2. CONTEXT
• Introduction
• Main goals of hepatoprotectors
• Mechanism of action
• Drugs having hepatoprotective action
• Herbal Drugs as hepatoprotectors
3. WHAT ARE HEPATOPROTECTORS?
Hepatoprotective drugs refer to drugs that can
improve liver function, promote liver cell
regeneration and/or enhance liver
detoxification.
In other words, they are the drugs that
protects the liver and maintain its overall health
and function.
4. MAIN GOALS OF HEPATOPROTECTIVE
AGENTS
• Protecting Liver Cells: Hepatoprotectors often work by shielding liver cells from damage,
reducing oxidative stress, and promoting cellular integrity.
• Supporting Liver Regeneration: Some hepatoprotective agents may stimulate the
regeneration of liver tissue, helping the liver recover from injury.
• Modulating Inflammation: Inflammatory processes play a role in many liver conditions.
Hepatoprotectors may have anti-inflammatory properties to reduce inflammation in the
liver.
• Enhancing Detoxification: The liver plays a crucial role in detoxifying harmful substances.
Hepatoprotectors may support the liver’s detoxification functions.
• Improving Bile Flow: Some hepatoprotective agents can enhance bile flow, which is
essential for digestion and the elimination of waste products from the liver.
5. MECHANISM OF ACTION OF
HEPATOPROTECTORS
• There are two mechanism of action-
• a) Drug may alter the structure of the outer membrane of the hepatocytes
in a such way as to prevent penetration of liver toxin into interior of the cell.
• B) Drug may stimulate the action of nucleolar polymerase A, resulting in
ribosomal protein synthesis, thus stimulate the regenerative ability of the
liver & formation of new hepatocytes.
6. LIST OF HEPATOPROTECTIVE AGENTS
• N-acetylcysteine
• Antioxidants
• Cardiotrophin 1
• S Adenosyl methionine
• Ursodeoxycholic acid
• Herbal medications
7. N-ACETYLCYSTEINE
• N-acetylcysteine (NAC) is a compound that contains the
amino acid cysteine, and it serves as a precursor to the
antioxidant glutathione.
• One of the well-established uses of NAC is in the
treatment of acetaminophen (paracetamol) overdose.
Acetaminophen metabolism can deplete glutathione levels
in the liver, leading to oxidative stress and liver damage.
NAC administration helps restore glutathione levels,
reducing the risk of severe liver injury.
8. ANTIOXIDANTS
• Antioxidants play a crucial role as hepatoprotectors by helping to counteract
oxidative stress in the liver. Oxidative stress occurs when there is an imbalance
between the production of reactive oxygen species (ROS) and the body’s ability to
neutralize them with antioxidants. The liver, being a central organ in metabolism and
detoxification, is particularly susceptible to oxidative damage.
• Vitamin E: Vitamin E, particularly its alpha-tocopherol form, is a fat-soluble
antioxidant that helps protect cell membranes from oxidative damage. It has been
studied for its potential benefits in various liver conditions.
• Vitamin C: Vitamin C, or ascorbic acid, is a water-soluble antioxidant that can
regenerate vitamin E. It helps protect against oxidative stress and supports the
immune system.
• Selenium: Selenium is a trace element that is a component of selenoproteins, which
have antioxidant functions. Selenium deficiency has been linked to liver diseases,
and supplementation may have hepatoprotective effects.
9. VITAMIN E
• Vitamin E is often considered a potential hepatoprotector, particularly due to its
antioxidant properties. Antioxidants help neutralize harmful free radicals in the body,
and the liver can benefit from this protective effect. Here are some aspects of how
Vitamin E may act as a hepatoprotector:
• Antioxidant Activity: Vitamin E is a fat-soluble antioxidant that can help protect cells,
including liver cells, from oxidative stress. Oxidative stress occurs when there is an
imbalance between the production of free radicals and the body’s ability to counteract
their harmful effects.
• Cell Membrane Protection: Vitamin E is incorporated into cell membranes, where it
helps protect cell structures, including liver cell membranes, from damage caused by
free radicals.
• Anti-Inflammatory Effects: Chronic inflammation can contribute to liver damage.
Vitamin E’s antioxidant properties may help mitigate inflammation and reduce the
inflammatory response in the liver.
10. CARDIOTROPHIN 1
Cardiotrophin-I (CT-I) belongs to the IL-6 family of cytokines.
CT-1 receptor activation induce cell survival through signal transduction mechanism mediated by
Stat3 (Signal transducer and activator of transcription), MAPK (mitogen- activated protein
kinase), PI3K (phosphatidylinositol 3-kinases).
CT-1 is induced in context of cell damage in several tissues.
1. Strong anti-apoptic effects on hepatocytes.
2. Reduce the cellular damage cause by ischemia/reperfusion.
3. Decrease oxidative damage.
4. Potent anti-inflammatory agent
It has been granted for its use in hepatic regeneration.
11. URSODEOXYCHOLIC ACID
• Ursodeoxycholic acid (UDCA) is a bile acid that is commonly used as a hepatoprotective agent, particularly
in the treatment of certain liver disorders. Here are key points about UDCA as a hepatoprotector:
• Primary Biliary Cholangitis (PBC): UDCA is often prescribed as the primary treatment for Primary
Biliary Cholangitis (PBC), a chronic liver disease characterized by progressive destruction of the bile
ducts. It helps improve liver function and slows down the progression of the disease.
• Cholestatic Liver Diseases: UDCA may be used in the management of other cholestatic liver diseases,
where there is impairment in the flow of bile. It can have a beneficial effect in reducing liver enzyme
levels and improving bile flow.
• Dissolution of Gallstones : UDCA is sometimes used to help dissolve certain types of gallstones,
particularly those made of cholesterol. However, this use is less common compared to other treatments
for gallstones.
• Anti-Inflammatory and Cytoprotective Effects: UDCA is believed to have anti-inflammatory and
cytoprotective effects on liver cells. It may help reduce inflammation and protect liver cells from
damage.
• Treatment of Liver Disorders in Pregnancy: In some cases of liver disorders that may occur during
pregnancy, UDCA may be prescribed to help manage the condition and protect the liver.
12. S-ADENOSYL METHIONINE
• S-Adenosyl methionine (SAMe) is a compound that occurs naturally in the body and
plays a crucial role in various biochemical processes, including the synthesis of
neurotransmitters and the maintenance of cell membranes. SAMe has been studied
for its potential hepatoprotective effects. Here are key points regarding SAMe as a
hepatoprotector:
• Antioxidant and Anti-Inflammatory Effects: SAMe exhibits antioxidant properties,
helping to neutralize free radicals and reduce oxidative stress in liver cells. It also
has anti-inflammatory effects, which may contribute to its hepatoprotective
properties.
• Detoxification and Methylation: SAMe is involved in the methylation process, a
biochemical reaction crucial for the detoxification of various substances in the liver.
By supporting methylation, SAMe may contribute to the liver’s ability to process and
eliminate toxins.
• Liver Regeneration: SAMe has been suggested to promote liver regeneration and
repair damaged liver tissue. This may be beneficial in conditions where the liver is
under stress or has experienced injury.
• Cholestasis and Liver Disorders: SAMe has been investigated for its potential use in
cholestatic liver disorders, where there is impaired bile flow. Some studies suggest
that SAMe may have a positive impact on liver function and symptoms in such
conditions.
14. SOME OF THE COMMONLY USED HERBAL
DRUGS
• Milk Thistle (Silymarin): Known for its antioxidant and anti-inflammatory properties, milk
thistle is widely used to support liver health. Silymarin is the active compound believed to
have hepatoprotective effects.
• Turmeric (Curcumin): Curcumin, the active compound in turmeric, has anti-inflammatory
and antioxidant properties. It is studied for its potential in protecting the liver from
damage.
• Schisandra (Schisandra chinensis): Used in traditional Chinese medicine, schisandra is
believed to have hepatoprotective effects. It has been studied for its potential benefits
in liver conditions.
• Dandelion (Taraxacum officinale): Dandelion root is traditionally used for liver and
digestive health. It may have diuretic and mild hepatoprotective properties.
• Artichoke (Cynara scolymus): Artichoke is studied for its potential in supporting liver
function and improving bile flow. It may have hepatoprotective effects.
15. • Licorice Root (Glycyrrhiza glabra): Licorice root has been used in traditional medicine
and may have anti-inflammatory and antioxidant effects. It is studied for its potential in
liver conditions.
• Ginger (Zingiber officinale): Ginger has anti-inflammatory and antioxidant properties and
may contribute to liver health. It has been studied for its potential in mitigating liver
damage.
• Burdock Root (Arctium lappa): Burdock root is traditionally used for liver support and
detoxification. It may have antioxidant and anti-inflammatory effects.
• Andrographis (Andrographis paniculata): Andrographis is studied for its potential
hepatoprotective effects. It is used in traditional medicine for various health purposes.
• Phyllanthus (Phyllanthus amarus): Phyllanthus is used in traditional medicine and is
studied for its potential benefits in liver disorders
16. SILYMARIN
• Silymarin is a natural compound derived from the species Silybum marianum,
which is commonly known as Milk thistle. This plant contains at least seven
flavoligands and the flavonoid taxifolin.
• The hepatoprotective and antioxidant activity of silymarin is caused by its
ability to inhibit the free radicals that are produced from the metabolism of
toxic substances such as ethanol, acetaminophen, and carbon tetrachloride.
• The generation of free radicals is known to damage cellular membranes and
cause lipoperoxidation. Silymarin enhances hepatic glutathione and may
contribute to the antioxidant defense of the liver.
• It has also been shown that silymarin increases protein synthesis in
hepatocytes by stimulating RNA polymerase I activity. A previous study on
humans reported that silymarin treatment caused a slight increase in the
survival of patients with cirrhotic alcoholism compared with untreated
controls
