Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis

https://www.kidney-international.org/article/S0085-2538(15)53305-X/pdf

Vitamin D levels and early mortality among incident hemodialysis patients.

Milk Thistle ( Silybum marianum ) for the Therapy of Liver Disease

Effects of flavonoids on immune and inflammatory cell functions

The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.

[Liver-protective action of silymarin therapy in chronic alcoholic liver diseases].

Superoxide dismutase activity and expression of the erythrocytes and lymphocytes of patients suffering from chronic alcoholic liver disease and those of healthy controls were investigated after in vitro incubation with silymarin. It was concluded that silymarin treatment in a concentration achievable by in vivo treatment (10 micrograms/ml) significantly increased the SOD activity of both the erythrocytes and lymphocytes of patients with liver disease, whereas the SOD expression of the lymphocytes enhanced to a considerable extent. These results indirectly indicate that the scavenger silymarin is able to increase the antioxidant protection of the cells by ameliorating the deleterious effects of free radical reactions.

Effect of the bioflavonoid silymarin on the in vitro activity and expression of superoxide dismutase (SOD) enzyme.

The frequency of hepatitis B surface antigen (HBsAg) has been studied in the sera and renal biopsies of 276 patients with various forms of glomerulonephritis (GN), the nephrotic syndrome and other nephropathies Using a modified Hepanosticon method, HBs antigenemia was detected in 32 of 196 patients (163%) with immune complex (IC) GN and the nephrotic syndrome Indirect immunofluorescence revealed HBsAg in 33 renal biopsy tissue specimens (168%) HBsAg was found in the sera of four of the 80 remaining patients with other renal diseases (5%), and in the renal biopsy tissues of another four (5%) Antibody against HBsAg could only be demonstrated in the serum of one glomerulonephritic patient The sera of 18,799 normal blood donors were used as controls; of these 186 (099%) had positive tests for HBsAg It is concluded that, in some patients with GN and the nephrotic syndrome, HBsAg-containing IC may be implicated in the development and/or progression of the disease

The role of hepatitis B surface antigen in the pathogenesis of glomerulopathies.

A double blind study. Antioxidant and antiperoxidative effects of the free radical scavenger agent silymarin (Legalon) were investigated in patients with chronic alcoholic liver disease in a double blind clinical trial. Six month treatment (at a daily dose of 420 mg) with silymarin significantly enhanced the originally low superoxide dismutase activity of erythrocytes and lymphocytes and also restored the diminished superoxide dismutase expression on lymphocytes as measured by flow-cytofluorimetry. In addition, silymarin therapy markedly increased the serum level of ree--SH groups and the activity of glutathione peroxidase. In contrast, a considerable fall in serum malondialdehyde concentration was detected in patients having received silymarin. However, in case of placebo-treated patients the above mentioned parameters of antioxidant defense system and lipid peroxidation failed to change significantly. These data indirectly suggest that antioxidant, antiperoxidative effects might be important factors in the mechanism of hepatoprotective action of silymarin.

Effect of silimarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double blind protocol)

The in vitro and in vivo effects of three hepatoprotective antioxidants (silymarin, (+)cyanidanol-3 and 4-amino-5-imidazole-carboxamide-phosphate) on the expression and activity of superoxide dismutase (SOD) enzyme were studied in erythrocytes and lymphocytes from patients with alcoholic cirrhosis. In vitro incubation with the drugs in a concentration corresponding to the usual therapeutic dosage markedly increased (i) the SOD expression of lymphocytes as measured by flow-cytofluorimetry following staining with monoclonal anti-Cu, Zn-SOD-antibody and FITC-conjugated anti-mouse Ig, as well as (ii) erythrocyte and lymphocyte SOD activities. In vivo treatment also restored the originally low SOD activity and expression of the patients' lymphocytes and erythrocytes. The data indirectly suggest that antioxidant activity might be one of the important factors in the hepatoprotective action of these agents.

Effect of free radical scavengers on superoxide dismutase (SOD) enzyme in patients with alcoholic cirrhosis.

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