Investigation of the Mechanism of Anti-Inflammatory Action and Cytotoxicity of a Semipurified Fraction and Isolated Compounds From the Leaf of Peltophorum africanum (Fabaceae)

Abstract

Peltophorum africanum extracts have been shown to possess many important medicinal benefits, including anti-inflammatory and antiviral activities. However, the mechanism of action is poorly understood. The mechanism of anti-inflammatory action was determined by measuring the synthesis of cytokines in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage cells in vitro. Compound 1 (CP1), compound 2 (CP2), and fraction F3.3.0 (F3.3.0) significantly reduced the synthesis of interleukin 1β (IL-1β) from RAW 264.7 cells (1.18, 1.32, and 0.92 ng/mL), respectively. Similarly, CP1, CP2, and F3.3.0 inhibited the production of IL-2 and tumor necrosis factor–α (TNF-α) by RAW 264.7 cells (0.41, 0.60, 0.74 and 0.11, 0.27, 0.24 ng/mL, respectively. In addition, CP1 and CP2 had lower cytotoxicity toward RAW 264.7 cells, with CP2 indicating the lowest cytotoxicity (LD50 = 207.88 µg/mL). The mechanism of action was found to be via the inhibition of pro-inflammation cytokines (IL-1 β and TNF-α). This observation may support the use of P africanum to treat pain-related conditions.

Screening of In-Vitro Anti-Inflammatory and Antioxidant Activity of Sargassum ilicifolium Crude Lipid Extracts from Different Coastal Areas in Indonesia

“…Although PI sample also showed a strong NO-inhibition effect on RAW 264.7 cells after LPS stimulation, this sample was not considered as potential anti-inflammatory sources because it gave the highest cytotoxicity to the cells. Both cytotoxic and biological activities of bioactive components need to be considered because they provide an overview of the safety and efficacy of the tested compound [ 41 , 42 , 43 ]. In the anti-inflammatory screening studies, Adebayo et al [ 41 ] and Somchit et al [ 42 ] used the selectivity index (SI) to ascertain that the observed anti-inflammatory effect of the tested compound was not due to a general metabolic toxic effect on the RAW 264.7 cell lines.…”

<p><em>Grewia mollis</em> Leaf Extracts and Fractions Demonstrated Good Inhibitory Activity on Pro-Inflammatory Enzymes and with Lower Cytotoxicity in vitro</p>

“…The higher the value of SI, the greater the probability that the observed bioactivity (anti-inflammatory) was not as a result of metabolic toxicity of the test extracts. 1 …”

“…Cyclooxygenases and 15-LOX are the key enzymes responsible for the synthesis and release of prostanoids and eicosanoids from poly-unsaturated fatty acids (PUFAs), respectively, that exacerbate chronic inflammation and other pathogenic and allergic disorders. 1 , 2…”

Lirioresinol B dimethyl ether inhibits NF-κB and COX-2 and activates IκBα expression in CCl4-induced hepatic fibrosis

“…Cells treated with DMSO served as a control. Cells were exposed to various concentrations (5,10,20,40, and 80 μM) of LBDE for 24 h. Then, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was dissolved in 1X PBS (5 mg/mL) and total of 50 μL was added to each well. After 2 h incubation at 37°C, total of 100 μL DMSO (Sigma) was added to dissolve the crystals in each well.…”

“…The concentration of LBDE that reduced cell proliferation by 50% (IC50) was calculated by nonlinear regression fit using GraphPad Prism. The selectivity index (SI) was also calculated from the IC50 ratio of HEK-293 and HePG2 cells as previously shown [20,21]. SI value indicates the selectivity of the LBDE against HEK-293 and HePG2 cell lines tested.…”