scholarly journals Comparison of Treatment Effects of Different Iron Chelators in Experimental Models of Sepsis

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 57
Author(s):  
Christian Lehmann ◽  
Maral Aali ◽  
Juan Zhou ◽  
Bruce Holbein
Keyword(s):  
Bacterial Pathogens ◽  
Normal Component ◽  
Abdominal Sepsis ◽  
Experimental Models ◽  
Water Soluble ◽  
Iron Chelators ◽  
Therapeutic Benefits ◽  
Anti Inflammatory

Growing evidence indicates that dysregulated iron metabolism with altered and excess iron availability in some body compartments plays a significant role in the course of infection and sepsis in humans. Given that all bacterial pathogens require iron for growth, that iron withdrawal is a normal component of innate host defenses and that bacterial pathogens have acquired increasing levels of antibiotic resistance, targeting infection and sepsis through use of appropriate iron chelators has potential to provide new therapeutics. We have directly compared the effects of three Food and Drug Administration (FDA)-approved chelators (deferoxamine—DFO; deferiprone—DFP; and deferasirox—DFX), as were developed for treating hematological iron overload conditions, to DIBI, a novel purpose-designed, anti-infective and anti-inflammatory water-soluble hydroxypyridinone containing iron-selective copolymers. Two murine sepsis models, endotoxemia and polymicrobial abdominal sepsis, were utilized to help differentiate anti-inflammatory versus anti-infective activities of the chelators. Leukocyte adhesion, as measured by intravital microscopy, was observed in both models, with DIBI providing the most effective reduction and DFX the poorest. Inflammation in the abdominal sepsis model, assessed by cytokine measurements, indicated exacerbation by DFX and DFO for plasma Interleukin (IL)-6 and reductions to near-control levels for DIBI and DFP. Peritoneal infection burden was reduced 10-fold by DIBI while DFX and DFP provided no reductions. Overall, the results, together with those from other studies, revealed serious limitations for each of the three hematological chelators, i.e., as potentially repurposed for treating infection/sepsis. In contrast, DIBI provided therapeutic benefits, consistent with various in vitro and in vivo results from other studies, supporting the potential for its use in treating sepsis.

scholarly journals A REVIEW ON IN VIVO AND IN VITRO EXPERIMENTAL MODELS TO INVESTIGATE THE ANTI-INFLAMMATORY ACTIVITY OF HERBAL EXTRACTS

2018 ◽  
Vol 11 (11) ◽  
pp. 29
Author(s):  
Inayat Kabir ◽  
Imtiyaz Ansari
Keyword(s):  
Reference Model ◽  
Experimental Models ◽  
Inflammatory Activity ◽  
Herbal Extracts ◽  
Double Positive ◽  
Arthritis Models ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The article emphasizes the anti-inflammatory effects of herbal extracts on different experimental models that are repeatedly used to test the in vivo anti-inflammatory activity of herbal components. Edema, granuloma and arthritis models are used to test the anti-inflammatory activity of plant extracts whereas formalin or acetic acid-induced writhing test and hot plate methods are the most repeatedly used to evaluate anti-nociceptive potentials of the herbal extracts. Although adjuvant-induced and collagen-induced arthritis models are also quite efficient, they have been used seldom to evaluate anti-inflammatory tendencies of the herbs. Here, we suggest a double positive reference model using both steroid and nonsteroidal anti-inflammatory drugs at the same time, instead of using only one of them either.

scholarly journals Extract from Bougainvillea xbuttiana (Variety Orange) Inhibits Production of LPS-Induced Inflammatory Mediators in Macrophages and Exerts a Protective Effect In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Rodolfo Abarca-Vargas ◽  
Vera L. Petricevich
Keyword(s):  
Inflammatory Mediators ◽  
Ethanolic Extract ◽  
Peritoneal Macrophages ◽  
Experimental Models ◽  
Nitric Oxide Release ◽  
Lps Challenge ◽  
Secretion Of Mediators ◽  
Anti Inflammatory

Background. Different pharmacological properties, such as antioxidant, antiproliferative, and anti-inflammatory properties, have been described among natural products. We previously described that the Bougainvillea xbuttiana (Variety Orange) ethanolic extract (BxbO) has an anti-inflammatory effect; however, this action is not fully understood. In this study, the action of the BxbO extract on the secretion of inflammatory mediators in two experimental models, in vitro and in vivo, after LPS challenge was evaluated. Methods. Peritoneal macrophages were obtained from female BALB/c mice and LPS-challenged with or without the BxbO extract. For the evaluation of mediators, the supernatants at 0, 12, 24, 36, and 48 hours were collected. For in vivo estimation, groups of female BALB/c mice were first intraperitoneously injected with different amounts of LPS and later administered the oral BxbO extract (v.o.) for 144 hours. To understand the mechanism of action, sera obtained from mice were collected at 0, 2, 4, 8, 12, and 24 hours after LPS challenge (with or without BxbO) for the detection of mediators. Results. The results showed that, in both peritoneal macrophages and sera of mice treated with the BxbO extract 1 hour before or together with LPS challenge, proinflammatory cytokines and nitric oxide release were unquestionably repressed. In contrast, in both systems studied here, the IL-10 levels were elevated to 5 to 9 times. At lethal doses of LPS, the BxbO extract treatment was found to protect animals from death. Conclusions. The results revealed that the inhibitory, protective, and benign effects of the BxbO extract were due to its capacity to balance the secretion of mediators.

scholarly journals Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Fernanda Paula R. Santana ◽  
Nathalia M. Pinheiro ◽  
Márcia Isabel B. Mernak ◽  
Renato F. Righetti ◽  
Mílton A. Martins ◽  
...  
Keyword(s):  
Natural Products ◽  
Herbal Medicine ◽  
Biological Activities ◽  
Biological Effects ◽  
Pulmonary Inflammation ◽  
Experimental Models ◽  
Chronic Obstructive ◽  
Anti Inflammatory

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effectsin vitroandin vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.

scholarly journals Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation

2010 ◽  
Vol 2 ◽  
pp. OED.S3612 ◽  
Author(s):  
Latif Abdul ◽  
Razique Abdul ◽  
R.R. Sukul ◽  
Siddiqui Nazish
Keyword(s):  
Clinical Practice ◽  
Experimental Models ◽  
Eye Diseases ◽  
Guinea Pig Ileum ◽  
Beneficial Effects ◽  
Vast Literature ◽  
Anti Inflammatory ◽  
Ophthalmic Formulation

The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.

scholarly journals Insightful Valorization of the Biological Activities of Pani Heloch Leaves through Experimental and Computer-Aided Mechanisms

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5153
Author(s):  
Naureen Banu ◽  
Najmul Alam ◽  
Mohammad Nazmul Islam ◽  
Sanjida Islam ◽  
Shahenur Alam Sakib ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Methanol Extract ◽  
Biological Activities ◽  
Biological Effects ◽  
Experimental Models ◽  
Clot Lysis ◽  
Control Group ◽  
Anti Inflammatory

Pani heloch (Antidesma montanum) is traditionally used to treat innumerable diseases and is a source of wild vegetables for the management of different pathological conditions. The present study explored the qualitative phytochemicals; quantitative phenol and flavonoid contents; in vitro antioxidant, anti-inflammatory, and thrombolytic effects; and in vivo antipyretic and analgesic properties of the methanol extract of A. montanum leaves in different experimental models. The extract exhibited secondary metabolites including alkaloids, flavonoids, flavanols, phytosterols, cholesterols, phenols, terpenoids, glycosides, fixed oils, emodines, coumarins, resins, and tannins. Besides, Pani heloch showed strong antioxidant activity (IC50 = 99.00 µg/mL), while a moderate percentage of clot lysis (31.56%) in human blood and significant anti-inflammatory activity (p < 0.001) was achieved with the standard. Moreover, the analgesic and antipyretic properties appeared to trigger a significant response (p < 0.001) relative to in the control group. Besides, an in silico study of carpusin revealed favorable protein-binding affinities. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity analysis and toxicological properties of all isolated compounds adopted Lipinski’s rule of five for drug-like potential and level of toxicity. Our research unveiled that the methanol extract of A. montanum leaves exhibited secondary metabolites that are a good source for managing inflammation, pyrexia, pain, and cellular toxicity. Computational approaches and further studies are required to identify the possible mechanism which responsible for the biological effects.

Anti-inflammatory, Antinociceptive, and Antioxidant Potentials of Algerian Zizyphus jujuba Mill. Fruits and Leaves In Vivo and In Vitro in Different Experimental Models

2019 ◽  
Author(s):  
N. Gadiri ◽  
C. Tigrine ◽  
Z. Lakache ◽  
A. Kameli
Keyword(s):  
Antioxidant Properties ◽  
Experimental Models ◽  
Protective Capacity ◽  
Aerial Parts ◽  
Antioxidant Agents ◽  
Zizyphus Jujuba ◽  
Anti Inflammatory ◽  
Dpph Scavenging

The ethanolic extracts of the aerial parts, leaves, and fruits, of Zizyphus jujuba Mill. were studied in vivo and in vitro for their anti-inflammatory, analgesic, and antioxidant properties, respectively. A preliminary phytochemical screening was carried out. It revealed the presence of several phytoconstituents such as flavonoids, phenols, and alkaloids. The acute toxicity study was conducted using a limit dose of 2,000mg/kg. The extracts studied showed no signs of toxicity or mortality. Anti-inflammatory activity, assessed by carrageenan-induced paw edema, and antinociceptive activity, assessed by pain-induced acetic acid in mice, were significantly reduced (P < 0.001). Moreover, both extracts showed considerable DPPH scavenging activity and β-carotene protective capacity. The present study suggests that leaf and fruit extracts from Zizyphus jujuba have a pharmacological interest probably related to the presence of some bioactive compounds and could be a potential source of antiinflammatory, antinociceptive, and antioxidant agents that should be further investigated.

scholarly journals In Vitro and In Vivo Screening of Wild Bitter Melon Leaf for Anti-Inflammatory Activity against Cutibacterium acnes

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4277
Author(s):  
Lu-Te Chuang ◽  
Ya-Hsin Shih ◽  
Wen-Cheng Huang ◽  
Lie-Chwen Lin ◽  
Chin Hsu ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Water Soluble ◽  
Hexane Fraction ◽  
Bitter Melon ◽  
In Vivo Inflammation ◽  
Cutibacterium Acnes ◽  
Mouse Ear ◽  
Anti Inflammatory

Cutibacterium acnes (formerly Propionibacterium acnes) is a key pathogen involved in the development and progression of acne inflammation. The numerous bioactive properties of wild bitter melon (WBM) leaf extract and their medicinal applications have been recognized for many years. In this study, we examined the suppressive effect of a methanolic extract (ME) of WBM leaf and fractionated components thereof on live C. acnes-induced in vitro and in vivo inflammation. Following methanol extraction of WBM leaves, we confirmed anti-inflammatory properties of ME in C. acnes-treated human THP-1 monocyte and mouse ear edema models. Using a bioassay-monitored isolation approach and a combination of liquid–liquid extraction and column chromatography, the ME was then separated into n-hexane, ethyl acetate, n-butanol and water-soluble fractions. The hexane fraction exerted the most potent anti-inflammatory effect, suppressing C. acnes-induced interleukin-8 (IL-8) production by 36%. The ethanol-soluble fraction (ESF), which was separated from the n-hexane fraction, significantly inhibited C. acnes-induced activation of mitogen-activated protein kinase (MAPK)-mediated cellular IL-8 production. Similarly, the ESF protected against C. acnes-stimulated mouse ear swelling, as measured by ear thickness (20%) and biopsy weight (23%). Twenty-four compounds in the ESF were identified using gas chromatograph–mass spectrum (GC/MS) analysis. Using co-cultures of C. acnes and THP-1 cells, β-ionone, a compound of the ESF, reduced the production of IL-1β and IL-8 up to 40% and 18%, respectively. β-ionone also reduced epidermal microabscess, neutrophilic infiltration and IL-1β expression in mouse ear. We also found evidence of the presence of anti-inflammatory substances in an unfractionated phenolic extract of WBM leaf, and demonstrated that the ESF is a potential anti-inflammatory agent for modulating in vitro and in vivo C. acnes-induced inflammatory responses.

scholarly journals Curcumin Niosomes Prepared from Proniosomal Gels: In Vitro Skin Permeability, Kinetic and In Vivo Studies

Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 791
Author(s):  
Tamer M. Shehata ◽  
Mahmoud M. Ibrahim ◽  
Heba S. Elsewedy
Keyword(s):  
Tween 80 ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Skin Permeability ◽  
Water Soluble Drug ◽  
Anti Inflammatory ◽  
Niosomal Gel ◽  
Span 60

Curcumin is a poorly water-soluble drug that is used for the treatment of inflammations, tumors, wound healing antioxidant and other diseases. In the current manuscript, it is successfully formulated into proniosome gels. The proniosomes are readily hydrated into niosomal formulations using warm water. Proniosomes were prepared using nonionic surfactants (tween 80, span 60) either solely or in combinations with cholesterol. The produced niosomal formulations were homogenous in size with vesicular sizes >343 and <1800 nm. The encapsulation efficiency percentage “EE%” of curcumin in niosomal formulations was different according to niosomal composition. It increased up to 99.74% in formulations of tween 80/Chol of 200 μmole/mL lipid concentration. Span 60/chol niosomes showed decreased curcumin EE%. Niosomal formulations showed increased SSTF and PC with enhancement ratios of more than 20-fold compared with curcumin suspension form. Kinetically, niosomes fitted to the Korsemeyer-Peppas model with non-Fickian transport according to their calculated n-values where curcumin suspension form showed Korsemeyer-Peppas kinetics with Fickian transport. Niosomal formulations deposited higher curcumin amounts in the skin compared with the suspension form. The best niosomal formulation (F9) was used for niosomal gel and emulgel fabrication. Finally, the anti-inflammatory activity of curcumin in various formulations was evaluated using a rat hind paw edema method and the % of swelling was 17.5% following 24 h in group treated with curcumin niosomal emulgel. In conclusion, this study suggests that the developed niosomal emulgel could significantly enhance the anti-inflammatory effect of curcumin and be an efficient carrier for the transdermal delivery of the drug.

scholarly journals Tryptophol acetate and tyrosol acetate, metabolites secreted by a probiotic yeast, halt cytokine storm

2021 ◽  
Author(s):  
orit malka ◽  
ravit malishev ◽  
marina bersudsky ◽  
manikand rajendran ◽  
mathumathi krishnamohan ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Ex Vivo ◽  
Fermented Foods ◽  
Cytokine Storm ◽  
Immune Functions ◽  
Therapeutic Benefits ◽  
Probiotic Yeast ◽  
Anti Inflammatory

Probiotic fermented foods are perceived as contributing to human health and capable of protecting against inflammation, however solid mechanistic evidence for the presumptive therapeutic benefits is lacking. Here we report that tryptophol acetate and tyrosol acetate, small molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus exhibit remarkable anti-inflammatory properties. Comprehensive in vivo, ex vivo and in vitro experiments, employing LPS-induced 'cytokine storm' models, reveal dramatic effects of the two molecules, added in tandem, on mice morbidity, laboratory parameters and mortality. In parallel, significant attenuation of pro-inflammatory cytokines including IL-6, IL-1α, IL-1β and TNF-κB, and reduction of reactive oxygen species were recorded. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress cytokine generation, but rather brought their concentrations back to baseline levels, further maintaining core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, attenuating NF-kB level. In addition, the two molecules had a significant impact on mice microbiome, increasing the abundance of the genus Bactericides, known to exhibit anti-inflammatory properties. Overall, this work illuminates pronounced and broad-based immune modulation properties of probiotic yeast-secreted metabolites, uncovering their mechanism of action and underscoring potential new therapeutic avenues for severe inflammation.

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