الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
Inflammation is the immune system’s reaction to harmful stimuli, which can include pathogens, damaged cells, toxic compounds, or irradiation. Its primary role is to eliminate these harmful agents and start the healing process, making it a crucial defense mechanism for overall health. During acute inflammatory responses, various cellular and molecular events work together efficiently to reduce potential injury or infection, leading to the restoration of tissue balance and resolution of the acute inflammation. However, if acute inflammation is not properly controlled, it can progress into a chronic state, leading to the development of various chronic inflammatory diseases. The inflammatory process is typically very closely controlled, involving both signals that start and keep the inflammation going, as well as signals that stop it. Cellular and tissue damage happens when inflammation is allowed to spread unchecked due to an imbalance between the two signals. Monocytes go into different tissues from the circulation and develop into macrophages. Antigen presentation, phagocytosis, and immunomodulation through the production of different cytokines and growth factors are the three main roles of macrophages in inflammation. Macrophages are essential to the beginning, continuation, and end of inflammation. In the course of inflammation, they are both activated and deactivated. Herbal medicine is becoming more common due to the fact that it is safer to use than synthetic compounds. Glycyrrhiza glabra, also known as ‘Liquorice,’ is an essential medicinal plant. The biological activities of this plant species have been published in the literature, including anti-inflammatory and expectorant properties. Natural products and other semisynthetic and synthetic derivatives were proved to be a valuable source for diverse anti-inflammatory drug. Therefore, the present work aimed to evaluate the anti-inflammatory activity for novel derivatives of glycyrrhizin and other synthetic and semisynthetic compounds in order to discover a new safe and effective anti-inflammatory drug. The activity was evaluated in vitro model on RAW 264.7 cell line through estimation of: 1. Gene expression of TNF-α, INF-γ, COX-2 and INOS by RT-PCR. 2. Changes in the cytokines concentration in RAW 264.7 after treating with studied compounds by ELISA such as TNF-α and INF-γ, and changes in protein expression of STAT3 and NF—κB proteins by western blot. 3. Levels of inflammatory markers as nitric oxide. The selected compounds were subjected for initial screening using Raw264.7 macrophage cell lines followed by MTT assay to detect cell viability, real time PCR to detect gene expression of TNF-α, INF-γ, COX-2 and INOS, ELISA assay to measure cytokines concentration such as INFγ, and TNF-α, western blot for detecting protein expression as STAT3 and NF-κB proteins and determination of nitric oxide level by Griess assay. The following results were obtained: Treatment with selected compounds did not reduce RAW 264.7 cell viability with the most of spirooxindoles but with glycyrrhizin derivatives and compounds, SG010, DSE157 and DSE120 reduced cell viability. Therefore, we had focused on spirooxindoles compounds such as pys-40A, pys-40C, pys-40J,pys-40I, pys-40L, pys-40D and pys-40P which were thoroughly studied using MTT assay, nitric oxide assay, real time PCR, ELISA assay, western blot and nitric oxide assay. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that spirooxindoles significantly reduced mRNA levels of TNF-α, INF-γ, INOS and COX-2 in LPS induced macrophages. The expression of TNF-α and INF-γ was inhibited. The level of STAT3 and NF-κB proteins was reduced. Spirooxindoles showed significantly inhibition in the production of LPS induced nitric oxide (NO). from the present study, it may be concluded that: Spirooxindoles compounds might serve as helpful starting points for the creation of more effective and targeted anti-inflammatory drugs. Moreover, glycyrrhizin has protective effects by preventing the generation of TNF-α and INF-γ and reducing STAT3 and NF-κB protein levels. Thus, these compounds might be helpful in the treatment of inflammatory diseases.