Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative

Abstract

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1β, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.

Novel pyrrolopyrimidine derivatives: design, synthesis, molecular docking, molecular simulations and biological evaluations as antioxidant and anti-inflammatory agents

“…In which the inhibition of PGE synthesis is considered an important anti-inflammatory strategy 93 , 97 , 98 . PGE2 is generated by the conversion of arachidonic acid (AA), which is released and used by 2 different cyclooxygenases (COXs), COX-1 (constitutive) and COX-2 (inducible) 53 , 74 , 88 , 89 , 91 , 99–104 . COX-2 is responsible for prostaglandin production during different pathological processes involving inflammation 97 , 98 , 105 .…”

Semisynthesis and Evaluation of Anti-Inflammatory Activity of the Cassane-Type Diterpenoid Taepeenin F and of Some Synthetic Intermediates

“…Cellular subpopulations, with different DNA contents, were visualized, using a fluorescence-activated cell sorter (FACS) at 488 nm in an Epics XL flow cytometer (Coulter Corporation, Hialeah, FL, USA). Changes in DNA levels are characteristic of cell-cycle arrest and cell differentiation . For this assay, 12 × 10 4 RAW 264.7 murine macrophage/monocyte cells stimulated with LPS were plated in 24-well plates with 1.5 mL of medium and incubated with the compounds under study for 24 h, at 3/4IC 50 and 1/2IC 50 concentrations.…”

“…Changes in DNA levels are characteristic of cell-cycle arrest and cell differentiation. 36 For this assay, 12 × 10 4 RAW 264.7 murine macrophage/monocyte cells stimulated with LPS were plated in 24-well plates with 1.5 mL of medium and incubated with the compounds under study for 24 h, at 3/4IC 50 and 1/2IC 50 concentrations. Several controls were analyzed in parallel.…”

Anti-Inflammatory Activity of Three Triterpene from Hippophae rhamnoides L. in Lipopolysaccharide-Stimulated RAW264.7 Cells

“…Terpenes are widely distributed in nature and many derivatives inhibit tumor progression, inflammation, and lipid peroxidation. The anti-inflammatory activity of the triterpenoid acids OA, asiatic acid (AA), and MA has been separately demonstrated [ 5 , 6 , 7 ]. Oleanolic acid is an oleanane-type five-ring triterpenoid compound.…”