https://orcid.org/0000-0001-5751-270X
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Abstract
The global scientific community is striving to understand the pathophysiological mechanisms and develop effective therapeutic strategies for COVID-19. Despite overwhelming data, there is limited knowledge about the molecular mechanisms involved in the prominent cytokine storm syndrome and multiple organ failure and fatality in COVID-19 cases. The aim of this work is to investigate the possible role of of α-lipoic acid (ALA) and palmitoylethanolamide (PEA), in countering the mechanisms in overproduction of reactive oxygen species (ROS), and inflammatory cytokines. An in vitro model of lipopolysaccharide (LPS)-stimulated human epithelial lung cells that mimics the pathogen-associated molecular pattern and reproduces the cell signaling pathways in cytokine storm syndrome has been used. In this model of acute lung injury, the combination effects of ALAPEA, administered before and after LPS injury, were investigated. Our data demonstrated that a combination of 50 µM ALA + 5 µM PEA can reduce ROS and nitric oxide (NO) levels modulating the major cytokines involved on COVID-19 infection when administered either before or after LPS-induced damage. The best outcome was observed when administered after LPS, thus reinforcing the hypothesis that ALA combined with PEA to modulate the key point of cytokine storm syndrome. This work supports for the first time that the combination of ALA with PEA may represent a novel intervention strategy to counteract inflammatory damage related to COVID-19 by restoring the cascade activation of the immune response and acting as a powerful antioxidant.
Acknowledgements
Authors thank Mariangela Fortunato for reviewing the language. Authors also thank Laborest spa which donated the substances.
Declaration of interest
The authors declare that they have no competing interests. FU and CM are co-founder of noivita srls start up at University of Eastern Piedmont.
Authors’ contributions
Conceptualization, FU; methodology, SR and RG; formal analysis, SR, RG and MF; investigation, FU and CM; writing—original draft preparation, MF and SR; supervision, FU; project administration, FU and CM; funding acquisition, FU and CM. All authors have read and agreed to the published version of the manuscript.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
About the authors
Francesca Uberti, Researcher in Physiology on “Aging Project” funding at the University of Eastern Piedmont (Italy). During her scientific activity she has dealt with the extraskeletal effects of vitamin D, as well as with mechanisms related to degenerative processes also in the field of neurophysiology. He is also co-founder of the university spin-off noiVita s.r.l.s., and co-owner of patents in the field of natural extracts suitable for the preparation of food supplements. Member of the Italian Society of Physiology and of the American Physiological Society. Editor of numerous peer reviewed scientific journals. He is a member of the Governance group of the AGING project.
Sara Ruga, Second year PhD student in “Food, Health and factor promoting longevity” in the translational medicine department of the Eastern Piedmont University (Italy). His scientific activity focuses on Aging and the mechanisms involving metabolic dysregulation and hormones related to aging; in particular, the line of research focuses on biological mechanisms that act directly on muscle and bone. In addition, he is co-author of numerous articles in the nutraceutical field.
Mahitab Farghali, Third year PhD student in “Biological and Biotechnological Sciences” in the translational medicine department of the University of Eastern Piedmont (Italy). During her scientific activity she has been involved in neuroscience at the University of Alexandria in Egypt. His research topics currently focus on the study of targeted antioxidants to protect brain aging. He is also co-author of numerous articles in the nutraceutical field.
Rebecca Galla, Master’s Degree in Medical Biotechnology at the University of Eastern Piedmont (Italy). Winner of the “Fondazione Goria e Fondazione CRT, Master dei talenti della Società Civile 2020” in which she is carrying out in-depth studies on the problems related to hypolactasia. In addition, he is co-author of articles in the nutraceutical field.
Claudio Molinari, Associate Professor of Physiology at the University of Eastern Piedmont (Italy). Over the years he has also dealt with regulatory neurophysiology, heart rate variability and extraskeletal effects of vitamin D. He is co-founder of the university spin-off noiVita srls, and co-owner of patents in the field of natural extracts suitable for the preparation of food supplements. Member of numerous scientific societies of Physiology, Italian and foreign. Member of the Italian Sports Medicine Federation. Member of the Piedmont Region Commission for Complementary Medicines. It has an intense activity of public engagement and scientific dissemination. He is a member of the Governance group of the Aging Project and of the editorial board of the site.