The Liver

Another area of therapy that is exceptionally well suited for herbal treatment
is that of liver disease. In the unique and often infuriatingly unscientific
language of traditional herbalist’s, much attention is given to `detoxifying
the liver’. The incredible complexity of liver chemistry and its fundamental
role in human physiology is so daunting to researchers that the thought that
simple plant remedies might have something to offer is both laughable and even
insulting! This highlights again the limiting trap of the current research
paradigm.

The liver serves to metabolize carbohydrates and store them as glycogen
metabolize lipids (including cholesterol and certain vitamins) and proteins
manufacture bile filter impurities and toxic material from the blood produce
blood-clotting factors and destroy old, worn-out red blood cells. Certain
reticuloendothelial cells (the Kupffer cells) play a role in immunity. It is
able to regenerate itself after being injured or diseased if, however, a
disease progresses beyond the tissue’s capacity to regenerate new cells, the
body’s entire metabolism is severely affected. Any number of disorders can
affect the liver and interfere with the blood supply, the hepatic and Kupffer
cells, and the bile ducts.

From the ecological perspective offered earlier it becomes apparent that our
evolutionary home – the environment in which we live – will nurture and heal
many of the ills of the liver. After all, the liver and its wonderful
biochemistry is part of the ecosystem as well.

With remedies such as Dandelion, Balmony, Fringe Tree Bark and the bitter tonic
herbs already mentioned, a powerful materia medica is available. Treatment can
range through conditions requiring gentle liver stimulation to even profound
liver disease. As with most claims made by the medical herbalist,
pharmacological and clinical research is starting to support traditional
experience and provide a chemical insight into the mechanisms
involved.

An abundance of research has been done into the hepato-protective effects of a
number of herbs. This provides us with a good example of the quality of
research being undertaken. The information in this section comes from a number
of excellent literature reviews on this fascinating branch of Phytotherapy.
Please refer to:

Hikino & Kiso (1988) Natural Products for Liver Diseases. In
“Economic and Medicinal Plant Research Vol.2.” (Wagner, Hikino &
Farnsworth) Academic Press, London.

Murray, M.T. (1995) The Healing Power of Herbs. Prima Publishing,
Rocklin.

Vogel, G. (1977) Natural Substances with Effects on the Liver. In “New
Natural Products and Plant Drugs with Pharmacological, Biological or
Therapeutic Activity.” (Wagner & Wolff) Springer-Verlag, Heidelberg.




Phyto-Therapy Research and Liver Disease


The main causes of liver disease are:

  • viral infection

  • hepatotoxic chemicals such as:


  • ethyl alcohol

  • peroxides (particularly peroxidized edible oil)

  • toxins in food (especially aflatoxins)

  • pharmaceuticals (mainly antibiotics, chemotherapeutics and CNS-active
    drugs)

  • environmental pollutants

Although such hepatotoxins induced liver lesions may be reversed in the early
stages, they cannot be healed only by removal of the toxins after critical
periods, highlighting the need for effective remedies for liver diseases. A
number of herbs that have been long used for their curative effects on liver
disorders in traditional medicine around the world have revealed their unique
potential to pharmacological investigation. Research into these plants has
resulted in the isolation of a number of `active principles’, including
dramatically anti-hepatotoxic constituents.

Much of the laboratory studies have been done in the unfortunately usual mode
of pharmacology. This author in no way endorses or supports animal experiments
with herbs. The reasons are discussed at length elsewhere. The reasons for
introducing such tainted research findings here is to illustrate the way in
which such science is “proving” to itself what herbalist’s already know.

Of the herbs discussed here Carduus is more often used in Europe and
North America, Glycyrrhiza in Japan, Schizandra in China, and
Bupleurum in Japan and China.




Milk Thistle & Silymarin

The importance of botanical accuracy is highlighted here. In different places
this herb is called Milk Thistle, Mary Thistle and even Sow Thistle.
Historically this herb has been used in Europe as a liver tonic and current
Phytotherapy indicates its use in a whole range of liver and gall bladder
conditions including hepatitis and cirrhosis. It may also have value in the
treatment of chronic uterine problems. A wealth of research done in Germany is
revealing exciting data about reversal of toxic liver damage as well as
protection from potential hepatotoxic agents. A number of chemical
components of herb are now being shown to have this protective effect on liver
cells. They are all flavones and flavo-lignins, the flavones often grouped
together as silymarin.

In laboratory tests a range of effects have been demonstrated
including:

  • silymarin reduced the harmful actions on the liver of hepatotoxins
    such as carbon tetrachloride, thioacetamide, a-amanitin and phalloidin.

  • a protective effect against carbon tetrachloride induced liver damage in
    rats.

  • a reduction of the prolongation of hexobarbital sleeping time produced by
    carbon tetrachloride. This is a common method for assessing protective effects
    on the liver against the effects of chemical toxins. Hexobarbital causes a
    consistent pattern of sleep in the unfortunate experimental animals, and any
    change in sleep time reflects some disturbance of the liver ability to
    metabolize the sedative. An increase in sleeping time implies impairment of the
    livers ability to metabolize the hexobarbital. Carbon tetrachloride produces
    such a change. When Milk Thistle is added the increase in sleeping time
    normally produced by the carbon tetrachloride is reduced by up to 60%,
    suggesting that the herb is protecting liver function from the toxin.

  • prevention of the inhibition of hepatic metabolism of
    p-oxyphenylpyruvic acid (OH) caused by carbon tetrachloride. This
    chemical is metabolized exclusively in the liver during the degradation of
    tyrosine. Any unmetabolized OH is excreted in the urine, thus, its level in
    the urine increases following the administration of a liver toxin. Substances
    that counteract the toxin bring urine OH levels back to normal. Histological
    studies of the liver reveal how much structural damage has occurred. The
    histological finds from carbon tetrachloride poisoning is very similar to that
    of hepatitis, and it increases OH levels in the urine dramatically. Milk
    Thistle significantly counteracts the effects of the carbon tetrachloride, so
    much so, that the results are almost indistinguishable from controls.

  • carbon tetrachloride raises serum levels of enzymes such as
    glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)
    and sorbitol dehydrogenase (SDH), but under treatment with silymarin these
    increases were significantly diminished.

  • i.p. injection of D-galactosamine (GalN) to rats causes an acute hepatitis
    that is similar to viral hepatitis in humans. Silymarin has a protective action
    against such liver lesions.

  • poisoning with DL-ethionine leads to accumulation of triglycerides in the
    liver of rats. Silymarin inhibited such increases.

  • it counteracted the effects of cadmium, an pollutant that accumulates in
    human tissues over time, causing hypertension, liver, kidney & neural
    damage, and hemorrhagic necrosis of the liver and testes. Milk Thistle
    pretreatment almost completely prevented death and necrosis whilst reducing
    nerve damage.

  • the hepatotoxic salts of such rare earth metals as praseodymium, indium and
    cerium cause necrosis and fatty degeneration in the liver. Pretreatment with
    Milk Thistle reduces or prevented this altogether. The researchers suggest a
    number of possible mechanism:

    • that it facilitates a more rapid elimination of the metals from the body

    • it stimulates the formation of metal-binding proteins which detoxify the
      metals

    • it may inhibit the binding of these metals with cells at receptor sites

  • thioacetamide is a hepatotoxin which causes a development of conditions in
    rats that are similar to human liver. When silymarin was given with the poison
    in the feed, animals lost less weight and their survival times increased.
    Injecting thioacetamide increases the serum levels of the enzymes GPT, GOT,
    SDH, and glutamate dehydrogenase, which were also prevented by silymarin.

  • it partially counteracts alcohol damage to the liver.

  • mitochondrial changes caused by ethanol are almost completely prevented by
    silymarin.

  • ethanol increases malondialdehyde formation and spontaneous chemiluminescence
    in the rat liver. Silymarin given prior to the ethanol suppresses both effects
    completely.

  • Milk thistle has an extraordinary hepato-protective effect, blocking damage
    from the toxins of the Avenging Angel mushroom Amanita phalloides,
    phalloidin and a-amanitin. It has both protective and curative effects on
    survival time and death rate of mice after administration of a-amanitin, also
    antagonizing the toxicity of phalloidin. It inhibits the loss of weight
    observed in poisoned animals. Animals fed sub-lethal doses of amanitine lose
    weight very rapidly and gain it back very slowly. Animals fed a combination of
    amanitine and Milk Thistle lose weight much more slowly and gain it back much
    more rapidly. It greatly increased life-span in the poisoned animals. When
    administered later than 20 minutes after poisoning, it was no longer possible
    to detect any anti-hepatotoxic effect, suggesting that silymarin prevents
    penetration of the toxins by competing for the same receptor sites on cell
    membranes.

  • it has blocked the hepatotoxic effects of some viruses on laboratory
    animals.

  • silybin enhances ribosomal RNA synthesis as a result of the
    stimulation of DNA-dependent RNA-polymerase A.





Cellular Mechanisms

Such impressive effect upon toxic damage to liver cells is probably due
to a combination of two main mechanisms:

  1. an alteration of cell membranes, such that only small amounts of toxins may
    penetrate into the cell

  2. an acceleration of protein synthesis, thus stimulating cell
    regeneration.

Mechanisms that may explain the inhibition of ethanol induced changes by
silymarin include scavenging of free radicals and increases levels of both
reduced and oxidized glutathione.




Clinical Research

This remarkable herb has therapeutic effects, not only in toxic and
metabolic liver damage, but also in liver diseases. Clinical trials have
replicated the laboratory evidence of its ability to reverse many liver
disorders from acute viral hepatitis to cirrhosis. It stimulates hepatocytes to
replace diseased tissue. The liver can regenerate but this innate ability slows
or stops altogether when infected or damaged by alcohol or other drugs.

Clinical indicators of improvement in the health of the liver include:

  • assessment of general condition, appetite, epigastric discomfort,
    enlargement and consistency of the liver,

  • blood plasma tests.

  • changes in membrane permeability are deduced from measurements of
    glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT),
    lactic acid dehydrogenase (LDH), sorbitol dehydrogenase, and gamma glutamyl
    transpeptidase (GGT)

  • membranotropic properties and the excretory functions of the liver are
    assessed through measurements of bilirubin, LAP, gamma-GT, alkaline
    phosphatase, and bromethalein

  • synthesizing ability is assessed through prothrombin, triglycerides, and
    cholesterin

  • measurements of mesenchymic activity include clotting factors, alpha, beta
    and gamma globulin, immunoglobulins IgA, and IgG.

Clinical studies have demonstrated its value in therapy:

  • One study involved 129 patients and a control group of 56 for a period
    of about one month. Their conditions included toxic-metabolic liver damage,
    fatty degeneration of the liver for various reasons, and chronic hepatitis.
    Milk Thistle markedly changed both subjective and objective symptoms, brought a
    return to normal enzymatic activities, and improved digestive disorders.
    Enlarged livers diminished substantially in volume. A 50% regression in
    pathological symptoms, versus 25% in controls, occurred. No cases of
    intolerance, side effects, or allergic reactions were observed.

  • in a double-blind study, serum bilirubin, GOT, and GPT in 28 patients treated
    with silymarin were compared with those in 29 patients treated with a placebo.
    The silymarin treated group were more improved than those in the control group
    after the 5th day of treatment. The number of patients having attained normal
    values after 3 weeks’ treatment was higher in the silymarin-treated group than
    in the control group.

  • Toxic damage was tested in 33 patients treated with silymarin. The parameters
    GOT, GPT, and g-glutamyltranspeptidase (g-GTP) were improved significantly by
    silymarin, sometimes returning to normal in a much shorter time than in the
    control group.

  • 106 patients with liver disease, mostly induced by alcohol, were selected on
    the basis of elevated serum transaminase levels and randomly allocated into the
    silymarin-treated and control groups. Decreases of serum GPT and GOT in the
    treated group were statistically significant over those of the controls.

  • in chronic liver disease, silymarin prevented the decrease of seralbumin from
    3 months of therapy to the end of the study. The histopathological findings of
    focal necrosis and fibrosis were also much improved. Silymarin proved to be
    beneficial in the parameters of parenchymal disorders, intralobular mesenchymal
    reaction, and fibrosis.

  • Long-term treatment with silymarin on chronic hepatopathies caused by
    psycho-pharmaceuticals resulted in significant improvements in the liver
    function parameters such as GOT, GPT, and BSP during treatment.

  • two cases of food poisoning caused by flagellates responded very rapidly to
    Milk Thistle, showing subjective, biochemical and histological improvements.






Therapeutic Indications

This wonderful plant is effective in many types of liver disease. The
clinical findings highlight such problems as:

  • toxic/metabolic liver disease (including both alcohol & drug induced
    forms),

  • acute viral hepatitis,

  • chronic-persistent hepatitis,

  • chronic-aggressive hepatitis,

  • cirrhosis of the liver,

  • fatty degeneration of the liver

The best results are found in toxic-metabolic hepatitis and cirrhosis. It
shortens the course of viral hepatitis and minimizes post hepatitis
complications and also protects the liver against problems resulting from liver
surgery. This all goes to make it is an excellent remedy to use in the
prevention and treatment of many liver disorders. The earlier treatment is
commenced the better the prognosis, but effective treatment is possible at
virtually every stage. Milk Thistle arrests the course of these diseases as
well as stimulating hepatocyte regeneration.

Over time, complete restoration of the liver is possible, with regeneration at
four times the normal rate. Many psychopharmacologic drugs and agents are
detoxified by the liver. The cumulative effect of drug use on the liver can be
devastating. Thus Milk Thistle should be taken by people who want or need to
take such drugs. It has been shown to prevent liver damage caused by such
drugs.

This all suggest that taking the herb regularly will provide protection to
either the sick or healthy liver during the course of daily life. By
stabilizing cell membranes, by encouraging the regeneration of cells destroyed
during the normal detoxification process, Milk Thistle provides the liver and
the body with the ability to cope with the deleterious effects of daily
encounters with air- water- and food-borne toxins. Using Milk Thistle daily,
and combining it with other hepatics, offers an effective and safe approach to
liver protection.




Liquorice & Glycyrrhizin

The root of licorice, Liquorice L. and Chinese licorice, G.
uralensis
, is an important medicine around the world. Glycyrrhizin is one
of the main components of licorice root. During the course of such clinical
use, glycyrrhizin preparations were found to be effective for chronic hepatitis
and have been widely used for chronic hepatitis and liver cirrhosis in Japan.

  • Glycyrrhizin inhibits liver cell injury but does not reverse reduced protein
    synthesis. It is effective against carbon tetrachloride, benzene hexachloride,
    PCB and GalN.

  • Antibody production is enhanced by glycyrrhizin. When mononuclear cells from
    human peripheral blood were stimulated with pokeweed mitogen in the presence of
    glycyrrhizin, polyclonal antibody production was significantly enhanced.
    Glycyrrhizin may facilitate antibody formation through the production of
    interleukin I.

  • glycyrrhizin inhibits the growth of several DNA and RNA viruses, inactivating
    Herpes simplex virus particles irreversibly.

  • its effect against chronic hepatitis was demonstrated in a double-blind test
    with 133 patients. Elevated serum transaminase and y-GTP levels were reduced.

  • it appears to be effective on the pretreatment of post-transfusion hepatitis.
    In one trial comparing glycyrrhizin and an inactive placebo in 336 patients, a
    significant reduction of the incidence of non-B hepatitis after transfusion was
    observed in the treated group. Because a remarkable reduction of the incidence
    of post-transfusion hepatitis was observed from 2 weeks to 6 weeks after
    transfusion, suggesting that the incidence of short-incubation post-transfusion
    hepatitis might be suppressed by using glycyrrhizin.

  • it helps prevent post-transfusion hepatitis. When i.v. administration was
    continued for about 2 weeks, starting on the day of transfusion, the incidence
    of hepatitis was reduced from 17.6 to 12.8%. From these and other results, it
    was concluded that the use of this phytochemical is effective for the
    prevention of post-transfusion hepatitis.

Invalid OAuth access token.
David L. Hoffmann BSc Hons MNIMH Written by David L. Hoffmann BSc Hons MNIMH