Inhibition of Inflammatory Cytokine Secretion by Plant-Derived Compounds Inuviscolide and Tomentosin: The Role of NFκB and STAT1

Abstract

The plant Inula viscosa has been shown to possess many important medicinal benefits, including anti-inflammatory, anti-oxidant, anti-bacterial, and anti-fungal activities, but the plant metabolites that mediate these effects and their mechanism of action are poorly understood. In a previous study, we demonstrated a reduced expression of the p65 subunit of nuclear factor kappa B (NFκB) in melanoma cells treated with the purified sesquiterpene lactone compounds, Inuviscolide (Inv) and Tomentosin (Tom), extracted from Inula viscosa leaves. In this study, we tested the invitro effect of these purified compounds on the secretion of pro-inflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) upon stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). Their possible mechanism of action was also studied. The results showed that both agents caused decreased production of IL-2, IL-1β, IFNγ, and slightly increased secretion of TNFα, whereas secretion of IL-6 was not affected. The elevated levels of TNFα did not appear to affect the viability of human PBMCs. Western blot analysis revealed a reduction in the protein level of both the transcription factor component p65/RelA of nuclear factor-κB (NFκB) and the signal transducer and activator of transcription 1 (STAT1) through proteosomal degradation. However, no change was observed in the expression level of the nuclear factor-κB component, p50 (NFκB), or the signal transducer and activator of transcription 3 (STAT3). Taken together, our results indicate the possible future use of these agents as an anti-inflammatory treatment in cases where overstimulation of cytokine secretion is the basis for the pathological symptoms.

Antimicrobial and anti-inflammatory potential therapy for opportunistic microorganisms

“…Abrham et al [44] evaluated the anti-inflammatory effect of purified compounds of I. viscosa leaves on the secretion of pro-inflammatory cytokines from PBMCs upon stimulation with LPS or phorbol myristate acetate (PMA). Their results showed no effect on the secretion of IL-6.…”

Effects of Aqueous and Butanol Leaf Fractions of Olax subscorpioidea Oliv. on Inflammatory Cytokines in Wistar Rats

“…These leaf fractions may also serve as a prophylactic agent for malignancies; as inflammation, supported by pro-inflammatory cytokines; precede tumor appearance. 36 In this study, the concentrations of a potent pro-inflammatory cytokine, TNF-α, and that of a potent anti-inflammatory cytokine, IL-10, were not affected by the leaf fractions. The reasons may be due to the complexity in regulatory networks that govern inflammatory cytokine secretion upon specific stimulation, which might contribute to the different effects of the various cytokines tested.…”

“…The reasons may be due to the complexity in regulatory networks that govern inflammatory cytokine secretion upon specific stimulation, which might contribute to the different effects of the various cytokines tested. 36 These also suggest that measuring just one inflammatory cytokine may be misleading and may also give an unreliable result. Phytochemicals have been shown to modulate various points in inflammatory processes by disconnecting the amplification of inflammatory processes and thereby reducing subsequent diseases risk.…”

Anti-inflammatory Activity of Dichloromethane Extract of Auricularia auricula-judae in RAW264.7 Cells

“…Inflammatory response plays an important role not only in the normal physiology but also in pathology when inflammation is recognized as a major driving force leading to development of malignancy such as cancer. Medicinal plants and their products have been used for many centuries to treat different kinds of acute and chronic inflammatory diseases like wound healing, edema and rheumatoid arthritis (Abrham et al ., 2010) . However, regardless of the recognized effects of several traditionally used medicinal herbs, their pharmacological activities have not been thoroughly investigated concerning their immunological effects.…”