Antimicrobial activity of natural products against Helicobacter pylori: a review

Throughout the genetic and physiological evolution of microorganisms, the microbiological sciences have been expanding the introduction of new therapeutic trials against microbial diseases. Special attention has been paid to the bacterium Helicobacter pylori, which induces gastric infections capable of causing damage, ranging from acute and chronic gastritis to the development of gastric cancer and death. The use of compounds with natural origins has gained popularity in scientific research focused on drug innovation against H. pylori because of their broad flexibility and low toxicity. The aim of this study was to describe the use of natural products against H. pylori in order to clarify important parameters for related fields. The study demonstrated the vast therapeutic possibilities for compounds originating from natural sources and revealed the need for innovations from future investigations to expand the therapeutic arsenal in the fight against H. pylori infection.

Medicinal plants in pregnancy and lactation: perception of the health risk and practical educational group in Araraquara, São Paulo State, Brazil

The use of medicinal plants among pregnant women and lactating is a common practice in diverse countries. However, many medicinal plants are contraindicated during pregnancy and lactating, due to various adverse effects, such as teratogenic, embryotoxic and abortive effects, exposing these women, their fetus and babies to health unknown risks. Thus, the purpose of this commentary, was to analyze the perception about the use of medicinal plants by pregnant women and lactating registered in the "baby on board" NGO, Araraquara, São Paulo state, Brazil, between 2010 at 2013. The group was constituted by 48 women, between the first and last trimester of pregnancy or whilst breastfeeding. Information was collected during group meetings by oral interview, using a questionnaire, as script. The nature of the study was a qualitative analysis. The results were based on reports about the use of medicinal plants by pregnant women during group meetings: use, indication of use, knowledge about risks. All participants received written and oral information about the study and they gave a written informed consent. The use of medicinal plants is a reality among pregnant and lactating women of the "baby on board" NGO. They reported that they feel that "natural" products are not harmful for their health. The primary information sources for the majority of women about medicinal plants during pregnancy are family, neighbors and herbalists. The plants most cited (in popular name in Brazil) were: senna, chamomile, boldo, lemon balm, lemon grass. They were used mainly for: nausea, heartburn, indigestion, flatulence, intestinal and abdominal pain, anxiety, intestinal constipation and low milk production. The pregnant and lactating women lacked knowledge about the health risks of the use of medicinal plants and herbal medicines in pregnancy and lactation. They also reported difficulties in clarifying some questions about the use of medicinal plants with their doctors. The results of the present study showed that educative actions about the rational use of medicinal plants in pregnancy and breastfeeding could be part of the operating protocols to promote the maternal and child health programs in Araraquara. Thus, our results also suggest the importance of creating institutionalized places, to the implementation of continued education programs about rational use of medicinal plants in pregnancy and lactation. These targeted programs are not only for health professionals, but also for community members, pregnant women and breastfeeding. Our results pointed out the importance of guidance of doctors and healthcare professionals on the scientific studies about medicinal plants and herbal medicines and the risk/benefit of using herbs during pregnancy. Finally, it is noted the importance of the health professionals to inform women of childbearing on risks to their health, as well as on possibilities of utilization of herbs during fertile period, giving special attention to the potential risk of self-medication.

EVAPORATIVE LIGHT-SCATTERING DETECTOR FOR ANALYSIS OF NATURAL PRODUCTS

EVAPORATIVE LIGHT-SCATTERING DETECTOR FOR ANALYSIS OF NATURAL PRODUCTS. The interest in the use of evaporative light scattering detector (ELSD) for the analysis of different classes of natural products has grown over the years. This is because this detector has become an excellent alternative compared to other types of detectors, such as the refractive index detector and the ultraviolet (UV) detector. This review describes the basic principles of ELSD functioning and discusses the advantages and disadvantages in using an ELSD for the analysis of organic compounds. Additionally, an overview, covering the last 23 years, of ELSD applications in natural products analysis (saponins, terpenes, carbohydrates, glycosides, alkaloids, steroids, flavonoids, peptides, polyketides, coumarins and iridoids) is presented and discussed.

Marine natural products: chemical and biological potential of seaweeds and their endophytic fungi

Marine natural products have currently been recognized as the most promising source of bioactive substances for drug discovery research. In this review, extraordinary metabolites from marine algae species are illustrated, as well as approaches for their isolation and determination of their biological properties and pharmaceutical potential. Furthermore, marine endophytic microorganisms (from marine algae) are presented as a new subject for extensive investigation to find novel natural products, which make them a potentially rich and innovative source for new drug candidates.

Use of essential oils and biocontrol cultures for the improvement of shelf-life of fresh cut products

The demand of minimally processed fruits and vegetables has increased in the last years. However, their intrinsic characteristics may favor the growth of pathogens and spoilage microbiota. The negative effects on human health reported for some traditional chemical sanitizers have justified the search for substitutes to guarantee food safety and quality. In this work we have evaluate the potential of some essential oils and their components to improve the safety and the shelf life of Lamb’s lettuce (Valerianella locusta) and apples (Golden delicious). Moreover, the effects of selected lactic acid bacteria alone or in combination with essential oils or their components, on the shelf-life and safety as well as organoleptic properties of minimally processed products, were evaluated. Since the lack of knowledge of microbial cell targets of essential oils represent one of the most important limit to the use of these molecules at industrial level, another aim of this thesis was the study of the action mechanisms of essential oils and their components. The results obtained showed the beneficial effects of the natural antimicrobials as well as the selected lactic acid bacteria on minimally processed fruit and vegetable safety and shelf-life, without detrimental effects on the quality parameters. The beneficial effects obtained by the use of the selected biocontrol agents were further increased combining them with selected natural antimicrobials. The natural antimicrobial employed induced noticeable modifications of membrane fatty acid profiles and volatile compounds produced by microbial cells during the growth. The modification of the expression in genes involved in fatty acid biosynthesis suggesting that the cytoplasmic membrane of microbial cells is one of the major cellular target of essential oils and their components. The comprehension of microbial stress response mechanisms can contribute to the scaling up of natural antimicrobials and bio-control agents at industrial level.

Natural products as leads for anticancer drug discovery: discovery of new chemotypes of microtubule stabilizers through reengineering of the epothilone scaffold

Epothilones are bacterial macrolides with potent microtubule-stabilizing and antiproliferative activity, which have served as successful lead structures for the discovery of several clinical candidates for cancer treatment. Overall, seven epothilone-type agents have been advanced to clinical evaluation in humans so far and one of these has been approved by the FDA in 2007 for clinical use in breast cancer patients. Notwithstanding these impressive numbers, however, the structural diversity represented by the collection of epothilone analogs that have been (or still are) investigated clinically is rather limited and their individual structures show little divergence from the original natural product leads. In contrast, we have elaborated a series of epothilone-derived macro-lactones, whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of conformationally constrained side chains, the removal of the C(3)-hydroxyl group, and the replacement of C(12) with nitrogen. The latter modification leads to aza-macrolides that may be described as 'non-natural natural products'.

Anticancer drugs from nature--natural products as a unique source of new microtubule-stabilizing agents

This review article provides an overview on the current state of research in the area of microtubule-stabilizing agents from natural sources, with a primary focus on the biochemistry, biology, and pharmacology associated with these compounds. A variety of natural products have been discovered over the last decade to inhibit human cancer cell proliferation through a taxol-like mechanism. These compounds represent a whole new range of structurally diverse lead structures for anticancer drug discovery.

Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone mineral

OBJECTIVES The application of an enamel matrix derivative (EMD) for regenerative periodontal surgery has been shown to promote formation of new cementum, periodontal ligament, and alveolar bone. In intrabony defects with a complicated anatomy, the combination of EMD with various bone grafting materials has resulted in additional clinical improvements, but the initial cellular response of osteoblasts coming in contact with these particles have not yet been fully elucidated. The objective of the present study was to evaluate the in vitro effects of EMD combined with a natural bone mineral (NBM) on a wide variety of genes, cytokines, and transcription factors and extracellular matrix proteins on primary human osteoblasts. MATERIAL AND METHODS Primary human osteoblasts were seeded on NBM particles pre-coated with versus without EMD and analyzed for gene differences using a human osteogenesis gene super-array (Applied Biosystems). Osteoblast-related genes include those transcribed during bone mineralization, ossification, bone metabolism, cell growth and differentiation, as well as gene products representing extracellular matrix molecules, transcription factors, and cell adhesion molecules. RESULTS EMD promoted gene expression of various osteoblast differentiation markers including a number of collagen types and isoforms, SMAD intracellular proteins, osteopontin, cadherin, alkaline phosphatase, and bone sialoprotein. EMD also upregulated a variety of growth factors including bone morphogenetic proteins, vascular endothelial growth factors, insulin-like growth factor, transforming growth factor, and their associated receptor proteins. CONCLUSION The results from the present study demonstrate that EMD is capable of activating a wide variety of genes, growth factors, and cytokines when pre-coated onto NBM particles. CLINICAL RELEVANCE The described in vitro effects of EMD on human primary osteoblasts provide further biologic support for the clinical application of a combination of EMD with NBM particles in periodontal and oral regenerative surgery.

Effects of different types of solid feeds on health status and performance of Swiss veal calves. I. Basic feeding with milk by-products

The objective of this study was to identify a suitable alternative to the current practice of complementing the feeding of milk by-products with straw. The influence of 5 different types of solid feeds on health and performance of Swiss veal calves was investigated in 2 production cycles of 200 veal calves each with a mean initial age of 40 days (d). The calves were housed in groups of 40 in stalls with outside pen. Liquid feeding consisted of a milk by-product combined with an additional skim milk powder ad libitum. Groups were assigned to 1 of the 5 following experimental solid feeds provided ad libitum: mix (composition: soy flakes, corn, barley, wheat, oat, barley middling, plant oil, molasses), whole plant corn pellets, corn silage, hay, and wheat straw as control. Daily dry matter intake per calf averaged 2.25 kg of the liquid food, 0.16 kg of straw, 0.33 kg of mix, 0.47 kg of corn silage, 0.38 kg of corn pellets, and 0.39 kg of hay. No significant differences (P > 0.05) among groups were found in calf losses that amounted to 4.8 % (68 % because of gastrointestinal disorders). Four percent of the calves were slaughtered prematurely. Daily doses of antibiotics were higher in the mix (36.9 d, P < 0.01) and in the corn silage groups (35 d, P < 0.01) compared to control. Compared to the 4 other groups, calves of the straw group showed the highest prevalence of abnormal ruminal content (73 %, P < 0.05), of abnormal ruminal papillae (42 %, P < 0.05), of abomasal fundic lesions (13.5 %, P < 0.1), and the lowest number of chewing movements per bolus (45, P < 0.05). The hemoglobin concentration averaged 85 g/l at the beginning and 99 g/l at the end of the fattening period with no significant differences among groups (P > 0.1). The duration of the fattening period averaged 114 d, slaughter age 157 d, and carcass weight 122 kg. The average daily weight gain (ADG) was highest in the control group straw (1.35 kg), and lowest in the hay group (1.22 kg, P < 0.01). The number of carcasses classified as C, H, and T (very high to medium quality) was lower in the hay group compared to straw (P < 0.01). No significant differences between groups were found in meat color (P > 0.1): 73 % of the carcasses were assessed as pale (267/364), 18 % as pink (66/364), and 9 % (31/364) as red. The results reveal that whole-plant corn pellets are most consistent with an optimal result combining the calves' health and fattening performance. Therefore, it can be recommended as an additional solid feed for veal calves under Swiss conditions.

Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule.

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional profiling revealed that celastrol treatment induces a battery of oxidant defense genes in addition to heat shock genes. Celastrol activated the yeast Yap1 oxidant defense transcription factor via the carboxy-terminal redox center that responds to electrophilic compounds. Antioxidant response genes were likewise induced in mammalian cells, demonstrating that the activation of two major cell stress pathways by celastrol is conserved. We report that celastrol's biological effects, including inhibition of glucocorticoid receptor activity, can be blocked by the addition of excess free thiol, suggesting a chemical mechanism for biological activity based on modification of key reactive thiols by this natural product.