Quercetin reverses experimental cirrhosis by immunomodulation of the proinflammatory and profibrotic processes

Abstract

The ability of quercetin to reverse an established cirrhosis has not yet been investigated. Therefore, the aim of this study was to examine the efficacy of this flavonoid in reversing experimental cirrhosis. Cirrhosis was induced by intraperitoneal administration of TAA (200 mg/kg of body weight) three times per week for 8 weeks or by intraperitoneal petrolatum-CCl (400 mg/kg of body weight) administration three times per week for 8 weeks. To determine the capacity of quercetin to prevent liver fibrosis, the flavonoid (50 mg/kg of body weight, p.o.) was administered daily to rats during the CCl or TAA treatment. To evaluate the ability of quercetin to reverse the previously induced cirrhosis, we first treated rats with CCl for 8 weeks, as previously described and then the flavonoid was administered for four more weeks. We found that the liver anti-inflammatory and antinecrotic effects of quercetin are associated with its antioxidant properties, to the ability of the flavonoid to block NF-κB activation and in consequence to reduce cytokine IL-1. The ability of quercetin to reverse fibrosis may be associated with the capacity of the flavonoid to decrease TGF-β levels, hepatic stellate cell activation, and to promote degradation of the ECM by increasing metalloproteinases. The main conclusion is that quercetin, in addition to its liver protective activity against TAA chronic intoxication, is also capable of reversing a well-stablished cirrhosis by blocking the prooxidant processes and by downregulating the inflammatory and profibrotic responses.

Rebaudioside A administration prevents experimental liver fibrosis: an in vivo and in vitro study of the mechanisms of action involved

“…All the experiments were performed in triplicate. The degree of purple discoloration of the mixture indicates the degree of scavenging activity of Reb A (Casas‐Grajales et al, ). As a positive control and for comparison purposes, quercetin was utilized.…”

Stevia rebaudianatea prevents experimental cirrhosis via regulation of NF‐κB, Nrf2, transforming growth factor beta, Smad7, and hepatic stellate cell activation

“…The control group received 1 ml of tap water (AES vehicle) daily p.o. The TAA group received 200 mg/kg of TAA via IP injections three times per week, as described previously (Casas‐Grajales et al, ). The TAA + AES group received TAA via the same route as the TAA group plus 1 ml of AES (100 mg stevia/kg body weight/ml) p.o.…”

“…Plasma was obtained to analyze the activities of the alanine aminotransferase, gamma‐glutamyl transpeptidase enzymes, and the bilirubin concentration; liver sections were utilized to determine the glycogen (Hernández‐Aquino et al, ), glutathione (GSH) and glutathione disulfide (GSSG) contents, the degree of lipid peroxidation, and the collagen concentrations, as previously described (Casas‐Grajales et al, ).…”

“…Liver sections were prepared for immunohistochemistry, hematoxylin and eosin staining, or Masson's trichrome staining using previously reported methods (Casas‐Grajales et al, ).…”

“…Several medicinal plants have been extensively used in the traditional system of medicine for the management of liver diseases. Because cirrhosis is a major health problem throughout the world, and due to the lack of effective treatments, several studies have suggested that the use of medicinal herbs and phytochemicals could protect against liver damage by several mechanisms, such as the inhibition of oxidative damage, inflammation, and fibrogenesis (Casas‐Grajales et al, ; Hernández‐Aquino et al, ; Ramos‐Tovar et al, ). In this regard, Stevia rebaudiana (stevia), which is a small perennial shrub from Paraguay, has exhibited important antioxidant and anti‐inflammatory properties that suggest that this plant can be an effective antifibrotic and anticirrhotic remedy (Ramos‐Tovar & Muriel, ).…”