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Photobiomodulation therapy (PBMT) is a non-thermal therapeutic procedure widely used in clinical practice. It is considered an effective modality of treatment for the control of various inflammatory conditions with fewer adverse effects as compared to conventional therapy. However, despite the clinical effects, the mechanisms of action and dosimetric parameters of PBMT are not fully understood. This study was performed to describe the effects of two different doses of PBMT on experimental models of inflammation. Male Swiss mice were administered with 0.9% of saline or phlogistic agents (carrageenan, dextran, serotonin, histamine, or bradykinin) by intra-plantar injection and were treated with PBMT at a dose of 1 or 5 J/cm2; right after, the variation of the paw volume was made, and histopathological analysis and myeloperoxidase assay of the carrageenan-induced edematous paw tissues were performed. The action of PBMT on carrageenan-induced vascular permeability was further evaluated. Our results showed that PBMT (1 J/cm2) led to an improvement in paw edema induced by the phlogistic agents and further reduced the histological scores. Inhibition of neutrophil migration was observed following the administration of 1 and 5 J/cm2 of PBMT. However, only 1 J/cm2 of PBMT showed beneficial effects on carrageenan-induced edema. Laser at a dose of 1 J/cm2 showed cellular and vascular effects since it was able to reverse all the inflammatory parameters, and laser at a dose of 5 J/cm2 probably has only cellular effects in the presence of acute inflammation.

The aim of this study was to evaluate the effects of glutamine supplementation or exercise on gastric emptying and intestinal inflammation in rats with ulcerative colitis (UC). Strength exercise consisted of jump training 4 × 10 repetitions/5 days a week/8 weeks with progressive overload. Endurance exercise consisted of swimming without overload for a period of 1 h a day/5 days a week/8 weeks. Another group (sedentary) of animals was supplemented with L-glutamine (1 g/kg of body weight) orally for 8 weeks before induction of UC. Colitis was induced by intra-colonic administration of 1 mL of 4% acetic acid. We assessed gastric emptying, macroscopic and microscopic scoring, oxidative stress markers, and IL-1β, IL-6, and (TNF-α) levels. The UC significantly increased (p < 0.05) the gastric emptying compared with the saline control group. We observed a significantly decrease (p < 0.05) in body weight gain in UC rats compared with the control groups. Both exercise interventions and L-glutamine supplementation significantly prevented (p < 0.05) weight loss compared with the UC group. Strength and endurance exercises significantly prevented (p < 0.05) the increase of microscopic scores and oxidative stress (p < 0.05). L-glutamine supplementation in UC rats prevented hemorrhagic damage and improved oxidative stress markers (p < 0.05). Strength and endurance exercises and glutamine decreased the concentrations of inflammatory cytokines IL-1β, IL-6, and TNF-α compared with the UC group (p < 0.05). Strength and endurance exercises and L-glutamine supplementation prevented intestinal inflammation and improved cytokines and oxidative stress levels without altering gastric dysmotility in rats with UC.

Anacardic acid (AA), a compound extracted from cashew nut liquid, exhibits numerous pharmacological activities. The aim of the current investigation was to assess the anti-inflammatory, antinociceptive, and antioxidant activities of AA in mouse models. For this, Swiss albino mice were pretreated with AA (10, 25, 50 mg/kg, intraperitoneally, ip) 30 min prior to the administration of carrageenan, as well as 25 mg/kg of prostaglandin E2, dextran, histamine, and compound 48/80. The antinociceptive activity was evaluated by formalin, abdominal, and hot plate tests, using antagonist of opioid receptors (naloxene, 3 mg/kg, ip) to identify antinociceptive mechanisms. Results from this study revealed that AA at 25 mg/kg inhibits carrageenan-induced edema. In addition, AA at 25 mg/kg reduced edema and leukocyte and neutrophilic migration to the intraperitoneal cavity, diminished myeloperoxidase activity and malondialdehyde concentration, and increased the levels of reduced glutathione. In nociceptive tests, it also decreased licking, abdominal writhing, and latency to thermal stimulation, possibly via interaction with opioid receptors. Taken together, these results indicate that AA exhibits anti-inflammatory and antinociceptive actions and also reduces oxidative stress in acute experimental models, suggesting AA as a promising compound in the pharmaceutical arena.

This study aims to determine the antitumor potential of cashew gum in vitro and in vivo. The cashew gum (CG) structure is similar to already showed in literature. The cytotoxicity effect of CG was performed by MTT assay, and B16-F10 melanoma model was used to evaluate antitumor effect. The tumor inhibition was calculated based on tumor weight. Hematological, histopathological, FTIR, oxidative stress and Western Blot analysis were performed to elucidate the mechanism of inhibition and toxic effects. As results, CG did not demonstrate cytotoxicity in vitro, however showed a significant tumor inhibition in vivo, with about 36.9 to 43% of reduction in tumor mass, with no toxicity to organs. Animals treated with CG did not show toxicity in normal tissues, FTIR spectrum and oxidative stress analysis of the tumor tissue indicated that CG cause tumor inhibition with the presence of apoptosis morphotype cells, without alterations in the levels of antioxidants components. In addition, it was observed that CG reduced the expression of γH2AX without changing the expression of caspase-3. With this, we can suggest that this polymer can assist in the anticancer activity and/or decrease the side effects of standard drugs used in treatment of cancer.

Significance Carbon monoxide (CO) is an endogenous gaseous mediator that plays an important role in maintaining gastrointestinal (GI) tract homeostasis, acting in mucosal defence, and providing negative modulation of pathophysiological markers of clinical conditions. Recent Advances: Preclinical studies using animal models and/or cell culture show that CO can modulate the inflammatory response and oxidative stress in GI mucosal injuries and pathological conditions, reducing pro-inflammatory cytokines and reactive oxygen species, while increasing antioxidant defence mechanisms. Critical issues CO has potent anti-inflammatory and antioxidant effects. The defence mechanisms of the GI tract are subject to aggression by different chemical agents (e.g., drugs and ethanol) as well as complex and multifactorial diseases, with inflammation and oxidative stress as strong triggers for the deleterious effects. Thus, it is possible that CO acts on a variety of molecules involved in the inflammatory and oxidative signalling cascades, as well as reinforcing several defence mechanisms that maintain GI homeostasis. Future directions CO-based therapies are promising tools for the treatment of GI disorders, such as gastric and intestinal injuries, inflammatory bowel disease, and pancreatitis. Therefore, it is necessary to develop safe and selective CO-releasing agents and/or donor drugs to facilitate effective treatments and methods for analysis of CO levels that are simple and inexpensive.

Not applicable.

© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications., Alexandra Plácido is a recipient of a post-doctoral grant from the project FCT (PTDC/BII-BIO/31158/2017). Renato Socodato and Camila Cabral Portugal hold postdoctoral fellowships from FCT (Refs: SFRH/BPD/91833/2012 and FRH/BPD/91962/2012, respectively). This work was funded through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT 2020

Bombesin mediates several biological activities in the gastrointestinal (GI) tract and central nervous system in mammals, including smooth muscle contraction, secretion of GI hormones and regulation of homeostatic mechanisms. Here, we report a novel bombesin-like peptide isolated from Boana raniceps. Its amino acid sequence, GGNQWAIGHFM-NH

Sulfated polysaccharides (PLS) extracted from the marine algae of the genus Gracilaria showed biological activity in different inflammatory models, except for periodontitis. Thus, this study aimed to evaluate the effectiveness of the treatment with PLS from Gracilaria caudata in ligature-induced periodontitis. 40 animals distributed into 5 groups were used (the control group (unligated), the ligated untreated group, and the ligated groups treated with 2.5, 5.0 and 10.0 mg/kg of PLS with intraperitoneal injection, respectively). After 20 days of treatment, the animals were killed and the following parameters were evaluated: Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), Myeloperoxidase (MPO) activity, Alveolar Bone Loss (ABL) for periodontal tissues; histopathological examination of gingival and liver tissues (Steatosis score); glutathione and malondialdehyde concentrations in the liver, serum levels of alanine aminotransferase and aspartate aminotransferase. The data revealed that treatment with 2.5 mg/kg of PLS showed the best anti-inflammatory effects with reduction of GBI, PPD and MPO activity, as well as oxidative stress and steatosis in liver. Our results indicated that the adjunct treatment with PLS from Gracilaria caudata could prevent the periodontal and hepatic tissue alteration caused by periodontitis.

This study aimed to explore the effect of topically administering an orabase gel containing cashew gum (CG), a complex polysaccharide from Anacardium occidentale L., on the transcription of important proinflammatory (COX-2, NOS-2, INF-γ, OSCAR, and MYD88) and anti-inflammatory genes (IL-10, IL-4, and TGFβ1) in the gingival tissues of rats with ligature-induced periodontitis, compared to the effect observed upon topically applying a well-known antibiofilm agent (chlorhexidine) under the same experimental conditions. The gene expression profile in the gingival tissues of rats with periodontitis treated with CG did not statistically significantly differ from that observed in the group of animals treated with chlorhexidine. Results showed that CG is able to attenuate general inflammation in the periodontium by reducing the transcription of proinflammatory mediators in a MYD88-independent manner, and not by inducing the expression of anti-inflammatory factors. In conclusion, this study demonstrated that CG and chlorhexidine treatment reduced significantly the gene overexpression (COX-2, NOS-2, INF-γ, OSCAR, and TGFβ1) in the model of ligature-induced periodontitis.

Ulcerative colitis is an idiopathic inflammatory bowel disease characterized by intestinal inflammation; blocking this inflammatory process may be the key to the development of new naturally occurring anti-inflammatory drugs, with greater efficiency and lower side effects. The objective of this study is to explore the effects of bergenin (BG) in TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced acute colitis model in rats in order to assist in the studies for the development of novel natural product therapies for inflammatory bowel disease. 48 Wistar rats were randomized into six groups: (i) Control and (ii) TNBS control; (iii) 5-ASA 100 mg/kg/day (iv) BG 12 mg/kg/day (v) BG 25 mg/kg/day and (vi) BG 50 mg/kg/day. Colitis was induced by instillation of TNBS. Colitis was evaluated by an independent observer who was blinded to the treatment. Our results revealed that bergenin decreased the macroscopic and microscopic damage signs of colitis, and reduced the degree of neutrophilic infiltration in the colon tissue; also, it was capable to down-regulate COX-2, iNOS, IkB-α, and pSTAT3 protein expression. Similarly, using a protocol for indirect ELISA quantification of cytokines, bergenin treatment reduced IL-1β, IFN-γ and IL-10 levels, and inhibited both canonical (IL-1) and non-canonical (IL-11) NLRP3/ASC inflammasome signaling pathways in TNBS-induced acute colitis. Conclusion: Our study has provided evidence that administration of bergenin reduced the damage caused by TNBS in an experimental model of acute colitis in rats, reduced levels of pro-inflammatory proteins and cytokines probably by modulation of pSTAT3 and NF-κB signaling and blocking canonical and non-canonical NLRP3/ASC inflammasome pathways.

Latex proteins extracted from Plumeria pudica (LPPp) have anti-inflammatory activity in different experimental models. Considering this relevant result, we evaluated the toxicological aspects of the treatment of mice with LPPp. Acute and subchronic toxicities were determined by daily intraperitoneal administration of 40 mg/kg of LPPp for 10 or 20 days, respectively, and were followed by behavioral, hematological, biochemical and histopathological evaluation. Results showed no significant changes in body weight and organs of animals treated with LPPp. Total and differential blood leukocyte counts of LPPp groups did not differ from controls. There was no significant difference in aspartate aminotransferase, alanine aminotransferase, creatinine and urea measurements for the group treated for 20 days. The level of glutathione in the kidney was significantly higher in animals treated with LPPp in the acute toxicity test, but no differences were observed for the subchronic evaluation. The concentration of malondialdehyde and myeloperoxidase activity in the organs did not differ from controls. Histopathological examination of kidney, spleen and liver tissue of animals treated with LPPp revealed normal structures or reversible alterations. Intraperitoneal LD50 of LPPp was higher than 2,000 mg/kg. The data obtained reveal that LPPp is nontoxic at 40 mg/kg. Las proteínas extraídas del látex de Plumeria pudica (LPPp) tienen actividad antiinflamatoria en diferentes modelos experimentales. Ante este relevante resultado, evaluamos los aspectos toxicológicos del tratamiento de ratones con LPPp. La toxicidad aguda y subcrónica se determinó mediante la administración intraperitoneal diaria de 40 mg/kg de LPPp durante 10 o 20 días, respectivamente, y fueron seguidas por evaluación conductual, hematológica, bioquímica e histopatológica. Los resultados no mostraron cambios significativos en el peso corporal y los órganos de los animales tratados con LPPp. El recuento de leucocitos total y diferencial en la sangre de los grupos LPPp no difirió de los controles. No hubo diferencias significativas en las mediciones de aspartato aminotransferasa, alanina aminotransferasa, creatinina y urea para el grupo tratado durante 20 días. El nivel de glutatión en los riñones fue significativamente mayor en los animales tratados con LPPp en la prueba de toxicidad aguda, pero no se observaron diferencias para la evaluación subcrónica. La concentración de malondialdehído y la actividad de la mieloperoxidasa en los órganos no difirieron de los controles. El examen histopatológico del tejido renal, el bazo y el hígado de los animales tratados con LPPp reveló estructuras normales o cambios reversibles. La LD50 de LPPp administrada por vía intraperitoneal fue superior a 2000 mg / kg. Los datos obtenidos revelan que LPPp no es tóxico a dosis de 40 mg/kg. Proteínas extraídas do látex de Plumeria pudica (LPPp) apresentam atividade anti-inflamatória em diferentes modelos experimentais. Diante desse relevante resultado, avaliamos os aspectos toxicológicos do tratamento de camundongos com LPPp. A toxicidade aguda e subcrônica foram determinadas pela administração intraperitoneal diária de 40 mg/kg de LPPp por 10 ou 20 dias, respectivamente, e foram seguidas por avaliação comportamental, hematológica, bioquímica e histopatológica. Os resultados não mostraram alterações significativas no peso corporal e órgãos dos animais tratados com LPPp. A contagem total e diferencial de leucócitos no sangue dos grupos LPPp não diferiu dos controles. Não houve diferença significativa nas medidas de aspartato aminotransferase, alanina aminotransferase, creatinina e uréia para o grupo tratado por 20 dias. O nível de glutationa nos rins foram significativamente maior nos animais tratados com LPPp no teste de toxicidade aguda, mas nenhuma diferença foi observada para a avaliação subcrônica. A concentração de malondialdeído e a atividade da mieloperoxidase nos órgãos não diferiram dos controles. O exame histopatológico do tecido renal, do baço e do fígado de animais tratados com LPPp revelou estruturas normais ou alterações reversíveis. A DL50 de LPPp administrada por via intraperitoneal foi superior a 2.000 mg/kg. Os dados obtidos revelam que LPPp não é tóxico na dose de 40 mg/kg.

Oral mucositis is an inflammation of the oral mucosa mainly resulting from the cytotoxic effect of 5-fluorouracil (5-FU). The literature shows anti-inflammatory action of l-cysteine (l-cys) involving hydrogen sulfide (H2S). In view of these properties, we investigate the effect of l-cys in oral mucositis induced by 5-FU in hamsters. The animals were divided into the following groups: saline 0.9%, mechanical trauma, 5-FU 60–40 mg/kg, l-cys 10/40 mg and NaHS 27 µg/kg. 5-FU was administered on days 1st to 2nd; 4th day excoriations were made on the mucosa; 5th–6th received l-cys and NaHS. For data analysis, histological analyses, mast cell count, inflammatory and antioxidants markers, and immunohistochemistry (cyclooxygenase-2(COX-2)/inducible nitric oxide synthase (iNOs)/H2S) were performed. Results showed that l-cys decreased levels of inflammatory markers, mast cells, levels of COX-2, iNOS and increased levels of antioxidants markers and H2S when compared to the group 5-FU (p

The use of bisphosphonates constitutes the gold-standard therapy for the control and treatment of bone diseases. However, its long-term use may lead to gastric problems, which limits the treatment. Thus, this study aimed to formulate a nanostructured system with biodegradable polymers for the controlled release of alendronate sodium. The nanoparticles were characterized, and its gastric toxicity was investigated in rats. The synthesis process proved to be effective for encapsulating alendronate sodium, exhibiting nanoparticles with an average size of 51.02 nm and 98.5% of alendronate sodium incorporation. The release tests demonstrated a controlled release of the drug in 420 min, while the morphological analyzes showed spherical shapes and no apparent roughness. The biological tests demonstrated that the alendronate sodium nanoformulation reversed the gastric lesions, maintaining the normal levels of malondialdehyde and myeloperoxidase. Also, the encapsulated alendronate sodium showed no toxicity in murine osteoblastic cells, even at high concentrations.

Diarrhea, which is a gastrointestinal disease, has as its main characteristic the rapid passage of gastric contents through the intestine, which leads to the loss of water and electrolytes and consequent dehydration. The most common fluid replacement is the use of oral rehydration solution (ORS) together with the use of the drug loperamide. However, the use of this medication can cause severe bacteremia followed by sepsis and even death. Currently, there is no effective pharmacological treatment for diarrhea, therefore, it is noted the importance of seeking new therapeutic targets for the treatment of this disease. Thus, the aim of the present study was to conduct a research on the biological activities already described for Diminazene Aceturate with a special focus on antidiarrheal agents. For this, a survey was carried out, through patent filing searches, in the USPTO, EPO, WIPO and INPI databases, using keywords and Boolean operators. Thus, it was found in the international patent databases the number of documents referring to the use of Diminazene Aceturate in several areas, mainly in the pharmaceutical industry, but with a relatively low number of documents regarding the description of possible antidiarrheal action of the compound under study , which reinforces the innovative character of research involving the use of Diminazene Aceturate as an antidiarrheal agent. La diarrea, que es una enfermedad gastrointestinal, tiene como característica principal el rápido paso del contenido gástrico a través del intestino, lo que conduce a la pérdida de agua y electrolitos y la consiguiente deshidratación. El reemplazo de líquidos más común es el uso de solución de rehidratación oral (SRO) junto con el uso del fármaco loperamida, sin embargo, el uso de este medicamento puede causar bacteriemia grave seguida de sepsis e incluso la muerte. Actualmente, no existe un tratamiento farmacológico eficaz para la diarrea, por lo que se destaca la importancia de buscar nuevas dianas terapéuticas para el tratamiento de esta enfermedad. Así, el objetivo del presente estudio fue realizar una investigación sobre las actividades biológicas ya descritas para el Aceturato de Diminazene con un enfoque especial en los agentes antidiarreicos. Para ello, se realizó una encuesta, a través de búsquedas de presentación de patentes, en las bases de datos de la USPTO, EPO, WIPO e INPI, utilizando palabras clave y operadores booleanos. Así, se encontró en las bases de datos internacionales de patentes la cantidad de documentos referentes al uso del Aceturato de Diminazene en varias áreas, principalmente en la industria farmacéutica, pero con un número relativamente bajo de documentos en cuanto a la descripción de la posible acción antidiarreica del compuesto en estudio. , que refuerza el carácter innovador de la investigación que implica el uso de Diminazene Aceturate como agente antidiarreico. A diarreia, que é uma doença gastrointestinal, tem como principal característica a passagem rápida do conteúdo gástrico pelo intestino, o que leva à perda de água e eletrólitos e consequente desidratação. A reposição hídrica mais comum é o uso de solução de reidratação oral (SRO) juntamente com o uso do fármaco loperamida, Porém, o uso deste medicamento pode causar bacteremia grave seguida de sepse e até morte. Atualmente, não existe um tratamento farmacológico eficaz para a diarreia, com isso, nota-se a importância de buscar novos alvos terpêuticos para o tratamento dessa doença. Assim, o objetivo do presente estudo foi realizar uma pesquisa sobre as atividades biológicas já descritas do Aceturato de Diminazeno com foco especial nos agentes antidiarreicos. Para isso, foi realizado um levantamento, por meio de pesquisas de depósito de patentes, nas bases de dados USPTO, EPO, WIPO e INPI, utilizando palavras-chave e operadores booleanos. Assim, constatou-se nas bases de dados internacionais de patentes o número de documentos referentes ao uso do Aceturato de Diminazeno em diversas áreas, principalmente na indústria farmacêutica, mas com número relativamente baixo de documentos quanto à descrição de possível ação antidiarreica do composto em estudo, o que reforça o caráter inovador das pesquisas envolvendo o uso do Aceturato de Diminazeno como agente antidiarreico.

Introduction The Pilates method is an approach to body and mind exercises that has as its foundation the gain of stability, strength and flexibility, and the work of muscular control, posture and breathing, which can generate repercussions on oxidative stress and ROS production, it is expected that Pilates can satisfactorily influence glycemic and oxidative stress reduction in elderly diabetes. Aim To analyze the effect of a Pilates protocol on variables indicative of metabolic control and oxidative stress in patients with Type 2 Diabetes Mellitus. Method Randomized clinical trial in type 2 diabetics enrolled in Hiperdia Parnaiba. A Pilates protocol was performed for 8 weeks, with 2 weekly consultations. The tested variables were: blood glucose, glycated hemoglobin, lipid profile, C-reactive protein and malondialdehyde. ANOVA tests, correlation of Wilcoxon, Friedman and Spearman, were used, with a significance level of 5%. Results 44 diabetics participated in the study (intervention group: 22; control: 22), with a mean age of 61.23 ± 8.49years, the majority being female (77.3%), married (59.1%), literate (31.8%), with an average BMI of 26.96 ± 4.35 kg/m2. When analyzing the effects of the protocol, there was a significant reduction in glycated hemoglobin (p = 0.002) and oxidative stress (p = 0.004) in the intervention group, however, there were no differences in fasting glucose (p = 0.055) and in the profile lipid, expressed by the total cholesterol (p = 0.654), HDL (p = 0.591), LDL (p = 0.564) and triglycerides (0.192). There was a moderate positive correlation between oxidative stress and glycated hemoglobin (r = 0.44, p = 0.000). Conclusion: The exercise protocol based on the Pilates method produced a reduction in glycated hemoglobin and oxidative stress.

Recently, a new coronavirus (SARS-CoV-2) was discovered in China. Due to its high level of contagion, it has already reached most countries, quickly becoming a pandemic. Although the most common symptoms are related to breathing problems, SARS-CoV-2 infections also affect the gastrointestinal tract culminating in inflammation and diarrhea. However, the mechanisms related to these enteric manifestations are still not well understood. Evidence shows that the SARS-CoV-2 binds to the angiotensin-converting enzyme receptor 2 (ACE2) in host cells as a viral invasion mechanism and can infect the lungs and the gut. Other viruses have already been linked to intestinal symptoms through binding to ACE2. In turn, this medical hypothesis article conjectures that the ACE2 downregulation caused by the SARS-CoV-2 internalization could lead to decreased activation of the mechanistic target of mTOR with increased autophagy and lead to intestinal dysbiosis, resulting in diarrhea. Besides that, dysbiosis can directly affect the respiratory system through the lungs. Although there are clues to other viruses that modulate the ACE2/gut/lungs axis, including the participation of autophagy and dysbiosis in the development of gastrointestinal symptoms, there is still no evidence of the ACE2/mTOR/autophagy pathway in SARS-CoV-2 infections. Thus, we propose that the new coronavirus causes a change in the intestinal microbiota, which culminates in a diarrheal process through the ACE2/mTOR/autophagy pathway into enterocytes. Our assumption is supported by premises that unregulated intestinal microbiota increases the susceptibility to other diseases and extra-intestinal manifestations, which can even cause remote damage in lungs. These putative connections lead us to suggest and encourage future studies aiming at assessing the aforementioned hypothesis and regulating dysbiosis caused by SARS-CoV-2 infection, in order to confirm the decrease in lung injuries and the improvement in the prognosis of the disease.

The present work aimed at carrying out the isolation and biochemical characterization of a sulfated polysaccharide fraction (PLS) from the marine algae Gracilaria intermedia and investigating its anti-inflammatory and antinociceptive potential. PLS was obtained through enzymatic digestion with papain and analyzed by means of gel permeation chromatography and Nuclear Magnetic Resonance to 1H and 13C. In order to evaluate the potential of anti-inflammatory action of PLS, we performed paw edema induced by carrageenan, dextran, compound 48/80, histamine and serotonin. In addition, we also measured the concentration of myeloperoxidase, cytokines, the count of inflammatory cells and performed tests of the nociception. The PLS isolated was of high purity and free of contaminants such as proteins, and had molecular weight of 410 kDa. The same macromolecule was able to decrease the paw edema induced by all inflammatory agents (P

Polysaccharide from marine alga Gracilaria caudata has potential health benefits, such as anti-inflammatory, gastroprotective and antidiarrheal effects. Here, we investigated the effect of a sulfated polysaccharide from G. caudata (SP-GC) on hypernociception and inflammatory response in arthritis models. The animals received SP-GC (3, 10 or 30 mg/kg) 1 h before tibio-tarsal injection of zymosan. Hypernociception, histopathology, edema, vascular permeability, myeloperoxidase (MPO) activity, cell influx, interleukin (IL)-1β and nitric oxide (NO) levels were evaluated in acute phase. In another protocol, animals received SP-GC (30 mg/kg) 2 h post-complete Freund's adjuvant (CFA). Hypernociception, edema and arthritis index were determined in acute, sub-chronic and chronic phases. Rota-rod test measured the motor performance. SP-GC significantly reduced, in a dose-dependent manner, the zymosan-induced hypernociception with maximal effect at 30 mg/kg. The microscopic inflammation, joint edema, MPO activity, cell influx, IL-1β and NO levels were also reduced by SP-GC. In the CFA-induced arthritis, SP-GC inhibits the hypernociception, edema and arthritic index in acute, sub-chronic and chronic phases. SP-GC did not alter the motor performance of animals. In conclusion, SP-GC exerts protective effect in models of arthritis due to the modulation of cell influx, IL-1β and NO levels, culminating in the reduction of hypernociception and edema.

Background and objective Periodontitis may crosstalk with renal diseases, yet that remains unclear. We investigated whether the renal alterations caused by induced periodontitis are reversible after removal of the ligatures in experimental ligature-induced periodontitis. Material and methods Twenty-four female rats were divided into three groups: control (without periodontitis), periodontitis (20 days of ligature-induced periodontitis), and P20-20 (20 days of ligature-induced periodontitis and 20 days after ligature removal). The following periodontal parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, and alveolar bone height. For renal tissues, histopathology, malonaldehyde (MDA) levels, glutathione (GSH) content, and renal weight were evaluated. In the blood, creatinine, uric acid, albumin, total cholesterol, total protein, and glucose levels were assessed. Total protein and creatinine levels in urine were also investigated. Results Rat renal tissues did not demonstrate reversal of periodontitis-related changes in the P20-20 group in terms of MDA, GSH, and histopathological evaluations when compared to the periodontitis group. Accordingly, only total cholesterol levels were reversible in the P20-20. Conclusion Renal alterations caused by ligature-induced periodontitis persisted even after removal of ligatures in rats.

Anadenanthera colubrina var. cebil (Griseb.) Altschul (Fabaceae family), commonly known as the red angico tree, is a medicinal plant found throughout Brazil&rsquo, s semi-arid area. In this study, a chemical analysis was performed to investigate the antidiarrheal activity and safety profile of red angico gum (RAG), a biopolymer extracted from the trunk exudate of A. colubrina. Upon FT-IR spectroscopy, RAG showed bands in the regions of 1608 cm&minus, 1, 1368 cm&minus, 1, and 1029 cm&minus, 1, which relate to the vibration of O&ndash, H water molecules, deformation vibration of C-O bands, and vibration of the polysaccharide C-O band, respectively, all of which are relevant to glycosidic bonds. The peak molar mass of RAG was 1.89 &times, 105 g/mol, with the zeta potential indicating electronegativity. RAG demonstrated high yield and solubility with a low degree of impurity. Pre-treatment with RAG reduced the total diarrheal stool and enteropooling. RAG also enhanced Na+/K+-ATPase activity and reduced gastrointestinal transit, and thereby inhibited intestinal smooth muscle contractions. Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that RAG can interact with GM1 receptors and can also reduce E. coli-induced diarrhea in vivo. Moreover, RAG did not induce any signs of toxicity in mice. These results suggest that RAG is a possible candidate for the treatment of diarrheal diseases.

Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2S), NO, and CO. Mice were pretreated with AICAR (20 mg/kg, an AMPK activator) alone or with 50% ethanol. Other groups were pretreated with respective gaseous mediator inhibitors PAG, l-NAME, or ZnPP IX 30 min prior to AICAR, or with gaseous mediator donors NaHS, Lawesson's reagent and l-cysteine (H2S), SNP, l-Arginine (NO), Hemin, or CORM-2 (CO) 30 min prior to ethanol with or without compound C (10 mg/kg, a non-selective AMPK inhibitor). H2S, nitrate/nitrite (NO3-/NO2-), bilirubin levels, GSH and MDA concentration were evaluated in the gastric mucosa. The gastric mucosa was also collected for histopathological analysis and AMPK expression assessment by immunohistochemistry. Pretreatment with AICAR attenuated the ethanol-induced injury and increased H2S and bilirubin levels but not NO3-/NO2- levels in the gastric mucosa. In addition, inhibition of H2S, NO, or CO synthesis exacerbated the ethanol-induced gastric damage and inhibited the gastroprotection by AICAR. Pretreatment with compound C reversed the gastroprotective effect of NaHS, Lawesson's reagent, l-cysteine, SNP, l-Arginine, CORM-2, or Hemin. Compound C also reversed the effect of NaHS on H2S production, SNP on NO3-/NO2- levels, and Hemin on bilirubin levels. Immunohistochemistry revealed that AMPK is present at basal levels mainly in the gastric mucosa cells, and was increased by pretreatment with NaHS, SNP, and CORM-2. In conclusion, our findings indicate that AMPK activation exerts gastroprotection against ethanol-induced gastric damage and mutually interacts with H2S, NO, or CO to facilitate this process.

Hydrogen sulphide (H2S) is a gasotransmitter that participates in various physiological and pathophysiological processes within the gastrointestinal tract. We studied the effects and possible mechanism of action of H2S in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of H2S were investigated using an intestinal fluid secretion model in isolated intestinal loops on anaesthetized mice treated with CT. NaHS and Lawesson's reagent and l-cysteine showed antisecretory activity through reduction of intestinal fluid secretion and loss of Cl- induced by CT. Pretreatment with an inhibitor of cystathionine-γ-lyase (CSE), dl-propargylglycine (PAG), reversed the effect of l-cysteine and caused severe intestinal secretion. Co-treatment with PAG and a submaximal dose of CT increased intestinal fluid secretion, thus supporting the role of H2S in the pathophysiology of cholera. CT increased the expression of CSE and the production of H2S. Pretreatment with PAG did not reverse the effect of SQ 22536 (an AC inhibitor), bupivacaine (inhibitor of cAMP production), KT-5720 (a PKA inhibitor), and AICAR (an AMPK activator). The treatment with Forskolin does not reverse the effects of the H2S donors. Co-treatment with either NaHS or Lawesson's reagent and dorsomorphin (an AMPK inhibitor) did not reverse the effect of the H2S donors. H2S has antisecretory activity and is an essential molecule for protection against the intestinal secretion induced by CT. Thus, H2S donor drugs are promising candidates for cholera therapy. However, more studies are needed to elucidate the possible mechanism of action.

Cannabis sativa has been applied for medicinal purposes for thousands of years. Cannabidiol is the main non-psychotropic compound in Cannabis sativa, and has its therapeutic effect extremely linked to the central nervous system, presenting pharmacological properties with great potential for the treatment of several pathologies. The aim is to identify and relate the therapeutic effects of cannabidiol in medicine, focusing on its therapeutic potential in epilepsy, autism, Parkinson's disease, Alzheimer's disease, oncological diseases, and chronic pain. In addition to presenting a brief history of cannabidiol and its chemical and pharmacological properties acting on the Central Nervous System. Integrative literature review, where articles were reviewed in Portuguese and English, based on PubMed, Scielo and Public Agencies. In 1960, the chemical structures of the main components of cannabis were identified, characterizing cannabidiol as a cannabinoid, which binds to cannabinoid receptors throughout the human body, known as CB1 and CB2. The endocannabinoid system, described in 1990, further demonstrated the therapeutic properties of cannabidiol, elucidating its neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti- inflammatory, anti-tumor, antioxidant, and anticonvulsant properties. Cannabinoids may, in the future, be an important therapeutic option in the treatment of Parkinson's and Alzheimer's diseases, epilepsy, autism, neoplasms and still acting in the relief of pain. This is due to the absence of psychoactive effects and cognition, safety, good tolerability, clinical trials with positive results and the wide spectrum of pharmacological actions. El Cannabis sativa se ha aplicado con fines medicinales durante miles de años. El cannabidiol es el principal compuesto no psicotrópico de Cannabis sativa, y su efecto terapéutico está sumamente ligado al sistema nervioso central, presentando propiedades farmacológicas con gran potencial para el tratamiento de diversas patologías. El objetivo es identificar y relacionar los efectos terapéuticos del cannabidiol en la medicina, centrándose en su potencial terapéutico en epilepsia, autismo, enfermedad de Parkinson, enfermedad de Alzheimer, enfermedades oncológicas y dolor crónico. Además de presentar una breve historia del cannabidiol y sus propiedades químicas y farmacológicas actuando sobre el Sistema Nervioso Central. Revisión de literatura integradora, donde se revisaron artículos en portugués e inglés, con base en PubMed, Scielo y Agencias Públicas. En 1960, se identificaron las estructuras químicas de los principales componentes del cannabis, caracterizando al cannabidiol como un cannabinoide, que se une a los receptores de cannabinoides en todo el cuerpo humano, conocidos como CB1 y CB2. El sistema endocannabinoide, descrito en 1990, demostró además las propiedades terapéuticas del cannabidiol, dilucidando sus propiedades neuroprotectoras, antiepilépticas, ansiolíticas, antipsicóticas, antiinflamatorias, antitumorales, antioxidantes y anticonvulsivas. Los cannabinoides pueden, en el futuro, ser una opción terapéutica importante en el tratamiento de las enfermedades de Parkinson y Alzheimer, epilepsia, autismo, neoplasias y aún actuando en el alivio del dolor. Esto se debe a la ausencia de efectos psicoactivos y cognitivos, seguridad, buena tolerabilidad, ensayos clínicos con resultados positivos y el amplio espectro de acciones farmacológicas. A Cannabis sativa tem sido aplicada para fins medicinais há milhares de anos. O canabidiol é o principal composto não psicotrópico da Cannabis sativa, e tem seu efeito terapêutico extremamente ligado ao sistema nervoso central, apresentando propriedades farmacológicas com grande potencial para o tratamento de diversas patologias. O objetivo é identificar e relacionar os efeitos terapêuticos do canabidiol na medicina, com foco em seu potencial terapêutico na epilepsia, autismo, doença de Parkinson, doença de Alzheimer, doenças oncológicas e dores crônicas. Além de apresentar um breve histórico do canabidiol e de suas propriedades químicas e farmacológicas atuando no Sistema Nervoso Central. Revisão integrativa da literatura, onde os artigos foram revisados ​​em português e inglês, com base no PubMed, Scielo e Agências Públicas. Em 1960, foram identificadas as estruturas químicas dos principais componentes da cannabis, caracterizando o canabidiol como um canabinoide, que se liga a receptores canabinoides em todo o corpo humano, conhecidos como CB1 e CB2. O sistema endocanabinoide, descrito em 1990, demonstrou ainda as propriedades terapêuticas do canabidiol, elucidando suas propriedades neuroprotetoras, antiepilépticas, ansiolíticas, antipsicóticas, antiinflamatórias, antitumorais, antioxidantes e anticonvulsivantes. Os canabinóides podem, no futuro, ser uma importante opção terapêutica no tratamento das doenças de Parkinson e Alzheimer, epilepsia, autismo, neoplasias e ainda atuando no alívio da dor. Isso se deve à ausência de efeitos psicoativos e cognição, segurança, boa tolerabilidade, ensaios clínicos com resultados positivos e amplo espectro de ações farmacológicas.

Inflammation is a protective reaction of the microcirculation. However, sustained inflammation can lead to undesired effects. Thuja occidentalis Linn has many pharmacological properties but has no anti-inflammatory activity described. Thus, this study aims evaluating the anti-inflammatory activity of the aqueous extract (AE) and the polysaccharide fraction (PLS) of T. occidentalis L. in mice. The results of our evaluations in various experimental models indicated that AE and PLS (3, 10, and 30mg/kg, i.p.) reduced (p˂0.05) paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin (5-HT), bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, it inhibited neutrophils recruitment; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, vascular permeability, nitrite concentration, and MDA concentration; and maintained the GSH levels in the peritoneal exudate. The AE and PLS reduced neutrophil infiltration and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) immunostaining in paw tissue. Treatment with the AE and PLS (300mg/kg) did not induce gastric toxicity. In conclusion, these results show that the AE and PLS reduced the inflammatory response by inhibiting vascular and cellular events, inhibiting pro-inflammatory cytokine production, and reducing oxidative stress. Furthermore, they did not induce gastric toxicity at high doses.

Myrtenol is a bicyclic monoterpene with anti-in fl ammatory properties. However, the mechanisms involved are partially unknown. Here, we investigated the effect of myrtenol during experimental chronic arthritis and the possible modulating activity of oxidative stress and neutrophil migration. Complete Freund's Adjuvant (CFA)-sensitized rats were treated with vehicle (1 mL/kg, po), myrtenol (12.5, 25 or 50 mg/kg, po), indomethacin (10 mg/kg, po) or dexamethasone (0.4 mg/kg) followed by intra-articular injection of CFA (0.5 mg/mL, 50 m L per joint). Then, paw edema and articular incapaci- tation (paw elevation time) were evaluated for 14 days. On the last day, a blood concentration superoxide dismutase (SOD) and nitrite was determined. In another experimental setting, human neutrophils were incubated with vehicle (sterile saline, 1 mL) or myrtenol (10 e 100 ng/mL) and the in vitro chemotaxis to N-formylmethionine-leucyl-phenylalanine (fMLP) (10 7 M/well) was evaluated. In addition, antiin- fl ammatory effect of myrtenol was investigated in carrageenan-induced peritonitis. We found that CFA induced a prominent paw swelling and incapacitation of the joint, which were signi fi cantly prevented by myrtenol ( P < 0.05). In addition, blood accumulation nitrite was attenuated by myrtenol when compared with vehicle-treated CFA group ( P < 0.05). Furthermore, plasma levels of SOD were signi fi cantly increased by myrtenol versus vehicle-treated CFA group ( P < 0.05). Moreover, fMLP-triggered neutrophil chemotaxis and carrageenan-induced peritonitis were markedly prevented by myrtenol ( P < 0.05). Therefore, myrtenol showed anti-in fl ammatory and antinociceptive effects on experimental chronic arthritis, which seems to be related to the direct modulation of neutrophil migration and antioxidant activity

Background and Objective Periodontitis may promote harmful systemic effects such as changes in hepatic tissues. The purpose of this study was to investigate whether the steatosis and oxidative stress caused by experimental periodontitis are reversible in the liver. Material and Methods Twenty-four rats were divided into three groups: control, periodontitis and P20-20 (20 days with experimental periodontitis and 20 days without experimental periodontitis, to verify the reversibility of hepatic injuries). The following parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, alveolar bone loss for periodontal tissues; liver weights, histopathological scores for steatosis, inflammation and necrosis in liver; glutathione, malondialdehyde, total cholesterol and triglyceride concentrations in hepatic tissues; and blood levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase, total cholesterol and random glucose. Results Gingival bleeding index, probing pocket depth, myeloperoxidase and alveolar bone loss parameters demonstrated the development of periodontitis. There was a significant reduction in the steatosis score of animals from the P20-20 group when compared with the periodontitis group. P20-20 group presented significantly higher glutathione (11 times) and lower malondialdehyde (nearly 23%), total cholesterol (both in blood and hepatic tissue) and triglyceride concentrations compared with the periodontitis group. For levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase and random glucose, a significant difference between the groups was not observed. Conclusion Our results demonstrate that the microvesicular steatosis caused by periodontitis in rats is reversible after removal of the ligature, which is associated with the increase in oxidative stress and lipid peroxidation in the liver.

Hydrogen sulfide (H2S) is a signaling molecule in the gastrointestinal tract. H2S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H2S to specific tissues. This study was designed to evaluate the concentration and effects of H2S (generated by d-amino acid oxidase [DAO] from d-cysteine) in the gastric mucosa and the protective effects against ethanol-induced lesions in mice. Mice were treated with l-cysteine or d-cysteine (100 mg/kg per os). Other groups received oral l-propargylglycine (cystathionine γ-lyase inhibitor, 100 mg/kg) or indole-2-carboxylate (DAO inhibitor), and 30 min later, received d- or l-cysteine. After 30 min, 50% ethanol (2.5 mL/kg, per os) was administered. After 1 h, the mice were euthanized and their stomachs excised and analyzed. Pretreatment with either l-cysteine or d-cysteine significantly reduced ethanol-induced lesions. Pretreatment of d-cysteine- or l-cysteine-treated groups with indole-2-carboxylate reversed the gastroprotective effects of d-cysteine but not l-cysteine. Histological analysis revealed that pretreatment with d-cysteine decreased hemorrhagic damage, edema, and the loss of the epithelium, whereas the administration of indole-2-carboxylate reversed these effects. d-Cysteine also reduced malondialdehyde levels but maintained the levels of reduced glutathione. Furthermore, pretreatment with d-cysteine increased the synthesis of H2S. Thus, an H2S-generating pathway (involving d-cysteine and DAO) is present in the gastric mucosa and protects this tissue from ethanol-induced damage by decreasing direct oxidative damage.

Sulphated polysaccharides extracted from algae have been extensively studied for their diverse biological activities. Thus, the purpose of this study was to evaluate the chemical composition, the anti-diarrhoeal effect and acute toxicity of a sulphated polysaccharide fraction obtained from Gracilaria intermedia (SP-Gi). Initially, the FT-IR of SP-Gi revealed to be an agaran with sulphation at C-6 of the l-galactosyl residues. The anti-diarrhoeal activity of SP-Gi was evaluated in a castor oil-induced diarrhoea model. The effects of SP-Gi on enteropooling, Na +-K +-ATPase activity, gastrointestinal transit, and gastric emptying were then examined. Subsequently, the effect of SP-Gi on diarrhoea induced by cholera toxin (CT) and Escherichia coli was examined. In addition, an acute toxicity test was conducted in accordance with OECD guideline 423. Pre-treatment with SP-Gi reduces the total faeces, total diarrhoeal faeces, and enteropooling. SP-Gi (30mg/kg p.o.) increased Na+/K+-ATPase activity and reduced gastrointestinal transit through anticholinergic mechanisms. ELISA demonstrated that SP-Gi can interact with GM1 receptors and CT. SP-Gi reduced diarrhoea induced by E. coli and prevented weight loss in the animals. Moreover, SP-Gi did not induce any toxicity signs. These results suggest that SP-Gi is a possible candidate for the treatment of diarrhoeal illnesses.

Objective This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats. Methods Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30 mg/kg, p.o. or i.p. , groups 3–5, respectively) twice daily, for 2 days. After 1 h, NAP (80 mg/kg, p.o. ) was given. The control group received only vehicle (group 1) or vehicle + naproxen (group 2). Rats were euthanized on 2nd day, 4 h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated. Results EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10 mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4 ± 0.3 U/mg of gastric tissue) and inhibited changes in MDA (70.4 ± 8.3 mg/g of gastric tissue) and GSH (246.2 ± 26.4 mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group. Conclusion Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF.

BACKGROUND AND OBJECTIVE This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (βCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-βCD (ligature), and 25 mg/kg of αTPN-βCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS The treatment with αTPN-βCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-βCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION The results obtained suggest that the treatment with αTPN-βCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-βCD.

Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (C15H26O), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE2, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.

Alendronate is a bisphosphonate widely used for the treatment of osteoporosis; however, one of its main adverse reactions is gastric ulcer. Metformin is an oral antihyperglycemic agent that has several beneficial effects, including healing, gastroprotective and anti-tumoral action. This study aimed to evaluate the gastroprotective activity of metformin in alendronate-induced gastric damage in normoglycemic and hyperglycemic rats. The treatment with 100 mg/kg of metformin showed a significant gastroprotective effect in damage induced by alendronate (50 mg/kg) in macroscopic analysis and the analysis of light microscopy and atomic force microscopy. The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6), myeloperoxidase activity, and malondialdehyde levels. Also, the results suggested that metformin induces the maintenance of basal levels of collagen and increase the production of mucus. Interestingly, with the presence of the AMPK inhibitor (Compound C), metformin presented impairment of its gastroprotective action. The gastroprotective effect of metformin might be related to the activation of the AMPK pathway. These findings revealed that metformin has a gastroprotective action and may be considered a therapeutic potential for the prevention and treatment of gastric lesions induced by alendronate.

Diosgenin is a phytoestrogen and a constituent of Dioscorea. It has several biological effects, and some of them are anti-inflammatory, antidiabetic, antitumor, and vasodilatory. The present study investigated both the vasorelaxing and antioxidant mechanisms of diosgenin in isolated rat aortic rings. Female rats weighing 200-220 g were subjected to sham or OVX operations at 8 weeks of age. Ovariectomy was performed for menopause induction after anesthesia. Diosgenin (10

This study aimed to evaluate the effect of Lactobacillus reuteri DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 108 CFU•g body wt−1•day−1 of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm2) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 μmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of antioxidant parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.

Inflammation is the body's response to harmful stimuli such as infections, trauma, or injury. The inflammatory cascade can lead to the development of numerous diseases, and the current drug-therapeutic intervention consists of the use of corticosteroids and non-steroidal anti-inflammatory drugs. However, the use of these is associated with several serious side effects, so it is necessary to search for new alternatives that can minimize this effect. In this prospecting, the objective was to conduct a study on biological activities already described for vanillic acid, with special emphasis on its semi-synthetic derivative of isopropyl vanylate as an anti-inflammatory agent. For this, information was obtained on patent documents based on the INPI, USPTO and EPO databases, using the keywords: vanillic acid, anti-inflammatory agents, isopropyl vanylate, always used in the search field related to the summary of works. As results obtained in the present technological prospection study, it was found that in the international patent databases the documents related to the theme were very scarce and some had a higher number of patents, on vanillic acid, few refer to its anti- inflammatory, and no documents were found on the use of isopropyl vanillate as an anti-inflammatory agent, reinforcing the innovative character of research involving its use in this technology. La inflamación es la respuesta del cuerpo a estímulos dañinos como infecciones, traumatismos o lesiones. La cascada inflamatoria puede conducir al desarrollo de numerosas enfermedades, y la intervención farmacoterapéutica actual consiste en el uso de corticosteroides y antiinflamatorios no esteroideos. Sin embargo, el uso de estos se asocia a varios efectos secundarios graves, por lo que es necesario buscar nuevas alternativas que puedan minimizar este efecto. En esta prospección, el objetivo fue realizar un estudio sobre las actividades biológicas ya descritas para el ácido vainílico, con especial énfasis en su derivado semisintético de vanilato de isopropilo como agente antiinflamatorio. Para ello, se obtuvo información sobre documentos de patente basados ​​en las bases de datos del INPI, USPTO y EPO, utilizando las palabras clave: ácido vainílico, agentes antiinflamatorios, vanilato de isopropilo, siempre utilizados en el campo de búsqueda relacionado con el resumen de trabajos. Como resultados obtenidos en el presente estudio de prospección tecnológica, se encontró que en las bases de datos internacionales de patentes los documentos relacionados con el tema eran muy escasos y algunos tenían un mayor número de patentes, sobre el ácido vainílico, pocos se refieren a su antiinflamatorio, y no se encontraron documentos sobre el uso de isopropil vainilla como agente antiinflamatorio, lo que refuerza el carácter innovador de las investigaciones que involucran su uso en esta tecnología. Inflamação é a resposta do corpo à estímulos nocivos tais como: infecções, traumas ou lesões. A cascata inflamatória pode levar ao desenvolvimento de inúmeras doenças, e a intervenção farmacoterapêutica atual consiste no uso de corticosteroides e de anti-inflamatórios não-esteroides. Entretanto, a utilização destes está associada a vários efeitos secundários graves, por isso é necessária a busca por novas alternativas que possam minimizar esse efeito. Nesta prospecção, objetivou-se realizar um estudo sobre atividades biológicas já descritas para o ácido vanílico, com especial destaque para o seu derivado semissintético vanilato de isopropila enquanto agente anti-inflamatório. Para isso, foram obtidas informações sobre documentos de patentes nas bases INPI, USPTO e EPO, com o uso das palavras-chave: ácido vanílico, agentes anti-inflamatórios, vanilato de isopropila, sempre utilizados no campo de busca relativo ao resumo dos trabalhos. Como resultados obtidos no presente estudo prospecção tecnológica verificou-se que nas bases de dados internacionais de patente os documentos referentes à temática eram muito escassos e algumas tinham um maior número de patentes, sobre o ácido vanílico, poucas referem-se a sua atividade anti-inflamatória, e não foram encontrados documentos sobre a utilização do vanilato de isopropila como agente anti-inflamatório, reforçando o caráter inovador das pesquisas que envolvem o seu uso nesta tecnologia.

Objetivo: Desenvolver um modelo de dieta rica em gordura (DRG) que sozinho não resultou em doença hepática gordurosa não alcoólica (DHGNA), permitindo estudar a associação de comorbidades com o modelo de dieta rica em gordura. Material e métodos: Os ratos foram divididos em 2 grupos: dieta padrão e dieta rica em gordura, cada grupo com 8 animais. Os ratos foram submetidos à análise dos seguintes parâmetros no tecido hepático: dosagem de malondialdeído (MDA), glutationa (GSH) e atividade da mieloperoxidase (MPO). As amostras de fígado também foram avaliadas histopatologicamente quanto aos níveis séricos de alanina aminotransferase (ALT), aspartato aminotransferase (AST), albumina (ALB), fosfatase alcalina (FAL), ácido úrico e colesterol total (TC), cálcio (CA), ureia e HDL. Resultados: Mostraram que houve diferença significativa em MDA, GSH, colesterol total (CT), ALT, ALB, ácido úrico (AU), cálcio (CA) e HDL. A avaliação histopatológica apresentou escore baixo, insuficiente para a classificação da DHGNA. Conclusão: Este estudo demonstrou que o modelo de dieta rica em gordura não causou DHGNA. Esse achado permite utilizar a dieta hiperlipídica caracterizada neste estudo para investigar as possíveis alterações hepaticas causadas por outras comorbidades.

BACKGROUND Periodontitis is an inflammatory disease that causes periodontium and hepatic alterations. Liver disease is related to the intake of foods rich in fat and sugars (high-fat). The objective of this study was to evaluate whether a high-fat diet can aggravate the liver disease caused by ligature-induced periodontitis in rats. METHODS Twenty-one female rats were divided into three groups (n = 7 in each group): control; periodontitis (periodontitis induced with ligature) and high-fat + periodontitis (received hypercaloric diet and induction of periodontitis). The rats were submitted to the analyses of the following periodontal parameters: gingival bleeding index (GBI), probing pocket depth (PPD), tooth mobility (TM), and alveolar bone height. In the hepatic tissue, the levels of malondialdehyde (MDA), glutathione (GSH), total cholesterol, and myeloperoxidase activity (MPO) were measured. Liver samples were also histopathologically evaluated. Finally, blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, cholesterol high-density lipoprotein (HDL), and uric acid were measured. RESULTS The high-fat + periodontitis group presented an increase in the steatosis score (P

Diarrhea is one of the leading causes of infant death in the world accounting for high child mortality rate. It is also present in different pathophysiologies related to several etiological agents. The aim of this study is to investigate the antidiarrheal effect of α –Terpineol (α-TPN) in different diarrhea models in rodents. The antidiarrheal effect of α-TPN in the treatment of acute diarrhea and enteropooling induced by castor oil or PGE2 in Swiss mice pretreated orally with saline (NaCl 0.9%), Loperamide (5 mg/kg) and α-TPN (6.25, 12.5, 25 and 50 mg/kg) was analyzed. Additionally, parameters of severity, total weight of faeces and post-treatment for 4 h were evaluated. Modulation of the opioid and cholinergic pathways was performed and intestinal transit model using activated charcoal as marker was also used. The effect of α-TPN on secretory diarrhea was investigated using the model of fluid secretion in intestinal loops isolated from cholera toxin-treated mice. α-TPN showed antidiarrheal effect (*p

Background Periodontitis not only causes injury to the periodontium, but also damages other tissues such as: articulate, renal, cardiac, and hepatic. The objective of this study was to investigate periodontitis induced alterations in liver function and structure using an experimental model. Methods Twenty female rats (Rattus norvegicus) were allocated into two groups: control and periodontitis. Gingival bleeding index and oxidative stress parameters and specific circulating biomarkers were measured. Immunohistochemistry was carried out using alkaline phosphatase (AlkP) staining of the liver. Hepatic tissues, cytokines, and lipid contents were measured. Histopathologic evaluation of the liver was carried out using light and electron microscopy. Results Liver histopathologic and immunohistochemistry assessment showed increase in steatosis score, and presence of binucleate hepatocytes and positive cells for AlkP in periodontitis versus control group. Ultrastructural evaluation showed significant increase in size and number of lipid droplets (LD), distance between the cisterns of rough endoplasmic reticulum (RER), mitochondria size, foamy cytoplasm, and glycogen accumulation in the liver of the periodontitis group compared with the control group. In addition, plasma levels of AlkP, high-density lipoprotein (HDL), triglycerides, and total cholesterol were also changed. Conclusion Experimental periodontitis caused immunohistochemistry, histopathologic, ultrastructural, oxidative, and biochemical changes in the liver of rats.

Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H

The bioactive compounds found in foods and medicinal plants are attractive molecules for the development of new drugs with action against several diseases, such as those associated with inflammatory processes, which are commonly related to oxidative stress. Many of these compounds have an appreciable inhibitory effect on oxidative stress and inflammatory response, and may contribute in a preventive way to improve the quality of life through the use of a diet rich in these compounds. Eugenol is a natural compound that has several pharmacological activities, action on the redox status, and applications in the food and pharmaceutical industry. Considering the importance of this compound, the present review discusses its anti-inflammatory and antioxidant properties, demonstrating its mechanisms of action and therapeutic potential for the treatment of inflammatory diseases.

Nesta prospecção, objetivou-se realizar um estudo sobre atividades biológicas já descritas para o mastruz, com especial destaque para as eventuais aplicações farmacológicas desta planta. Para isso, foram obtidas informações sobre artigos científicos nas bases Web of ScienceTM, ScienceDirect, PubMed e Scielo, bem como sobre documentos de patentes nas bases USPTO, EPO, WIPO e INPI, com o uso da palavra-chave: Chenopodium ambrosioides, sempre utilizada nos campos de busca relativos ao título e ao resumo dos trabalhos. Desse modo, verificou-se que em bases de dados internacionais de artigos científicos, muitos são os trabalhos publicados envolvendo o mastruz, mas há número relativamente baixo de documentos de patentes, principalmente, no que se refere à descrição de eventual ação farmacológica da planta. Isso demonstra que há grandes oportunidades de pesquisa envolvendo a descrição da atividade biológica de extratos ou óleos essesnciais de plantas, como o mastruz.