Acmella oleracea Is a Medicinal Plant That Decreases Chymase Activity, Oxidative Stress, and Inflammation: Possible Role in the Adjuvant Treatment of COVID-19.

Abstract

Journal of Medicinal FoodVol. 24, No. 11 Letter to the EditorFree AccessAcmella oleracea Is a Medicinal Plant That Decreases Chymase Activity, Oxidative Stress, and Inflammation: Possible Role in the Adjuvant Treatment of COVID-19Eduardo Luis Konrath, Markus Berger, Rafael Lopes da Rosa, and Walter Orlando Beys-da-SilvaEduardo Luis KonrathAddress correspondence to: Eduardo Luis Konrath, PhD, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752, Porto Alegre 90610-000, Rio Grande do Sul, Brazil, E-mail Address: eduardo.konrath@ufrgs.brhttps://orcid.org/0000-0003-1838-4228Faculty of Pharmaceutical Sciences, Post-Graduation Program in Pharmaceutical Sciences and Post-Graduation Program in Cellular and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.Search for more papers by this author, Markus BergerExperimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, Brazil.Search for more papers by this author, Rafael Lopes da RosaFaculty of Pharmaceutical Sciences, Post-Graduation Program in Cellular and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.Search for more papers by this author, and Walter Orlando Beys-da-SilvaFaculty of Pharmaceutical Sciences, Post-Graduation Program in Cellular and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.Search for more papers by this authorPublished Online:17 Nov 2021AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Dear Editor:Acmella oleracea (Asteraceae), popularly known as “paracress” or “jambú,” is an edible herb widely used in culinary as a condiment in dishes in northern Brazil and for medicinal purposes in analgesic, anesthetic, and anti-inflammatory folk preparations. Recently, we became aware that A. oleracea leaves and flowers extracts (AOE), as well as its main N-alkylamide component spilanthol, can potently inhibit chymase enzyme activity, working as a mediator of the renin-angiotensin system (RAS) and displaying an acute anti-inflammatory effect.1The RAS has attracted widespread interest since one of its components, the angiotensin converting enzyme 2 (ACE2), was identified as the cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),2 the virus that causes coronavirus disease 2019 (COVID-19) pandemic. ACE2 is the main regulator of the vasodilatory and cytoprotective axis of RAS, converting angiotensin (Ang) I and Ang II into Ang 1-9 and Ang 1-7, respectively.3 The axis formed by ACE2, Ang 1-7 and its receptor MAS, elicits protective effects against hypertension, thromboembolic diseases, and also alleviates pulmonary injury, lung fibrosis, and vascular damage, as already demonstrated by several in vivo/in vitro models.4The glycosylated spike protein from SARS-CoV-2 binds to the extracellular domain of ACE2, a membrane bound carboxypeptidase expressed in lung alveolar epithelial cells, heart and vascular system, among others tissues, leading to virus internalization. The direct consequence of SARS-CoV-2 internalization is the reduction of ACE2 presence in cell surface, reduction of the carboxypeptidase activity, and decrease in Ang II degradation and Ang 1-7 generation.5 Thus, the host develops an imbalance between Ang II and Ang 1-7 levels, being the vasoconstrictor axis formed by Ang II and its receptor, AT1R, upregulated. All these events further exacerbate lung damage, inflammation, and thromboembolism observed during COVID-19, since the increase in Ang II can upregulate proinflammatory and procoagulant cytokines, whereas the decrease in ACE2/Ang1-7 can favor platelet aggregation and thrombus formation.Owing to the RAS imbalance during COVID-19, some therapeutic strategies acting on this system have emerged. Accordingly, chymase, a chymotrypsin-like serine-protease able to generate directly Ang II independently from ACE activity might be considered an interesting target to be explored in COVID-19 pathological situations.AOE from flowers and leaves similarly reduced the inflammatory process in a preclinical model on vascular smooth muscle cells and rats, with an expressive inhibition of nitric oxide (NO) production and no signs of liver and kidney toxicity. The mechanism of action of both AOE and spilanthol is based on the simultaneous inhibition of the proinflammatory chymase enzyme and the counteraction of oxidative species overproduction (Fig. 1). Furthermore, spilanthol proved to prevent not only direct chymase increase, but also to downregulate efficiently its expression, inhibiting strongly the NO production during the inflammatory process.1 These properties demonstrate the possibility to obtain therapeutic derivatives from A. oleracea, a traditional edible plant commonly used in Brazil. An effective player in the war against SARS-CoV2 infection consequences is needed, and chymase inhibitors show reasonable evidence to prevent or reduce the COVID-19 acute inflammation and consequently the mortality rate of infected individuals.FIG. 1. Acmella oleracea/spilanthol anti-chymase activity as a potential anti-inflammatory alternative for COVID-19 acute inflammation. COVID-19, coronavirus disease 2019.Author Disclosure StatementNo competing financial interests exist.Funding InformationWe would like to thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for RLR fellowship.