Alpha-terpineol complexed with beta-cyclodextrin reduces damages caused by periodontitis in rats.

BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) 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-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (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-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD 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-ßCD 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-ßCD.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. METHODS: We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. CONCLUSION: Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection.

Effect of N-salicyloyltryptamine (STP), a novel tryptamine analogue, on parameters of cell viability, oxidative stress, and immunomodulation in RAW 264.7 macrophages.

Immunomodulatory actions exerted by some classes of tryptamines, such as benzoyltryptamine analogues, suggest these molecules as promising candidates to develop new therapies to treat conditions associated to acute and chronic pain and inflammation. N-salicyloyltryptamine (STP) was observed to act as an anticonvulsive agent and exert antinociceptive effects in mouse. In the present work, we performed a screening of cytotoxic, cytoprotective, immunomodulatory, and redox properties of STP in RAW 264.7 macrophages challenged with hydrogen peroxide and LPS. Our results show that STP presents no cytotoxicity in the range of 0.001 to 1 µg/mL, but doses of 50 and 100 µg/mL caused loss of cell viability (IC(50) = 22.75 µg/mL). Similarly, STP at 0.001 to 1 µg/mL did not cause oxidative stress to RAW 264.7 cells, although it did not prevent cell death induced by H(2)O(2) 0.5 mM. At 1 µg/mL, STP reversed some redox and inflammatory parameters induced by LPS. These include thiol (sulfhydryl) oxidation, superoxide dismutase activation, and morphological changes associated to macrophage activation. Besides, STP significantly inhibited LPS-induced TNF-α and IL-1ß release, as well as CD40 and TNF-α protein upregulation. Signaling events induced by LPS, such as phosphorylation of ERK 1/2 and IκBα and p65 nuclear translocation (NF-kB activation) were also inhibited by STP. These data indicate that STP is able to modulate inflammatory parameters at doses that do not interfere in cell viability.

Photobiological effect of eugenol-derived 3-benzoylcoumarin associated with led lights against MDR microorganisms.

The problem of antibiotic resistance by bacteria threatens human health. Therefore, studies in this area seek alternatives to circumvent it. The study with coumarins and eugenol has already proven that these classes of compounds act against bacteria. In this same aspect, exposure to LED also shows a bactericidal effect. Seeking a possible enhancement of this effect, the present work studied coumarins derived from eugenol in association with LED to investigate the bactericidal effect. Four compounds were tested. For this, minimum inhibitory concentrations (MICs) and modulation with three antibiotics against Escherichia coli and Staphylococcus aureus bacteria were determined. To test the behavior of the activity against exposure to LED, the plates were exposed for 20 min to blue light, 415 nm and then incubated at 37°C for 24 h. For control, duplicates were made, and one of them did not undergo this exposure. C1 exhibited better activity against S. aureus, as synergism prevailed under the conditions tested. C3 and C4 were promising against E. coli as they showed synergism in association with the three antibiotics both with and without LED exposure. Thus, the compounds showed bactericidal activity, and LED was shown to enhance synergism.

Inhibition of Staphylococcus aureus Efflux Pump by O-Eugenol and Its Toxicity in Drosophila melanogaster Animal Model.

Background: Efflux pumps are transmembrane proteins that expel drugs out of a bacterial cell contributing to microorganism drug resistance. Several studies addressing the use of natural products with medicinal properties have intensified given the above. Thus, the aim of the present study was to investigate the antibacterial activity and the O-eugenol potential in Staphylococcus aureus resistance reversal by efflux pump inhibition, as well as to evaluate its toxicity in the Drosophila melanogaster arthropod model. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the O-eugenol efflux pump inhibition. For the D. melanogaster toxicity assays, mortality and locomotor system damage were performed using the fumigation method. Results: O-eugenol presented a MIC of 1024 µg/mL against S. aureus. The association of this compound with the antibiotic tetracycline demonstrated a synergistic effect (p < 0.0001), this also being observed when the antibiotic was associated with ethidium bromide (p < 0.0001); thus, these results may be attributable to an efflux pump inhibition. The D. melanogaster mortality and geotaxis assays revealed the compound is toxic, with an EC50 of 18 µg/mL within 48 hours of exposure. Conclusions: While we can conclude that the tested product has an efflux pump inhibitory effect, further studies are needed to elucidate its mechanisms of action, in addition to assays using other strains to verify whether the substance has the same inhibitory effect.

Anti-inflammatory and modulatory effects of steroidal saponins and sapogenins on cytokines: A review of pre-clinical research.

BACKGROUND: Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models. PURPOSE: The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines. STUDY DESIGN AND METHODS: This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved. RESULTS: Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways. CONCLUSION: Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation.

The Therapeutic Value of Hydralazine in Reducing Inflammatory Response, Oxidative Stress, and Mortality in Animal Sepsis: Involvement of the PI3K/AKT Pathway.

ABSTRACT: Sepsis is an amplified systemic immune-inflammatory response produced by a microorganism, which involves activation of inflammatory cytokine signaling pathways and oxidative stress. A variety of studies have shown that hydralazine (HDZ) has potent antioxidant and anti-inflammatory proprieties. Therefore, we hypothesize that HDZ can improve the clinical outcome of sepsis. Thus, this work aimed to evaluate therapeutic value of HDZ in reducing inflammatory response, oxidative stress, and mortality in animal sepsis, and to investigate its possible mechanism of action. Sepsis was induced by the cecal ligation and puncture (CLP) method in Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis, and sepsis + HDZ (1 mg/kg, s.c.). All groups were monitored for 48 h to assess survival rate, and clinical, hemodynamic, biochemical, and cellular parameters. After euthanasia, blood, spleen, liver, and kidneys were collected for analysis. Blood serum cytokines, tissue myeloperoxidase (MPO) activity, and oxidative stress parameters were assessed. Involvement of the PI3K/Akt pathway was also investigated. Sepsis was successfully induced by the CLP technique. HDZ treatment increased the survival rate (from 50% to 90%), improved glycemia control, reduced the clinical severity sepsis and mean arterial pressure; and prevented increased MPO activity, TNF-α, IL-1ß, IL-10 levels, and oxidative damage markers. Additionally, HDZ significantly prevented the increase of Akt activation in the liver and kidney. HDZ largely mitigated the effects of sepsis by suppressing inflammatory and antioxidant responses via the PI3K/Akt pathway. These findings provide evidence that HDZ can be a new therapeutic alternative for treating sepsis.

Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection.

Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.

Rapid diagnosis of COVID-19 in the first year of the pandemic: A systematic review.

BACKGROUND: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health threat and remains a challenge for modern medicine. Rapid and accurate diagnosis of COVID-19 is vital for proper disease and outbreak management. Our review aimed to analyze scientific articles published in the literature addressing the rapid tests available for COVID-19 diagnosis at the first year of the pandemic. METHODS: A systematic review was performed from October 22 to 27, 2020, searching data published in PubMed and Google Scholar databases, using subject headings or keywords related to point of care and rapid test diagnostic for SARS-CoV-2 and COVID-19. RESULTS: The first survey identified 403 articles, but only 23 met the defined criteria for the systematic analysis. The sensitivity and specificity parameters were assessed in 19 studies, and the data suggested that there was lower sensitivity in the period 1 to 7 days after the emergence of symptoms (∼38%) higher sensitivity at 8 to 14 days (∼90%), and the highest at 15 to 39 days (∼98%). Accuracy was reported in six studies, reporting values above 50%. Only three studies reported a possible cross-reaction. CONCLUSIONS: Our findings indicate that the rapid tests used in the first year of the pandemic were tested with a small number of samples and not adequately validated. And the studies that described them were conducted with little scientific rigor.

Modulation of interleukin expression by medicinal plants and their secondary metabolites: A systematic review on anti-asthmatic and immunopharmacological mechanisms.

BACKGROUND: Asthma is one of the most common chronic inflammatory conditions of the lungs in modern society. Asthma is associated with airway hyperresponsiveness and remodeling of the airways, with typical symptoms of cough, wheezing, shortness of breath and chest tightness. Interleukins (IL) play an integral role in its inflammatory pathogenesis. Medicinal herbs and secondary metabolites are gaining considerable attention due to their potential therapeutic role and pharmacological mechanisms as adjunct tools to synthetic bronchodilator drugs. PURPOSE: To systematically review the literature on the use of single or mixed plants extracts therapy in vivo experimental systems for asthma, emphasizing their regulations on IL production to improve lung. METHODS: Literature searches were performed on PubMed, EMBASE, Scopus and Web of Science databases. All articles in English were extracted from 1999 up to September 2019, assessed critically for data extraction. Studies investigating the effectiveness and safety of plant extracts administered; inflammatory cell count, immunoglobulin E (IgE) production and regulation of pro-inflammatory cytokine and T helper (Th) 1 and Th2-driven cytokine expression in bronchoalveolar lavage fluid (BALF) and lung of asthmatic animals were included. RESULTS: Four hundred and eighteen publications were identified and 51 met the inclusion criteria. Twenty-six studies described bioactive compounds from plant extracts. The most frequent immunopharmacological mechanisms described included reduction in IgE and eosinophilic recruitment, decreased mucus hypersecretion and airway hyperreactivity, enhancement of the balance of Th1/Th2 cytokine ratio, suppression of matrix metallopeptidase 9 (MMP-9) and reversal of structural alterations. CONCLUSION: Plant extract therapies have potential control activities on asthma symptoms by modulating the secretion of pro-inflammatory (IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10, IL-23, IL-31, IL-33), Th1 (IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines, reducing the level of biomarkers of airway inflammation.

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties.

BACKGROUND: Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities. PURPOSE: We reviewed whether essential oils and their bioactive compounds of plant origin could modulate cytokines' immune responses and improve asthma therapy in experimental systems in vitro and in vivo. METHODS: Electronic and manual search of articles in English available from inception up to November 2018 reporting the immunomodulatory activity of essential oils and their bioactive compounds for the management of asthma. We used PubMed, EMBASE, Scopus and Web of Science. Publications reporting preclinical experiments where cytokines were examined to evaluate the consequence of anti-asthmatic therapy were included. RESULTS: 914 publications were identified and 13 were included in the systematic review. Four articles described the role of essential oils and their bioactive compounds on bronchial asthma using cell lines; nine in vivo studies evaluated the anti-inflammatory efficacy and immunomodulating effects of essential oil and their secondary metabolites on cytokines production and inflammatory responses. The most important immunopharmacological mechanisms reported were the regulation of cytokine production, inhibition of reactive oxygen species accumulation, inactivation of eosinophil migration and remodeling of the airways and lung tissue, modulation of FOXP3 gene expression, regulation of inflammatory cells in the airways and decreasing inflammatory mediator expression levels. CONCLUSION: Plant derived essential oils and related active compounds have potential therapeutic activity for the treatment of asthma by modulating the release of pro-inflammatory (TNF-α, IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10), Th1 (IFN-γ, IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines and the suppression of inflammatory cell accumulation.

Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models.

BACKGROUND: Flavonoids are naturally occurring compounds, extensively distributed in plants. T helper (Th)1 and Th2 cytokines balance plays an essential role in the reaction of inflammatory, allergic and infectious processes and transplantation rejection. PURPOSE: This systematic review focuses on various classes of flavonoids with a view to evaluate whether Th1/Th2 cytokine-mediated pathways of immunoenhancement could reduce immune overwhelming reactions. METHODS: Articles in English published from inception to December 2017 reporting flavonoids with immunomodulatory activity for the management of immune-mediated disorders were acquired from PubMed, EMBASE, Scopus and Web of Science and a animal experiments where Th1 and Th2 cytokines were investigated to assess the outcome of immunoregulatory therapy were included. CHAPTERS: 1809 publications were identified and 26 were included in this review. Ten articles described the effect of flavonoids on allergic inflammation in an animal model of asthma; eleven in vivo studies evaluated the immunomodulating and immunosuppressive effects of flavonoids on Th1/Th2 cytokines production and five reports described the regulatory role of flavonoids for Th1/Th2 cytokine responses to experimental arthritis and myocarditis. Modulation of Th1/Th2 cytokine balance, inhibition of eosinophil accumulation and remodeling of the airways and lungs, downregulation of Notch and PI3K signaling pathways, regulation of CD4 + /CD8 + lymphocytes ratio and decreasing inflammatory mediator expressions levels are among the most important immunopharmacological mechanisms for the retrieved flavonoids. CONCLUSION: Naturally occurring flavonoids discussed in the present article have optimal immunomodulation to prevent immune-mediated disorders through management of Th1/Th2 cytokine balance.

Phytochemical profile and mechanisms involved in the anti-nociception caused by the hydroethanolic extract obtained from Tocoyena formosa (Cham. & Schltdl.) K. Schum (Jenipapo-bravo) leaves in mice.

Tocoyena formosa, a small ornamental tree growing in the dry regions of central Brazil, is commonly known as 'genipapo do bravo'. This is a medicinal plant traditionally used as an analgesic for rheumatic pain, lower back pain and myalgia, however its use is carried out without scientific evidence, which thus justifies the development of studies to investigate and prove its therapeutic potential. Therefore, the objective of this study was to evaluate the phytochemical profile of Tocoyena formosa (Cham. & Schlecht.) K. Schum (TFLHE) and the mechanisms involved in its anti-nociceptive effect. The TFLHE revealed the presence of gallic acid, catechin, chlorogenic acid, caffeic acid, ellagic acid, rutin, quercetin and luteolin. The TFLHE at doses of 200 and 400mg/kg significantly decreased acetic acid-induced abdominal contortions, the reaction time for the formalin test in both phases and increased the paw withdrawal time in the hot plate thermal stimulus test. The 200mg/kg dose also significantly inhibited the plantar mechanical hyperalgesia intensity induced by formalin within 24h. TREATMENT: with the TFLHE did not cause significant changes in motor performance and coordination in the Rota Rod test. The investigation on the possible mechanism of antinociceptive action of TFLHE indicates the involvement of opioid, glutamatergic, nitric oxide/cGMP and vanilloid systems. It is concluded that the TFLHE has an antinociceptive effect promoted by the aforementioned mechanisms.

Effects of luteolin and quercetin 3-ß-d-glucoside identified from Passiflora subpeltata leaves against acetaminophen induced hepatotoxicity in rats.

Passiflora subpeltata has many beneficial effects in the treatment of various diseases including inflammation, pain and fever. This study was aimed to analyze the phytochemical compounds present in acetone extract of P. subpeltata leaves and to evaluate their performance against paracetamol induced hepatotoxicity activity. HPLC-DAD method was used to identify and quantify the phytochemical compounds. Hepatoprotective activity of acetone extract in the treatment of rat liver functions was monitored by the measurement of blood parameters and serum biochemical parameters such as SGOT, SGPT, ALP and in vivo antioxidant parameters viz. SOD, CAT and LPO. Further, liver tissues were also subjected to histopathological analysis. The HPLC-DAD results showed the luteolin and quercetin 3-ß-d-glucoside as newly identified compounds in P. subpeltata species. Pre-treatment with acetone extract of P. subpeltata leaves at 200 and 400mg/kg doses significantly elevated the WBC, RBC and HB counts and retained the serum biochemical and enzymatic antioxidants levels to normal level. Based on this detailed study we conclude that acetone extract of P. subpeltata leaves offered better protection against hepatotoxicity induced by the acetaminophen.

Side effects of the therapy with peginterferon and ribavirin in chronic hepatitis C: a small audit.

This study sought to decribe, quantify, and classify any adverse reactions occurring in patients with chronic hepatitis C treated with peginterferon and ribavirin, as well as verify the occurrence of potential medication interactions. The most prevalent reactions were fatigue (84.8%), fever (83%), weight loss (80%), irritability (74%), and body pain (72%). Most of the reactions were classified as mild (95%), whereas 4.5% were classified as moderate and 0.4% as severe. Adverse reactions led to the rearrangement of therapy for 9 patients (20%), where there was a reduction in dose for 7 (15%), temporary interruption of treatment for 5 (11%), and permanent discontinuation for 3 patients (7%). A total of 11 potential medication interactions were identified in 9 patients (20%), with the most frequent between peginterferon-α2a and captopril (45%). Given the above, it is observed that the treatment of chronic hepatitis C is marked by several adverse reactions of varying severity, which can interfere with the patient's quality of life or in treatment compliance, and that can be aggravated by potential drug-drug interactions.