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

Abstract

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.

D-Limonene: Promising and Sustainable Natural Bioactive Compound

“…Moreover, D-limonene is cardioprotective and gastroprotective [20,164], in addition to inhibiting the activity of cardiotoxicity biomarkers, such as alanine aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase MB, and the MAPK/NF-κB pathway; to reduce the damage of myocardial infarction, it also prevents cardiac histopathological changes [159,165]. Furthermore, oral D-limonene can increase local gastric mucosal defense mechanisms, such as mucus secretion, regulation of oxidative stress and inflammatory responses, and inhibition of the NF-κB pathway, to exert gastroprotective effects [17].…”

Lippia origanoides Essential Oil or Thymol in Combination with Fluconazole Produces Damage to Cells and Reverses the Azole-Resistant Phenotype of a Candida tropicalis Strain

“…This may provide an opportunity to discover EOs with antifungal activity. The aromatic species of plants of the Lippia (Verbenaceae) genus, have been studied in Colombia for their biological activities [ 33 , 34 , 35 ]. Lippia origanoides is a species of aromatic plant commonly known as “mountain oregano” and has been used by native communities for its medicinal properties [ 36 , 37 ].…”