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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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
This entry was posted in Biology Biochem and tagged , , , , , . Bookmark the permalink.

11 Responses to Barberry Berberine Diabetes & Fat Mice

  1. Graeme No.3 says:

    Perfluorooctanoic acid etc. are subject to claims that they cause cancer. As they were used in fire fighting foams (for petrol, jet fuel etc.) and persisted in soil at low levels, they are currently causing much knicker twisting in Australia.

  2. E.M.Smith says:

    A trip to the local “Mediterranean Market” (AKA Persian Market run by Iranian refugees – Christian I think, but nice folks whatever they believe) has yielded a nice tub of “dried barberries”. They are like little lentil or pea sized dried cranberries. Sweet tart flavor just rinsed and chewed. $5.44 for a 1/2 pound. Even lists the tare weight on the package.

    There’s an odd after effect on the tongue. Like some activity is going on. Not unpleasant. Not quite a flavor. Kind of like having bit a slice of lime leaves an acid tingle.

    So now I need to figure out how to use them in cooking. The Proprietor (when I said I had no idea what I was going to do with them so would be experimenting and needed enough to try a few times – they had 3 sizes of tubs…) informed me you could toss them in just about anything. Chicken, salads, something that sounded like a soup… or just eat them straight from the tub.

    IF I suddenly start having dramatic “pudge” reduction, I’ll let you’all know… 8-)

    Oh, and I also scored a bottle of Avocado Oil there. Interesting label, says it was made in either Mexico OR Spain… So I’m going to try it in salad dressing, in some cooking, and even try a batch of Mayo made with it (since several folks recommended it).

    https://chiefio.wordpress.com/2018/01/11/mayonnaise/

    Interesting shop. They sell more kinds of tea than I can count, have various tuna, sprats, etc. from all over the globe ( I like the sprats with a Russian language lable- deep smoke flavor), many kinds of oils, and a spice rack full of interesting things. Some canned goods you can’t find anywhere else, some Persian style tea sets and pots / pans. Then there is a small vegetable section, meat section, and cold cases. Plus a large specialty desert counter. Not a lot of generic stuff, but all the things you can’t find somewhere else. It is one of my favorite stores and I go there about once a month. I’m now addicted to their good tea that makes the regular store stuff taste like crap. They also sell interesting kinds of rice not found elsewhere for that authentic flavor and texture of “wherever”… (some middle-east, some more India).

    If you have not tried it, stop in the various odd tiny Indian, Middle Eastern, and other ethnic food stores. It’s a treat.

    So, I now have a tub of Barberry… let the experimenting and dining begin!

    Oh, I probably ought to add, while talking about food: Bought a bottle of Newman’s Own Sesame Ginger salad dressing. While I like it (in moderation) it was way too spicy for spousal use nor was it “like on the salad at the sushi place – light and subtle”…

    Instead of just buying more bottle of stuff and hoping, I went recipe hunting. Found one for a simple plain base that was close, then adjusted it: https://www.thespruce.com/basic-japanese-salad-dressing-2031180

    Seems I already had all the ingredients. I ended up at:
    1 tsp sugar
    2 Tablesp. Kikkoman Soy Sauce
    4 Tablesp. Rice Vinegar (that I use when making sushi rice…)
    6 Tablesp. Oil. I used Canola for this batch, but olive or avocado in the next. Maybe Sunflower..

    I just dumped it in a pint canning jar, tightened the lid, and shook it vigorously a while. Worked great.

    Made a dressing more like we wanted. I may add a tsp or two of the sesame ginger dressing to it IFF we want more complexity.

  3. E.M.Smith says:

    A link to medicinal use guidelines for barberry.
    https://www.drugs.com/npp/barberry.html
    Roots are the strong stuff, berries may have mild effect. Looks like jam & wine can and are made from them.

    FWIW, the dry ones I got are best rehydrated a bit and sprinkled on things after cooking, or included in wet cooking. On a bit of chicken being roasted, they just turned into charred things… but those in the pan juices were ok and the ones soaked in water and sprinkled over were a bit of a flavor treat.

  4. Graeme No.3 says:

    Zereshk Polo involves cooking chicken (with onion and turmeric), then marinating it in Yoghurt with saffron (& egg) then layering it in the middle of cooked rice. The barberies are washed then cooked wih almond slivers and sugar briefly before being mixed with some of the rice and that used to cover the chicken. The fried onion plus turmeric and the resulting stock goes on top and the whole is slowly steamed. Too complicated for me to tackle.
    Cooked them in water with rice turns out pink rice. Suggested uses are in apple pies or in muffins. A persian idea is that they can be added to mutton (and vegetable) stews (khoreshts) to help get a sweet sour taste.
    A source of ideas Middle Eastern Cooking by arto der haroutunian (reprinted 2010, 2012, 2014).

  5. Eric Fithian says:

    What jumped out at me from the list from the Wikipedia entry re Berberine was “Goldenseal.”
    That is available as an extract at Health Food stores.
    I suspect I have a bottle on my shelf, in Denver (presently doing lighting-retrofit in Summit County, Colorado)….

  6. E.M.Smith says:

    @Eric:

    Minor polish point: Barberry is not the same plant as Goldenseal, but they both have berberine in them. So you need an “in” in yor sentence: “entry re Berberine was IN “Godenseal”.

    Yeah, a nit-pick. Just doing it so someone not reading carefully some years in the future doesn’t think the two plants are the same and confuse dose / strength / whateever of one for the other…

  7. beng135 says:

    I have two Japanese barberries planted. Very handsome evergreens, but the thorns are quite nasty. They bloom w/attractive, bright-yellow blooms fairly early — mid-April or so. Honeybees & bumblebees like them. Fruit develops, but for some reason the fruit on mine almost all fall off (abort) before they fully develop. Have no idea why.

  8. p.g.sharrow says:

    beng135; your bayberries are likely propagated cuttings and therefor genetically the same plant. Many fruiting woody plants are not self pollinating and require the pollen from a non related plant to set seeds. If seed is not set or viable the fruit will abort before it matures…pg

  9. E.M.Smith says:

    Cherries are like that. Folks check out the nearby homes with cherry trees to assure they have a different cultivar so they will pollinate and develop. Nature’s way of preventing inbreeding depression. (And no, that is NOT the same as unhappy desperate relationships with your cousin…)

  10. Sole Public says:

    RE: microbes causing/contributing to diabetes…supporting your Ho – people who get their stomachs stapled (but not banded), have their diabetes resolve before they are out of the hospital. This is a time frame that would fit with the microbial starvation hypothesis (assuming ~20 min microbial generation time and a few hours to clear the gut – even faster if the patients do the colonoscopy prep).

    Eating barberries is probably preferable to a fecal transplant from a thin person – at least for many people.

    Your description of the effect of berberine on mitochondria made me guess that it causes a short circuit resulting in a futile cycle – making heat not ATP (e.g. thin people you can put in the center of a room instead of a heater). So’ nuf – https://www.nature.com/articles/ncomms6493

    Not sure why that would lead to an anti-aging effect (less reactive oxygen and free radical damage???) – a lot of aging is the accumulation of messed up mitochondria. Their function is critical to your neurons, muscles and any active tissue (heart, lungs, liver, kidney, bone marrow, immune system….).

    Interesting. Thanks!

  11. E.M.Smith says:

    @Sole Public:

    that article you cited is interesting…

    Berberine activates thermogenesis in white and brown adipose tissue

    Zhiguo Zhang, Huizhi Zhang, Bo Li, Xiangjian Meng, Jiqiu Wang, Yifei Zhang, Shuangshuang Yao, Qinyun Ma, Lina Jin, Jian Yang, Weiqing Wang & Guang Ning

    Nature Communications volume 5, Article number: 5493 (2014)
    doi:10.1038/ncomms6493
    Download Citation
    AdipocytesDrug developmentMechanism of actionObesity

    Received:
    15 August 2014
    Accepted:
    06 October 2014
    Published online:
    25 November 2014

    Abstract

    Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity.

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