scholarly journals In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5064 ◽  
Author(s):  
Mathieu Gendrot ◽  
Julien Andreani ◽  
Priscilla Jardot ◽  
Sébastien Hutter ◽  
Océane Delandre ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
In Vitro Study ◽  
Experimental Models ◽  
In Vivo Evaluation ◽  
Study Results ◽  
Anti Inflammatory ◽  
Approved Drugs

In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Despite containment measures, SARS-CoV-2 spread in Asia, Southern Europe, then in America and currently in Africa. Identifying effective antiviral drugs is urgently needed. An efficient approach to drug discovery is to evaluate whether existing approved drugs can be efficient against SARS-CoV-2. Doxycycline, which is a second-generation tetracycline with broad-spectrum antimicrobial, antimalarial and anti-inflammatory activities, showed in vitro activity on Vero E6 cells infected with a clinically isolated SARS-CoV-2 strain (IHUMI-3) with median effective concentration (EC50) of 4.5 ± 2.9 µM, compatible with oral uptake and intravenous administrations. Doxycycline interacted both on SARS-CoV-2 entry and in replication after virus entry. Besides its in vitro antiviral activity against SARS-CoV-2, doxycycline has anti-inflammatory effects by decreasing the expression of various pro-inflammatory cytokines and could prevent co-infections and superinfections due to broad-spectrum antimicrobial activity. Therefore, doxycycline could be a potential partner of COVID-19 therapies. However, these results must be taken with caution regarding the potential use in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results to actual clinical treatment in patients. In vivo evaluation in animal experimental models is required to confirm the antiviral effects of doxycycline on SARS-CoV-2 and more trials of high-risk patients with moderate to severe COVID-19 infections must be initiated.

scholarly journals Formulation Development, Statistical Optimization, In Vitro and In Vivo Evaluation of Etoricoxib-Loaded Eucalyptus Oil-Based Nanoemulgel for Topical Delivery

2021 ◽  
Vol 11 (16) ◽  
pp. 7294
Author(s):  
Nabil A. Alhakamy ◽  
Sabna Kotta ◽  
Javed Ali ◽  
Md Shoaib Alam ◽  
Khaled M. Hosny ◽  
...  
Keyword(s):  
Tween 20 ◽  
Formulation Development ◽  
In Vivo Evaluation ◽  
Apparent Permeability ◽  
Eucalyptus Oil ◽  
Rat Paw Edema ◽  
Study Results ◽  
Anti Inflammatory

Pain is a common distress in chronic inflammatory diseases, and etoricoxib (ETB) is frequently used in its management. It possesses fewer adverse effects when compared with other non-steroidal anti-inflammatory drugs (NSAIDs). In the present study, ETB-loaded nanoemulsion (ETB-NE) was formulated and optimized. Eucalyptus oil, Tween 20, and PEG 200 were chosen as the oil, surfactant, and co-surfactant, respectively. The formulation was optimized using the Box–Behnken design. The optimized ETB-NE contained oil, Smix, and water in concentrations of 11.5, 38, and 50% respectively. It had droplet size, polydispersity index, and zeta potential values of 179.6 ± 4.21 nm, 0.373 ± 0.02, and −10.9 ± 1.01 mV, respectively. The optimized ETB-NE sample passed the thermodynamic stability and dispersibility tests. Transmission electron microscopy confirmed the spherical morphology of the NE droplets. The ETB-NE showed a biphasic drug release pattern and released 85.3 ± 1.8% of ETB at 12 h. The ETB-NE was formulated into nanoemulsion gel (NEG) by using 1% carbopol 934. ETB-NEG was characterized for pH, viscosity, drug content, and percentage entrapment efficiency. During in vitro permeation studies, the apparent permeability coefficient value was 0.072 cm−2 h−1 for ETB-NEG, while it was only 0.047 cm−2 h−1 for the ETB gel. The skin histopathology study results confirmed that the ETB-NEG formulation was non-irritant and safe for topical use. The maximum possible analgesia observed for ETB-NEG was significantly high (p < 0.05) with a value of 47.09% after 60 min. Similarly, a formalin-induced acute inflammatory pain study in rats also demonstrated higher analgesia for the ETB-NEG, with % inhibition values of 37.37 ± 5.9 and 51.95 ± 4.4 in the acute and late phases, respectively. Further, ETB-NEG showed 78.4 ± 3.5% inhibition at 8 h in the in vivo anti-inflammatory testing by rat paw edema method. The ETB-NEG was found to enhance the in vivo analgesic and anti-inflammatory effects of ETB. The study results could stimulate further studies in this area for establishing a clinically successful NEG formulation of ETB.

In vitro and in vivo evaluation of the anti-inflammatory effects of Arzanol from Helichrysum italicum

Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
Anti Inflammatory

scholarly journals Ketorolac-dextran conjugates: Synthesis, in vitro and in vivo evaluation

2007 ◽  
Vol 57 (4) ◽  
pp. 441-450 ◽  
Author(s):  
Savita Vyas ◽  
Piyush Trivedi ◽  
Subhash Chaturvedi
Keyword(s):  
Human Plasma ◽  
Parent Drug ◽  
Aqueous Solubility ◽  
Spectrophotometric Analysis ◽  
In Vivo Evaluation ◽  
Gastrointestinal Side Effects ◽  
Molecular Masses ◽  
Anti Inflammatory

Ketorolac-dextran conjugates: Synthesis,in vitroandin vivoevaluationKetorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. Invitrohydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics.In vivobiological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

scholarly journals Properties of a New Food Supplement Containing Actinia equina Extract

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 945
Author(s):  
Marika Lanza ◽  
Giovanna Casili ◽  
Giovanna Loredana La Torre ◽  
Daniele Giuffrida ◽  
Archimede Rotondo ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Neutrophil Infiltration ◽  
Food Supplement ◽  
Biologically Active ◽  
In Vivo Model ◽  
Related Factor ◽  
Nuclear Factor ◽  
Anti Inflammatory

Marine species represent a great source of biologically active substances; Actinia equina (AE), an Anthozoa Cnidaria belonging to the Actinidiae family, have been proposed as original food and have already been included in several cooking recipes in local Mediterranean shores, and endowed with excellent nutraceutical potential. The aim of this study was to investigate some unexplored features of AE, through analytical screening and an in-vitro and in-vivo model. An in-vitro study, made on RAW 264.7 stimulated with H2O2, showed that the pre-treatment with AE exerted an antioxidant action, reducing lipid peroxidation and up-regulating antioxidant enzymes. On the other hand, the in-vivo study over murine model demonstrated that the administration of AE extracts is able to reduce the carrageenan (CAR)-induced paw edema. Furthermore, the histological damage due to the neutrophil infiltration is prevented, and this highlights precious anti-inflammatory features of the interesting food-stuff. Moreover, it was assessed that AE extract modulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and The nuclear factor erythroid 2–related factor 2 (Nrf-2) pathways. In conclusion, our data demonstrated that thanks to the antioxidant and anti-inflammatory properties, AE extract could be used as a new food supplement for inflammatory pathology prevention.

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 Broad-Spectrum Antiviral Activity of 3’-Deoxy-3’-Fluoroadenosine against Emerging Flaviviruses

2020 ◽  
Author(s):  
Luděk Eyer ◽  
Pavel Svoboda ◽  
Jan Balvan ◽  
Tomáš Vičar ◽  
Matina Raudenská ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Nucleotide Metabolism ◽  
Modified Nucleosides ◽  
Bioactive Molecules ◽  
Nucleoside Analogues ◽  
Phase Imaging ◽  
Structural And Functional Properties

Emerging flaviviruses are causative agents of severe and life-threatening diseases, against which no approved therapies are available. Among the nucleoside analogues, which represent a promising group of potentially therapeutic compounds, fluorine-substituted nucleosides are characterized by unique structural and functional properties. Despite having been first synthesized almost 5 decades ago, they still offer new therapeutic opportunities as inhibitors of essential viral or cellular enzymes active in nucleic acid replication/transcription or nucleoside/nucleotide metabolism. Here we report evaluation of the anti-flaviviral activity of 28 nucleoside analogues, each modified with a fluoro substituent at different positions of the ribose ring and/or heterocyclic nucleobase. Our antiviral screening revealed that 3′-deoxy-3′-fluoroadenosine exerted a low-micromolar antiviral effect against tick-borne encephalitis virus (TBEV), Zika virus, and West Nile (WNV) virus (EC50 values from 1.1 ± 0.1 μM to 4.7 ± 1.5 μM), which was manifested in host cell lines of neural and extraneural origin. The compound did not display any measurable cytotoxicity up to concentrations of 25 μM but had an observable cytostatic effect, resulting in suppression of cell proliferation at concentrations of >12.5 μM. Novel approaches based on quantitative phase imaging using holographic microscopy were developed for advanced characterization of antiviral and cytotoxic profiles of 3′-deoxy-3′-fluoroadenosine in vitro. In addition to its antiviral activity in cell cultures, 3′-deoxy-3′-fluoroadenosine was active in vivo in mouse models of TBEV and WNV infection. Our results demonstrate that fluoro-modified nucleosides represent a group of bioactive molecules with excellent potential to serve as prospective broad-spectrum antivirals in antiviral research and drug development.

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 Anti-Inflammatory and Antibacterial Activity Constituents from the Stem of Cinnamomum validinerve

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3382 ◽  
Author(s):  
Chi-Lung Yang ◽  
Ho-Cheng Wu ◽  
Tsong-Long Hwang ◽  
Chu-Hung Lin ◽  
Yin-Hua Cheng ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Immune Cell ◽  
Intraperitoneal Administration ◽  
In Vitro Study ◽  
Human Neutrophils ◽  
Infection Model ◽  
Ic50 Values ◽  
Anti Inflammatory

One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC50 values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 μg/mL, 16 μg/mL, and 500 μg/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections.

scholarly journals Effects of Berries on High-Fat Diet-Induced Inflammation

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 449-449
Author(s):  
Patricia Perez ◽  
Desiree Wanders ◽  
Hannah Land ◽  
Kathryn Chiang ◽  
Rami Najjar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Inflammatory Markers ◽  
In Vitro Study ◽  
Vitro Study ◽  
In Vivo Study ◽  
High Fat ◽  
Anti Inflammatory

Abstract Objectives Studies suggest that inflammation mediates the link between obesity and its comorbidities including type 2 diabetes and cardiovascular disease. Hence, there is a demand for effective alternative or complementary approaches to treat obesity-associated inflammation. The objective of this study was to determine whether consumption of blackberries (BL) and raspberries (RB) alone or in combination reduce obesity-induced inflammation. Methods In Vitro Study: RAW 264.7 macrophages were pretreated with either BL, RB, or BL + RB, each at a final concentration of 200 µg/mL for 2 h. LPS (1 ng/mL) was then added to the media for 16 h. mRNA expression of inflammatory cytokines was measured. In Vivo Study: Five-week-old mice were acclimated to a low-fat low-sucrose (LFLS) diet for one week after which mice were randomized 10 per group to one of five groups: 1) LFLS, 2) high-fat high-sucrose (HFHS), 3) HFHS + 10% BL, 4) HFHS + 10% RB, or 5) HFHS + 5% BL + 5% RB. Expression of inflammatory markers was measured in the liver as well as epididymal and inguinal white adipose tissue. Results In Vitro Study: Each berry alone and in combination suppressed the LPS-induced increase in inflammatory markers, with the combination (BL + RB) having the greatest effect. The combination suppressed LPS-induced expression of Ccl2, Tnfa, F4/80, and Il6 by 3.7−, 5.3−, 5.3−, and 4.4-fold, respectively. In Vivo Study: Gene expression analysis indicated that berry consumption had no significant effect on proinflammatory (Ccl2, Il1b, Tnfa, Il6, Itgam) or anti-inflammatory (Adipoq, Arg1, Mgl1) markers in adipose tissue depots or liver. However, relatively low gene expression of inflammatory markers in the tissues indicates that the mice fed the HFHS diet failed to develop a robust inflammatory state. Conclusions BL and RB have direct anti-inflammatory effects on immune cells. Initial analysis indicates that consumption of BL and RB has no significant effects on markers of inflammation in a diet-induced mouse model of obesity. However, it is possible that the relatively low levels of inflammation in these mice masked the anti-inflammatory potential of BL and RB. Ongoing analysis will provide additional insights into the effects of BL and RB on inflammation in these tissues. Funding Sources Lewis Foundation Award.

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