Dr Akash C Chudasama
Abstract:
Carduus marianus is most potent remedy for liver disorders. It has an affinity towards acute as well as chronic disease. On of the important chemical composition of carduus marianus is silymarin. It is a complex of polyphenolic compounds that reduces liver inflammation. In this article how silymarin act on liver by various processes and various type of disease.
Key words:
Carduus marianus, Silymarine, liver cirrhosis, Non alcoholic fatty liver disease, drug induced liver injury, viral hepatitis.
Antioxidant effect:
The production of reactive oxygen species (ROS) is a natural consequence of a variety of essential biochemical reactions in the liver, mostly related to the processes involved in detoxification. Exposure to high levels of toxins (e.g., alcohol, hepatotoxic drugs) or intensive oxidation of free fatty acids (i.e., insulin resistance) leads to abnormal production of ROS; the endogenous antioxidants may also become depleted. For example, it is widely acknowledged that ethanol promotes the formation of various free radicals in several cell types, including hepatocytes, Kupffer cells, endothelial cells and infiltrating inflammatory leukocytes. The consequent imbalance, with persistent presence of ROS that are not neutralized by endogenous antioxidants, creates a condition called ‘‘oxidative stress’’, which is implicated in the pathogenesis of a variety of liver disorders including liver fibrosis.
Silymarin protects liver cells by a number of mechanisms. First, it stabilizes membrane permeability through inhibition of lipid per oxidation, thereby helping the liver to maintain levels of its own protective antioxidant, glutathione. Silymarin also protects against injury from various toxic chemicals such as carbon tetrachloride, for example, by inhibiting the production of tumor necrosis factor-alpha (TNF-a), interferon-gamma, interleukin (IL)-2 and IL-4 as a consequence of blocking hepatic nuclear factor kappa B (NFjB) activation. Silymarin is able to reduce the cellular uptake of xenobiotics, including mushroom poisons, by blocking organic ion uptake transporters on the surface of hepatocytes. It also inhibits TNF-a expression, for example, when induced by a amanitin toxin from poisonous mushrooms. The hepatoprotective properties of silibinin are widely attributed to these antioxidant activities. (1)
Anti-Inflammatory effect:
Chronic inflammation has been associated with progressive hepatic fibrosis and the development of cirrhosis, and oxidative stress may be the common underlying mechanism in the initiation and progression of hepatic inflammation in various liver disorders. NF-jB is an important transcriptional regulator of the inflammatory response and plays an essential role in regulating inflammatory signaling pathways in the liver. Moreover, NF-jB is activated in virtually every chronic liver disease, including AFLD, NAFLD, viral hepatitis and biliary liver disease. There is increasing evidence that demonstrates the overall inhibition by silymarin of inflammatory mediators such as NF-jB and inflammatory metabolites (e.g., prostaglandin E2 [PGE2] and leukotriene B4 [LTB4])
Kupffer cells are resident liver macrophages that appear to be involved in innate immune responses and host defense through the expression and secretion of inflammatory mediators. In isolated rat Kupffer cells, silymarin weakly inhibited PGE2 formation but strongly inhibited LTB4 formation, even at low concentrations (15 lmol/l). This selective inhibition of LTB4 formation by Kupffer cells and possibly other cell types may account for the anti-inflammatory potential of silymarin. (1)
Antifibrotic Effects:
Silibinin has demonstrated antifibrogenic effects in animal and in vitro models. Hepatic fibrogenesis, which results from chronic liver tissue damage, is characterized by activation of hepatic stellate cells (HSCs), a liver-specific type of pericyte. Activated HSCs develop into myofibroblasts, which are responsible for the deposition of collagen fibers leading to liver cirrhosis. In an in vitro model of human hepatic fibrogenesis, silibinin demonstrated antifibrogenic properties by dose dependently inhibiting the growth factor-induced production of pro-collagen in activated human HSC. (1)
Liver Cirrhosis/Alcohol-Related Liver Disease Fatty liver disease (FLD) is caused by the accumulation of excess fat in the liver, which can lead to serious liver disease for many people. In individuals who consume too much alcohol, alcoholic fatty liver disease (AFLD) is the earliest stage of alcoholic-related liver disease. Silymarin has been investigated in a number of clinical studies in patients with liver cirrhosis and/or alcohol-related liver disease. (1)
NAFLD and Non-Alcoholic Steatohepatitis:
NAFLD is another major cause of chronic liver disease in the absence of significant alcohol consumption and is frequently associated with insulin resistance, central obesity, type-2 diabetes and dyslipidemia. Due to the exploding prevalence of these comorbidities, NAFLD is recognized as a major worldwide health problem and the leading cause of liver disease in Western countries with a prevalence up to 33%. There is also an increasing prevalence of NAFLD in Eastern countries, reflecting the increasing incidence of obesity and obesity-related diseases in these regions. NAFLD encompasses a wide spectrum of disorders, ranging from benign fat accumulation (simple steatosis), with or without varying degrees of hepatic inflammation (steatohepatitis), to progressive fibrosis and ultimately to cirrhosis and end-stage liver disease. Approximately 20% of patients with NAFLD (simple steatosis) will go on to develop the more severe form known as non-alcoholic steatohepatitis (NASH). To date, the combination of dietary modifications and increased physical activity remains the mainstay of NAFLD management. Unfortunately, however, many patients find instituting lifestyle changes difficult over the long term. Oxidative stress is regarded as the key pathogenic component involved in the progression of simple steatosis to NASH. Endogenous antioxidants function as direct scavengers of ROS and are thus able to either delay or prevent oxidative stress as well as other parameters of hepatocyte damage. Glutathione is the most abundant cellular antioxidant that protects hepatocytes against the toxic effects of ROS. Recent literature strongly suggests that treatment with antioxidant agents and other putative free radical scavengers is beneficial in improving biochemical and histologic parameters in NASH. (1)
Drug-Induced Liver Injury:
It is well known that many drugs undergo hepatic metabolism and can induce, directly or through their active metabolites, hepatotoxicity. As has been observed with anti-tuberculosis drugs (ATDs), this may result in increased morbidity or mortality. Hepatotoxicity may necessitate treatment discontinuation, drug interruption and substitution or dose adjustment. Drug-induced liver injury (DILI) is still the most common cause of acute liver failure in Western societies. (1)
Viral Hepatitis:
Because there are safe and effective direct antiviral treatments available, the use of silymarin for this indication has not been extensively investigated. Nevertheless, studies suggest silymarin may have a role as supportive treatment for patients with acute or chronic hepatitis. It should be noted that silymarin is approved for liver support, not for treatment of viral hepatitis. In a pre-planned analysis, data on baseline silymarin use were collected for patients enrolled in the large HALT-C (Hepatitis C Antiviral Long Term Treatment against Cirrhosis) trial; the primary aim of the trial was to assess the long-term use of peginterferon alpha-2a in hepatitis C patients with advanced fibrosis or cirrhosis in whom standard care had failed. (1)
Materia medica:
The action of this drug is centred in the liver, and portal system, causing soreness, pain, jaundice. Has specific relation to the vascular system. Abuse of alcoholic beverages, especially beer. Dropsical conditions depending on liver disease, and when due to pelvic congestion and hepatic disease. (2)
Influenza when liver is affected. Haemorrhages, especially connected with hepatic disease. Cirrhosis, with dropsy. (2)
References:
- Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review – Anton Gillessen. Hartmut H.-J. Schmidt – Received: December 2, 2019
- Boericke W. BOERICKE’S New Manual of Homoeopathic MATERIA MEDICA With REPERTORY. Third Revised & Augmented Edition Based on Ninth Edition ed. Noida: B. JAIN PUBLISHERS (P) LTD.; 2021.
Dr. Akash C. Chudasama
PG Scholar Part 2 (Practice of Medicine) C.D. Pachchigar College of Homoeopathic Medicine and Hospital, Surat, Gujarat.
Email : chudasamaakash65@gmail.com
Be the first to comment