scholarly journals BENEFICIAL OUTCOMES AFTER COMBINED THERAPY WITH AZATHIOPRINE AND PIOGLITAZONE IN PRECLINICAL ARTHRITIC MODELS

Author(s):  
VEERESH BABU PRATAP ◽  
SOUNDARYA VARLA ◽  
GANGA RAJU M

Objectives: The present study was designed to investigate the antioxidant and anti-arthritic activities of azathioprine-pioglitazone combination therapy to check whether it has an add on benefit over monotherapy with azathioprine or pioglitazone on disease activity in rodent models. Methods: The antioxidant activity of test drugs and their combination was screened by H2O2 and nitric oxide scavenging assays. They were further evaluated for anti-arthritic activity using in vitro models such as protein denaturation and membrane stabilization and in vivo methods such as formaldehyde and complete Freund’s adjuvant (CFA)-induced arthritis. Results: The combination of test drugs showed better inhibition of free radicals in both H2O2 and nitric oxide scavenging assay than individual counterparts revealing its potential antioxidant activity. They also showed significant inhibition of protein denaturation and proliferation of the red blood cell in in vitro models. The test drugs showed significant inhibition of the paw volume in both the formaldehyde and CFA-induced arthritis along with reverting the altered biochemical parameters. These findings were corroborated by radiological and histopathological studies. Conclusions: Combination of azathioprine and pioglitazone exhibited better antioxidant and anti-arthritic effect than the individual drugs showing synergistic interaction between them.

2017 ◽  
Vol 9 (1) ◽  
pp. 123
Author(s):  
P Veeresh Babu ◽  
T Ashwini ◽  
M. Vamsi Krishna ◽  
M. Ganga Raju

<p><em>Smilax zeylanica </em>Linn has been traditionally used in the treatment of rheumatoid arthritis but, no scientific data has been published supporting the claimed ethanomedical use. This study was designed to investigate the immunomodulatory and antiarthritic activities of <em>Smilax zeylanica</em>.</p><p>Methanolic extract of <em>Smilax zeylanica </em>(MESZ) roots was tested for its immunomodulatory activity by NBT reduction test. Antiarthritic activity of the same was tested by <em>in vitro </em>protein denaturation and <em>in vivo </em>complete Freunds adjuvant (CFA) induced arthritis.<strong> </strong></p><p>MESZ<strong> </strong>showed its significant effect on both cell mediated and humoral immunity to suppress stimulated immune responses in NBT reduction test . It also markedly inhibited protein denaturation in <em>in vitro </em>model. Extract at 200 mg/kg and 400 mg/kg showed statistically significant inhibition ( p&lt;0.05) of the edema formation in CFA model. Histopathological studies of ankle joints also supported this finding.</p>The presence of steroids in the extract might be responsible for the prominent immunomodulatory and antiarthritic activities of the plant. Hence the present study concluded that <em>Smilax zeylanica</em> holds immunomodulatory and antiarthritic activities.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3169
Author(s):  
Kevin Doello ◽  
Cristina Mesas ◽  
Francisco Quiñonero ◽  
Gloria Perazzoli ◽  
Laura Cabeza ◽  
...  

Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.


Author(s):  
Thriveni Vasanth Kumar ◽  
Manjunatha H. ◽  
Rajesh Kp

Objective: Dietary curcumin and capsaicin are well known for their health beneficial potencies. The current study was done to assess the anti-inflammatory activity of curcumin, capsaicin and their combination by employing in vitro and in vivo models.Methods: We investigated the protective effect of curcumin, capsaicin and their combination using in vitro heat induced human red blood cell (HRBC) membrane stabilisation, in vivo 3% agar induced leukocyte mobilisation and acetic acid induced vascular permeability assay.Results: Curcumin, capsaicin and their combination exhibited concentration dependent protective effect against heat-induced HRBC membrane destabilisation, while combined curcumin and capsaicin restored 87.0±0.64 % membrane stability and it is found to be better than curcumin, capsaicin and diclofenac sodium (75.0±0.25. 72±0.9 and 80.0±0.31 %) protective effect. In agar suspension induced leukocyte mobilization assay, the combined curcumin and capsaicin had shown 39.5±1.58 % of inhibition compared to individual curcumin and capsaicin, which showed moderate inhibition of 16.0±3.14 and 21.6±2.17 % respectively. Besides, the combined curcumin and capsaicin had shown highly significant inhibition of acetic acid-induced vascular permeability in rats (62.0±3.14 %), whereas individual curcumin and capsaicin showed moderate inhibition of vascular permeability with 36.0±2.41 and 43.0±1.92 % respectively.Conclusion: This study demonstrates the significant anti-inflammatory property of combined curcumin and capsaicin at half of the individual concentration of curcumin and capsaicin.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Priscila Ausina ◽  
Jessica R. Branco ◽  
Thainá M. Demaria ◽  
Amanda M. Esteves ◽  
João Gabriel B. Leandro ◽  
...  

AbstractMelanoma is the most aggressive and fatal type of skin cancer due to being highly proliferative. Acetylsalicylic acid (ASA; Aspirin) and salicylic acid (SA) are ancient drugs with multiple applications in medicine. Here, we showed that ASA and SA present anticancer effects against a murine model of implanted melanoma. These effects were also validated in 3D- and 2D-cultured melanoma B16F10 cells, where the drugs promoted pro-apoptotic effects. In both in vivo and in vitro models, SA and ASA triggered endoplasmic reticulum (ER) stress, which culminates with the upregulation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). These effects are initiated by ASA/SA-triggered Akt/mTOR/AMPK-dependent activation of nitric oxide synthase 3 (eNOS), which increases nitric oxide and reactive oxygen species production inducing ER stress response. In the end, we propose that ASA and SA instigate anticancer effects by a novel mechanism, the activation of ER stress.


2007 ◽  
Vol 4 (4) ◽  
pp. 425-430 ◽  
Author(s):  
Hui Liao ◽  
Linda K. Banbury ◽  
David N. Leach

Danzhixiaoyao Wan (DW) is a common 10 herbs formulation in China for regulating several clinical conditions affecting women. This research tried to explain one of DW's functions, purging heat, usingin vitropharmacological analyses. The whole formulation and each single herb of DW were compared based on antioxidant activity with the oxygen radical absorbance capacity (ORAC) assay, and for their inhibitory effect (IE) on nitric oxide (NO) production by lipopolysaccharide (LPS)-activated RAW 264.7 macrophages with the Griess assay. The results showed that DW as a whole formulation had both antioxidant activity and an IE on NO production, while the individual herb component of DW varied in their ORAC values and inhibition of NO production. The ORAC value of the whole DW was 450 μmol TE g−1. The order of antioxidant (ORAC) activity of the single herbs was:Mentha haplocalyx(1352 μmol TE g−1) >Glycyrrhiza uralensis(1184 μmol TE g−1) >Gardenia jasminoides(1129 μmol TE g−1) >Paeonia suffruticosa(465 μmol TE g−1), with the contributions being additive rather than synergistic. The production of nitrite by stimulated RAW 264.7 murine macrophages (unstimulated: 0.5 ± 0.1 μM versus LPS: 38.9 ± 2.3 μM) was significantly inhibited (P< 0.05) byM. haplocalyx,G. jasminoides,Bupleurum chinenseandPaeonia lactiflora. DW as a whole had an IE on NO production, but this was not significant. The single herbM. haplocalyxhad the highest ORAC value and the highest IE on NO production, followed byG. jasminoides. Both of these herbs have the ‘purging heat’ property in the theory of traditional Chinese medicine and this property of the samples may be correlated with the antioxidant activity and IE on NO production.


Author(s):  
Laouini Salah Eddine ◽  
Ladjel Segni ◽  
Gherraf Noureddine ◽  
Ouahrani Mohammed Redha ◽  
Mokni Sonia

In this study we investigate the antioxidant, anti-inflammatory, and antidiabetic activities of ethanolic leaves extracts of three selected varieties of Phoenyx dactylifera L. namely: “Ghars”, “Deglet Nour” and “Hamraya”. The assessment of the antioxidant potential of crude leaves extracts, using superoxide anions inhibition, DPPH and total antioxidant activity essays, was carried out. Furthermore, the anti-inflammatory properties of the extracts were determined by measuring the inhibition of nitric oxide (NO) production. Moreover, the antidiabetic effect was evaluated by inhibition of α-amylase enzymes. The total phenolic content measured by Folin-Ciocalteu method was as well conducted. The raw leaves extracts of the selected varieties was found to contain a high content of total phenolic content (342.45 mg GAE/gDW for GE) and therefore exhibited a higher antioxidant activity and inhibitory effect of radicals scavenging activity against DPPH and superoxide anion (IC50 = 7.44 μg/mL and 39.11 μg/mL respectively). The three varieties exhibited significant inhibition nitric oxide using In Vitro assay (IC50 = 240.28 μg/mL for GE). The extracts also displayed high inhibition actions against α-amylase enzymes. The results suggest that the leaves of the three selected varieties of Phoenyx dactylifera can be considered as a good source of natural antioxidant and anti-inflammation drugs as well as potent antidiabetic medicine.


2019 ◽  
Vol 3 (3) ◽  
pp. 150 ◽  
Author(s):  
Mujeeb Hoosen

African plants have been used for medicinal purposes for many centuries. Many of these African medicinal plants are assumed to be safe but have yet to be scientifically validated. Aspalathus linearis (rooibos) is a commercialised South African tea recognised for its phytopharmaceutical potential. Aspalathus linearis (rooibos) has been gaining popularity globally for its health benefits and accepted as a nutraceutical due to the growing evidence of its efficacy. The bioactive constituents found in Aspalathus linearis (rooibos) have been reported to exert both anti-inflammatory and antioxidant activity however a few in vitro studies has suggested otherwise. Aspalathus linearis (rooibos) has shown to modify the actions of the immune system by influencing the regulation of messenger molecules like cytokines and nitric oxide however most of these studies have been conducted in vitro with a very few studies reaching in vivo application. Divergent in vitro cell models has shown to produce varying results regarding cytokine and nitric oxide NO activity of Aspalathus linearis (rooibos). This review highlights recent studies on the (NO) and cytokine activities of Aspalathus linearis (rooibos) both in vitro and in vivo. Most studies report on its anti-inflammatory and antioxidant activity however a few in vitro studies suggests opposite effects which should be considered for prolonged use especially when prescribed in a supplementation form. Many studies have looked at aspects of safety and toxicity of Aspalathus linearis (rooibos) however no complete toxicological studies have been done as yet.International Journal of Human and Health Sciences Vol. 03 No. 03 July’19. Page: 150-157


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mbiantcha Marius ◽  
Dawe Amadou ◽  
Atsamo Albert Donatien ◽  
Ateufack Gilbert ◽  
Yousseu Nana William ◽  
...  

Combretum fragrans (Combretaceae) is a Cameroonian medicinal plant containing various secondary metabolites and traditionally used for the treatment of several pathologies. Two cycloartane-type triterpenes, Combretin A and Combretin B, were isolated from this plant. This study was aimed at evaluating the anti-inflammatory, antioxidant, and anticolitis effects of these compounds. In vitro anti-inflammatory properties were evaluated by inhibition of cyclooxygenase, 5-lipoxygenase, and denaturation of the protein; antioxidant properties were assessed by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), (2,2’-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) ABTS•+, capacity tests ferric reducing antioxidant (FRAP), and trapping nitric oxide. For in vivo analysis, we used the model of ulcerative colitis induced by Dextran Sulfate Sodium (DSS). Studies of the anti-inflammatory activity showed that Combretin A and Combretin B had maximal inhibitory activity on cyclooxygenase (71.92% and 89.59%), 5-lipoxygenase (76.68% and 91.21%), and protein denaturation (63.93% and 87.78%). Antioxidant activity on DPPH, ABTS•+, ferric reducing antioxidant capacity (FRAP), and nitric oxide scavenging showed that Combretin A and Combretin B showed good antioxidant activities. These compounds significantly reduced the signs of DSS-induced colitis in the treated animals by preventing the weight loss of the animals, by significantly reducing the disease activity index, improving the condition of the stool, preventing the reduction of the length of the colon, and preventing the degradation of the colon. This study revealed that Combretin A and Combretin B have anti-inflammatory, antioxidant, and curative properties against colitis experimentally induced by DSS in rats.


2021 ◽  
pp. 002203452110269
Author(s):  
A. Zhang ◽  
N. Ye ◽  
W. Aregawi ◽  
L. Zhang ◽  
M. Salah ◽  
...  

Due to the severe mechano-biochemical conditions in the oral cavity, many dental restorations will degrade and eventually fail. For teeth restored with resin composite, the major modes of failure are secondary caries and fracture of the tooth or restoration. While clinical studies can answer some of the more practical questions, such as the rate of failure, fundamental understanding on the failure mechanism can be obtained from laboratory studies using simplified models more effectively. Reviewed in this article are the 4 main types of models used to study the degradation of resin–composite restorations, namely, animal, human in vivo or in situ, in vitro biofilm, and in vitro chemical models. The characteristics, advantages, and disadvantages of these models are discussed and compared. The tooth–restoration interface is widely considered the weakest link in a resin composite restoration. To account for the different types of degradation that can occur (i.e., demineralization, resin hydrolysis, and collagen degradation), enzymes such as esterase and collagenase found in the oral environment are used, in addition to acids, to form biochemical models to test resin–composite restorations in conjunction with mechanical loading. Furthermore, laboratory tests are usually performed in an accelerated manner to save time. It is argued that, for an accelerated multicomponent model to be representative and predictive in terms of both the mode and the speed of degradation, the individual components must be synchronized in their rates of action and be calibrated with clinical data. The process of calibrating the in vitro models against clinical data is briefly described. To achieve representative and predictive in vitro models, more comparative studies of in vivo and in vitro models are required to calibrate the laboratory studies.


2015 ◽  
Vol 7 ◽  
Author(s):  
Sulaiman Mohsin ◽  
R Mahadevan ◽  
A.S. Sumayya ◽  
G. Muraleedhara Kurup

<p>Even though anti thrombotic effects have been reported with polysaccharides isolated from various marine algae of dictyotaceae, containing uronic acid as the main constituent. But a new polysaccharide was isolated from a species of marine algae from the Kerala coast with a composition different from those reported so far. The antiplatelet and antithrombotic activities of polysaccharides from <em>Padina tetrastromatica</em> were investigated on platelet aggregation in vitro and on pulmonary thrombosis in vivo. The polysaccharide fractions showed concentration dependent inhibitory effects on ADP-induced platelet aggregation. Using an <em>in vivo </em>mouse thrombotic model in which mice were challenged with an intravenous injection of collagen and epinephrine mixture, oral administration of the polysaccharide prior to the injection produced a significant inhibition of thrombotic death or paralysis. Aspirin showed a significant inhibition of thrombotic death similar to polysaccharide of higher dose. Polysaccharide fractions showed significant prolongation of mouse tail bleeding time. The present findings showed clear evidence of protection against thromboembolism and had good antithrombotic activity. Available data obtained by in vitro models suggest that there is a correlation between the sulfate content and antithrombotic activity.</p>


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