ABSTRACT
Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B2 antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.
ABSTRACT
Malpighia emarginata (Malpighiaceae), popularly known as "acerola", is a tropical and subtropical fruit native to the Americas. Despite its high vitamin C content, which gives it a high antioxidant property, soluble dietary fibers, such as polysaccharides, are also abundant constituents of acerola (10% of the dried fruit). The acerola cold-water soluble (ACWS) fraction presented anti-fatigue and antioxidant effects in vivo and in vitro. To infer further systemic effects of ACWS, this study aimed to investigate the antinociceptive, anti-inflammatory, and antioxidant effects of ACWS in murine models of pain. In formalin-induced nociception, ACWS (0.1, 1, and 10 mg/kg) reduced only the inflammatory phase, and also (10 and 30 mg/kg) attenuated the acetic acid-induced writhing and leukocyte migration in the peritoneal cavity. The mechanical allodynia and paw edema induced by intraplantar injection of carrageenan were greatly reduced by ACWS (10 mg/kg). At the inflammatory pick induced by carrageenan (4 h), ACWS significantly reduced myeloperoxidase activity, TNF-α, IL-1ß, and PGE2 levels, and restored IL-10 levels. ACWS also exhibited antioxidant properties by decreasing lipid hydroperoxides content, increasing GSH levels, and restoring superoxide dismutase and catalase activities in the carrageenan model and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. Collectively, these results support the antinociceptive, anti-inflammatory, and antioxidant effects of ACWS and reveal a promising candidate for the treatment of inflammatory pain conditions.
Subject(s)
Malpighiaceae , Pectins , Animals , Mice , Pectins/chemistry , Antioxidants/analysis , Carrageenan , Fruit/chemistry , Polysaccharides/chemistry , Pain/chemically induced , Pain/drug therapy , Anti-Inflammatory Agents/chemistry , Ascorbic Acid/analysis , Water/analysis , Analgesics/pharmacology , Malpighiaceae/chemistryABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the gastrointestinal tract. The etiology is not fully understood, but environmental, microbial, and immunologic factors, as well as a genetic predisposition, play a role. UC is characterized by episodes of abdominal pain, diarrhea, bloody stools, weight loss, severe colonic inflammation, and ulceration. Despite the increase in the frequency of UC and the deterioration of the quality of life, there are still patients who do not respond well to available treatment options. Against this background, natural products such as polysaccharides are becoming increasingly important as they protect the intestinal mucosa, promote wound healing, relieve inflammation and pain, and restore intestinal motility. In this study, we investigated the effect of a polysaccharide isolated from the biomass of Campomanesia adamantium and Campomanesia pubescens (here referred to as CPW) in an experimental model of acute and chronic ulcerative colitis induced by dextran sulfate sodium (DSS). CPW reversed weight loss, increased disease activity index (DAI), bloody diarrhea, and colon shortening. In addition, CPW reduced visceral mechanical hypersensitivity, controlled oxidative stress and inflammation, and protected the mucosal barrier. CPW is not absorbed in the intestine, does not inhibit cytochrome P450 proteins, and does not exhibit AMES toxicity. These results suggest that CPW attenuates DSS-induced acute and chronic colitis in mice and may be a potential alternative treatment for UC.
Subject(s)
Colitis, Ulcerative , Humans , Animals , Mice , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Quality of Life , Disease Models, Animal , Inflammation , Weight Loss , DiarrheaABSTRACT
Piper regnellii is a plant popularly known as "Pariparoba" and it is widely used in folk medicine to treat pain, inflammation, among others. This work presents the extraction, purification and characterization of polysaccharides present in the plant leaves and evaluation of their anti-inflammatory and antinociceptive activities. From the crude aqueous extract of P. regnellii leaves, a polysaccharide fraction named PR30R, predominantly constituted of arabinose, galactose and galacturonic acid monosaccharide units, was obtained. Methylation and NMR analysis showed that the main polysaccharides of PR30R are a type II arabinogalactan, formed by a ß-D-Galp-(1 â 3) main chain, substituted at O-6 by side chains of ß-D-Galp-(1 â 6), which are substituted at O-3 by non-reducing α-L-Araf ends, and a homogalacturonan, formed by â4)-α-D-GalpA-(1â units. Intraperitoneal administration of the crude polysaccharide fraction PRSF reduced significantly nociception induced by acetic acid in mice at the doses tested, and the PR30R fraction, derived from PRSF, presented antinociceptive and anti-inflammatory effects at a dose of 0.1096 mg/kg (PRSF ED50). These data support the use of the plant leaves in folk medicine as an herbal tea to treat pain and inflammation.
Subject(s)
Piper , Animals , Mice , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Polysaccharides/analysis , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/analysis , Inflammation , Analgesics/pharmacology , Analgesics/therapeutic use , Plant Leaves/chemistry , Pain/drug therapyABSTRACT
OBJECTIVE: We evaluated the performance of an early-warning algorithm, based on ward-specific incidence cutoffs for detecting Clostridioides difficile transmission in hospitals. We also sought to determine the frequency of intrahospital Clostridioides difficile transmission in our setting. DESIGN: Diagnostic performance of the algorithm was tested with confirmed transmission events as the comparison criterion. Transmission events were identified by a combination of high-molecular-weight typing, ward history, ribotyping, and whole-genome sequencing (WGS). SETTING: The study was conducted in 2 major and 2 minor secondary-care hospitals with adjacent catchment areas in western Sweden, comprising a total population of â¼480,000 and â¼1,000 hospital beds. PATIENTS: All patients with a positive PCR test for Clostridioides difficile toxin B during 2020 and 2021. METHODS: We conducted culturing and high-molecular-weight typing of all positive clinical samples. Ward history was determined for each patient to find possible epidemiological links between patients with the same type. Transmission events were determined by PCR ribotyping followed by WGS. RESULTS: We identified 4 clusters comprising a total of 10 patients (1.5%) among 673 positive samples that were able to be cultured and then typed by high-molecular-weight typing. The early-warning algorithm performed no better than chance; patient diagnoses were made at wards other than those where the transmission events likely occurred. CONCLUSIONS: In surveillance of potential transmission, it is insufficient to consider only the ward where diagnosis is made, especially in settings with high strain diversity. Transmission within wards occurs sporadically in our setting.
Subject(s)
Clostridioides difficile , Clostridium Infections , Humans , Clostridioides difficile/genetics , Ribotyping , Clostridium Infections/diagnosis , Clostridium Infections/epidemiology , Hospitals , Disease OutbreaksABSTRACT
Soursop fruits are widely used in the folk medicine to treat a variety of health conditions. Once the chemical structure of dietary fibers from fruits is closely related to its biological functions in the human body, we aimed to explore structural features and biological activity of dietary fibers from soursop. Polysaccharides that constitute the soluble and insoluble fibers were extracted and further analyzed using monosaccharide composition, methylation, molecular weight determination and 13C NMR data. Soursop soluble fibers (SWa fraction) were characterized as having type II arabinogalactan and a highly methyl esterified homogalacturonan, while non-cellulosic insoluble fibers (SSKa fraction) were mainly composed by a pectic arabinan, a xylan-xyloglucan complex and a glucuronoxylan. The oral pre-treatment with SWa and SSKa promoted antinociception in mice writhing test, reducing the number of pain-like behaviors (in 84.2 % and 46.9 %, respectively, at 10 mg/kg) and peritoneal leucocyte migration (55.4 % and 59.1 %, at 10 mg/kg), effects possibly associated with the pectins present in fruit pulp extractions. SWa also significantly inhibited the plasmatic extravasation of Evans blue dye in 39.6 % at 10 mg/kg. This paper describes for the first time the structural features of soursop dietary fibers that may be of biological significance in future.
Subject(s)
Annona , Mice , Humans , Animals , Annona/chemistry , Fruit/chemistry , Polysaccharides/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/analysis , Analgesics/pharmacology , Analgesics/analysisABSTRACT
In the past, the high intraspecific variation of wing pattern within the genus Phaselia Guene, [1858] repeatedly led to misidentifications. In this study, we applied an integrative approach using external and internal morphological characters, along with DNA barcoding and distribution data to review the taxonomy of the genus Phaselia in the Middle East and Central Asia. For this study, 710 specimens, including type specimens and 242 genitalia slides were prepared and examined. As a result, P. phaeoleucaria (Lederer, 1855) stat. rev. is reinstated from synonymy of P. serrularia; P. phaeoleucaria shurensis Wehrli 1941 comb. nov. is regarded as a subspecies of P. phaeoleucaria stat. rev. instead of a subspecies of P. serrularia; P. serrularia catharia Wehrli, 1941 syn. nov. is regarded as a junior synonym of P. phaeoleucaria shurensis comb. nov.; P. narynaria Oberthr, 1913 syn. nov. is regarded as a junior synonym of P. serrularia (Eversmann, 1847); P. pithana Wehrli, 1941 bona sp. is raised to species level from subspecies of P. serrularia. Furthermore, two species and two subspecies are described as new to science: P. smettboi sp. nov., P. sihvoneni sp. nov., P. erika jonubi ssp. nov. and P. erika sindhi ssp. nov. Wing pattern, and both male and female genitalia of all discussed taxa are illustrated, their distribution patterns are shown on a map and CO1 data is evaluated to confirm our taxonomic decisions.
Subject(s)
Genitalia , Moths , Female , Male , Animals , Animal Distribution , Middle East , DNAABSTRACT
OBJECTIVE: To identify early follicular phase microribonucleic acids (miRNAs) that are altered in serum of women with endometriosis. DESIGN: Case-control study. SETTING: Large university-affiliated in vitro fertilization center. PATIENT(S): Women with (n = 21) and without (n = 24) endometriosis. INTERVENTION(S): Serum samples were obtained from laparoscopy-confirmed patients with endometriosis. MAIN OUTCOME MEASURE(S): The differential expression of serum miRNAs relative to controls was measured using the NanoString nCounter technology and validated by quantitative real-time polymerase chain reaction in an independent cohort of 27 patients with endometriosis and controls (n = 24). Microribonucleic acid target signaling pathways and genes were analyzed bioinformatically. A chemically modified stable miR-34-3p oligonucleotide was used to examine the effect on proliferation of VK2E6/E7 endometrial cells in vitro. RESULT(S): Eighteen miRNAs were significantly up-regulated, and 1 miRNA (hsa-miR-34c-3p) was significantly down-regulated in the follicular phase of patients with endometriosis. The analysis of target signaling pathways using TargetScan predicted regulation of the mitogen-activated protein kinase, phosphoinositide 3-kinase/protein kinase B, Hippo, adenosine monophosphate-activated protein kinase, transforming growth factor beta, and endometrial cancer pathways, which have been implicated in the pathogenesis of endometriosis, by these miRNAs. The analysis of sequence complementarity identified prostaglandin E2 receptor 4, interleukin 6 signal transducer, and polo-like kinase 4 genes as possible direct targets of hsa-miR-34-3p. DSDI-1, a chemically modified stable miR-34-3p oligonucleotide, reduced cell proliferation in VK2E6/E7 endometrial cells in vitro. CONCLUSION(S): The follicular phase miRNA levels are altered in serum of women with endometriosis and may be useful as reproducible detection biomarkers for early diagnosis of endometriosis. hsa-miR-34-3p is significantly down-regulated in endometriosis, targets endometriosis genes, and reduces endometrial cell proliferation in vitro. These results support hsa-miR-34-3p as a potential therapeutic target in endometriosis.
Subject(s)
Endometriosis , MicroRNAs , Biomarkers , Case-Control Studies , Endometriosis/genetics , Female , Follicular Phase , Humans , MicroRNAs/genetics , Oligonucleotide Array Sequence Analysis , Oligonucleotides , Phosphatidylinositol 3-Kinases/genetics , Pilot ProjectsABSTRACT
Inflammatory bowel disease (IBD) includes two distinct diseases: Crohn's disease (CD) and ulcerative colitis (UC). IBD is a chronic systemic disease of the gastrointestinal tract, characterized by an inflammatory process. The mechanisms by which diseases develop are still unknown, but it is known that it results from a complex interaction between genetic variability, the host's immune system, and environmental factors. One of the main complaints of patients is abdominal pain, which may be associated with the release of inflammatory mediators, changes in the normal motility of the digestive tract, and increased intestinal permeability. Currently available drugs for abdominal pain are not satisfactory, therefore, it is extremely necessary to seek new therapeutic options for the treatment of abdominal pain. Polysaccharides extracted from fruits have attracted interest, as these molecules protect the intestinal mucosa and promote wound healing, attenuating inflammation, pain, and altered intestinal motility. In this study, we investigated the ability of pectic polysaccharides obtained from guavira pomace, named CPW to reduce visceral hypersensitivity, regulate intestinal motility, and control diarrhea in mice. Acetic acid, capsaicin, or mustard oil were used to assess visceral pain in normal mice. CPW reduced abdominal writhing, cell migration, and capsaicin-induced visceral nociception. Furthermore, it regulated intestinal motility and all measured parameters of castor oil-induced diarrhea. CPW treatment reversed the increase in mucosal permeability, TEER, and tissue weight caused by acetic acid. In addition, molecular docking analysis showed that specific the CPW units binds to the 3N8V, 5COX, 2J67 and 6RBF proteins. Thus, the results suggest that CPW has attractive therapeutic characteristics for the treatment of abdominal pain and ulcerative colitis.
Subject(s)
Colitis, Ulcerative , Inflammatory Bowel Diseases , Abdominal Pain/drug therapy , Animals , Capsaicin , Colitis, Ulcerative/drug therapy , Diarrhea , Dietary Carbohydrates , Fruit , Humans , Mice , Molecular Docking Simulation , Polysaccharides/pharmacologyABSTRACT
Neuropathic and postoperative pain are clinical conditions that impair the patient's quality of life. The current pharmacotherapy of both painful states is ineffective and accompanied by several side effects. In order to develop new therapeutics targets, the secondary metabolites of plants have been extensively studied. Acmella oleracea ("jambu") is a native plant from the Amazon region and rich in alkylamides, bioactive compounds responsible for inducing anesthetic and chemesthetic sensations. We previously demonstrated that the intraplantar administration of an hexanic fraction (HF) rich in alkylamides from jambu and the synthetic isobutylalkyl amide (IBA) at 0.1 µg/20 µL can promote antinociceptive and anti-inflammatory effects. Thus, this study aimed to evaluate the local effect of HF and IBA (0.1 µg/20 µL) on neuropathic (partial sciatic nerve ligation, PSNL) and postoperative pain (plantar incision surgery, PIS) models in mice. Seven days after the PSNL, the mechanical (von Frey test) and cold (acetone-evoked evaporative cooling) allodynia, and digital gait parameters were analyzed. The intraplantar HF and IBA treatments attenuated the mechanical and cold allodynia as well as the static (max. Contact and print area) and dynamic (stand duration) parameters of digital gait analyses. On the day after PIS, the mechanical allodynia, heat hyperalgesia (hot plate, 52 ± 0.1°C), and spontaneous nociception scores were evaluated. Topical treatment with HF reduced the mechanical allodynia, heat hyperalgesia, and spontaneous nociception scores. In contrast, IBA treatment only partially reduced the mechanical allodynia. In summary, the local treatment with HF was effective on both neuropathic and postoperative pain, as opposed to IBA, which only had an effect on neuropathic pain.
Subject(s)
Asteraceae , Neuralgia , Amides/pharmacology , Animals , Disease Models, Animal , Hyperalgesia/drug therapy , Mice , Molecular Structure , Neuralgia/drug therapy , Neuralgia/metabolism , Pain, Postoperative/drug therapy , Quality of LifeABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.
Subject(s)
Anti-Ulcer Agents/pharmacology , Sedum/chemistry , Stomach Ulcer/prevention & control , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/isolation & purification , Antioxidants/isolation & purification , Antioxidants/pharmacology , Disease Models, Animal , Female , Omeprazole/pharmacology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Polyphenols/isolation & purification , Polyphenols/pharmacology , Rats , Rats, Wistar , Sucralfate/pharmacologyABSTRACT
In late 2019, an outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated in Wuhan, Hubei province, China. The major clinical symptoms described for coronavirus disease (COVID-19) include respiratory distress and pneumonia in severe cases, and some patients may experience gastrointestinal impairments. In accordance, viral RNA or live infectious virus have been detected in feces of patients with COVID-19. Binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) is a vital pathway for the virus entry into human cells, including those of the respiratory mucosa, esophageal epithelium as well as the absorptive enterocytes from ileum and colon. The interaction between SARS-CoV-2 and ACE2 receptor may decrease the receptor expression and disrupt the function of B0AT1 transporter influencing the diarrhea observed in COVID-19 patients. In this context, a fecal-oral transmission route has been considered and points out a role for the digestive tract in disease transmission and severity. Here, in order to further understand the impact of COVID-19 in human physiology, the cellular and molecular mechanisms of SARS-CoV-2 infection and disease severity are discussed in the context of gastrointestinal disturbances.
ABSTRACT
The coronavirus disease 19 (COVID-19) is caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected the global population despite socioeconomic status and amazed surveillance agencies for its incidence, mortality, and recovery rates. COVID-19 affects all age groups; however, it is suggested to progress into severe disease and cause mortality in over 10% of the confirmed cases, depending on the individual characteristics of the affected population. One of the biggest unanswered questions it is why only some individuals develop into the severe stages of the disease. Current data indicate that most of the critically ill are the elderly or those with comorbidities such as hypertension, diabetes, and asthma. However, it has been noted that, in some populations, severe disease is mostly observed in much younger individuals (<60-years old) with no reported underlying medical conditions. Certainly, many factors may contribute to disease severity including intrinsic host factors such as genetic variants, the expression levels of tissue proteins, among others. Considering all these aspects, this review aims to discuss how the expression levels of tissue proteases and the different profiles of immune responses influence the susceptibility to COVID-19 as well as disease severity and outcome.
ABSTRACT
Chamomile is one of the most ancient medicinal herbs known to mankind and among its traditional uses are the calming effects. However, few studies explored its effects on the central nervous system (CNS). In this study we further proceed with structural elucidation of polysaccharides from chamomile tea. A highly substituted 4-O-methyl-glucuronoxylan (fraction SN-50R) was purified and chemically characterized, presenting Xyl:GlcA ratio of 1.7:1, Mw of 500 kDa and total sugar content of 98%. Its bioactivity on pain and on CNS was explored. Animals treated with SN-50R presented antinociceptive effect and a dose-dependent decrease in the number of crossings in the activity chamber and in the open field test, as well as a significant reduction in the number of marbles buried when compared to control. These results suggest that SN-50R presented sedative and anxiolytic-like effects and may be contributing for the calming effects obtained by chamomile tea ingestion.
Subject(s)
Analgesics/pharmacology , Anti-Anxiety Agents/pharmacology , Chamomile/chemistry , Hypnotics and Sedatives/pharmacology , Plant Extracts/pharmacology , Tea/chemistry , Xylans/pharmacology , Animals , Female , Male , Mice , Plants, Medicinal/chemistry , Polysaccharides/pharmacologyABSTRACT
Handroanthus albus, commonly known as yellow ipê, is a native and widely distributed tree in Brazil. An aqueous soluble polysaccharide fraction (HASP) was obtained from its leaves, and monosaccharide composition, glycosidic linkage analysis by methylation and NMR spectroscopy indicated that HASP is mainly composed of a type II arabinogalactan, and suggested that other polysaccharides could also be present in a smaller proportion. HASP was able to promote antinociception in formalin-induced (second phase) and on glutamate-induced nociception tests, besides reducing the number of abdominal contortions induced by acetic acid in mice. Moreover, HASP reduced acetic acid-induced leukocyte infiltration in the peritoneal cavity and showed anti-edematogenic activity, decreasing mechanical allodynia and myeloperoxidase activity in the carrageenan-induced paw edema model. These results showed that the polysaccharide fraction HASP from H. albus leaves has interesting antinociceptive and anti-inflammatory activities.
Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Bignoniaceae/chemistry , Plant Extracts/pharmacology , Polysaccharides/pharmacology , Analgesics/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Leukocytes/drug effects , Mice , Plant Extracts/chemistry , Polysaccharides/chemistryABSTRACT
Acmella oleracea ("jambu") is an Amazonian plant rich in alkylamides. Its flowers are widely used in folk medicine to treat toothache due to tingling, numbness, and local anaesthesia caused in the mouth. Our group previously demonstrated that the intraplantar (i.pl.) injection of an alkylamide-rich hexane fraction (HF) obtained from jambu flowers and a synthetic isobutylalkyl amide (IBA) displayed antinociceptive and anesthetic effects in acute pain models. Thus, here we evaluated the effects of HF and IBA on carrageenan-induced acute inflammation. Mice were pretreated with HF or IBA (0.01, 0.1, and 1 µg/20 µL, i.pl.) 15 min before carrageenan injection (300 µg/20 µL, i.pl.). Mechanical allodynia and paw oedema were evaluated previously (basal) and at 0.5 until 6 h following carrageenan. Both HF and IBA at 0.1 µg promoted effective and long-lasting antiallodynic and anti-oedematogenic activities until 3 and 5 h, respectively, in comparison to the different doses evaluated. At the inflammatory peak, the plantar surfaces were excised for measurement of inflammatory and oxidative stress parameters. HF and IBA (0.1 µg) reduced the myeloperoxidase activity, TNF-α and IL-1ß levels, prevented the production of lipid hydroperoxides, and the decrease of antioxidant agents, namely superoxide dismutase and catalase activities, and glutathione contents. Furthermore, only HF maintained IL-10 levels and decreased PGE2 synthesis. On the basis of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, HF and IBA are devoid of antioxidant activity in vitro. Collectively, our results demonstrated the promising anti-inflammatory effect of local pretreatment with alkylamides, supporting the potential of these molecules to treat acute inflammatory pain conditions.
Subject(s)
Amides/pharmacology , Anti-Inflammatory Agents/pharmacology , Asteraceae/chemistry , Inflammation/drug therapy , Amides/chemistry , Amides/isolation & purification , Analgesics/chemistry , Analgesics/isolation & purification , Analgesics/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Carrageenan , Disease Models, Animal , Edema/drug therapy , Edema/pathology , Flowers , Hyperalgesia/drug therapy , Hyperalgesia/pathology , Inflammation/pathology , Male , Mice , Oxidative Stress/drug effects , Pain/drug therapy , Pain/pathology , Plant Extracts/pharmacologyABSTRACT
A polysaccharide fraction from Handroanthus heptaphyllus leaves was obtained with a simple and quick purification method. Methylation analysis and NMR spectroscopy indicated the presence of a complex polysaccharide fraction mainly constituted by a type II arabinogalactan. This is the first report in literature on structural elucidation of polysaccharides of species from genus Handroanthus. Oral and intraperitoneal administration of the polysaccharide fraction from Handroanthus heptaphyllus (HHSF) protected the gastric mucosa in an acute model of gastric lesion induced by ethanol, preserving gastric mucus. Furthermore, in the indomethacin model, HHSF reduced wounded area and inhibited mucus and GSH depletion. HHSF also accelerated gastric ulcer healing, accompanied by the maintenance of GSH levels. In addition, in an oxidative stress model with human epithelial cell line (Caco-2), HHSF was able to preserve GSH levels and was not toxic to cells. Collectively, these results showed that HHSF has an interesting antiulcerogenic activity and could constitute an interesting option for the treatment of gastric ulcer.
Subject(s)
Gastric Mucosa , Plant Extracts , Polysaccharides/pharmacology , Stomach Ulcer/drug therapy , Tabebuia/metabolism , Animals , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/pharmacology , Caco-2 Cells , Female , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Humans , Oxidative Stress/drug effects , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/metabolism , Rats , Rats, WistarABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is a medicinal plant employed in Mexican and Brasilian folk medicine as juice or infusion, as remedy for the treatment of different diseases, including gastric disorders. AIM OF THE STUDY: Although some studies carried out with Sedum dendroideum have demonstrated its gastroprotective effect, the purpose of this study was to elucidate the chemical constituents, antioxidant, cytotoxic and mechanisms underlying the gastrointestinal properties of Sedum dendroideum accordingly its traditional use, as fresh leaves tea infusion (SDI). MATERIALS AND METHODS: Chemical constituents were analyzed using high performance liquid chromatography and mass spectrometry (HPLC-MS). Antioxidant and cytotoxicity were evaluated in in vitro assays. The efficacy of the SDI on macroscopic ulcer appearance, mucus and GSH maintenance on ethanol- and indomethacin-induced ulcer models, gastric acid secretion and gastrointestinal motility were investigated. RESULTS: Phytochemical analysis by HPLC-MS revealed the presence of different flavonol glycosides, containing myricetin and quercetin, along with the kaempferol as aglycones. In vitro pharmacological investigation of SDI demonstrated potent antioxidant activity in DPPH assay (IC50: 13.25⯱â¯3.37⯵g/mL) and absence of cytotoxicity in Caco-2 cells by MTT method. Oral administration of SDI (ED50 of 191.00⯱â¯0.08â¯mg/kg) in rats promoted gastroprotection against ethanol or indomethacin in rats through reinforcement of gastric wall mucus, GSH content and nitric oxide release, without present antisecretory properties. The gastroprotective effect was maintained when SDI (19â¯mg/kg) was administrated by intraperitoneal route. Furthermore, SDI (150â¯mg/kg) unchanged the gastric emptying but increase small bowel transit in mice through cholinergic pathways. CONCLUSIONS: Collectively, this study confirmed that Sedum dendroideum promotes gastroprotection through preventing of endogenous defense mechanisms, represented by mucus and GSH without changes gastric acid secretion. Sedum dendroideum tea infusion features a chemical profile that contributes to the antioxidant and gastric health-promoting effects, supporting the use in folk medicine for the treatment of gastrointestinal disorders.