Cacalol Acetate, a Sesquiterpene from Psacalium decompositum, Exerts an Anti-inflammatory Effect through LPS/NF-KB Signaling in Raw 264.7 Macrophages

Abstract

Inflammatory diseases remain critical health problems worldwide. The search for anti-inflammatory drugs is a primary activity in the pharmaceutical industry. Cacalol is a sesquiterpene with anti-inflammatory potential that is isolated from Psacalium decompositum, a medicinal plant with several scientific reports supporting its anti-inflammatory activity. Cacalol acetate (CA) is the most stable form. Nevertheless, the participation of CA in the main signaling pathway associated with inflammation is unknown. Our aim was to study the anti-inflammatory effect of CA and to determine its participation in NF-κB signaling. In TPAinduced edema in mice, CA produced 70.3% inhibition. To elucidate the influence of CA on the NF-κB pathway, RAW 264.7 macrophages were pretreated with CA and then stimulated with LPS, evaluating NF-ΚB activation, IKK phosphorylation, IΚB-α, p65, cytokine expression, and COX-2 release and activity. CA inhibited NF-κB activation and its upstream signaling, decreasing phosphorylation IKB-α and p65 levels. CA also reduced expression and secretion of TNF-α, IL-1β, and IL-6. Additionally, it decreased the activity and expression of COX-2 mRNA. These data support that CA regulates the NF-κB signaling pathway, which might explain, at least in part, its anti-inflammatory effect. CA is a bioactive molecule useful for the development of anti-inflammatory agents with innovative mechanisms of action.

Contributions from Mexican Flora for the Treatment of Diabetes Mellitus: Molecules of Psacalium decompositum (A. Gray) H. Rob & Brettell

“…The results point out that the cacalol extract regulates the NF-κB signaling pathway, participating in the decrease of its activation, thus inhibiting a large number of inflammation mediators, thus reducing the inflammatory process in the generation of edema. In this manner, the participation of the natural products obtained from P. decompositum continues to contribute novel anti-inflammatory mechanisms that could establish the bases for new and future drugs [ 110 ].…”

Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM2.5

“…The transcription factor NF-κB may be related with the anti-inflammatory properties of PM 2.5 exposure. The proteins p65 and IKK are the important subunits of the NF-κB family and their expression is correlated with NF-κB activity (15). Our results revealed that the expression levels of p65 and IKK in the PM 2.5 group were markedly higher than that in the NC group.…”

Preparation of 2-Nitrocacalol Acetate From a Sesquiterpene Isolated From Roots of Psacalium decompositum. Evaluation of α-Glucosidase and Acetylcholinesterase Inhibition

“…Cacalol acetate ( 2 ) was obtained as a white crystal, in which, the chemical shifts of H 1 and C 13 were according with those reported in the literature. 19,20 In the mass spectrum, an m/z ratio of 273 can be observed for the molecular ion [M+H] + , which corresponds to the expected mass for the cacalol acetate.…”