Immunomodulation and Antioxidant Activities as Possible Trypanocidal and Cardioprotective Mechanisms of Major Terpenes from Lippia alba Essential Oils in an Experimental Model of Chronic Chagas Disease

• Published in: Antioxidants Vol. 10; no. 11; p. 1851
• Main Authors: Espinel-Mesa, Denerieth Ximena, González Rugeles, Clara Isabel, Mantilla Hernández, Julio César, Stashenko, Elena E., Villegas-Lanau, Carlos Andrés, Quimbaya Ramírez, John Jaime, García Sánchez, Liliana Torcoroma
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 22-11-2021; MDPI
• Subjects: antioxidant; Antioxidants; Benznidazole; Cardiomyopathy; Cardiovascular disease; Caryophyllene; Caryophyllene oxide; Chagas disease; Chromatography; chronic Chagas disease; Chronic illnesses; Chronic infection; Coronary artery disease; Essential oils; FDA approval; Heart diseases; Immune response; immunohistochemistry; Immunomodulation; Infections; Inflammation; Interleukin 10; Interleukin 4; Laboratory animals; Limonene; Lippia alba; Nifurtimox; Nitric-oxide synthase; Oils & fats; Oxidative stress; Parasites; Terpenes; Testing laboratories; Toxicity; Trypanosoma cruzi; Tumor necrosis factor-α; γ-Interferon; Colombia; Palo Alto California; United States > US
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox10111851

In the late phase of Trypanosoma cruzi infection, parasite persistence and an exaggerated immune response accompanied by oxidative stress play a crucial role in the genesis of Chronic Chagasic Cardiomyopathy (CCC). Current treatments (Benznidazole (BNZ) and Nifurtimox) can effect only the elimination of the parasite, but are ineffective for late stage treatment and for preventing heart damage and disease progression. In vivo trypanocidal and cardioprotective activity has been reported for Lippia alba essential oils (EOs), ascribed to their two major terpenes, limonene and caryophyllene oxide. To investigate the role of antioxidant and immunomodulatory mechanisms behind these properties, chronic-T. cruzi-infected rats were treated with oral synergistic mixtures of the aforementioned EOs. For this purpose, the EOs were optimized through limonene-enrichment fractioning and by the addition of exogenous caryophyllene oxide (LIMOX) and used alone or in combined therapy with subtherapeutic doses of BNZ (LIMOXBNZ). Clinical, toxicity, inflammatory, oxidative, and parasitological (qPCR) parameters were assessed in cardiac tissue. These therapies demonstrated meaningful antioxidant and immunomodulatory activity on markers involved in CCC pathogenesis (IFN-γ, TNF-α, IL-4, IL-10, and iNOS), which could explain their significant trypanocidal properties and their noteworthy role in preventing, and even reversing, the progression of cardiac damage in chronic Chagas disease.