French Lilac: A Medicinal Plant that Led to a Key Treatment for Type II Diabetes

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French Lilac: A Medicinal Plant That Led to a Key
Treatment for Type-2 Diabetes
By: Charles Spielholz, Ph.D.
rench lilac (Galega officinalis) is an old world flower that has been introduced
to temperate zones throughout most of the world. As a perennial, it blooms in
the summer. It is cultivated for
use as a flower as well as other
commercial purposes. However, French
lilac (also known as Spanish sanfoin,
goat's rue and professor weed) provided
the basis for the development of one of
the most important drugs used to treat
type-2 diabetes. French lilac is an
extraordinary example of an herbal
remedy that led to an important pharmaceutical because of scientific observation,
experimentation and clinical testing.
The symptoms of diabetes mellitus have been known for thousands of years.
Although ancients did not have the medical tests to understand the mechanism of the
diabetes mellitus, they clearly understood that the presence of sweet urine and physical
wasting were symptoms of the disease. In the middle ages, French lilac was used to treat
the symptoms of what we now call type-2 diabetes or insulin resistant diabetes. (Type-1
diabetes is characterized by a lack of insulin because the insulin producing cells of the
pancreas have been destroyed by an autoimmune response). In addition to its use in
F

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treating diabetes, people of medieval Europe also used French lilac to treat a variety of
other aliments including plague, worms, animal bites, poisoning, dysuria (painful
urination) and even miasma (bad odor). French lilac was also used to increase milk
production in certain domesticated farm mammals (hence the genus name Galenga). But
it was the ability of French lilac to reverse the symptoms of diabetes mellitus that caught
the attention of the biomedical community in modern times.1
Analysis of the chemical composition of French lilac in the late 1800's indicated
that the plant contained significant amounts of guanidine. By the early 1900's, it was
shown that this molecule had the ability to lower blood glucose levels in laboratory
animals. Unfortunately, guanidine itself was quite toxic causing extracts of French lilac
high in guanidine to not be useful for treating diabetes mellitus. For a short time, a less
toxic extract of French lilac rich in a related molecule, known as galegine, was used to
treat diabetics.2,3,4
The toxicity of guanidine, however, actually stimulated the development of a
class of compounds related to guanidine called the diguanides. Clinical testing showed
that the diguanides were antigylcemic and were also less toxic then guanidine.
Diguanides were used to treat the symptoms of diabetes mellitus in the first half of the
twentieth century.
The diguanides were displaced by the discovery of insulin. Administration of
high concentrations of insulin to insulin resistant diabetics forced the insulin pathway to
respond basically because of mass action. High concentrations of insulin forced the
binding of hormone to receptor. However, a simple to use antiglycemic drug in tablet
form that would exhibit few adverse side effects was still being researched at the

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chemical level. The next generation of antiglycemic drugs to be developed from that
research occurred around 1930 and was called the biguanides. The biguanides were
proven to be non-toxic in laboratory animals. Starting in the late 1940's and throughout
much of the 1950's, chemical modifications and clinical trials performed in France lead to
the development of the biguanide drug metformin. In 1957, metformin was introduced to
the scientific and clinical world. Its use was first approved for treatment of diabetes in
France in 1979. It is still used around the world today.5,6
The similarity of guanidine to metformin is
shown in the accompanying figure of chemical
structures. The similarity of the structures of the
two molecules is striking. Metformin is non-toxic
derivative of the natural molecule isolated from a
botanical. Metformin decreases blood glucose
levels without significant adverse side effects.
Metformin also decreases the death rate of diabetics
with heart disease or who are obese. This important
antiglcemic drug was developed based on scientific
observations of a botanical/herbal remedy used in
the middle ages. Although the development of
metformin took about 70 years from the time
guadinine was first isolated from French lilac, that
time course would be much shorter in the present because of the advances made in both
chemistry and biochemistry.
Molecular structure of Metformin
Molecular structure of Guanidine

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It is important to note that even with all the research and development of
metformin, the exact biological mechanism by which it exerts it antiglycemic effects is
still not understood. Without a biological explanation for the function of metformin
means that the drug could not be designed by biochemists. Metformin was discovered
because of excellent biological and chemical research coupled with clinical studies based
on the careful scientific observations regarding the efficacy of a medieval herbal
preparation on diabetes mellitus.
References
1) Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes
Care. 1989 Sep;12(8):553-564.
2) Watanabe CK. Studies in the metabolic changes induced by administration of
guanidine bases. J Biol Chem. 1918 33:253-265.
3) Sterne J. Pharmacology and mode of action of the hypoglyaemic guanidine
derivatives. In Oral Hypoglaemic Agents. Campell GD (ed.) London: Academic Press.
1969 pp 193-245
4) Beckman R. Biguanide. In Handbook of Experimental Pharmacology. Maske H (ed.)
Berlin: Springer Verlag. 1971 pp 439-596.
5) Sterne J. Du nouveau dans les antidiabetiques. La NN dimethylamine guanyl guanide.
Maroc Med. 1957 Sep;36(388):873-884
6) Ungar G, Freedman L, Shapiro SL. Pharmacological studies of a new oral
hypoglycemic drug. Proc Soc Exp Biol Med. 1957 May;95(1):190-192.