decursin and Inflammation

Topics: Angelica; Animals; Apoptosis; Benzopyrans; Butyrates; Cytokines; Hair; HMGB1 Protein; Inflammation; Male; Mice; Mice, Inbred C57BL; Plant Extracts; Plant Roots; Skin

In this study, the anti-inflammatory effects of α-lipoic acid (LA) and decursinol (Dec) hybrid compound LA-Dec were evaluated and compared with its prodrugs, LA and Dec. LA-Dec dose-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) generation in BV2 mouse microglial cells. On the other hand, no or mild inhibitory effect was shown by the Dec and LA, respectively. LA-Dec demonstrated dose-dependent protection from activation-induced cell death in BV2 cells. LA-Dec, but not LA or Dec individually, inhibited LPS-induced increased expressions of induced NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in a dosedependent manner in both BV2 and mouse macrophage, RAW264.7 cells. Furthermore, LA-Dec inhibited LPS-induced expressions of iNOS, COX-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β mRNA in BV2 cells, whereas the same concentration of LA or Dec was ineffective. Signaling studies demonstrated that LA-Dec inhibited LPS-activated signal transducer and activator of transcription 3 and protein kinase B activation, but not nuclear factor-kappa B or mitogen-activated protein kinase signaling. The data implicate LA-Dec hybrid compound as a potential therapeutic agent for inflammatory diseases of the peripheral and central nervous systems. [BMB Reports 2019; 52(8): 508-513].

Topics: Animals; Benzopyrans; Butyrates; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Microglia; Nitrites; RAW 264.7 Cells; Structure-Activity Relationship; Thioctic Acid

Inflammation is known to be closely associated with the development of cancer. Decursinol angelate (DA), a coumarin compound isolated from Angelica gigas and related compounds have been shown to possess potent anti-inflammatory activities. However, little is known about their effects on the inflammatory processes associated with cancer. In this study, the anti-inflammatory effect of DA was evaluated in cancer cell lines with respect to cellular invasion through the extracellular matrix (ECM) and the expression of pro-inflammatory mediators such as cytokine, cell adhesion molecules and matrix metalloproteinase (MMP)-9. DA inhibited the invasion of fibrosarcoma cell line, HT1080 and breast cancer cell line, MDA-MB-231 in the Matrigel invasion assay. DA-mediated suppression of cancer cell invasion was accomplished by suppression of PI3K activity known to be associated with cytoskeletal rearrangement related to cellular migration. DA also suppressed the adhesion of cancer cells to ECM mediated by down-regulation of beta(1)-integrin expression levels. Furthermore, DA inhibited the expression of pro-inflammatory cytokines and MMP-9 through suppression of PI3K, ERK and NF-kappaB activation. These results demonstrate that DA suppresses invasion and inflammatory activation of cancer cells through modulation of PI3K/AKT, ERK and NF-kappaB. These anti-inflammatory activities of DA may contribute to its anti-cancer activity.

Topics: Angelica; Anti-Inflammatory Agents; Antineoplastic Agents; Benzopyrans; Breast Neoplasms; Butyrates; Cell Adhesion; Cell Line, Tumor; Cell Movement; DNA Primers; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases; Female; Fibrosarcoma; Flow Cytometry; Gelatin; Humans; Inflammation; Matrix Metalloproteinase 9; Neoplasm Invasiveness; NF-kappa B; Phosphatidylinositol 3-Kinases; Protein Kinase C; Reverse Transcriptase Polymerase Chain Reaction