Taheebo Polyphenols Attenuate Free Fatty Acid-Induced Inflammation in Murine and Human Macrophage Cell Lines As Inhibitor of Cyclooxygenase-2

Abstract

Aim of studyTaheebo polyphenols (TP) are water extracts of Tabebuia spp. (Bignoniaceae), taken from the inner bark of the Tabebuia avellanedae tree, used extensively as folk medicine in Central and South America. Some anti-inflammatory drugs act by inhibiting both cyclooxygenase-2 (COX-2) and COX-1 enzymes. COX-2 syntheses prostaglandin (PG) E2, which is a species of endogenous pain-producing substance, whereas COX-1 acts as a house-keeping enzyme. Inhibiting both COX-1 and -2 simultaneously can have side effects such as gastrointestinal bleeding and renal dysfunction. Some polyphenols have been reported for its selective inhibiting activity toward COX-2 expression. Our study aimed to demonstrate the potential and mechanisms of TP as an anti-inflammation action without the side effects of COX-1 inhibition.Materials and methodsFree fatty acid-stimulated macrophage cell lines were employed to mimic macrophage behaviors during lifestyle-related diseases such as atherosclerosis and non-alcoholic steatohepatitis. Real-time polymerase chain reaction was used to detect expression of inflammatory cytokine mRNA. Griess assay was used to measure the production of nitric oxide (NO). ELISA was used to measure PG E2 production. Molecular docking was adopted to analyze the interactions between compounds from T. avellanedae and COX-2.ResultsTP significantly suppressed the production of NO production, blocked the mRNA expression of iNOS, and COX-2 in both cell lines, blocked the mRNA expression of TNF-α, IL-1β, IL-6, and PGE2 in the murine cell line. However, there was no inhibitory effect on COX-1. Molecular docking result indicated that the inhibitory effects of TP on COX-2 and PGE2 could be attributed to acteoside, which is the main compound of TP that could bind to the catalytic zone of COX-2. After the interaction, catalytic ability of COX-2 is possibly inhibited, followed by which PGE2 production is attenuated. COX inhibitor screening assay showed TP as a selective inhibitor of COX-2 enzyme.ConclusionThe anti-inflammatory effects of TP can possibly regulate macrophages due to the targeted inhibition of COX-2 activity, without affecting COX-1 activity with other anti-inflammatory effects including suppression of iNOS and inflammatory cytokines. As such, TP is potentially useful in prevention and treatment of lifestyle-related disease by attenuating inflammation caused by macrophages infiltration.

Single Dose Administration of Taheebo Polyphenol Enhances Endurance Capacity in Mice

“…The main finding of the present study is that TP administration enhanced endurance capacity via up-regulation of muscle glycogen levels. Several studies which investigated the effects of taheebo extract have reported that taheebo has anti-cancer, anti-obesity, anti-inflammation and antioxidant effects 20 – 23 , 26 . The present study is the first report that lights up the mechanisms by which TP benefits endurance capacity.…”

Flavonoids and Other Phenolic Compounds from Medicinal Plants for Pharmaceutical and Medical Aspects: An Overview

“…Mattos; ], a medicinal plant with extensively use as folk medicine in Central and South America, as an anti-inflammation agent without undesirable side effects from COX-1 inhibition. This work was conducted using in vitro free fatty acid-stimulated macrophage cell lines and combined molecular docking to investigate the interactions between the phenolic compounds and COX-2; the obtained results illustrated anti-inflammatory effects of phenolics from this medicinal plant to regulate macrophages by targeting COX-2 activity inhibition without any action on COX-1 activity [ 71 ]. Furthermore, phenolics and flavonoids from bark of Vitex peduncularis Wall.…”

“…The concreted example can be seen in the study of Kaczmarczyk-Sedlak and his research group; their results indicated that moderate dose of isoflavane glabridin from root of Glycyrrhiza glabra L. or licorice plant showed no effect on bone loss in ovariectomized rats, an in vivo model of osteoporosis from estrogen deficiency in postmenopausal women [ 103 ]. The secondary metabolites discovered in medicinal plants such as flavonoids and other phenolics may avoid the negative side effect of synthetic medicines, because they must accumulate within the cells and tissues of living organisms [ 71 , 95 , 96 ]. Moreover, many medicinal herbs contain novel or valuable secondary metabolites with different biological properties, and a huge numbers of them are waiting for discovery.…”

“…As a plant secondary metabolites, flavonoids and the other phenolics are found in several plant species, type and amount of the chemical components are vary depending on species and affecting by environmental factors i.e., mineral at the growth locality and geographic origin [ 70 ]. Nowadays, there is a significant increase in the number of research on potential of medicinal plant species for pharmaceutical and medical purposes focusing on natural phenolic compounds and flavonoids [ 1 , 4 , 9 , 16 , 18 , 51 , 63 , 71 , 73 , 104 ].…”

Cytokine Response to Exercise and Its Modulation

“…Intestinal permeability increases following exercise, and endotoxemia occurs, which induces systemic inflammation [ 4 , 39 , 43 , 44 ]. Therefore, other countermeasures such as intake of some functional foods for gut barrier protection, bioavailability, and distribution [ 3 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ], and appropriate immune responsiveness should be examined in future studies.…”