scholarly journals Anti-Inflammatory Potential of Complex Extracts of Ligularia stenocephala Matsum. & Koidz. and Secale cereale L. Sprout in Chronic Gingivitis: In Vitro Investigation and Randomized Clinical Trial

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1586
Author(s):  
Inpyo Hong ◽  
Jin-Young Park ◽  
Yoo-Hun Noh ◽  
Su-Hee Jeon ◽  
Jeong-Won Paik ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Viability ◽  
Secale Cereale ◽  
Test Group ◽  
Number Of Patients ◽  
In Vitro Investigation ◽  
Secale Cereale L ◽  
Anti Inflammatory ◽  
Ligularia Stenocephala

Complex extracts of Ligularia stenocephala Matsum. & Koidz. (LSE) and Secale cereale L. sprout (SCSE) (TEES-10®) were prepared. The purposes of the study were to evaluate anti-inflammatory activities of TEES-10® in vitro and to observe resolution of gingivitis in human with oral administration of TEES-10®. The effects of TEES-10® on normal periodontal ligament (PDL) cell viability, lipopolysaccharide (LPS) induced PDL cell viability and the changes of inflammatory mediator expression were evaluated in vitro. In the clinical trial, 150 mg of TEES-10® powder containing capsule was administered twice daily to the test group, while the control group administered placebos in a total 100 participants with gingivitis. Probing depth (PD), bleeding on probing (BOP), clinical attachment loss, gingival index (GI) and plaque index (PI) were measured at baseline and 4 weeks. Administering TEES-10® showed significant increase in PDL cell viability compared to administering LSE or SCSE alone. In addition, treating TEES-10® to LPS induced PDL cell significantly increased PDL cell viability compared to control. TEES-10® suppressed expression of NF-κB, p-ERK, ERK, COX-2, c-Fos and p-STAT and promoted expression of PPARγ in LPS induced PDL cells. In the clinical trial, significant improvement of GI and BOP was observed in the test group at 4 weeks. In addition, the number of patients diagnosed with gingivitis was significantly reduced in the test group at 4 weeks. Salivary MMP-8 and MMP-9 was also significantly decreased compared to placebo group. Within the limitations of this study, the TEES-10® would have an anti-inflammatory potential clinically in the chronic gingivitis patients.

MO1048PHYTOTHERAPY ON RENAL HYPOXIA: THE PREVENTIVE EFFECTS OF HYDROXYTYROSOL - PRELIMINARY IN VITRO RESULTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Terézia Kamasová ◽  
Ana Sofia Abreu ◽  
Fátima Paiva-Martins ◽  
Luís Belo ◽  
Alice Santos-Silva ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Line ◽  
Therapeutic Potential ◽  
Quantitative Polymerase Chain Reaction ◽  
Oxidative Status ◽  
Hypoxic Conditions ◽  
Thiazolyl Blue Tetrazolium Bromide ◽  
Anti Inflammatory ◽  
Preventive Effects

Abstract Background and Aims Renal hypoxia plays a key role in the pathophysiology of acute kidney injury and in the progression of chronic kidney disease, potentiating other important risk factors for renal disease, such as oxidative stress, renal fibrosis, and inflammation. Hydroxytyrosol (HT) is a phenolic compound extracted from olives and olive-derived products, that has been shown to detain potent in vitro antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the preventive therapeutic potential of HT on a cellular model of renal hypoxia. Method A cell line of normal adult proximal tubular epithelium (HK-2 cell line) was used to determine the effects of the chemical induction of hypoxia with cobalt chloride (CoCl2), as well as the preventive potential of HT on the elicited effects. For this purpose, HK-2 cells were exposed for 24 h to 254 µM CoCl2, to mimic the hypoxic conditions, or pre-incubated for 1 h with 5 µM HT and further exposed to the CoCl2 for 24 h more. Cell viability was assessed by the thiazolyl blue tetrazolium bromide reduction assay. Oxidative status was evaluated by the measurement of reactive oxygen and nitrogen species (ROS and RNS) and reduced glutathione (GSH) levels, by using standardized fluorometric and colorimetric assays. The expression of several genes related to the hypoxic, inflammatory, and fibrotic responses was determined by quantitative polymerase chain reaction (PCR). Results CoCl2-exposed HK-2 cells (hypoxic conditions) showed a significant decrease in cell viability (p < 0.0001 vs. control), and a disruption of the oxidative status, characterized by an increase of ROS and RNS production of about 6-fold over control cells (p < 0.0001) and a decrease in GSH intracellular levels of nearly 50 % (p < 0.05). Although the pre-exposure to HT showed no significant effects on the loss of cell viability elicited by CoCl2, the presence of HT prior to induction of hypoxia reduced the generation of ROS and RNS (p < 0.05 for HT + CoCl2 vs. CoCl2) and prevented the GSH depletion (GSH levels for HT + CoCl2 were similar to those of control) elicited by CoCl2. When compared to control cells, CoCl2-exposed HK-2 cells also showed increased expression of genes related to hypoxia (HIF1A, p < 0.05; GAPDH, p < 0.0001), as well as of modulators of inflammation (IL6, p < 0.0001) and fibrosis (TGFB1, p < 0.05). Importantly, the expression of these genes was partially or even totally suppressed by the pre-exposure of cells to HT (GAPDH, p < 0.01 for HT + CoCl2 vs. CoCl2; expression of HIF1A, IL6 and TGFB1 for HT + CoCl2 was similar to that of control). Conclusion Our data supports the potential for a multiplicity of preventive effects of HT, providing antioxidant, anti-inflammatory and anti-fibrotic defenses to renal cells under hypoxic conditions. Importantly, the development of safe and effective therapeutic approaches based on phytochemicals such as HT, may present substantial advantages for renal patients over synthetic drugs, including fewer side effects, significantly lower price, and ease of administration in the form of dietary supplements. Acknowledgments This work was supported by Applied Molecular Biosciences Unit (UCIBIO), financed by national funds from FCT/MCTES (UIDB/04378/2020), by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024), and co-financed by FCT/MCTES (PTDC/OCE-ETA/32492/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-032492).

scholarly journals Direct Effect of Septic Plasma in Human Cell Lines Viability

2018 ◽  
Vol 47 (1-3) ◽  
pp. 270-276
Author(s):  
Grazia Maria Virzì ◽  
Chiara Borga ◽  
Chiara Pasqualin ◽  
Silvia Pastori ◽  
Alessandra Brocca ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cell Viability ◽  
Cell Lines ◽  
Caspase 3 ◽  
Test Group ◽  
Organ Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Renal Tubular Cells

Background: Sepsis is a life-threatening condition often associated with a high incidence of multiple organs injury. Several papers suggested the immune response by itself, with the production of humoral inflammatory mediators, is crucial in determining organ injury. However, little is known of how sepsis directly induces organ injury at the cellular levels. To assess this point, we set up an in vitro study to investigate the response of renal tubular cells (RTCs), monocytes (U937) and hepatocytes (HepG2) after 24 h-incubation with septic patients’ plasma. Methods: We enrolled 26 septic patients (“test” group). We evaluated cell viability, apoptosis and necrosis by flow cytometer. Caspase-3,-8,-9 and cytochrome-c concentrations have been analyzed using the Human enzyme-linked immunosorbent assay kit. Results: We found that a decrease of cell viability in all cell lines tested was associated to the increase of apoptosis in RTCs and U937 (p < 0.0001) and increase of necrosis in HepG2 (p < 0.5). The increase of apoptosis in RTCs and U937 cells was confirmed by higher levels of caspase-3 (p < 0.0001). We showed that apoptosis in both RTCs and U937 was triggered by the activation of the intrinsic pathway, as caspase-9 and cytochrome-c levels significantly increased (p < 0.0001), while caspase-8 did not change. This assumption was strengthened by the significant correlation of caspase-9 with both cytochrome-c (r = 0.73 for RTCs and r = 0.69 for U937) and caspase-3 (r = 0.69 for RTCs and r = 0.63 for U937). Conclusion: Humoral mediators in septic patients’ plasma induce apoptosis. This fact suggests that apoptosis inhibitors should be investigated as future strategy to reduce sepsis-induced organ damages.

scholarly journals Protective Effect of Opuntia dillenii Haw Fruit against Lead Acetate-Induced Hepatotoxicity: In Vitro and In Vivo Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Reza Shirazinia ◽  
Ali Akbar Golabchifar ◽  
Vafa Baradaran Rahimi ◽  
Abbas Jamshidian ◽  
Alireza Samzadeh-Kermani ◽  
...  
Keyword(s):  
Cell Viability ◽  
Lead Acetate ◽  
Male Rats ◽  
Tnf Α ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
Anti Inflammatory ◽  
Opuntia Dillenii

Lead is one of the most common environmental contaminants in the Earth’s crust, which induces a wide range of humans biochemical changes. Previous studies showed that Opuntia dillenii (OD) fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates OD fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received OHAE at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor-α (TNF-α) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( p < 0.001 for all cases). OHAE (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( p < 0.001 –0.05 for all cases). OHAE (20, 40, and 80 μg/ml) concentration dependently and significantly reduced the levels of MDA and TNF-α, while it increased the levels of GSH and cell viability in comparison to the Pb group ( p < 0.001 –0.05 for all cases). These data suggest that OHAE may have hepatoprotective effects against Pb-induced liver toxicity both in vitro and in vivo by its antioxidant and anti-inflammatory activities.

scholarly journals High efficacy of a dimeticone-based pediculicide following a brief application: in vitro assays and randomized controlled investigator-blinded clinical trial

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jorg Heukelbach ◽  
Doerte Wolf ◽  
John Marshall Clark ◽  
Hans Dautel ◽  
Kristina Roeschmann
Keyword(s):  
Clinical Trial ◽  
Test Group ◽  
Head Lice ◽  
Ovicidal Activity ◽  
Vitro Assay ◽  
Test Product ◽  
Randomized Controlled ◽  
Development Of Resistance ◽  
Reduced Risk

Abstract Background Increasing resistance of head lice against neurotoxic agents and safety concerns have led to the search for treatment alternatives. Dimeticones with a physical mode of action are safe, and bear a reduced risk for the development of resistance. Methods We performed in vitro bioassays to assess pediculicidal and ovicidal activities of a new dimeticone-based product, and a randomized controlled clinical trial to assess efficacy, following 10 min application. Of 153 individuals screened, 100 participants with active head louse infestations were randomly assigned to treatment with either a dimeticone-based test product, or a 0.5% permethrin-based reference product (50 participants per group). Participants received two topical applications of either the test (10 min) or reference products (45 min) at days 0 and 7 or 8. Outcome measures included the efficacies of treatment and their safety, as well as global and local tolerability at baseline, and days 1, 7, and 10. Results After 10 min exposure, all lice treated with the dimeticone test product were classified as non-viable in the in vitro assay. Ovicidal activity after treatment of eggs with the dimeticone test product was 96.8%. In the clinical trial, 96 patients completed all study visits. In the full analysis set (FAS) population, on day 1 after one application, 98% of patients were cured in the test group, as compared to 84% cured in the reference group. All participants in both groups were free of head lice on day 10, following two applications (100% cure rate). In total, 42 adverse events (AEs) in 23 patients of both treatment groups were recorded, with the majority of AEs classified as mild. Conclusions We have shown a high level of pediculicidal and ovicidal activity, and clinical efficacy and safety, of a brief application of a new dimeticone-based product. The short application time and reduced risk for the development of resistance are key drivers for improved patients’ compliance. Trial registration EU Clinical Trials Register EudraCT 2016–004635-20. Registered 14 November 2016.

scholarly journals Libidibia ferreaFruit Crude Extract and Fractions Show Anti-Inflammatory, Antioxidant, and Antinociceptive EffectIn Vivoand Increase Cell ViabilityIn Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Tamires Rocha Falcão ◽  
Aurigena Antunes de Araújo ◽  
Luiz Alberto Lira Soares ◽  
Iuri Brilhante de Farias ◽  
Wliana Alves Viturino da Silva ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Cell Viability ◽  
Gallic Acid ◽  
Cell Line ◽  
Crude Extract ◽  
Leukocyte Migration ◽  
Total Glutathione ◽  
Anti Inflammatory

Background.Libidibia ferrea(L. ferrea)is found throughout the northeastern region of Brazil, where it has been used in folk medicine with beneficial effects on many inflammatory disorders.Purpose. This study investigated the phytochemical composition of the crude extract and fractions ofL. ferreafruit and evaluated its anti-inflammatory and antinociceptive activitiesin vivoand effect on cell viabilityin vitro.Methods. Characterization of polyphenols present in crude extract (CE), hydroalcoholic fractions of 20-80% ethanol (CE20, CE40, CE60, and CE80), aqueous fraction (AqF), and ethyl acetate (EAF) fractions ofL. ferreafruit was performed by chromatographic analysis.Anti-inflammatory activity was evaluated by using a carrageenan-induced peritonitis model submitted to a leukocyte migration assay and myeloperoxidase activity (MPO) analysis. Total glutathione and malondialdehyde (MDA) levels were assessed to evaluate the oxidative stress level. Antinociceptive activity was evaluated by acetic acid-induced abdominal writhing and hot plate test.In vitrocell viability was determined by using MTT assay in a mouse embryonic fibroblast cell line (3T3 cells).Results. Chromatography revealed the presence of ellagic acid content in EAF (3.06), CE (2.96), and CE40 (2.89). Gallic acid was found in EAF (12.03), CE 20 (4.43), and CE (3.99).L. ferreacrude extract and all fractions significantly reduced leukocyte migration and MPO activity (p<0.001).L. ferreaantioxidant effect was observed through high levels of total glutathione and reduction of MDA levels (p<0.001). Acetic acid-induced nociception was significantly inhibited after administration ofL. ferreacrude extract and all fractions (p<0.001). Crude extract and all fractions significantly increased the viability of the 3T3 cell line (p<0.05).Conclusions. The appropriate extraction procedure preserves the chemical components ofL. ferreafruit, such as gallic acid and ellargic acid. Crude extract and fractions ofL. ferreafruit exhibited anti-inflammatory, antioxidant, antinociceptive activitiesin vivoand enhanced cell viabilityin vitro.

Dynamics of the Tissue-Specific Metabolism of Luteolin Glucuronides in the Mesophyll of Rye Primary Leaves (Secale cereale)

1988 ◽  
Vol 43 (3-4) ◽  
pp. 187-193 ◽  
Author(s):  
Margot Schulz ◽  
Gottfried Weissenböck
Keyword(s):  
Cinnamic Acid ◽  
Secale Cereale ◽  
Leaf Development ◽  
Glucuronic Acid ◽  
Developmental Stages ◽  
Leaf Tissue ◽  
Feeding Experiments ◽  
Secale Cereale L ◽  
Hydrolysis Of

Developing primary leaves of Secale cereale L. exhibit a dynamic metabolism of the major flavonoid luteolin 7-O-[β-ᴅ-glucuronosyl(1→2)β-ᴅ-glucuronide]-4′-O-β-ᴅ-glucuronide (R1). Final steps of R, biosynthesis are sequential glucuronidations of luteolin, which are catalyzed by three specific UDP-glucuronate: flavone glucuronosyltransferases. These enzymes reach highest activities at the fourth and fifth day of leaf development, coinciding with maximal R, accumulation. The activities decrease with advancing age of the leaves. In contrast, a R1-specific β-glucuronidase, responsible for the hydrolysis of glucuronic acid in position 4′, shows increasing activity up to the 5th or 6th day; but this activity, leading to luteolin 7-O-diglucuronide (R2), is not reduced in later developmental stages. In this phase of leaf development, the amount of R, drastically drops, whereas R2 accumulates only slightly. From in vitro results and from feeding experiments using [14C]cinnamic acid, a precursor of R, biosynthesis, we conclude that the anabolic sequential glucuronidation takes place in young and expanding leaf tissue, whereas deglucuronidation occurs in nearly mature and mature tissue. The three glucuronosyltransferases as well as the β-glucuronidase, and the flavonoids R1 and R2 are localized in the mesophyll.

scholarly journals Essential Oil of Common Sage (Salvia officinalisL.) from Jordan: Assessment of Safety in Mammalian Cells and Its Antifungal and Anti-Inflammatory Potential

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
M. S. Abu-Darwish ◽  
C. Cabral ◽  
I. V. Ferreira ◽  
M. J. Gonçalves ◽  
C. Cavaleiro ◽  
...  
Keyword(s):  
Gas Chromatography ◽  
Antifungal Activity ◽  
Cell Viability ◽  
Mammalian Cells ◽  
Skin Diseases ◽  
Gas Chromatography Mass Spectrometry ◽  
No Production ◽  
Mouse Macrophages ◽  
Anti Inflammatory

Salvia officinalisL. (Lamiaceae) is a Mediterranean species, naturalized in many countries. In Jordan, it is used in traditional medicine as antiseptic, antiscabies, antisyphilitic, and anti-inflammatory, being frequently used against skin diseases. This study aimed the assessment of the antifungal and anti-inflammatory potential of its essential oils, and their cytotoxicity on macrophages and keratinocytes. The oils were investigated by gas chromatography and gas chromatography-mass spectrometry and the antifungal activity was evaluated against yeasts, dermatophyte andAspergillusstrains. Assessment of cell viability was made by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and thein vitroanti-inflammatory potential was evaluated by measuring nitric oxide production using lipopolysaccharide-stimulated mouse macrophages. The main compounds ofS. officinalisoils were 1,8-cineole (39.5–50.3%) and camphor (8.8–25.0%). The oils revealed antifungal activity against dermatophyte strains and significantly inhibited NO production stimulated by LPS in macrophages, without affecting cell viability, in concentrations up to 0.64 μL/mL. This is the first report addressing thein vitroanti-inflammatory potential ofS. officinalisoil. These findings demonstrated that bioactive concentrations ofS. officinalisoils do not affect mammalian macrophages and keratinocytes viability making them suitable to be incorporated in skin care formulations for cosmetic and pharmaceutical purposes.

Rational Combinations Including a Novel Syk Inhibitor, Fostamatinib Disodium (FosD) in Diffuse Large B Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 283-283
Author(s):  
Randall M Rossi ◽  
Valerie Grose ◽  
Polly Pine ◽  
Richard I Fisher ◽  
Craig T. Jordan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Viability ◽  
B Cell ◽  
Cell Line ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
In Vivo Studies

Abstract Abstract 283 Certain malignant B-cells rely upon B-cell receptor-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the B-cell receptor-mediated signal. We and others have demonstrated that fostamatinib disodium (FosD: a prodrug of R406, a potent and specific inhibitor of Syk) induces apoptosis in lymphoma cell lines and primary tumors. A recent clinical trial has demonstrated significant clinical activity of FosD in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia, and minimal overlap in toxicities with conventional agents. Given this background, future development in B-cell NHL will include rational combinations of FosD and currently available therapies. Therefore, we conducted in vitro and in vivo studies of rational combinations including FosD, in anticipation of clinical trial development. First, using a human DLBCL cell line of GCB genotype, (OCI-Ly19), we analyzed in vitro the combination of R406 with the following agents: fludarabine, rapamycin, rituximab, bendamustine and bortezomib. Increased cytotoxicity was observed using in vitro culture assays with the addition of fludarabine, rapamycin, or rituximab to R406. Cell viability at 72 hours was 25% with R406 alone, 27% for fludarabine alone, and only 9% for the fludarabine/R406. At 48 hours, cell viability was 49% using R406 alone, 31% using rituximab alone, and 21% for rituximab/R406. At 120 hours using primary lymphoma cells (DLCL27), there were no viable cells treated with the rapamycin/FosD combination, compared with rapamycin alone (7%) or FosD alone (25%) The addition of bortezomib or bendamustine to FosD resulted in only a minimal additive increase in cytotoxicity. Results with all combinations were similar with the OCI-Ly10 human DLBCL line of ABC genotype. We then performed in vivo studies by subcutaneous transplantation of the DLBCL cell line OCI-Ly19, (engineered to express luciferase allowing for real time in vivo imaging) into immune deficient NOD/SCID mice which reproducibly formed tumors. Recipient animals were separated into uniform cohorts when the tumors were less than or equal to 500 mm3 in size. The animals were then simultaneously treated with FosD (n=7; 3 gm/kg ad. lib.; translates into 2-5 micromolar R406 systemically throughout the 24h period) and either bortezomib, (n=6; 0.4 mg/kg weekly IP), or rituximab, (n=13; 3 mg/kg, 2x weekly IP). Analysis of the OCI-Ly19 tumor volumes at day 46 showed a median of 2364 mm3 with bortezomib alone compared with 1823 mm3 with bortezomib and FosD. When FosD was combined with rituximab the most significant cytotoxicity was observed: (p=0.01; median tumor volume of 497 mm3 following the combination) in comparison to either FosD alone (3150 mm3) or rituximab alone (1764 mm3). We conclude that the addition of FosD appears to increase activity against NHL of several drugs, including fludarabine and rapamycin. These agents have significant activity in indolent and mantle cell NHL as well as CLL. Moreover, there is no evidence that FosD impedes rituximab responses in vitro or in vivo; in fact we have suggested possible synergy with the combination of rituximab and FosD. Based upon the documented single agent activity of FosD in humans, and this data, clinical trials are now indicated using these promising combinations in NHL and CLL. Disclosures: Pine: Rigel: Employment. Friedberg:Rigel: Research Funding.

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