnostic impression was a metastasis tumor. During surgery, a total resection was completed, and the appearance of the tumor was meningioma. This was later confirmed by histological analysis. The literature was reviewed in order to determine the importance of including intraparenchymal meningiomas in the differential diagnosis of intracranial lesions.

Medicinal Plants for Insomnia Related to Anxiety: An Updated Review.

Sleep disorders are common among the general population and can generate health problems such as insomnia and anxiety. In addition to standard drugs and psychological interventions, there are different complementary plant-based therapies used to treat insomnia and anxiety. This review aimed to find and examine the most recent research on the use of herbal medicines for treating anxiety and insomnia as compiled from clinical trials, as well as to assess the safety and efficacy of these medicines and to elucidate their possible mechanisms of action. The process entailed a search of PubMed, Scopus, and the Cochrane Library databases from 2010 to 2020. The search terms included "sleep disorder", "insomnia", "sedative", "hypnotic", "anxiety", "anxiolytic", and "clinical trial", combined with the search terms "herbs" and "medicinal plants", in addition to individual herbal medicines by both their common and scientific names. This updated review, which focuses mainly on clinical trials, includes research on 23 medicinal plants and their combinations. Essential oils and their associations have also been reviewed. The efficacy of medicinal plants depends on treatment duration, types of study subjects, administration route, and treatment method. More clinical trials with an adequate, standardized design are necessary, as are more preclinical studies to continue studying the mechanisms of action. As a result of our work, we can conclude that the 3 plants with the most potential are valerian, passionflower, and ashwagandha, with the combination of valerian with hops and passionflower giving the best results in the clinical tests.

Medicinal Plants in the Treatment of Depression: Evidence from Preclinical Studies.

Medicinal plants and their extracts are natural remedies with enormous potential for treating various diseases, including depression and anxiety. In the case of depression, hundreds of plants have traditionally been used in folk medicine for generations. Different plant extracts and natural products have been analyzed as potential antidepressant agents with validated models to test for antidepressant-like effects in animals, although other complementary studies have also been employed. Most of these studies focus on the possible mediators implicated in these potential effects, with dopamine, serotonin, and noradrenaline being the principal neurotransmitters implicated, both through interference with receptors and with their metabolism by monoamino oxidases, as well as through neuro-endocrine and neuroprotective effects. There are approximately 650 reports of antidepressant-like medicinal plants in PubMed; 155 of them have been compiled in this review, with a relevant group yielding positive results. Saffron and turmeric are the most relevant species studied in both preclinical and clinical studies; St. John's wort or kava have also been tested extensively. To the best of our knowledge, no review to date has provided a comprehensive understanding of the biomolecular mechanisms of action of these herbs or of whether their potential effects could have real benefits. The purpose of this narrative review is to provide an update regarding medicinal plants from the year 2000 to the present to examine the therapeutic potential of these antidepressant-like plants in order to contribute to the development of new therapeutic methods to alleviate the tremendous burden that depression causes worldwide.

Views of patients with inflammatory bowel disease during the COVID-19 pandemic: ACCU survey results.

INTRODUCTION AND OBJECTIVES: the SARS-COV-2 pandemic has forced a substantial change in the care of patients with digestive pathologies, especially for inflammatory bowel disease (IBD) patients taking immunosuppessive medications. In this regard, some national and international guidelines have indicated the standards to be taken into account. However, few studies have evaluated how patients have dealt with this infection. Therefore, this study was performed with the aim to determine how the SARS-COV-2 pandemic has affected our IBD patients. MATERIAL AND METHODS: an online survey was performed among the members (295) of the Association of Crohn's Disease and Ulcerative Colitis (ACCU), which consisted of 19 questions. Finally, it was completed by 168 patients. RESULTS: fifty-eight per cent of cases were female, 63.7 % had Crohn's disease (CD) and 53 % received biologic therapy. Five per cent were infected by SARS-CoV-2 and were male. The main concern of the patients was the fear of acquiring the infection (80.9 %). More than 90 % continued their treatments and half of the patients worked from home during the pandemic period. CONCLUSIONS: the perspective of the patients is necessary to achieve an adequate management and evolution of the disease. More studies are needed to assess the impact that exceptional situations, such as the COVID-19 pandemic, may have on IBD patients in order to improve adherence and control of the disease.

Cacao extract enriched in polyphenols prevents endocrine-metabolic disturbances in a rat model of prediabetes triggered by a sucrose rich diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Cocoa extracts rich in polyphenols are used as potential agent for treating diabetes. Cocoa polyphenols have been proved to ameliorate important hallmarks of type-2 diabetes (T2D). They can regulate glucose levels by increasing insulin secretion, promoting ß-cell proliferation and a reduction of insulin resistance. In addition, epidemiological evidence indicates that consumption of flavonoid decreases the incidence of T2D. AIM OF THE STUDY: T2D is preceded by a prediabetic state in which the endocrine-metabolic changes described in T2D are already present. Since epidemiological evidence indicates that consumption of flavonoid decreases its incidence, we evaluated possible preventive effects of polyphenol-enriched cocoa extract on a model of prediabetes induced by sucrose. MATERIALS AND METHODS: We determined circulating parameters and insulin sensitivity indexes, liver protein carbonyl groups and reduced glutathione, liver mRNA expression levels of lipogenic enzymes, expression of different pro-inflammatory mediators, fructokinase activity and liver glycogen content. For that, radioimmunoassay, real-time polymerase chain reaction, Western blot, spectrophotometry, and immunohistochemistry were used. RESULTS: We demonstrated that sucrose administration triggered hypertriglyceridemia, insulin-resistance, and liver increased oxidative stress and inflammation markers compared to control rats. Additionally, we found an increase in glycogen deposit, fructokinase activity, and lipogenic genes expression (SREBP-1c, FAS and GPAT) together with a decrease in P-Akt and P-eNOS protein content (P < 0.05). Sucrose-induced insulin resistance, hepatic carbohydrate and lipid dysmetabolism, oxidative stress, and inflammation were effectively disrupted by polyphenol-enriched cocoa extract (PECE) co-administration (P < 0.05). CONCLUSION: Dietary administration of cocoa flavanols may be an effective and complementary tool for preventing or reverting T2D at an early stage of its development (prediabetes).

Guia prático de atualização: medicamentos biológicos no tratamento da asma, doenças alérgicas e imunodeficiências / Practical update guide: biological drugs in the treatment of asthma, allergic diseases and immunodeficiencies

O presente guia apresenta revisão extensa sobre imunobiológicos utilizados, liberados e ainda sob estudo, para o tratamento da asma, doenças alérgicas e imunodeficiências. Além das características físico-químicas de alguns desses fármacos, são revisadas as indicações e os resultados de estudos clínicos realizados para avaliar eficácia e segurança. Separados por doença específica, são apresentados os principais agentes disponíveis e aprovados para utilização segundo as normas regulatórias nacionais.

This guide presents an extensive review of immunobiological drugs used, approved and/or under investigation for the treatment of asthma, allergic diseases and immunodeficiencies. In addition to the physicochemical characteristics of some of these drugs, their indications and results of clinical studies evaluating efficacy and safety are reviewed. The main agents available and approved for use in each specific disease according to national regulatory standards are presented.

Modulation of Diabetes by Natural Products and Medicinal Plants via Incretins.

Incretins are metabolic hormones released after a meal that increase insulin secretion from pancreatic ß-cells. The two main incretins are the intestinal peptides glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Both induce a decrease in glycemia, slow down the absorption of nutrients, and are inactivated by the enzyme dipeptidyl peptidase-4. Recently, incretin-based therapies have become a useful tool to treat diabetic patients, and different studies have focused on the identification of glucagon-like peptide-1 receptor agonists, including those of natural origin. This review focuses on the new findings of medicinal plants and natural products as possible active agents on the potentiation of incretin receptor signaling. Among these, soluble fiber from species of Plantago and guar gum show promising effects, iridoid derivatives are relevant activators of incretin receptors, and derivatives of cyanidin, especially diglycosylated ones, are an interesting source of dipeptidyl peptidase-4 inhibitors.

Activation of AMPK by Medicinal Plants and Natural Products: Its Role in Type 2 Diabetes Mellitus.

Type-2 Diabetes (T2D) is a metabolic disease characterized by permanent hyperglycemia, whose development can be prevented or delayed by using therapeutic agents and implementing lifestyle changes. Some therapeutic alternatives include regulation of glycemia through modulation of different mediators and enzymes, such as AMP-activated protein kinase (AMPK), a highly relevant cellular energy sensor for metabolic homeostasis regulation, with particular relevance in the modulation of liver and muscle insulin sensitivity. This makes it a potential therapeutic target for antidiabetic drugs. In fact, some of them are standard drugs used for treatment of T2D, such as biguanides and thiazolidindiones. In this review, we compile the principal natural products that are activators of AMPK and their effect on glucose metabolism, which could make them candidates as future antidiabetic agents. Phenolics such as flavonoids and resveratrol, alkaloids such as berberine, and some saponins are potential natural activators of AMPK with a potential future as antidiabetic drugs.

Depresión e inflamación: potencial terapéutico de curcumina / Depressão e inflamação: potencial terapêutico da curcumina / Depression and inflammation: therapeutic po-tential of curcumin

La depresión es un síndrome caracterizado por una tristeza profunda y por la inhibición de las funciones psíquicas, a veces acompañado de trastornos neurovegetativos. Hay pérdida de interés, anhedonia, apatía, cambios en el sueño y el apetito, tristeza y posible ideación suicida. Se trata de un trastorno multifactorial, con disfunciones en redes neuronales y sistemas de neurotransmisión, afectando principalmente a las monoaminas. También son relevantes otros factores como el desajuste en la funcionalidad del eje hipotálamo-hipófiso-suprarrenal y el aumento de diferentes mediadores proinflamatorios. Los daños oxidativo y nitrosativo causados por la disminución de las defensas antioxidantes están también implicados. Existen múltiples estudios sobre plantas medicinales utilizadas en patologías del sistema nervioso central, y especialmente en depresión. Entre ellas destaca el potencial farmacológico de la cúrcuma que ha mostrado su efecto antiinflamatorio y antidepresivo en diferentes ensayos clínicos, tanto en animal de experimentación como en humanos. En consecuencia, esta revisión se centra en los principales estudios realizados con esta especie y especialmente con su principio de mayor potencial terapéutico, la curcumina

A depressão é uma síndrome caracterizada por profunda tristeza e inibição das funções psíquicas, às vezes acompanhada de distúrbios neurovegetativos. Há perda de interesse, anedonia, apatia, alterações no sono e apetite, tristeza e possível ideação suicida. A depressão é uma doença multifactorial com disfunções em redes neuronais e sistemas de neurotransmissão, afectando principalmente as monoaminas, embora outros aspectos, como disfunções do eixo hipotálamo-hipófise-adrenal e o aumento de diferentes mediadores pró-inflamatórios também sejam relevantes. Estão também implicados nesta patología os danos oxidativos e nitrosativos causados pela diminuição das defesas antioxidantes. Há vários estudos sobre plantas medicinais utilizadas em patologias do sistema nervoso central, e especialmente na depressão. Destaca-se a raíz de cúrcuma como a de maior potencial farmacológico, estudada e reconhecida como anti-inflamatória e como antidepressiva em diferentes en-saios pré-clínicos e clínicos, tanto em animais como em seres humanos. Consequentemente, esta revisão centra-se nos principais estudos realizados com esta espécie e, especialmente, com o seu principio activo de maior potencial terapêutico, a curcumina

Depression is a syndrome characterized by deep sadness and inhibition of psychic functions, sometimes accompanied by neurovegetative disorders. There is loss of interest, anhedonia, apathy, changes in sleep and appetite, sadness and possible suicidal ideation. Depression is a multifactorial disorder, with dysfunctions in neural networks and neurotransmission systems, mainly affecting monoamines, although other facets are relevant, such as the dysfunction of the hypothalamic-pituitary-adrenal axis and different pro-inflammatory mediators. Oxidative and nitrosative damage caused by decreased antioxidant defenses is also implicated. There are multiple studies on medicinal plants used in pathologies of the central nervous system, There are multiple studies on medicinal plants used in pathologies of the cen-tral nervous system, and especially in depression. Of these, turmeric stands out as having the greatest pharmacological potential, since it has been studied and recognized as an anti-inflammatory and antidepressant in different works, both in experimental animals and in humans, through clinical trials. Consequently, this review focuses on the main studies conducted with this species and especially with its most relevant principle, curcumin

Cardioprotection and natural polyphenols: an update of clinical and experimental studies.

Myocardial ischemia is the leading cause of death worldwide. Despite better outcomes with early coronary artery reperfusion strategies, morbidity and mortality remain significant. The principal myocardial hallmark of myocardial ischemia is cell death and the associated impairment of cardiac contractility. In this way, the use of extracts from medicinal plants versus synthetic drugs to mitigate post-ischemic damage constitutes an alternative. Despite their proven beneficial effects in cardiovascular disorders, the use of many plants is questioned. Our aim is to update the clinical and experimental studies about the actions of medicinal plants and polyphenol-enriched extracts against ischemia-reperfusion injury and the involved mechanisms. A review of the recent scientific literature (last ten years) on cardioprotective medicinal plants was developed using the following bibliographic databases: PubMed, Scopus, Web of Knowledge and Google Scholar. Herein, the clinical and experimental studies on medicinal plants and their phenolic compounds have been reviewed. The second part of this review was centered on the search for medicinal plant extracts and natural products isolated from them as potential cardioprotective agents. The botanical names of the cited plants have been authenticated by searching the Plant List and Royal Botanical Garden, Kew databases. The data collected show that treatment with natural products diminishes post-ischemic damage through an improvement of the mitochondrial functionality mainly mediated by enhanced nitric oxide bioavailability. Despite these results, further studies must be carried out to validate their use to prevent or mitigate ischemia-reperfusion injury in the clinical setting.

A Pharmacological Update of Ellagic Acid.

Ellagic acid is a common metabolite present in many medicinal plants and vegetables. It is present either in free form or as part of more complex molecules (ellagitannins), which can be metabolized to liberate ellagic acid and several of its metabolites, including urolithins. While ellagic acid's antioxidant properties are doubtless responsible for many of its pharmacological activities, other mechanisms have also been implicated in its various effects, including its ability to reduce the lipidemic profile and lipid metabolism, alter pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, interleukin-6), and decrease the activity of nuclear factor-κB while increasing nuclear factor erythroid 2-related factor 2 expression. These events play an important role in ellagic acid's anti-atherogenic, anti-inflammatory, and neuroprotective effects. Several of these activities, together with the effect of ellagic acid on insulin, glycogen, phosphatases, aldose reductase, sorbitol accumulation, advanced glycation end-product formation, and resistin secretion, may explain its effects on metabolic syndrome and diabetes. In addition, results from recent research have increased the interest in ellagic acid, both as a potential protective agent of the liver and skin and as a potential anticancer agent, due to the specific mechanisms affecting cell proliferation, apoptosis, DNA damage, and angiogenesis and its aforementioned anti-inflammatory properties. Taken together, these effects make ellagic acid a highly interesting compound that may contribute to different aspects of health; however, more studies are needed, especially on the compound's pharmacokinetic profile. In this review, we selected papers published from 2005 to the present.

Shikonin Prevents Early Phase Inflammation Associated with Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer and Induces Apoptosis in Human Colon Cancer Cells.

Shikonin is the main active principle in the root of Lithospermum erythrorhizon, widely used in traditional Chinese medicine for its anti-inflammatory and wound healing properties. Recent research highlights shikonin's antitumor properties and capacity to prevent acute ulcerative colitis. The aim of the present study was to evaluate the ability of shikonin to prevent, in vivo, the early phases of colorectal cancer development, with special focus on its cytotoxic mechanism in vitro. We employed the azoxymethane/dextran sulfate sodium model of colitis in Balb/C mice. Body weight and drinking were monitored throughout the experiment, and length of colon and lesions of the colon were recorded on termination of the experiment in all of the experimental groups. Colons underwent histological evaluation and biochemical analyses [myeloperoxidase activity assay, measurement of interleukin-6, evaluation of proinflammatory enzymes (cyclooxygenase-2 and inducible nitric oxide synthase), and nuclear factor-κB activation by Western blot]. Caco-2 cells were used to evaluate, in vitro, the effect of shikonin on proliferation, cytotoxicity, cell cycle, and apoptosis. Our results reveal that shikonin significantly protected the intestinal tissue of our animals by preventing the shortening of the colorectum and ulcer formation in a dose-dependent manner. Shikonin attenuated the expression of cyclooxygenase-2 and inducible nitric oxide synthase, and myeloperoxidase activity, and inhibited the production of interleukin-6 and activation of nuclear factor-κB. It induced Bcl-2 and inhibited caspase 3. In conclusion, shikonin acts as a chemopreventive agent in the azoxymethane/dextran sulfate sodium model through inhibition of the proinflammatory milieu generated during the disease, an important risk factor in cancer development.

New Pharmacological Opportunities for Betulinic Acid.

Betulinic acid is a naturally occurring pentacyclic lupane-type triterpenoid usually isolated from birch trees, but present in many other botanical sources. It is found in different plant organs, both as a free aglycon and as glycosyl derivatives. A wide range of pharmacological activities has been described for this triterpenoid, including antiviral and antitumor effects. In addition, several other interesting properties have been identified in the fields of immunity and metabolism, namely antidiabetic, antihyperlipidemic, and anti-inflammatory activities. Taken together, these latter three properties make betulinic acid a highly interesting prospect for treating metabolic syndrome. The present review focuses on the therapeutic potential of this agent, along with several of its semisynthetic derivatives, which could open new frontiers in the use of natural product-based medicines.

[Melioidosis: report of the first case in a northern state of México]. / Melioidosis: reporte del primer caso en el estado de Sonora, México.

The melioidosis, is an infection caused by Burkhordelia pseudomallei that comprises heterogeneous clinical syndromes with acute or chronic evolution. The objective of this article is to report a case with unusual presentation and outside the known epidemiological context. We present the case of a 48-year-old man who came to our hospital with fever and a history of an abscess in the right subscapular region, physical examination showed hepatomegaly, splenomegaly, fever, without pulmonary symptoms. Within study it reveal multiple abscesses in liver and spleen, requiring surgical exploration and antibiotics (meropenem/vancomycin). Blood cultures reveal Burkhordelia pseudomallei adding trimethoprim/sulfamethoxazole with resolution of symptoms.

La melioidosis, infección ocasionada por la bacteria Burkhordelia pseudomallei, comprende síndromes clinicos heterogéneos de evolución aguda o crónica. El objetivo del presente artículo es informar de un caso con presentación poco habitual y fuera del contexto epidemiológico conocido. Presentamos el caso de un hombre de 48 años de edad que acude a nuestro hospital por fiebre e historia de absceso en región subescapular derecha, a la exploración física mostraba hepatomegalia, esplenomegalia y fiebre, sin manifestar síntomas pulmonares. Dentro de su protocolo de estudio se concluyó que padecía múltiples abscesos en hígado y bazo, requiriendo de exploracion quirurgica y antibióticos (meropenem/vancomicina). Mediante hemocultivos hubo desarrollo de Burkhordelia pseudomallei, agregando al manejo trimetropima/sulfametoxazol con resolución de síntomas.