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Propolis is a viscous resin consisting of plant material (shoots, flowers, and plant exudates), salivary secretions and waxes produced by Apis mellifera bees. Its popular use aroused the interests of scientific research, which proved to be a potential source of various bioactive substances. The chemical composition of propolis depends on several factors, such as the different types of plant sources collected by bees, geographic origin, and the time of year in which they are produced, but it is known that phenolic represent the main bioactive constituents of propolis. Baccharis dracunculifolia DC (Asteraceae) is the most important botanical source of propolis and a native to southeastern Brazil. It is widely known as the green propolis because of its deep green color. One of its major phenolic acids is artepillin C (Art-C), a diprenyl-p-hydroxycinnamic acid derivative. This review aims to provide a comprehensive summary of the pharmacological effects of Art-C. The limited number of publications on this topic over the past two decades have been collected from databases and summarized. Numerous biological activities have been described for the Art-C, such as gastroprotective, anti-inflammatory, antimicrobial, antioxidant, antitumor. This article describes aspects of occurrence, synthesis, biological activities and pharmacokinetic approaches.

Made available in DSpace on 2022-05-01T13:41:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. β-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, β-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the β-caryophyllene-Treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with β-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the β-caryophyllene-Treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1β and IL-6. After β-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. β-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of β-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms. São Paulo State University-UNESP Institute of Biosciences of Botucatu-IBB São Paulo State University-UNESP School of Veterinary Medicine and Zootechnics-FMVZ University of São Paulo-USP School of Pharmaceutical Science of Ribeirão Preto-FCFRP São Paulo State University-UNESP Institute of Biosciences of Botucatu-IBB São Paulo State University-UNESP School of Veterinary Medicine and Zootechnics-FMVZ

Guttiferones belong to the polyisoprenylated benzophenone, a class of compounds, a very restricted group of natural plant products, especially in the Clusiaceae family. They are commonly found in bark, stem, leaves, and fruits of plants of the genus Garcinia and Symphonia. Guttiferones have the following classifications according to their chemical structure: A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, and T. All of them have received growing attention due to its multiple biological activities. This review provides a first comprehensive approach to plant sources, phytochemical profile, specific pharmacological effects, and mechanisms of guttiferones already described. Studies indicate a broad spectrum of pharmacological activities, such as: anti-inflammatory, immunomodulatory, antioxidant, antitumor, antiparasitic, antiviral, and antimicrobial. Despite the low toxicity of these compounds in healthy cells, there is a lack of studies in the literature related to toxicity in general. Given their beneficial effects, guttiferones are expected to be great potential drug candidates for treating cancer and infectious and transmissible diseases. However, further studies are needed to elucidate their toxicity, specific molecular mechanisms and targets, and to perform more in-depth pharmacokinetic studies. This review highlights chemical properties, biological characteristics, and mechanisms of action so far, offering a broad view of the subject and perspectives for the future of guttiferones in therapeutics.

Wound healing involves inflammatory, proliferative, and remodeling phases, in which various cells and chemical intermediates are involved. This study aimed to investigate the skin wound healing potential of menthol, as well as the mechanisms involved in its effect, after 3, 7, or 14 days of treatment, according to the phases of wound healing. Skin wound was performed in the back of Wistar rats, which were topically treated with vehicle cream, collagenase-based cream (1.2 U/g), or menthol-based cream at 0.25%, 0.5%, or 1.0% over 3, 7, or 14 days. Menthol cream at 0.5% accelerated the healing right from the inflammatory phase (3 days) by decreasing mRNA expression of inflammatory cytokines TNF-α and Il-6. At the proliferative phase (7 days), menthol 0.5% increased the activity of antioxidant enzymes SOD, GR, and GPx, as well as the level of GSH, in addition to decreasing the levels of inflammatory cytokines TNF-α, IL-6, and IL-1β and augmenting mRNA expression for Ki-67, a marker of cellular proliferation. At the remodeling phase (14 days), levels of inflammatory cytokines were decreased, and the level of Il-10 and its mRNA expression were increased in the menthol 0.5% group. Menthol presented skin wound healing activity by modulating the antioxidant system of the cells and the inflammatory response, in addition to stimulating epithelialization.

The skin is the biggest organ of human body which acts as a protective barrier against deleterious agents. When this barrier is damaged, the organism promotes the healing process with several molecular and cellular mechanisms, in order to restore the physiological structure of the skin. The physiological control of wound healing depends on the correct balance among its different mechanisms. Any disruption in the balance of these mechanisms can lead to problems and delay in wound healing. The impairment of wound healing is linked to underlying factors as well as aging, nutrition, hypoxia, stress, infections, drugs, genetics, and chronic diseases. Over the years, numerous studies have been conducted to discover the correct approach and best therapies for wound healing, including surgical procedures and non-surgical treatments such as topical formulations, dressings, or skin substitutes. Thus, this general approach is necessary to facilitate the direction of further studies. This work provides updated concepts of physiological mechanisms, the factors that can interfere, and updated treatments used in skin wound healing.

Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. Natural products have shown to be effective in treating skin wounds. Lupeol is known to stimulate angiogenesis, fibroblast proliferation, and expressions of cytokines and growth factors involved in wound healing. The study is performed to evaluate the wound healing activity of lupeol in streptozotocin-induced hyperglycemic rats by macroscopical, histological, immunohistochemical, immunoenzymatic, and molecular methods. Percentage of wound closure and contraction was increased in the lupeol-treated group when compared to the Lanette group. Histopathological observation revealed decreased inflammatory cell infiltration and increased proliferation of fibroblasts, vascularization, and deposition of collagen fibers after lupeol treatment. Immunohistochemical analyses showed decreased intensity of NF

Natural products obtained in dietary components may aid the prevention and treatment of a variety of diseases. Reports in the scientific literature have demonstrated that the consumption of terpenes is a successful alternative in the treatment of several diseases, triggering beneficial biological effects in clinical and preclinical studies. The monoterpene limonene is largely used in alimentary items, cleaning products, and it is one of the most frequent fragrances used in cosmetics formulation. The therapeutic effects of limonene have been extensively studied, proving anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antihyperalgesic, antiviral, and gastroprotective effects, among other beneficial effects in health. In this review, we collected, presented, and analyzed evidence from the scientific literature regarding the usage of limonene and its activities and underlying mechanisms involved in combating diseases. The highlighting of limonene applications could develop a useful targeting of innovative research in this field as well as the development of a limonene-based phytomedicine which could be used in a variety of conditions of health and disease.

Made available in DSpace on 2019-10-06T16:38:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. Natural products have shown to be effective in treating skin wounds. Lupeol is known to stimulate angiogenesis, fibroblast proliferation, and expressions of cytokines and growth factors involved in wound healing. The study is performed to evaluate the wound healing activity of lupeol in streptozotocin-induced hyperglycemic rats by macroscopical, histological, immunohistochemical, immunoenzymatic, and molecular methods. Percentage of wound closure and contraction was increased in the lupeol-treated group when compared to the Lanette group. Histopathological observation revealed decreased inflammatory cell infiltration and increased proliferation of fibroblasts, vascularization, and deposition of collagen fibers after lupeol treatment. Immunohistochemical analyses showed decreased intensity of NF-κB and increased intensity of FGF-2, TGF-β1, and collagen III. ELISA results revealed downregulated IL-6 levels and upregulated IL-10 levels in response to lupeol. The mRNA expression levels of Hif-1α, Sod-2, and Ho-1 were significantly increased in response to lupeol as compared to Lanette whereas Nf-κb and Vegf-A levels were decreased in relation to insulin and lupeol treatment. These findings indicate that lupeol possesses wound healing potential in hyperglycemic conditions and may be useful as a treatment for chronic wounds in diabetic patients. Department of Morphology Institute of Biosciences São Paulo State University (UNESP) Department of Surgery and Veterinary Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University (UNESP) Kolling Institute of Medical Research University of Sydney at Royal North Shore Hospital Department of Pharmacy Federal University of São Francisco Valley (UNIVASF) Department of Morphology Institute of Biosciences São Paulo State University (UNESP) Department of Surgery and Veterinary Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University (UNESP)

Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1&beta, and IL-6) and gene and protein NF-&kappa, B expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-&beta, 1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.

Skin wound healing is a dynamic and complex process involving several mediators at the cellular and molecular levels. Lupeol, a phytoconstituent belonging to the triterpenes class, is found in several fruit plants and medicinal plants that have been the object of study in the treatment of various diseases, including skin wounds. Various medicinal properties of lupeol have been reported in the literature, including anti-inflammatory, antioxidant, anti-diabetic, and anti-mutagenic effects. We investigated the effects of lupeol (0.1, 1, 10, and 20 &mu, g/mL) on in vitro wound healing assays and signaling mechanisms in human neonatal foreskin keratinocytes and fibroblasts. Results showed that, at high concentrations, Lupeol reduced cell proliferation of both keratinocytes and fibroblasts, but increased in vitro wound healing in keratinocytes and promoted the contraction of dermal fibroblasts in the collagen gel matrix. This triterpene positively regulated matrix metalloproteinase (MMP)-2 and inhibited the NF-&kappa, B expression in keratinocytes, suggesting an anti-inflammatory effect. Lupeol also modulated the expression of keratin 16 according to the concentration tested. Additionally, in keratinocytes, lupeol treatment resulted in the activation of Akt, p38, and Tie-2, which are signaling proteins involved in cell proliferation and migration, angiogenesis, and tissue repair. These findings suggest that lupeol has therapeutic potential for accelerating wound healing.

Made available in DSpace on 2019-10-06T16:53:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 Made available in DSpace on 2019-10-06T16:53:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 Made available in DSpace on 2019-10-06T16:53:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 Made available in DSpace on 2019-10-06T16:53:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 Made available in DSpace on 2019-10-06T16:53:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: In an increasing search for natural products that may heal the ulcers and avoid its recurrence, limonene appears as a promising candidate. Hypothesis/Purpose: The present study aimed to investigate the protective effect of limonene in ethanol-induced gastric ulcers, in addition, to investigate the involvement of antioxidant and anti-inflammatory activities, besides the modulation of gene expression. Study Design: Male Wistar rats were orally treated with vehicle (8% tween 80), carbenoxolone (100 mg/kg) or limonene (25, 50 or 100 mg/kg) and then orally received ethanol to induce gastric ulcers formation. Methods: The activity of myeloperoxidase (MPO) was measured. Levels of glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured. We investigated the anti-inflammatory effect of limonene measuring the levels of pro-inflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1β (IL-1β) and anti-inflammatory cytokine interleukin-10 (IL-10) by ELISA. Additionally, we investigate through real-time PCR (qPCR) the gene expression of nuclear factor-kappa B (Nf-κb), Gpx, Il-1β Mpo, and Il-10. Results: Our results showed that limonene 50 mg/kg was the lowest effective dose, offering 93% of reduction in gastric ulcer area compared with the vehicle. There was an increase in mucus production and higher preservation of gastric mucosa integrity after treatment with limonene.There was a reduction in the MPO activity, a biomarker of neutrophils infiltration, and an increase in GPx activity, suggesting an antioxidant effect. Limonene displayed anti-inflammatory activity through decreasing the levels of TNF-a, IL-6, and IL-1β and increasing the level of IL-10. Limonene could down-regulate the expression of Nf-κb, Il-1β and Mpo and up-regulate the expression of Gpx. Conclusion: Our results demonstrate that oral treatment with limonene exerts gastroprotection through local mucosal defense mechanisms, such as increasing the mucus production, modulation of the oxidative stress and inflammatory response and inhibition of Nf-κb expression. Department of Morphology São Paulo State University (UNESP) Institute of Biosciences Department of Morphology São Paulo State University (UNESP) Institute of Biosciences FAPESP: 2016/25832-7

Ethnopharmacological relevance Serjania marginata (Sapindaceae), a medicinal plant commonly found in the Brazilian Cerrado, Paraguay, Bolivia and Argentina, is also known as “cipo-uva” or “cipo-timbo”. Ethnopharmacological studies indicate that the leaves from this medicinal plant are used in folk medicine to treat gastric pain. The overall objective of this study was to evaluate the gastroprotective and healing effect of the hydroalcoholic extract obtained from S. marginata (HESM) leaves using rodent experimental models. As part of the integrative study of this medicinal plant, we also evaluated the acute toxicity, antimicrobial, antidiarrheal, (anti)mutagenic, and hemodynamic effects. Material and methods We performed a pharmacological study to test the acute toxicity and antimutagenic effect (Ames assay) of the HESM. The HESM was tested against different necrosis-promoting agents and experimental manipulations, such as absolute ethanol, cysteamine, pyloric ligature, and ischemia–reperfusion (I/R) injury. The gastroprotective effect of the HESM was assessed by analyzing the gastric juice (volume, pH, total acidity) and the mucus in the gastric mucosa from rats. We assessed the levels of NO, sulfhydryl compounds, PGE 2 , vanilloid receptor, glutathione (GSH), and malondialdehyde (MDA), as well as the myeloperoxidase (MPO) activity. The gastric healing effects of the HESM were evaluated during 7 or 14 days of treatment. The intestinal motility, antidiarrheal action, and antibacterial effects (microdilution methods) of the HESM were also evaluated. Results The phytochemical analysis of the HESM revealed the presence of saponins, flavonoid glycosides, and tannins. The extract exhibited no sign of acute toxicity or mutagenic effect in vitro . In contrast, this extract exhibited a protective effect against the mutagenic action of direct- and indirect-acting mutagens. Only the oral administration of HESM (250 mg/kg) significantly decreased the severity of gastric damage induced by ethanol (60.13%) and I/R (58.31%). The HESM exerts its gastroprotective effects by decreasing the MPO and MDA activities in the gastric tissue and by increasing the amount of adherent mucus covering the gastric mucosa. In vitro , the extract also displayed evident antimicrobial effects against Helicobacter pylori . However, the preventive effect of the HESM was not accompanied by an ulcer-healing effect. The treatment with HESM (14 days) significantly increased gastric lesions in 99% of the tested animals compared with the control group. This result represents a highly relevant piece of evidence that should resonate as an alert against the chronic use of this medicinal plant as an antiulcer in folk medicine. Conclusions Despite the anti- H. pylori and gastroprotective actions of S. marginata in experimental models, the gastric injuries aggravation induced after chronic treatment with the HESM argues against the use of this plant species in folk medicine.

Made available in DSpace on 2018-12-11T17:14:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Made available in DSpace on 2018-12-11T17:14:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Made available in DSpace on 2018-12-11T17:14:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Made available in DSpace on 2018-12-11T17:14:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Made available in DSpace on 2018-12-11T17:14:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 The wound healing is a complex process which, sometimes, can be a problem in public health because of the possibility of physical disability or even death. Due to the lack of a gold standard drug in skin wound treatment and aiming at the discovery of new treatments in skin repair and the mechanisms involved in the process, we used oleoresin (OR) from Copaifera langsdorffii and hydroalcoholic extract of the leaves (EH) to treat rat skin wounds. For that, male Wistar rats were divided into groups (n=8): Lanette, Collagenase, 10% EH, or 10% OR and, after anesthesia, one wound of 2 cm was made in the back of animals. The wounds were treated once a day for 3, 7, or 14 days and the wound areas were measured. The rats were euthanized and skin samples destined to biochemical, molecular, and immunohistochemical analysis. The results showed a macroscopic retraction of the wounds of 10% EH and 10% OR creams and both treatments showed anti-inflammatory activity. Molecular and immunohistochemical results demonstrated the activity of Copaifera langsdorffii creams in angiogenesis, reepithelialization, wound retraction, and remodeling mechanisms. Department of Morphology Institute of Biosciences of Botucatu UNESP Department of Surgery and Veterinary Anesthesiology School of Veterinary Medicine and Animal Science UNESP Department of Pharmaceutical Sciences School of Pharmaceutical Sciences of Ribeiraõ Preto University of Saõ Paulo Campus Ribeiraõ Preto Department of Biostatistics Institute of Biosciences of Botucatu UNESP Department of Morphology Institute of Biosciences of Botucatu UNESP Department of Surgery and Veterinary Anesthesiology School of Veterinary Medicine and Animal Science UNESP Department of Biostatistics Institute of Biosciences of Botucatu UNESP

Este estudo objetivou caracterizar qualitativamente grupos de metabólitos secundários e alguns constituintes de 9 espécies de plantas medicinais nativas do cerrado utilizadas pela comunidade rural do Assentamento Vale Verde, identificando potencialidades biológicas e farmacológicas. As informações referentes às plantas de uso medicinal foram obtidas por meio de estudos etnobotânicos e etnofarmacológicos, realizados no período de 2010 a 2012. O material botânico coletado foi identificado e depositado no Herbário da Universidade Federal do Tocantins, Porto Nacional (TO). O extrato etanólico e metanólico foi obtido a partir do material seco em estufa, filtrado e concentrado em evaporador rotatório sob pressão reduzida, pesados e novamente colocados em estufa por 24h a 50ºC, obtendo o rendimento (m/m) resultante da relação entre a massa de extrato concentrado e após seco. A análise fitoquímica das plantas selecionadas foi feita usando a metodologia da Prospecção Preliminar, realizando testes para detecção de alguns constituintes importantes e dos principais grupos de metabólitos: saponinas, fenóis e taninos, catequinas, esteróides e triterpenóides, cumarinas, antraquinonas e flavonóides. Os testes foram considerados positivos através de reações de precipitados com colorações, formações de espumas e manchas coloridas. Os testes fitoquímicos realizados nos extratos revelarem a presença de constituintes do metabolismo secundário das plantas que podem contribuir para a identificação de marcadores químicos para as espécies estudadas, sendo estes indispensáveis para os testes de qualidade e integridade de fitoterápicos e uso popular mais seguro das plantas medicinais, possibilitando melhor controle farmacognóstico dessas espécies e direcionamento dos seus usos e aplicações na pesquisa pela bioatividade preliminarmente conhecida. Neste caso, especialmente devido às atividades antimicrobianas, antioxidantes e contra insetos, sugerindo relação com a presença de compostos fenólicos e flavonoídicos, positivos nos extratos da maioria das espécies. Estas informações são inéditas no Tocantins e estratégicas para fortalecimento das políticas de conservação de Áreas de Reserva Legal no âmbito do Cerrado, bioma prioritário para conservação da biodiversidade, melhorando a caracterização dos recursos medicinais ainda disponíveis na flora nativa regional bem como vislumbrando suas aplicações biológicas e farmacológicas. This qualitative study aimed to characterize the groups of secondary metabolites and some constituents of 9 species of native medicinal plants of the Cerrado region used by the rural community of Vale Verde Settlement, identifying their biological and pharmacological potential. The information on medicinal plants were obtained through ethnobotanical and ethnopharmacological studies performed during the period 2010-2012. The botanical material collected was identified and deposited in the Herbarium of the Federal University of Tocantins, Porto Nacional (TO). The ethanolic and methanolic extracts were obtained from the oven dried material, filtered and concentrated in a rotary evaporator under reduced pressure, then weighed and placed again in an oven for 24h at 50 ° C, obtaining the yield (m / m), resulting from the ratio between the mass of concentrated extract and the mass after drying. Phytochemical analysis of selected plants was done using the methodology of Preliminary Prospecting, with tests for the detection of some important constituents and of the main groups of metabolites: saponins, phenols and tannins, catechins, steroids and triterpenoids, coumarins, anthraquinones and flavonoids. The tests were considered positive by the reactions of precipitates with colorations, the formation of foams and colored stains. Phytochemical tests performed on the extracts revealed the presence of constituents of secondary metabolism of plants, which can help to identify chemical markers of species. These markers are indispensable for testing quality and integrity of phytochemicals and a safer popular use of medicinal plants, enabling a better pharmacognostic control of these species and guidance for their use and applications in research by the preliminarily known bioactivity. In this case, it is especially due to the antimicrobial, antioxidant and anti insect activities, suggesting an association with the presence of phenolic compounds and flavonoids, positive in extracts of most species. These data are novel in Tocantins and strategic for the strengthening of conservation policies of Legal Reserve Areas within the Cerrado, priority biome for the conservation of biodiversity, improving the characterization of medicinal resources still available in the regional native flora, also foreseeing their biological and pharmacological applications.

Made available in DSpace on 2018-12-11T17:00:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-23 The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smoothmuscle and/or intestinal transit. Departamento de Fisiologia Instituto de Biociências Universidade Estadual Paulista—UNESP Unidade Integrada de Farmacologia e Gastroenterologia Universidade São Francisco Departamento de Farmacologia Instituto de Biociências Universidade Estadual Paulista—UNESP Departamento de Ciências Biológicas Universidade Estadual Paulista—UNESP Departamento de Botânica Instituto de Biociências Universidade Estadual Paulista—UNESP Campus Experimental do Litoral Paulista Universidade Estadual Paulista-UNESP Departamento de Fisiologia Instituto de Biociências Universidade Estadual Paulista—UNESP Departamento de Farmacologia Instituto de Biociências Universidade Estadual Paulista—UNESP Departamento de Ciências Biológicas Universidade Estadual Paulista—UNESP Departamento de Botânica Instituto de Biociências Universidade Estadual Paulista—UNESP Campus Experimental do Litoral Paulista Universidade Estadual Paulista-UNESP

Diabetes mellitus is a chronic disease and a leading cause of death in western countries. Despite advancements in the clinical management of the disease, it is not possible to control the late complications of diabetes. The main characteristic feature of diabetes is hyperglycemia, which reflects the deterioration in the use of glucose due to a faulty or poor response to insulin secretion. Alloxan and streptozotocin (STZ) are the chemical tools that are most commonly used to study the disease in rodents. Many plant species have been used in ethnopharmacology or to treat experimentally symptoms of this disease. When evaluated pharmacologically, most of the plants employed as antidiabetic substances have been shown to exhibit hypoglycemic and antihyperglycemic activities, and to contain chemical constituents that may be used as new antidiabetic agents. There are many substances extracted from plants that offer antidiabetic potential, whereas others may result in hypoglycemia as a side effect due to their toxicity, particularly their hepatotoxicity. In this article we present an updated overview of the studies on extracts from medicinal plants, relating the mechanisms of action by which these substances act and the natural principles of antidiabetic activity.

The gastric mucosa is continuously exposed to damaging agents that are involved in the pathogenesis of gastric ulcers, the most common chronic gastrointestinal disease. Common habits such as stress, coffee ingestion, tobacco, alcohol, and nonsteroidal antiinflammatory drugs’ consumption contribute to the physiopathology of gastric ulcers. There is an ongoing search to discover novel bioactive gastroprotective and ulcer-healing compounds derived from medicinal plants. Among antiulcer studies using natural products, those focused on isolated compounds have brought promising results, which is important for developing new drugs against gastric ulcers. In this manuscript, we review the published antiulcer studies dedicated to isolated compounds, highlighting the chemical structure and mechanisms of action of each compound and trying to elucidate a structure–activity relationship for the tested compounds.

Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70 % (7.50 mg/kg) to 99 % (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71 % and the duodenal ulcers induced by cysteamine by 68 %. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.