SILMARIN
Natural products, especially the herbal ones, are regularly used in the management of liver disorders. Many of these have been traditionally used, while some, like Silymarin, have been extensively investigated by modern methods of animal and clinical research.
Sivylar Capsules contain Silymarin, a mixture of natural components, obtained from the fruits of Silybum marianum, also known as the “milk thistle”. Long known in European traditional medicine as the “liver herb”, Silymarin now has well documented role in the treatment of liver disorders.
Although the medicinal properties of Silybum marianum have been recognized since the Middle Ages, it was the isolation of the active ingredient Silymarin in the late 1960’s that stimulated further research in the liver protective properties of the drug. Over the last 20 years, Silymarin has been the subject of numerous biochemical, pharmacological and clinical investigations. This scientific investigation, which is still ongoing, has lead to the introduction of Silymarin, the active principle of Sylibum marianum, into clinical medicine.
CHEMISTRY
Silymarin is obtained from the fruits of Silybum marianum, the milk thistle. Silymarin contains three main components (Flavonolignans) namely, Silybin, Silychristin and Silydianin.
PHARMACOLOGY
Silymarin is reported to have a protective effect on liver cells (hepatoprotective). It has also been shown to stimulate regenerative activity in the liver cells (hepatoregerative). These properties are responsible for the protection of liver cells against various harmful substances, as well as repair & regeneration of injured liver cells, leading to recovery from liver disorders.
The mode of action of Silymarin is multifaceted. However, 2 principle mechanisms have been identified to be responsible for its beneficial effect on the liver:
1. Hepatoprotective Effect
Hepatoprotective effect of silymarin is as a result of both direct interaction with liver cell membrane, and an antioxidant effect.
Direct interaction with membrane phospolipids
Silymarin has a membrane stabilizing effect on liver cells. Silymarin has been shown to interact with cell membrane phospolipids, alter membrane characteristics, and prevent the uptake and transport of hepatotoxic substances. Silymarin is bound to the cell membrane by interacting with its lipid components. It alters the liver cell membrane structure in such a way that certain toxins cannot enter the cells.
Antioxidant activity :
It is now well established that free radicals play an important role in causing damage to liver cells due to various external hepatotoxic substances, as well as pathological processes such as inflammation, ischaemia, aging and cancers. Free radicals are liberated when hepatotoxic substances are activated in the endoplasmic reticulum. Pathological processes like inflammation, aging, ischaemia & cancers liberate free radicals of oxygen. These free radicals start “lipid peroxidation” of cell membrane – a chain reaction, which damages the cell membrane.
The two principal physiological defences against free radicals are the “glutathione”, a substance in the liver, and the enzyme “superoxide dismutase”. Glutathione combines with free radicals, making them less reactive, while superoxide dismutase takes care of the free oxygen radicals.
Silymarin acts as a “free radical scavenger”. It reacts with numerous free radicals, forming more stable and less reactive compounds.
A number of studies have also demonstrated that silymarin inhibits lipid peroxidation in a dose-dependent manner. This activity is found to be 10 times more potent than Vitamin E.
Silymarin has also been found to prevent depletion of liver glutathione & to stimulate the enzyme superoxide dismutase, thus strengthening physiological defence mechanisms of the liver against damage.
The liver-protective activity of Silymarin has been demonstrated against a number of toxic substances like carbon tetrachloride, galactosamine, thiocetamide, poisonous substances of death cap fungus and the mushroom toxins phalloidin and alpha-amanitine. Silymarin has also been shown to be protective against acetaminophen (paracetamol) toxicity, through its antioxidant properties, possibly acting as a free radical scavenger. Studies have also shown that pre-treatment with Silymarin inhibits alcohol induced liver damage.
2. Hepatoregenerative Activity
Hepatoregenerative effect of silymarin is achieved through stimulation of Protein synthesis. Silymarin stimulates RNA polymerase A (also known as RNA Polymerase I), enhances ribosomal protein synthesis, resulting in stimulation of hepatic cell development and regeneration. Silymarin is able to enter the nucleus of liver cells, stimulates RNA polymerase I, and the synthesis of ribosomal RNA. This increases speed of ribosome formation, and thus protein synthesis.
The effects of silymarin on protein synthesis are thought to be due to its structural similarity to steroids. It has been suggested that silymarin may bind to steroid receptors on the enzyme RNA polymerase I, mimicking their effects.
Stimulation of protein synthesis is an important property of silymarin. It results in repair of damaged liver cells and replacement of enzymes and structural components damaged by hepatotoxic reactions.
Silymarin has also been shown to increase DNA synthesis in animal experiments.
Studies have shown that treatment with Silymarin positively influences recovery from acute viral hepatitis as shown by the changes in serum levels of bilirubin, SGOT & SGPT. A favourable effect on mortality in patients with hepatic cirrhosis has also been demonstrated.
Other Pharmacological Effects
Favourable effect on lipid profile : Reviewing over 10 years of experience with silymarin, researchers have reported reduction in plasma total cholesterol, low density lipoproteins (LDL), and very low density lipoproteins (VLDL), but an increase in high density lipoproteins (HDL), in rats treated with silymarin.
Improved bile flow : From its use in traditional medicine, Silybum marianum is known to have choleretic properties (improving bile flow), inhibiting paracetamol & estrogen-induced sluggishness in bile circulation (cholestasis).
Anti-inflammatory & anti-allergic actions : In addition, studies with human white blood cells indicate that silymarin possesses anti-inflammatory and anti-allergic actions.