Immunomodulatory Effects of Lippia sidoides Extract: Induction of IL-10 Through cAMP and p38 MAPK-Dependent Mechanisms

Abstract

Lippia sidoides is an aromatic shrub that grows wild in the northeastern region of Brazil. In local traditional medicine, the aerial portions of this species are used as anti-infectives, antiseptics, spasmolytics, sedatives, hypotensives, and anti-inflammatory agents. In this research, we evaluate the potential immunological properties of Lippia extract through in vitro analysis of its ability to modulate intracellular cyclic adenosine monophosphate (cAMP) levels and interleukin-10 (IL-10) production. These results show that Lippia extract increases intracellular cAMP through the inhibition of phosphodiesterase activity. They also demonstrate that Lippia extract increases IL-10 production in THP-1 monocytes through both an increase in intracellular cAMP and the activation of p38 MAPK. These results suggest that the Lippia-mediated inhibition of phosphodiesterase activity and the subsequent increase in intracellular cAMP may explain some of the biological activities associated with L. sidoides. In addition, the anti-inflammatory activity of L. sidoides may also be due, in part, to its ability to induce IL-10 production through the inhibition of cyclic nucleotide-dependent phosphodiesterase activity and by its activation of the p38 MAPK pathway.

General Characteristics, Phytochemistry and Pharmacognosy of Lippia sidoides

“…Aerial parts extract increased the cyclic adenosine monophosphate (cAMP) intracellular concentration through inhibition of phosphodiesterase activity. The same extract caused an increase in interleukin-10 (IL-10) production in calcitrol-differentiated THP-1 monocytes through increase in the intracellular concentration of cAMP and p38MAPK activation [68]. These results demonstrate that the processes that modulate the mechanisms of cellular signaling are related to the anti-inflammatory activities found in the extract of L. sidoides.…”

Nortropane alkaloids as pharmacological chaperones in the rescue of equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome through mitochondrial potentiation, endoplasmic reticulum stress mitigation and insulin resistance alleviation

“…Thus, anti-apoptotic effect of calystegines, manifested by the upregulation of the Bcl-2 gene, could be partly related to modulation of cAMP production. Several studies have shown that certain secondary metabolites, such as hyoscyamine and atropine, which are like calystegines tropane metabolism-related alkaloid, possess the capacity to stimulate the cAMP pathway mainly by enhancing its synthesis [35–37].…”

Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro

“…34 Work of others on the anti-inflammatory activity of several natural agents has also shown effects on IL-10 and DCs. Lippia sidoides, an aromatic shrub, can induce IL-10 production in THP-1 monocytes; 35 PureCell Complex (PCT)-233, an active molecular complex from Spinacia oleracea, increased IL-10 production but did not significantly modulate TNF release in alveolar macrophages treated with PCT-233 and budesonide after LPS stimulation; 36 and a complex mixture of herbal extracts has been shown to modulate the innate responsiveness of murine DCs. 37 While we do not fully understand the underlying mechanisms of MRN-100's activation of DCs, MRN-100 could act by binding to DC surface receptors or by being phagocytized, ultimately triggering the signaling mechanisms for DC activation and cytokine secretion.…”