Barberry Berberine Diabetes & Fat Mice

I followed this chain from the Fat Mice study to end up on Barberry but I’m going to present it in reverse order.

The basic “story line” is that a connection has been found between gut bacteria, a particular “receptor” in the gut, and stimulation of particular gene expression, such that “metabolic syndrome” can be modulated via gut bacteria modulation. That, then, sent me looking at the things causing gene expression and that ended up at folk treatments for things like Diabetes using Barberry. Essentially it shows how barberry works by modulating those same gene expressing pathways and justifies the herbal medicine claims (to some extent).

I’d assert that this also explains why the “Fasting Cure” for Diabetes could also work. Fasting not only stresses the person fasting, it starves the bacterial and fungal populations of the gut and will cause significant shifts in them.

So, Barberry. It has a substance in it called Berberine. Also found in several other plants (including the California Poppy though they are a protected plant so don’t go eating them in public ;-)

https://en.wikipedia.org/wiki/Berberis

Berberis (/ˈbɜːrbərɪs/), commonly known as barberry, is a large genus of deciduous and evergreen shrubs from 1–5 m (3.3–16.4 ft) tall, found throughout temperate and subtropical regions of the world (apart from Australia). Species diversity is greatest in South America and Asia; Europe, Africa and North America have native species as well. The best-known Berberis species is the European barberry, Berberis vulgaris, which is common in Europe, North Africa, the Middle East, and central Asia, and has been widely introduced in North America. Many of the species have spines on the shoots and along the margins of the leaves.

So a very common plant found all over the place. Could it be that selling something growing like a weed is hard to do but selling all sorts of exotic drugs and diet plans makes a lot of money? I’m sure it was just an oversight that this plant might work… /sarc;

https://en.wikipedia.org/wiki/Berberine

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as Berberis (e.g. Berberis vulgaris – barberry, Berberis aristata – tree turmeric, Mahonia aquifolium – Oregon-grape, Hydrastis canadensis – goldenseal, Xanthorhiza simplicissima – yellowroot, Phellodendron amurense – Amur cork tree, Coptis chinensis – Chinese goldthread, Tinospora cordifolia, Argemone mexicana – prickly poppy, and Eschscholzia californica – Californian poppy. Berberine is usually found in the roots, rhizomes, stems, and bark.

Due to berberine’s strong yellow color, Berberis species were used to dye wool, leather, and wood. Wool is still dyed with berberine today in northern India. Under ultraviolet light, berberine shows a strong yellow fluorescence, so it is used in histology for staining heparin in mast cells. As a natural dye, berberine has a color index of 75160.
[…]
Culinary uses

Berberis vulgaris grows in the wild in much of Europe and West Asia. It produces large crops of edible berries, rich in vitamin C, but with a sharp acid flavour. In Europe for many centuries the berries were used for culinary purposes in ways comparable to how citrus peel might be used. Today in Europe they are very infrequently used. The country in which they are used the most, is Iran where they are referred to as “Zereshk” (زرشک) in Persian. The berries are common in Iranian (Persian) cuisine such as in rice pilafs (known as “Zereshk Polo”) and as a flavouring for poultry meat. Due to their inherent sour flavor, they are sometimes cooked with sugar before being added to Persian rice. Iranian markets sell Zereshk dried. In Russia they are sometimes used in jams (especially the mixed berry ones) and extract from them is a common flavouring for soft drinks and candies/sweets.

Berberis microphylla and B. darwinii (both known as calafate and michay) are two species found in Patagonia in Argentina and Chile. Their edible purple fruits are used for jams and infusions. The calafate and michay are symbols of Patagonia.

Traditional medicine

The dried fruit of Berberis vulgaris is used in herbal medicine. The chemical constituents include isoquinolone alkaloids, especially berberine. One study reports that it is superior to metformin in treating polycystic ovary syndrome.

Folk medicine

Berberine was supposedly used in China as a folk medicine by Shennong around 3000 BC. This first recorded use of berberine is described in the ancient Chinese medical book The Divine Farmer’s Herb-Root Classic.

So not only might one find it in “Health Food Stores”, but in Iranian Markets and perhaps a Hispanic food store with a Chilean or Argentinian focus.

Then “Traditional Medicine” used it and it might also be found at a Chinese Herbalist store.

So not exactly hard to find.

But no worries. Researchers have discovered it now… only a few thousand years later…

Research

Berberine is under investigation to determine whether it may have applications for treating arrhythmia, diabetes, hyperlipidemia, and cancer. Berberine exerts class III antiarrhythmic action. There is some evidence that berberine may have anti-aging (gero-suppressive) properties. Berberine is already being used as an ‘Insuin Sensitizer’ which is able to provide better glycaemic control in most of the users [Only upon prescription of a qualified physician]. In live cells, berberine localizes in mitochondria. Its mitochondrial localization is consistent with inhibition of complex I of respiratory chain, decrease of ATP production, and subsequent activation of AMPK, which leads to suppression of mTOR signaling. The bioavailability of berberine is low.[

Some research has been undertaken into possible use against methicillin-resistant Staphylococcus aureus (MRSA) infection. Berberine is considered antibiotic. When applied in vitro and in combination with methoxyhydnocarpin, an inhibitor of multidrug resistance pumps, berberine inhibits growth of Staphylococcus aureus and Microcystis aeruginosa, a toxic cyanobacterium.

Well. Guess I need to go on a shopping trip to strange stores looking for Barberry…

I got to Barberry by looking up one of the “receptors” that was involved in the Fat Mice Study.

https://en.wikipedia.org/wiki/Peroxisome_proliferator-activated_receptor

In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms.

Significantly involved in fat metabolism (of a couple of kinds) along with other functions, those receptors are important in what you do with your food and fat intake. Regulating them ought to have effects on things like diabetes and obesity, so no surprises here.

Hey, looks like the Drug Companies have even discovered it! I’ve bolded the bit that sent me off to Barberry land.

Pharmacology and PPAR modulators

Main article: PPAR modulator

PPARα and PPARγ are the molecular targets of a number of marketed drugs. For instance the hypolipidemic fibrates activate PPARα, and the anti diabetic thiazolidinediones activate PPARγ. The synthetic chemical perfluorooctanoic acid activates PPARα while the synthetic perfluorononanoic acid activates both PPARα and PPARγ. Berberine activates PPARγ, as well as other natural compounds from different chemical classes.

But why eat a bowl of berrys when you could be put on a drug regime of thiazolidinediones and perflourononanoic acid…

But about those Fat Mice…

https://www.sciencedaily.com/releases/2018/02/180212100618.htm

Goes into great detail about how they made some genetically altered mice to see what the particular “receptors” did in terms of making folks (er, mice…) fat. Then discovers that the particular bacteria in your gut have figured out how to make you eat more and get fatter…

Mouse study adds to evidence linking gut bacteria and obesity

Date:
February 12, 2018
Source:
Johns Hopkins Medicine
Summary:
A new study of mice with the rodent equivalent of metabolic syndrome has added to evidence that the intestinal microbiome — a ‘garden’ of bacterial, viral and fungal genes — plays a substantial role in the development of obesity and insulin resistance in mammals, including humans.

A new Johns Hopkins study of mice with the rodent equivalent of metabolic syndrome has added to evidence that the intestinal microbiome — a “garden” of bacterial, viral and fungal genes — plays a substantial role in the development of obesity and insulin resistance in mammals, including humans.

A report of the findings, published Jan. 24 in Mucosal Immunology, highlights the potential to prevent obesity and diabetes by manipulating levels and ratios of gut bacteria, and/or modifying the chemical and biological pathways for metabolism-activating genes.

“This study adds to our understanding of how bacteria may cause obesity, and we found particular types of bacteria in mice that were strongly linked to metabolic syndrome,” says David Hackam, M.D., Ph.D., surgeon-in-chief and co-director of Johns Hopkins Children’s Center and the study’s senior author. “With this new knowledge we can look for ways to control the responsible bacteria or related genes and hopefully prevent obesity in children and adults.”

Metabolic syndrome, a cluster of conditions including obesity around the waist, high blood sugar and increased blood pressure, is a risk factor for heart disease, stroke and diabetes. While no precise cause for metabolic syndrome is known, previous studies of Toll-like receptor 4 (TLR4), a protein that receives chemical signals to activate inflammation, have suggested that TLR4 may be responsible in part for its development.

Hmmm… connecting inflammation into the mix too. So they chopped it out of some mice guts, and they got obese on regular mouse chow rations. Then they played around with more of that (just chopping it out of the gut genome) and did more tests. Eventually deciding the gut bugs are involved too.

[…]
To investigate the role the bacterial makeup of the gut had on the mice, Hackam and his team then administered antibiotics to the normal and TLR4 intestinal epithelium-deficient mice. Antibiotics significantly reduced the amount of bacteria in the intestinal tract and prevented all symptoms of metabolic syndrome in the mice that lacked TLR4 in their intestinal epitheliums.

This demonstrates, the researchers say, that bacterial levels can be manipulated to prevent the development of metabolic syndrome.

To further explore the role of intestinal epithelial TLR4 on the development of metabolic syndrome, the research team analyzed fecal samples from the TLR4 intestinal epithelium-deficient and normal mice. The team found that specific clusters of bacteria that contribute to the development of metabolic syndrome were expressed differently in the deficient mice than in normal mice. They also determined that the bacteria expressed genes that made them “less hungry” and thus less able to digest the nutrients present in the mouse chow. This resulted in a greater abundance of food for the mouse to absorb, which contributed to obesity.

I question just how much ‘less hungry bacteria’ was the actual mechanism as opposed to direct modification of gene expression in the fat metabolism path of the host… but moving on…

The researchers then analyzed the genes expressed in the lining of the intestinal mucosa — the site at which food absorption occurs — in normal and TLR4 intestinal epithelium-deficient mice. Of note, the team determined that important genes in the perixisome proliferator-activated receptor (PPAR) metabolic pathway were significantly suppressed in the deficient mice. Administering antibiotics prevented the differences in gene regulation between the two groups of mice, as did administering drugs to activate the PPAR signaling pathway, further explaining the reasons for which obesity developed.

“All of our experiments imply that the bacterial sensor TLR4 regulates both host and bacterial genes that play previously unrecognized roles in energy metabolism leading to the development of metabolic syndrome in mice,” says Hackam.

Gee… a direct mode of action for BOTH Barberry and simple fasting to be effective treatments for diabetes, obesity, metabolic syndrom, and who knows what all else.

But I’m sure the Drug Industry will find a nice pill you can take to monetize this instead.

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