scholarly journals Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhen Qin ◽  
Kefa Xiang ◽  
Ding-Feng Su ◽  
Yang Sun ◽  
Xia Liu

The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.

2019 ◽  
pp. 3-15 ◽  
Author(s):  
Fabian Ifeanyi Eze ◽  
Philip F. Uzor ◽  
Peter Ikechukwu ◽  
Bonaventure C. Obi ◽  
Patience O. Osadebe

Anti-inflammatory activity study involves developing a model that mimics, or provokes the production or release of, the biochemical mediators of inflammation, and monitoring the response of these biochemicals to the test drugs. This report constitutes an updated review of the in vitro and in vivo study models for assessing anti-inflammatory activity in plant extracts and synthetic drugs. The materials, instrumentation, and methods involved, as well as the mechanism of anti-inflammatory activity tested in each model, are extensively described. The merits and limitations of each method have also been discussed. A comparative assessment of the in vivo animal models vis-à-vis, the in vitro enzyme models have been made to assist scientists and researchers in the choice of assay method in terms of sensitivity, reliability, duration of test, ethical, and cost considerations.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5064 ◽  
Author(s):  
Mathieu Gendrot ◽  
Julien Andreani ◽  
Priscilla Jardot ◽  
Sébastien Hutter ◽  
Océane Delandre ◽  
...  

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.


1993 ◽  
Vol 16 (11) ◽  
pp. 765-770 ◽  
Author(s):  
J.W. Costerton ◽  
A.E. Khoury ◽  
K.H. Ward ◽  
H. Anwar

Direct examination of medical devices that have been foci of chronic device-related bacterial infections has shown that the causative organisms grow predominantly in slime-enclosed biofilms. These adherent biofilms are inherently resistant to host defences (antibodies, phagocytes) and to conventional antibiotic therapy. Device-related infections can be prevented by careful cleaning and sterilization of the device, and by the avoidance of any manipulations that would allow the formation of even the most rudimentary biofilm prior to implantation. Once a device-related infection has become established, both the Minimum Inhibitory Concentration (MIC) and the Biofilm Eliminating Concentration (BEC) of the causative organism must be determined and therapeutic strategy must aim at the use of the MIC to control the acute phase caused by planktonic bacteria and of the BEC to eliminate the biofilm nidus of infection. The removal of the colonized device should be considered early in the course of treatment if the BEC cannot be delivered to the colonized device. We describe a new bioelectric technology presently in the in vitro stage of development which, if it can be reproduced in vivo, will be very effective in the prevention and control of device-related bacterial infections.


RSC Advances ◽  
2018 ◽  
Vol 8 (55) ◽  
pp. 31515-31528 ◽  
Author(s):  
Pei-Ying Li ◽  
Yu-Chia Liang ◽  
Ming-Jyh Sheu ◽  
Shyh-Shyun Huang ◽  
Che-Yi Chao ◽  
...  

The present study demonstrated that alpinumisoflavone exerts the significant effects of anti-inflammatory and anti-oxidative in both LPS-induced RAW264.7 macrophages and a mouse model of acute lung injury.


2015 ◽  
Author(s):  
Martin G Frasch ◽  
Mark Szynkaruk ◽  
Andrew P Prout ◽  
Karen Nygard ◽  
Ruud Veldhuizen ◽  
...  

Neuroinflammation in utero may contribute to brain injury resulting in life long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via CAP's afferent component of the vagus nerve. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measures reflecting fluctuations in vagus nerve activity. Measuring microglial activation in the ovine fetal brain near-term, we show in vivo that afferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labour. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.


2020 ◽  
Vol 7 (1) ◽  
pp. 1-8
Author(s):  
Sae Asayama ◽  
Ayaka Iwasaki ◽  
Shunya Sahara ◽  
Koichi Nakaoji ◽  
Masamitsu Ichihashi ◽  
...  

Background: Atopic Dermatitis (AD) is a chronic inflammatory skin disease that causes functional disruption of the skin barrier. We previously found that ethanol Extracts of Mallotus Philippinensis Bark (EMPB) promoted migration of mesenchymal stem cells and improved wound healing probably through anti-inflammatory action. However, direct evidence of the anti-inflammatory effect of EMPB and the underlying mechanisms of this action remain unknown. In the present study, we evaluated whether EMPB has an effective action on anti-inflammation using an in vitro and in vivo model. We found that topical application of EMPB improved house dust miteinduced AD-like skin inflammation in NC/Nga mice. In addition, EMPB significantly inhibited various kinds of inflammatory mediators such as interleukin-1ß, inducible nitric oxide synthases, and nuclear factorkappa B in lipopolysaccharide-stimulated macrophage cells. Moreover, EMPB exhibited marked radical scavenging ability. Taken together, these results suggest that EMPB may be useful in the treatment of skin inflammatory diseases such as AD. Keywords: Mallotus Philippinensis Bark; Anti-Inflammation; Atopic Dermatitis; Macrophages


2018 ◽  
Vol 9 (3) ◽  
pp. 435-439
Author(s):  
О. О. Boyko ◽  
O. G. Gavrilina ◽  
P. N. Gavrilin ◽  
Y. A. Gugosyan ◽  
V. V. Brygadyrenko

Formic acid (methanoic acid, HCOOH) is an organic compound which belongs to saturated monobasic acids. In natural conditions, it is secreted from the glands of ants, and also extracted from the leaves of stinging nettles. It is soluble in water in any proportions, which makes it practical to use for making aquatic solutions. It is broadly used as a preservative in the food industry – Е236 food additive (Codex Alimentarius), as a bactericide in medicine and veterinary medicine, and is also used against agricultural pest species of insects and mites. The in vitro and in vivo experiments revealed the anthelmintic properties of the acid against Strongyloides papillosus nematodes, parasites of the gastrointestinal tract of Ruminantia and rabbits. In the conditions of in vitro, 100% of (L1, L2, L3) nematode larvae died from a 1% solution of formic acid (10 g/l) after 24 hours exposure. When exposed to less strong concentrations of the acid (1, 0.1, 0.01, 0.001 g/l), vital forms of L3 S. papillosus were found. Non-invasive stages (L1, L2) are less resistant to the impact of the acid – death of 100% of the larvae was observed under the impact of 0.1% solution and up to 60% of larvae died at 0.01% solution of formic acid in the same conditions. LD50 for L3 invasive larvae of S. papillosus equaled 0.47%, and 0.0076% for L1, L2 non-invasive larvae of S. papillosus. In the conditions of in vivo experiment (with guinea pigs), the effective dose of formic acid was 0.4% ml/kg of the animal`s body weight. The results of the coproscopy after the treatment demonstrated absence of the helminth larvae in the feces of the laboratory animals during 10 days and their occurrence only on days 15–20 with a low intensity (90 larvae/g of feces on average). During an external examination of the corpses of the animals of the experimental group, no pathological changes were found. The intestine, the heart, the lungs and the liver of the animals from this group had no macroscopic changes – they were of natural colour and size. The hepatocytes looked normal and the structure of the liver lobes was maintained. In the tissues of the liver of the animals from the experimental and control groups, we found processes of passive congestion, and an insignificant degree of signs of hepatic steatosis.


Author(s):  
Shiva Murthy N. ◽  
Srinivas V. ◽  
Shanthi M.

Background: NSAIDS are associated with side effects and research should continue for developing safer drugs. This study aims to evaluate newer thiazolidine-4-ones for their anti-inflammatory and ulcerogenic activities in wister rats.Methods: Five groups of wister rats, 6 in each were used.  Anti-inflammatory and ulcerogenic activities of diclofenac (30mg/kg), nimesulide (50mg/kg), thia-1 (50mg/kg) and thia-2 (50mg/kg) are compared with control group (4% Gum Acacia). Carrageenin-induced paw edema, formaline induced acute peritonitis and cotton pellet-induced granulomatous tissue formation models were used for evaluating anti-inflammatory activity. After removing cotton pellets with granuloma on 8th day gastric ulcerogenicity was assessed by using macroscopic and microscopic scoring of ulcers.Results: Diclofenac, nimesulide and thia 2 reduced both paw edema and peritoneal exudate volume significantly (p <0.01). Wet weight of cotton pellets reduced significantly (p <0.01) by diclofenac, nimesulide and thia 2. Diclofenac (p <0.01) and thia 2 (p <0.05) reduced dry weight of cotton pellets significantly. nimesulide and thia-1 reduced it by 19.14% and 2.68% respectively and was considered statistically not significant (p>0.05). Nimesulide, thia-1 and thia-2 did not increase gastric ulcer score significantly (p >0.05). Diclofenac increased ulcer score significantly (p <0.01).Conclusions: Thia-2 demonstrated significant anti-inflammatory activity in acute and chronic models. In addition to inhibition of cyclooxygenase pathway, PPAR agonistic activity may be involved in its anti-inflammatory activity.  No significant ulcerogenicity was observed on comparing with nimesulide and control. Further in-vitro and in-vivo studies are recommended to confirm the results of this study.


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  

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