scholarly journals Orally Administered Natural Lipid Nanoparticle-Loaded 6-Shogaol Shapes the Anti-Inflammatory Microbiota and Metabolome

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1355
Author(s):  
Chunhua Yang ◽  
Dingpei Long ◽  
Junsik Sung ◽  
Zahra Alghoul ◽  
Didier Merlin
Keyword(s):  
Metabolic Profile ◽  
Treatment Time ◽  
Day Treatment ◽  
Drug Candidate ◽  
Microbiota Composition ◽  
Compositional Change ◽  
Functional Changes ◽  
Lipid Nanoparticle ◽  
Anti Inflammatory ◽  
Natural Lipid

The past decade has seen increasing interest in microbiota-targeting therapeutic strategies that aim to modulate the gut microbiota’s composition and/or function to treat chronic diseases, such as inflammatory bowel disease (IBD), metabolic symptoms, and obesity. While targeting the gut microbiota is an innovative means for treating IBD, it typically requires an extended treatment time, hampering its potential application. Herein, using an established natural-lipid nanoparticle (nLNP) platform, we demonstrate that nLNPs encapsulated with the drug candidate 6-shogaol (6S/nLNP) distinctly altered microbiota composition within one day of treatment, significantly accelerating a process that usually requires five days using free 6-shogaol (6S). In addition, the change in the composition of the microbiota induced by five-day treatment with 6S/nLNP was maintained for at least 15 days (from day five to day 20). The consequent alteration in the fecal metabolic profile stemming from this compositional change manifested as functional changes that enhanced the in vitro anti-inflammatory and wound-healing efficacy of macrophage cells (Raw 264.7) and epithelial cells (Caco-2 BBE1), respectively. Further, this metabolic compositional change, as reflected in an altered metabolic profile, promoted a robust anti-inflammatory effect in a DSS-induced mouse model of acute colitis. Our study demonstrates that, by near-instantly modulating microbiota composition and function, an nLNP-based drug-delivery platform might be a powerful tool for treating ulcerative colitis.

scholarly journals Cysteamine with In Vitro Antiviral Activity and Immunomodulatory Effects Has the Potential to Be a Repurposing Drug Candidate for COVID-19 Therapy

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 52
Author(s):  
Tonino Alonzi ◽  
Alessandra Aiello ◽  
Linda Petrone ◽  
Saeid Najafi Fard ◽  
Manuela D’Eletto ◽  
...  
Keyword(s):  
Treatment Time ◽  
Treatment Options ◽  
Drug Candidate ◽  
Immunomodulatory Effects ◽  
Novel Therapy ◽  
Blood Samples ◽  
Cytopathic Effects ◽  
Anti Inflammatory ◽  
Immune Response In Vitro

The ongoing pandemic of coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), needs better treatment options both at antiviral and anti-inflammatory levels. It has been demonstrated that the aminothiol cysteamine, an already human applied drug, and its disulfide product of oxidation, cystamine, have anti-infective properties targeting viruses, bacteria, and parasites. To determine whether these compounds exert antiviral effects against SARS-CoV-2, we used different in vitro viral infected cell-based assays. Moreover, since cysteamine has also immune-modulatory activity, we investigated its ability to modulate SARS-CoV-2-specific immune response in vitro in blood samples from COVID-19 patients. We found that cysteamine and cystamine decreased SARS-CoV-2-induced cytopathic effects (CPE) in Vero E6 cells. Interestingly, the antiviral action was independent of the treatment time respect to SARS-CoV-2 infection. Moreover, cysteamine and cystamine significantly decreased viral production in Vero E6 and Calu-3 cells. Finally, cysteamine and cystamine have an anti-inflammatory effect, as they significantly decrease the SARS-CoV-2 specific IFN-γ production in vitro in blood samples from COVID-19 patients. Overall, our findings suggest that cysteamine and cystamine exert direct antiviral actions against SARS-CoV-2 and have in vitro immunomodulatory effects, thus providing a rational to test these compounds as a novel therapy for COVID-19.

Cordycepin and its nucleoside analogs for the treatment of systemic COVID-19 infection

Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Chellapandi P ◽  
Saranya S
Keyword(s):  
Nucleoside Analogs ◽  
Drug Candidate ◽  
Rnase L ◽  
Structural Genomic ◽  
Human Rnase ◽  
Medicinal Fungi ◽  
Anti Inflammatory ◽  
The Individual ◽  
Human Viruses ◽  
Anti Inflammation

: Coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus isolated from Wuhan, China. It is a global health emergency, and there is no effective antiviral therapeutics available to date. Continuous structural genomic insights of SARS-CoV-2 proteins provide a warranty for the development of rational-based antivirals. Nevertheless, a structure-based drug candidate with multiple therapeutic actions would be a practical choice of medication in the treatment of severe COVID-19 patients. Cordycepin from medicinal fungi (Cordyceps spp.) and its nucleoside analogs targeting viral RNA-dependent RNA polymerase and human RNase L have potent antiviral activity against various human viruses with additional immunomodulatory and anti-inflammatory effects. Anti-inflammation treatment is of pivotal importance and should be timely tailored to the individual patient along with antivirals. Our perspective on the combined antiviral and anti-inflammatory effects of cordycepin and its analogs suggests them as new therapeutics in the treatment of systemic COVID-19 infection.

scholarly journals Multiple Disruptions of Glial-Neuronal Networks in Epileptogenesis That Follows Prolonged Febrile Seizures

2021 ◽  
Vol 12 ◽  
Author(s):  
Gary P. Brennan ◽  
Megan M. Garcia-Curran ◽  
Katelin P. Patterson ◽  
Renhao Luo ◽  
Tallie Z. Baram
Keyword(s):  
Neuronal Networks ◽  
Day Treatment ◽  
High Mobility ◽  
Febrile Seizures ◽  
Experimental Models ◽  
Normal Brain ◽  
Molecular Signaling ◽  
Rat Pups ◽  
Anti Inflammatory

Background and Rationale: Bi-directional neuronal-glial communication is a critical mediator of normal brain function and is disrupted in the epileptic brain. The potential role of aberrant microglia and astrocyte function during epileptogenesis is important because the mediators involved provide tangible targets for intervention and prevention of epilepsy. Glial activation is intrinsically involved in the generation of childhood febrile seizures (FS), and prolonged FS (febrile status epilepticus, FSE) antecede a proportion of adult temporal lobe epilepsy (TLE). Because TLE is often refractory to treatment and accompanied by significant memory and emotional difficulties, we probed the role of disruptions of glial-neuronal networks in the epileptogenesis that follows experimental FSE (eFSE).Methods: We performed a multi-pronged examination of neuronal-glia communication and the resulting activation of molecular signaling cascades in these cell types following eFSE in immature mice and rats. Specifically, we examined pathways involving cytokines, microRNAs, high mobility group B-1 (HMGB1) and the prostaglandin E2 signaling. We aimed to block epileptogenesis using network-specific interventions as well as via a global anti-inflammatory approach using dexamethasone.Results: (A) eFSE elicited a strong inflammatory response with rapid and sustained upregulation of pro-inflammatory cytokines. (B) Within minutes of the end of the eFSE, HMGB1 translocated from neuronal nuclei to dendrites, en route to the extracellular space and glial Toll-like receptors. Administration of an HMGB1 blocker to eFSE rat pups did not decrease expression of downstream inflammatory cascades and led to unacceptable side effects. (C) Prolonged seizure-like activity caused overall microRNA-124 (miR-124) levels to plunge in hippocampus and release of this microRNA from neurons via extra-cellular vesicles. (D) Within hours of eFSE, structural astrocyte and microglia activation was associated not only with cytokine production, but also with activation of the PGE2 cascade. However, administration of TG6-10-1, a blocker of the PGE2 receptor EP2 had little effect on spike-series provoked by eFSE. (E) In contrast to the failure of selective interventions, a 3-day treatment of eFSE–experiencing rat pups with the broad anti-inflammatory drug dexamethasone attenuated eFSE-provoked pro-epileptogenic EEG changes.Conclusions: eFSE, a provoker of TLE-like epilepsy in rodents leads to multiple and rapid disruptions of interconnected glial-neuronal networks, with a likely important role in epileptogenesis. The intricate, cell-specific and homeostatic interplays among these networks constitute a serious challenge to effective selective interventions that aim to prevent epilepsy. In contrast, a broad suppression of glial-neuronal dysfunction holds promise for mitigating FSE-induced hyperexcitability and epileptogenesis in experimental models and in humans.

scholarly journals Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis

2019 ◽  
Vol 20 (12) ◽  
pp. 3007 ◽  
Author(s):  
Lauri Polari ◽  
Santeri Anttila ◽  
Terhi Helenius ◽  
Anu Wiklund ◽  
Tero Linnanen ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Steroid Receptor ◽  
Receptor Activation ◽  
Selective Estrogen Receptor Modulator ◽  
Sex Steroid ◽  
Drug Candidate ◽  
Inflammatory Monocytes ◽  
Receptor Modulator ◽  
Anti Inflammatory ◽  
Novel Drug

Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors α and β and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds.

Discovery and preclinical development of IIIM-160, a Bergenia ciliata-based anti-inflammatory and anti-arthritic botanical drug candidate

2019 ◽  
Vol 17 (3) ◽  
pp. 192-204 ◽  
Author(s):  
Sandip B. Bharate ◽  
Vikas Kumar ◽  
Sonali S. Bharate ◽  
Bikarma Singh ◽  
Gurdarshan Singh ◽  
...  
Keyword(s):  
Drug Candidate ◽  
Preclinical Development ◽  
Botanical Drug ◽  
Anti Inflammatory

scholarly journals Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Audrey Vautrin ◽  
Laurent Manchon ◽  
Aude Garcel ◽  
Noëlie Campos ◽  
Laure Lapasset ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Drug Candidate ◽  
Anti Inflammatory ◽  
Novel Drug

scholarly journals Analgesic and Anti-Inflammatory Activities of Resveratrol through Classic Models in Mice and Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Guangxi Wang ◽  
Zhiqiang Hu ◽  
Xu Song ◽  
Qiankun Cui ◽  
Qiuting Fu ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Biological Activities ◽  
Drug Candidate ◽  
Hot Plate ◽  
Sod Activity ◽  
Analgesic Effects ◽  
Mouse Ear ◽  
Anti Inflammatory ◽  
Ear Oedema

Background. Inflammation and pain are closely related to humans’ and animals’ health.Resveratrol(RSV) is a natural compound with various biological activities. The current study is aimed to evaluate the analgesic and anti-inflammatory activities of RSV in vivo. Materials and Methods. The analgesic effects were assessed by the acetic acid-induced writhing and hot plate tests. The anti-inflammatory effects were determined using the xylene-induced mouse ear oedema, the acetic acid-induced rat pleurisy, and carrageenan-induced rat synovitis tests, respectively.Results. The analgesic results showed that RSV could significantly inhibit the number of writhes and improve the time and pain threshold of mice standing on hot plate. The anti-inflammatory results showed that RSV could inhibit the ear oedema of mice. In acetic acid-induced pleurisy test, RSV could significantly inhibit the WBC and pleurisy exudates, could decrease the production of NO, and elevate the activity of SOD in serum. In carrageenan-induced synovitis test, RSV could reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA.Conclusion. Shortly, these results indicated that RSV had potent analgesic and anti-inflammatory activities and could be a potential new drug candidate for the treatment of inflammation and pain.

scholarly journals THE USE OF LASER RADIATION IN COMPLEX TREATMENT OF PATIENTS WITH OCCLUSAL VIOLATIONS AND GENERALIZED PERIODONTITIS

2018 ◽  
Vol 22 (2) ◽  
pp. 88-92
Author(s):  
O. I Efimovich ◽  
Lima Abbasova Mamedova
Keyword(s):  
Clinical Study ◽  
Laser Radiation ◽  
Laser Therapy ◽  
Treatment Time ◽  
Complex Treatment ◽  
Moderate Severity ◽  
Periodontal Inflammation ◽  
Anti Inflammatory ◽  
Rapid Relief

A clinical study of the effectiveness correction occlusive disorders and treatment of generalized periodontitis moderate severity using the local laser and the anti-inflammatory therapy. 79 patients were treated with periodontitis moderate having occlusive disorders. It was revealed that the administration use of laser therapy reduces treatment time and leads to a rapid relief of periodontal inflammation.

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