LIVER FIBROSIS: PATHOPHYSIOLOGY, DIAGNOSIS, AND EMERGING THERAPEUTIC TARGETS FOR A COMMON COMPLICATION OF CHRONIC LIVER DISEASES.

Fibrosis of the liver, which can be caused by either viral or chemical chronic liver illnesses, is a serious issue for the world's health. Collagen is crucial for the development of the illness and the possibility of developing hepatocellular carcinoma (HCC), which is linked to the progression of liver damage. Although there are various mechanisms for acute liver injury and diseases-specific cells response, almost all of fatty liver aetiologies share similar trends in the development of fibrous liver damage. The scientific community's knowledge of the fundamental causes of fibrosis of the liver has undergone a significant shift during the last ten years. It has been shown that the fundamental trigger, such as the control or management of an infectious disease, can be eradicated or eliminated in order to reverse liver fibrosis. Reversing frequently occurs prematurely or too rarely, particularly in severe fibrosis, to avoid possibly fatal effects. Therefore, there is an urgent need for anti-fibrotic medications to halt the progression of liver damage and the appearance of HCC. Even though various anti-fibrotic medication options have shown strong anti-fibrotic effects in lab animals, research studies have only seen a small amount or none of these advantages. There is not an approved remedy for the condition as a result. In this article, we give a general overview of the physiological and molecular origins of collagen in chronic liver disease and investigate how these causes can impact the quickly developing field of anti-fibrotic treatments.

Quercitrin neutralizes sPLA2IIa activity, reduces the inflammatory IL-6 level in PC3 cell lines, and exhibits anti-tumor activity in the EAC-bearing mice model.

Human phospholipase A2 group IIa (sPLA2IIa) is an inflammatory enzyme that plays a significant role in tumorigenesis. Inhibiting the sPLA2IIa enzyme with an effective molecule can reduce the inflammatory response and halt cancer progression. The present study evaluates quercitrin, a biflavonoid, for sPLA2IIa inhibition and anticancer activity. Quercitrin inhibited sPLA2IIa activity to a greater extent-at 86.24% ± 1.41 with an IC50 value of 8.77 µM ± 0.9. The nature of sPLA2IIa inhibition was evaluated by increasing calcium concentration from 2.5 to 15 µM and substrate from 20 to 120 nM, which did not alter the level of inhibition. Intrinsic fluorescence and far UV-CD studies confirmed the direct interaction of quercitrin with the sPLA2IIa enzyme. This significantly reduced the sPLA2IIa-induced hemolytic activity and mouse paw edema from 97.32% ± 1.23-16.91% ± 2.03 and 172.87% ± 1.9-118.41% ± 2.53, respectively. As an anticancer activity, quercitrin reduced PC-3 cell viability from 98.66% ± 2.51-18.3% ± 1.52 and significantly decreased the IL-6 level in a dose-dependent manner from 98.35% ± 2.2-37.12% ± 2.4. It increased the mean survival time (MST) of EAC-bearing Swiss albino mice from 30 to 35 days. It obeyed Lipinski's rule of five, suggesting a druggable property. Thus, all the above experimental results were promising and encouraged further investigation into developing quercitrin as a therapeutic drug for both inflammatory diseases and cancers.