β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: May 14, 2021

Coronavirus disease (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic and presents a public health emergency. It has affected millions of people continues to affect more, despite tremendous social preventive measures. Identifying candidate drugs for the prevention treatment COVID-19 crucial. The pathogenesis complications with advanced infection mainly involve immune-inflammatory cascade. Therefore, therapeutic strategy relies on suppressing infectivity inflammation, along immune modulation. One most promising targets modulation responses endocannabinoid system, particularly activation cannabinoid type receptors (CB2R), G-protein coupled receptor which mediates anti-inflammatory properties modulating numerous signaling pathways. To pharmacologically activate CB2 receptors, naturally occurring ligand, beta-caryophyllene (BCP), received attention due its potent anti-inflammatory, antiviral, immunomodulatory properties. BCP recognized as full selective functional agonist produces effects activating nuclear peroxisome proliferator-activated (PPARs). regarded first dietary abundant presence across cannabis non-cannabis plants, including spices other edible plants. showed tissue protective favorably modulates pathways inhibits inflammatory mediators, cytokines, chemokines, adhesion molecules, prostanoids, eicosanoids. Based pharmacological properties, molecular mechanisms, potential immunomodulator, organ-protective, we hypothesize that could be and/or target triad infection, immunity, inflammation in COVID-19. In line studies proposed cannabinoids COVID-19, may compound pharmaceutical nutraceutical development unique selectivity, wide availability accessibility, bioavailability, nonpsychoactivity, negligible toxicity druggable favorable pharmacokinetic physicochemical reasonable mechanisms speculate investigated against will inspire further preclinical clinical studies.

Language: Английский

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An Update on the Role of Nrf2 in Respiratory Disease: Molecular Mechanisms and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8406 - 8406

Published: Aug. 5, 2021

Nuclear factor erythroid 2-related (Nrf2) is a transcriptional activator of the cell protection gene that binds to antioxidant response element (ARE). Therefore, Nrf2 protects cells and tissues from oxidative stress. Normally, Kelch-like ECH-associated protein 1 (Keap1) inhibits activation by binding contributes break down ubiquitin proteasomes. In moderate stress, Keap1 inhibited, allowing be translocated nucleus, which acts as an antioxidant. However, under unusually severe Keap1-Nrf2 mechanism becomes disrupted results in tissue damage. Oxide-containing atmospheric environment generally development respiratory diseases, possibly leading failure pathway. Until now, several studies have identified changes signaling models such acute distress syndrome (ARDS)/acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic fibrosis (IPF), asthma. These confirmed activators can alleviate symptoms diseases. Thus, this review describes how expression functions different diseases explains protective effects reversing expression.

Language: Английский

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TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2

Expert Opinion on Therapeutic Targets, Journal Year: 2021, Volume and Issue: 25(6), P. 491 - 508

Published: April 17, 2021

: The COVID-19 pandemic remains aglobal challenge. While there are mRNA agents on the horizon as apotential prevention, adefinitive drug therapy is an unmet medical need. hyperinflammatory response, known 'cytokine storm', chiefly responsible for complications and deaths. binding of spike-glycoprotein SARS-CoV-2 to TLR4 receptors has been documented in several studies found play arole hyperinflammation; hence, interest target.

Language: Английский

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Can Echinacea be a potential candidate to target immunity, inflammation, and infection - The trinity of coronavirus disease 2019

Heliyon, Journal Year: 2021, Volume and Issue: 7(2), P. e05990 - e05990

Published: Feb. 1, 2021

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public health emergency. The pathogenesis and complications advanced with infection mainly involve immune-inflammatory cascade. Therefore, the therapeutic strategy relies on immune modulation, reducing infectivity inflammation. Given interplay of axis, natural products received attention for preventive usage in COVID-19 due to their potent antiviral anti-immunomodulatory activities. Recently, Echinacea preparations, particularly E. purpurea, have been suggested be important agent useful modulating virus entry, internalization replication. In principle, response resultant inflammatory process are elimination infection, but may a significant impact SARS-CoV-2 play role clinical spectrum COVID-19. Considering pharmacological effects, potential, molecular mechanisms Echinacea, we hypothesize that it could reasonably possible candidate targeting immunity, inflammation recent recognition cannabinoid-2 (CB2) receptors peroxisome proliferator-activated receptor gamma (PPARγ) mediated bioactive components make them notable immunomodulatory, anti-inflammatory agent. plausible reason our hypothesis presence numerous agents different parts plants synergistically exert polypharmacological actions regulating axis Our proposition scientifically contemplate perspective prospect potential limit severity progression disease. Based infections, relative safety humans, further studies evidence-based approach needed. We do hope immunomodulation prevention treatment

Language: Английский

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Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19

International Archives of Allergy and Immunology, Journal Year: 2021, Volume and Issue: 182(4), P. 324 - 338

Published: Jan. 1, 2021

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or vanilloid (TRPV1) activation as well desensitization. TRPA1 and TRPV1 induce inflammation play a key role the physiology of almost all organs. They augment sensory or vagal nerve discharges to evoke pain several symptoms COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden severe loss smell taste. can activated by reactive oxygen species therefore up-regulated COVID-19. channels pungent compounds many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading channel Interactions between Nrf2-associated nutrients TRPA1/TRPV1 partly responsible for severity some symptoms. The regulation Nrf2 is still unclear, but suggested from very limited clinical evidence. it proposed rapid desensitization TRAP1/TRPV1 ingredients could reduce symptom provide new therapeutic strategies.

Language: Английский

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