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Goat’s Rue Plant, Metformin, and Medication Action in the Body

Linda Crampton is a science writer with a first-class honors degree in biology. She has many years of experience in teaching science.

Goat's Rue and the Metformin Medication

The goat’s rue or French lilac (Galega officinalis) is an interesting plant that has been used in several ways. It contains a biologically active chemical called galegine. The plant was once valued in folk medicine, though today it's known to have toxic characteristics. Modern studies of galegine led to the creation of metformin, which is a useful medication for treating type 2 diabetes.

In science, the word "medication" is interchangeable with the word drug. This article explores the fate and behavior of the metformin drug in the body. There is much that still needs to be learned about the substance, even though it has been used to treat diabetes for over sixty years. It's believed to affect the body in multiple ways and by multiple mechanisms. It's an intriguing chemical that is being explored as a treatment for other disorders in addition to diabetes

Galega officinalis, goat's rue, or French lilac has attractive flowers.

Galega officinalis, goat's rue, or French lilac has attractive flowers.

The Goat's Rue or French Lilac Plant

Galega officinalis belongs to the pea family, or the Fabaceae. The family is also known as the Leguminosae. "Rue" means regret, so perhaps the plant was given the name goat's rue because it was toxic for animals. It's also known as French lilac and as professor weed. The plant is native to the Middle East but has spread to Western Asia and Europe.

Goat's rue is a perennial and herbaceous plant. Its pea-like flowers are white, blue, purple, and occasionally pink. They are borne on a structure called a raceme. This structure consists of flowers arranged in vertical rows along a tall stem. The most mature flowers are at the bottom of the raceme and the youngest ones at the top. Though the flowers of goat's rue are attractive, the plant itself can become unruly. The fruits are small pods.

The plant's leaves are pinnately compound. A row of narrow leaflets is present on either side of the rachis, which is an extension of the leaf's stem. The plant grows from a taproot. A taproot is a thick root that grows downwards and has relatively thin lateral roots. Carrots and parsnips are taproots of their species.

The name "goat's rue" is also used for a North American plant with the scientific name Tephrosia virginiana. This might be confused with G. officinalis. The latter plant is found in the United States and Canada, though it's not given much respect due to its toxicity to livestock. It's classified as a noxious weed in the United States. Strangely, it was once used as a forage crop until its toxic effects were discovered. The plant has killed grazing animals.

History of Galegine Use and Metformin

Goat's rue was used as a folk medicine as long ago as the medieval period. It was prescribed for people who were experiencing frequent urination. This is a symptom that might indicate the existence of diabetes. Though the plant may have been at least somewhat effective as a medicine, as time progressed people became dissatisfied with its mild benefits. In addition, they disliked its potentially toxic effects.

As science and technology advanced, scientists were able to explore some of the chemicals in goat's rue. In the late 1800s, they discovered that the plant was rich in a substance called guanidine. This substance lowered the blood glucose level, but at the same time it was obviously too toxic to use as a medicine. Researchers then turned their attention to a related chemical in the plant called galegine, or isoamylene guanidine. This also lowered the glucose level and was less toxic than guanadine. For a short while, galegine was used as a medicine.

Scientists created chemicals related to galegine that were more effective medicines, but they were unable to create a nontoxic drug that was sufficiently helpful in lowering the blood glucose level. Some of the effective chemicals, such as phenformin and buformin, had an unacceptable risk of increasing the concentration of lactic acid in the blood to a dangerous level. The acid produced a very serious condition called lactic acidosis. Thankfully, the situation eventually changed.

Jean Sterne (1909–1997) was a French physician. He investigated the effects of another chemical related to galegine. He tested dimethylbiguanide (metformin) on a high blood glucose level and discovered that it had an excellent combination of effectiveness and safety. Sterne called the medication glucophage, a designation that is used as a trade name today. The name means "glucose eater". Metformin is the generic name of the medication.

Metformin Structure

Metformin has two nitrogen-containing units that are quite similar, as can be seen in the illustration of the molecule's skeletal formula below. Each unit is known as a guanidine ring. Metformin's full chemical name is N, N-dimethylbiguanide.

In a skeletal formula for an organic compound, carbon atoms aren't shown. They are understood to be at the vertices where lines representing the bonds join. The existence of the hydrogen atoms attached to the carbon atoms is implied. Each carbon atom can form four bonds in total. If a carbon atom is joined to a nitrogen atom (for example), the other three atoms joined to the carbon are assumed to be hydrogen ones.

The illustrations below show that half of the galegine molecule is identical to half of the metformin one. The metformin molecule is said to be a structural analog of the galegine one. Structural analogues are similar to each other with respect to their molecular structure but have a section that is different. The difference may be important with respect to a molecule's properties. Galegine is said to be at least somewhat toxic. Metformin is considered to be much safer.

Skeletal formula of a galegine molecule

Skeletal formula of a galegine molecule

Skeletal formula of a metformin molecule

Skeletal formula of a metformin molecule

Blood Sugar Regulation and Type 2 Diabetes

Normal Regulation of Blood Sugar

Glucose is the primary energy source for our cells. In order for glucose to be absorbed through the cell membrane, insulin must be attached to a receptor on the membrane. The glucose then enters the cell and is used as an energy source. Insulin is a hormone made by the pancreas. It travels to the body's cells via the bloodstream.

The circulatory system also transports glucose to the cells. Glucose in the blood is sometimes known as blood sugar. When glucose from foods and drinks enters our bloodstream, some of it is sent to the liver. Here it's stored in the form of a molecule called glycogen.

If our blood sugar level falls too slow, glucose is released from the glycogen and enters our blood stream. The liver can also make glucose from amino acids and other molecules. This process is known as gluconeogenesis. A healthy body is able to keep the blood sugar level fairly constant by balancing the blood sugar level and the glucose requirements of cells.

Type 2 Diabetes

In type 2 diabetes, cells become partially resistant to the presence of insulin. The blood sugar level rises because glucose can't leave the blood and get into the cells. In addition, the pancreas may be unable to release enough insulin to overcome the resistance. The disorder is sometimes a combination of insulin resistance and pancreatic insufficiency. A continuously high blood sugar level can cause harmful effects in various parts of the body.

Medication Facts

Metformin is said to be the most commonly prescribed medication for type 2 diabetes. It lowers the blood glucose level, generally without causing it to fall too low, provided it's taken according to a doctor's recommendations. Metformin also has other effects, at least in lab experiments. Evidence suggests that it may be helpful in protecting the heart and in treating some types of cancer.

Despite the fact that it seems to be involved in multiple processes in the body, metformin has a good safety record when used according to a physician's instructions. "Good" doesn't mean perfect, however. A physician's knowledge and care is essential because in very rare cases the drug has caused lactic acidosis. It may cause less serious side effects in some people.

An enterocyte in the small intestine; the three organelles at the bottom of the cell and two organelles higher up are mitochondria.

An enterocyte in the small intestine; the three organelles at the bottom of the cell and two organelles higher up are mitochondria.

Absorption of Metformin in the Intestine

Foods and drinks that we ingest are digested in the small intestine. Nutrients are then absorbed through the lining of the intestine. Metformin must be transported through the lining via a carrier protein, except perhaps when it's present at a very high concentration. In this case, it may move by diffusion. Carrier proteins are also required on or in membranes in other parts of the body in order for metformin to be absorbed.

Some of the carriers needed for metformin absorption are present on the enterocytes that line the inner surface of the small intestine. Appropriate carrier proteins are also present on the cell membrane of the hepatocytes, or liver cells, and on the cells of the kidneys. Metformin is transported between organs in the bloodstream.

Researchers are investigating how structural alterations in carrier proteins affect the activity of metformin. Defects in the genes coding for the proteins might contribute to the fact that although in general the medication is very useful, it's less effective in some people than in others. Major carrier proteins are listed below.

  • PMAT (plasma membrane monoamine transporter) on the enterocytes, which enables absorption from the lumen (cavity) of the intestine
  • OCT1 (organic cation transporter one) on the basolateral membrane of the enterocytes, which enables metformin to reach the bloodstream.
  • OCT1 and perhaps OCT3 on the hepatocytes
  • OCT2 on renal epithelial cells in the kidneys
  • MATE1 and MATE2 (multidrug and toxin extruder 1 and 2) for transporting metformin into the urine

Metformin has a high absorption rate in the liver compared to its absorption in other areas. This organ seems to be a major location of the drug's beneficial activities in treating diabetes.

Evidence obtained so far indicates that the metformin molecule isn't metabolized. The molecule stays intact as it exerts its effects and is eventually excreted in the urine. It does undergo a minor alteration in the body to become a positive ion, or a cation, but other than this it doesn't change.

Many proteins in the body seem to be involved in the activity of metformin. Genes contain the "instructions" for making the proteins. The instructions are encoded in the structure of a gene. If a gene's structure is incorrect or altered, a defective protein may be made.

Some Effects After Absorption

Based on discoveries made so far, metformin appears to help type 2 diabetes by four methods, particularly the first one in the list below.

  1. Inhibition of gluconeogenesis in the liver
  2. To a lesser extent, increasing the sensitivity of tissues to insulin
  3. Also to a lesser extent, inhibition of glucose absorption in the intestine
  4. Possibly, by stimulating glucose absorption by other tissues

Identifying all of the chemical reactions that metformin affects is proving to be difficult. A huge number of reactions occur in the human body. Human biochemistry is a fascinating but complex subject.

Despite the difficulties involved, researchers have made two discoveries that appear to be significant.

  • Metformin inhibits a complex of proteins in the mitochondria known as respiratory-chain complex 1.
  • Metformin stimulates the activity of an enzyme known as AMPK (AMP-activated protein kinase), especially in the liver. AMP stands for adenosine monophosphate.

Pharmacological activation of AMPK promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and insulin sensitivity; processes that are reduced in obesity and contribute to the development of insulin resistance.

— Hayley M. O'Neill, Diabetes and Metabolism Jourbnal

Effects on the Mitochondria and Beyond

The Mitochondria

Metformin is thought to produce many (but not all) of its effects by influencing the mitochondria of cells. These organelles produce most of the ATP (adenosine triphosphate) needed by a cell. ATP molecules provide the energy that a cell needs. Some of our cells contain hundreds of mitochondria.

ATP is made when ADP (adenosine diphosphate) joins to phosphate. Energy is absorbed during this process. AMP (adensosine monophosphate) contains only one phosphate and is used to make both ADP and ATP.

Metformin's Effects

Experimental evidence from multiple experiments suggests that metformin inhibits respiratory-chain complex 1 in the mitochondria.

  • The inhibition of respiratory-chain complex 1 causes the concentration of ATP to decrease, since ATP is made in the mitochondria.
  • The decrease in ATP causes a decrease in gluconeogenesis, since several steps in the process require ATP as an energy source.
  • The relative amounts of ADP and AMP increase compared to the amount of ATP because the first two chemicals are no longer being used for ATP production (or are being used to a lesser extent).
  • The increase in AMP availability causes an increase in the concentration of AMPK.
  • AMPK triggers many processes, some of which are believed to be helpful with respect to type 2 diabetes. The substance is often referred to as an "energy-sensing protein".
  • AMPK-triggered activities that may be useful in type 2 diabetes include absorption of glucose by cells other than intestinal ones (thereby lowering its concentration in the blood) and increased sensitivity of cells to insulin.

More research is needed to clarify all of the details involved in the processes described above. If the mitochondria are inhibited by metformin, as the evidence suggests, it would be interesting to know if a cell is adversely affected by a decrease in ATP production.

Further Studies Are Required

The information obtained so far in relation to metformin is interesting, but further studies are needed. The substance seems to have widespread effects in the body. Its therapeutic reach might be wider than realized. It's possible that the beliefs about the drug's behavior in the body that are described above will be modified as more discoveries are made. I will be watching the research reports with interest.

Though the creation of new medications is important, learning about the behavior of old ones could be very helpful in the treatment of disease. This could be the case with respect to metformin. It's an intriguing drug.

References

  • Goat's rue plant facts from CABI (Centre for Agriculture and Biosciences International) Invasive Species Compendium
  • The goat's rue plant in King County, Washington
  • Information about type 2 diabetes from the Mayo Clinic
  • Facts about the liver and blood sugar from the University of California, San Francisco Medical Center
  • The botanical background of metformin from Practical Diabetes and the Wiley Online Library
  • Metformin: From Mechanisms of Action to Therapies from Cell Metabolism and Science Direct
  • AMPK and Exercise: Glucose Uptake and Insulin Sensitivity from Diabetes and Metabolism Journal
  • Goat's rue information and concerns from WebMD

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2020 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on March 28, 2020:

Thanks for the comment, Adrienne. The plant kingdom has many benefits and seems to have many surprises for us. It's interesting to explore.

Adrienne Farricelli on March 28, 2020:

It's was very interesting learning about the medical uses of goat's rue. Funny how many plants that are considered noxious weeds have so many medicinal benefits.

Linda Crampton (author) from British Columbia, Canada on March 07, 2020:

Thank you very much, Eddy!

Eiddwen from Wales on March 07, 2020:

You are obviously very knowledgeable on this subject Linda and thank you for sharing this knowledge with us. A very well written and informative hub. Great work.

Linda Crampton (author) from British Columbia, Canada on February 05, 2020:

Thank you very much for the comment and the congratulations, Rajan.

Rajan Singh Jolly from From Mumbai, presently in Jalandhar, INDIA. on February 05, 2020:

Interesting and thought-provoking article. All drugs need to be used with proper caution. Thanks for sharing and congrats on bagging the Hubbie award.

Linda Crampton (author) from British Columbia, Canada on January 31, 2020:

Thank you very much for the congratulations and the comment, Flourish!

Linda Crampton (author) from British Columbia, Canada on January 31, 2020:

Thank you so much, Chitrangada. I appreciate you visit and your kind comment a great deal.

FlourishAnyway from USA on January 31, 2020:

Congratulations on your Hubbie award! Well deserved!

Chitrangada Sharan from New Delhi, India on January 31, 2020:

I have visited this wonderful article earlier. But came back to Congratulate you for your Hubbie award. So well deserved. Your high quality articles are an asset for HubPages.

Thank you for sharing valuable information, through your articles.

Linda Crampton (author) from British Columbia, Canada on January 30, 2020:

Thank you very much, Mel. I always appreciate your visits.

Mel Carriere from San Diego California on January 30, 2020:

Once again you have enlightened me on an organism that has outstanding benefits for mankind. Pretty flowers or not, I do not think I will try to grow it in my garden. Great article.

Linda Crampton (author) from British Columbia, Canada on January 25, 2020:

Hi, Rachelle. Thank you very much for the comment. Good luck with your steps to prevent diabetes. They sound excellent.

Rachelle Williams from Tempe, AZ on January 25, 2020:

Wow! This article really made me think about a lot of things. Ever since I was diagnosed as being pre diabetic, I have been in research mode about the disease. It really striking how Goat's Rue was used back in the day to treat symptoms of diabetes. Right now I'm in the mode of prevention via diet and exercise, hopefully I won't need Metformin, but I'm so grateful to you for publishing this hub, just in case...

Linda Crampton (author) from British Columbia, Canada on January 22, 2020:

Thanks for the visit and the comment, Nithya. Nature seems to hold many surprises!

Nithya Venkat from Dubai on January 22, 2020:

I knew about Metformin but after reading your article I got to know about Goat's Rue in relation to metformin. It is amazing how a plant can be poisonous to animals and at the same time be of great use to humans. Thank you for sharing an interesting and informative article, enjoyed the reading.

Linda Crampton (author) from British Columbia, Canada on January 20, 2020:

Thank you very much for the kind comment and for sharing your experience, Manatita. I hope you have a good week.

Linda Crampton (author) from British Columbia, Canada on January 20, 2020:

Hi, Dora. Metformin has been proven to be useful for some people, not the plant, but your advice about strictly obeying a doctor's instructions is excellent. I appreciate your comment.

manatita44 from london on January 20, 2020:

What a beautifully described Hub, Linda. I always learn a lot from you. Good to read about the plant also. I like the French name.

Metformin in my experience as a nurse, works very well for some patients but does not in others. We are all different. It can also affect some organs with long-tern use. An informative and educational Hub

Dora Weithers from The Caribbean on January 20, 2020:

As usual, we learn much from your articles. It seems that for this plant, the key is strict obedience to the doctor's instructions. Since it has been proved useful, we just need a way to keep its usage safe. Thanks for the information.

Linda Crampton (author) from British Columbia, Canada on January 17, 2020:

Thanks, Chris. The mechanism of action of medications is an interesting topic. I have a lot of respect for the scientists who study the chemicals.

Chris Mills from Traverse City, MI on January 17, 2020:

Solid article, Linda. Yes, it has been around for a long time. It is interesting how little we know about some medications, but we still prescribe them. The benefits far outweigh the negatives...we hope. I work in the medical field and have a lot of respect and trust in how we do our science.

Linda Crampton (author) from British Columbia, Canada on January 17, 2020:

Hi, Denise. The USDA has created a map showing the distribution of goat's rue in North America. It shows the plant in the northeastern part of the United States, in a few places in the central part of the country, and in Washington. I wouldn't be surprised if it's spread to other areas, though, including California.

Blessings to you as well. I hope you have a great weekend.

Denise McGill from Fresno CA on January 17, 2020:

When I had a herb garden I grew rue even though I didn't know what to do with it. This goat rue looks like some wild plants I've seen about. I wonder if that's possible.

Blessings,

Denise

Linda Crampton (author) from British Columbia, Canada on January 17, 2020:

Hi, Linda. The effectiveness of the intact plant in lowering the blood sugar level is uncertain and there are concerns about its safety, but metformin, which is related to a chemical in the plant, is certainly helpful. The plant chemical triggered the production of the medication. I think that’s a very important argument for protecting plant species from destruction.

Linda Chechar from Arizona on January 17, 2020:

I had no idea that these specific plants can lower blood glucose levels. Your scientific article is full of informative

Linda Crampton (author) from British Columbia, Canada on January 17, 2020:

Thank you very much, Heera.

Heera from India on January 17, 2020:

Great article. Truly informative. Thank you.

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

Thank you very much, Liz. I appreciate your visit and the kind comment.

Liz Westwood from UK on January 16, 2020:

This is a fascinating and detailed article. I would never have made the link between this plants and the medication without reading your excellent article.

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

The statement by your doctor is interesting, Heidi. Nature has a lot to offer us!

Heidi Thorne from Chicago Area on January 16, 2020:

One of my doctors told me that all prescription drugs have a basis in nature. And this definitely seems to bear that out.

And if this could be used in some form for the treatment of Type 2 diabetes, that would be wonderful. We shall see as the research continues.

I always learn something new from your posts. Thank you for sharing your knowledge and insight, as always!

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

Hi, Peggy. I'm interested in seeing what else researchers discover about the drug. Its potential benefits in diseases besides type 2 diabetes are very intriguing.

Peggy Woods from Houston, Texas on January 16, 2020:

I know someone who has just been prescribed this drug, so I read this with interest. It is interesting that metformin may have additional benefits to simply treating type 2 diabetes. The plant from which it derives is a beauty.

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

I appreciate your visit and comment very much, Chitrangada. To be honest, I don't like referring to Goat's rue as a medicinal plant today. I've added a WebMD reference to the article that goes into more detail about the situation.

Chitrangada Sharan from New Delhi, India on January 16, 2020:

The French Lilac is also called Goat’s Rue plant—I had no idea about that. These flowers are so pretty in colour. I am aware about their medicinal properties.

You have very well explained the details about this useful flower/ plant.

Thanks for sharing this excellent information in this well researched article.

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

Thank you very much, Pamela. I'm glad that the researchers were able to make a safe chemical based on the one in the plant. Nature can be very helpful, even when we need to modify what it offers us.

Pamela Oglesby from Sunny Florida on January 16, 2020:

I found this well-written article to be so interesting as this was all new to me. Those beautiful flowers having a medicinal effect is great. Diabetes II can be so difficult to control sometimes, so I am glad they will continue their research.

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

Hi, Bill. No, it's not similar to tansy, except for the fact that it's toxic to animals. Thank you for the comment.

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

Thank you very much for the visit and the comment, Devika.

Linda Crampton (author) from British Columbia, Canada on January 16, 2020:

I'm sorry that your mom and grandmother have diabetes, Flourish. I hope they are able to manage the problem as well as possible. Thanks for the comment.

Bill Holland from Olympia, WA on January 16, 2020:

It sounds similar to tansy? Is it? We have to pull tansy out of the horse pasture around here because it can kill horses. Anyway, another informative and interesting article, Linda.

Devika Primić from Dubrovnik, Croatia on January 16, 2020:

Hi Linda you have an interesting subject and your impressive knowledge of this plant tells me everything I need to know in detail and presented with a lovely photo.

FlourishAnyway from USA on January 16, 2020:

I’m intrigued how centuries ago people could associate certain plants With alleviation of specific symptoms. This is a well researched and interesting article. My mom and grandmother have diabetes.

Linda Crampton (author) from British Columbia, Canada on January 15, 2020:

Hi, Mary. Thanks for the comment. I like the plant too, especially the flowers.

Mary Norton from Ontario, Canada on January 15, 2020:

My husband took metformin but I never understood until now how it works. The plant is lovely.

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