Top INDEX
• Basics: Enhancement.
• About Berberine.
• Health: Uses of Berberine.
• Scientific: Health Benefits.
• Dangers: Berberine in Health.
• Article: Berberine enhances the Antibacterial activity of ... Antibiotics.
• Research: Berberine enhances Chemosensitivity & Induces apoptosis.
• Summary: more Facts and Info.

  Product Possibilities, NOT Recommendations.

  Product: Berberine-500, Thorne Research.

  Product: Berberis Formula, Genestra.

• Definitions.

Comment : If your want the Truth, be aware of the influence of Semantics.

• -Focus-: Monographs on Toxins and Enhancers.

Basics: Enhancement. INDEX
http://www.life-enhancement.com/magazine/article/
2901-the-berberine-story-gets-better-and-better

LINK 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850468/
Enhancement of Sodium Caprate on Intestine Absorption & Antidiabetic action of Berberine.
AAPS PharmSciTech. 2010 Mar; 11(1): 372–382.

Berberine is an isoquinoline alkaloid extracted from Rhizoma Coptidis.
Berberine, a plant alkaloid used in traditional Chinese medicine, has a wide spectrum of pharmacological actions, but the poor bioavailability limits its clinical use. It was initially used as an anti-inflammatory drug in clinical practice.
(It is now believed) that it has a wide spectrum of pharmacological actions in the treatment of diabetes, cardiovascular diseases, hypertension, hypercholesterolemia, and tumors. ...

However, berberine also displays numerous limitations or side effects including low bioavailability, poor intestinal absorption, and the need for repeated administration. It has been reported that berberine is a xenobiotic with poor bioavailability. Consequently, its clinical application has been greatly limited.

High doses of berberine oral administration usually causes gastrointestinal side effects, which greatly limit its clinical application on diabetes mellitus. Therefore, combination with sodium caprate could lower the dose of berberine, which may offer advantages of better pharmacological action and lower adverse reaction.

Coadministration with absorption enhancer is a good way.
Sodium caprate is a well-recognized absorption enhancer without any serious toxicity.
A low bioavailability of berberine may be related to the action of P-glycoprotein, a drug efflux pump, and sodium caprate has been reported to inhibit the excretion pump function of P-glycoprotein. ...

Compared with berberine alone, the absorption rate in the small intestine at 4 h was increased to 18.5% when sodium caprate co-incubated. The uptake of berberine was also elevated at a different level in medium- and high-dose groups when it was combined with sodium caprate. ... sodium caprate can significantly increase the absorption of berberine in the small intestine.

(Experimentation) showed that the absorption of berberine in the small intestine was poor and that sodium caprate could significantly improve the poor absorption of berberine in the small intestine. ... After coadministration, the area under the plasma concentration -- time curve of berberine was increased 28% than that in the absence of sodium caprate.

Several reports have shown that the most sensitive segment of intestine for the action of sodium caprate is colon.
... berberine is scarcely absorbed in the colon segment .... Therefore, we only investigated the promoting function of sodium caprate in duodenum, jejunum, and ileum segments.

... the increase level of AUC (28%) in vivo model is not as noticeable as the vitro models (above 100%), owing to the complex environment of the whole organism. The concentration of sodium caprate was diluted by food or water in the intestine. Otherwise, all the conditions, such as pH, temperature, or secretions, could influence the drug absorption.

... sodium caprate could enhance the bioavailability of berberine ..., the treatment effect of berberine coadministrated with sodium caprate on hyperglycemia has further confirmed this point. Berberine with sodium caprate could remarkably decrease the blood glucose level and the areas under the glucose curves, compared with berberine treatment group. ...

... both berberine and coadministration with sodium caprate orally could significantly decrease fasting blood glucose and improve glucose tolerance in diabetic rats. The hypoglycemic effect of coadministration group was remarkably stronger, and the areas under the glucose curves was decreased 22.5%, compared with berberine treatment group. ... sodium caprate could significantly promote the absorption of berberine in intestine and enhance its antidiabetic effect without any serious mucosal damage.

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

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids.

It is 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.

Berberine is an alkaloid derived from tyrosine.
L-DOPA and 4-hydroxypyruvic acid both come from L-tyrosine.
Although two tyrosine molecules are used in the biosynthetic pathway, only the phenylethylamine fragment of the tetrahydroisoquinoline ring system is formed via DOPA, the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde. L-DOPA loses carbon dioxide to form dopamine.

As a natural dye, berberine has a color index of 75160.

Health: Uses of Berberine. INDEX
https://en.wikipedia.org/wiki/Berberine
LINK 2: https://well.ca/products/thorne-research-berberine-500_141056.html

Berberine exerts class III antiarrhythmic action.

In live cells, berberine localizes in mitochondria.

Potential Benefits include
• antiarrhythmic,
• anti-aging (gero-suppressive),
• antibiotic,
• mild laxative,
• glucose metabolism,
• insulin sensitivity,
• cardiac support,
• weight management,
• gastrointestinal health,
• immune modulation,
• cognitive support,
• maintenance of healthy lipid levels,
• inhibits growth of Staphylococcus aureus,
• inhibits growth of Microcystis aeruginosa, a toxic cyanobacterium.

Scientific: Health Benefits. INDEX
https://selfhacked.com/blog/berberine-19-health-benefits-of-berberine-with-references/
20 Scientific Health Benefits 2017-10-24
by Joseph Cohen

Joseph Cohen
At the age of 25, with lots of questions and very few satisfying answers, Joe decided to embark on a journey of self-experimentation – something that has since become known as “bio-hacking”. Thousands of experiments later, he is now a thriving writer/author, entrepreneur, investor and founder of SelfHacked & SelfDecode. ...

LINK: What is Berberine?
LINK: Berberine That I use

1. LINK: BerberineShop Now
2. LINK: Pros
3. LINK: Cons

• LINK: 01) Berberine Improves Learning & Memory
• LINK: 02) Berberine Supports Gut Health
• LINK: 03) Berberine is an Anti-Depressant
• LINK: 04) Berberine Treats Inflammation
• LINK: 05) Berberine Improves Blood Sugar Balance
• LINK: 06) Berberine Promotes Weight Loss
• LINK: 07) Berberine is Anti-Cancer
• LINK: 08) Berberine Improves Cholesterol Stats
• LINK: 09) Berberine Lowers Blood Pressure
• LINK: 10) Berberine Prevents Heart Disease
• LINK: 11) Berberine Prevents Alzheimer's Disease
• LINK: 12) Berberine Helps Arthritis
• LINK: 13) Berberine Protects the Liver
• LINK: 14) Berberine Prevents and Arrests Colitis/IBD
• LINK: 15) Berberine is Anti-Bacterial
• LINK: 16) Berberine is Anti-Parasitic
• LINK: 17) Berberine is Anti-Viral
• LINK: 18) Berberine Heals Canker Sores
• LINK: 19) Berberine Treats Diabetic Nephropathy
• LINK: 20) Berberine Improves Mitochondrial Function
• LINK: DI) Drug Interactions
• LINK: AE) Adverse Effects
• LINK: BB) Buying Berberine

What is Berberine? INDEX
Berberine is a compound found in many different plants, including Barberry (Berberis vulgaris), Oregon Grape (Berberis aquifolium), Goldenseal (Hydrastis canadensis), and Chinese Golden thread (Coptis chinensis).

Berberine has a 3000-year history of use in Traditional Chinese Medicine.
Modern medicine is now proving scientifically the benefits that have been known for ages, as well as identifying new applications for the ailments of modern civilization.

Berberine That I use INDEX
I just make sure to get my berberine from a reliable source.
...

BerberineShop Now INDEX

LINK: (His personal choice.

Pros INDEX

• Improves learning and memory.
• Heals the gut and improves the gut microbiome.
• Is anti-diabetic – Improves blood sugar balance.
• Is anti-infectious.
• Shows potential as an anti-cancer agent.

Cons INDEX

• May cause constipation at too high of a dose.
• Conversely, it may also cause diarrhea if taken before food.
• It can also cause abdominal discomfort (nausea, distension) if taken on an empty stomach.

Berberine Improves Learning & Memory INDEX

Berberine improves learning and memory in diabetic animal studies.

Berberine may improve memory by

stimulating cholinergic enzyme activity and reducing inflammation.
preventing the destruction of neurons in patients with reduced blood flow (low oxygen) to the brain.

Berberine is neuroprotective in strokes and may be useful for neuroinflammation-associated disorders.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/23099256

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21262264

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22563252

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22982719

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22119079

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22100227

Berberine Supports Gut Health INDEX

Berberine is anti-diarrheal, a property which may be mediated by its ability to delay the small intestinal transit.

Berberine reduces “leaky gut“ (intestinal epithelial tight junction damage) in a mouse model of endotoxemia.

It protects the mucosal lining of the gut from damage due to heavy drinking.

Berberine also reduces the damaging effects of TNF-alpha inflammation on the intestinal lining.

Berberine beneficially inhibits particular human intestinal bacteria, preferentially increasing short-chain fatty acid (SCFA) producers.

Berberine’s normalizing effect on gut bacteria was able to improve symptoms of fatty liver disease in mice.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/7719104

Reference: http://www.ncbi.nlm.nih.gov/pubmed/7035365

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21592990

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26226164

Reference: http://www.ncbi.nlm.nih.gov/pubmed/23671580

Reference: http://www.ncbi.nlm.nih.gov/pubmed/10552394

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26396057

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26923892

Berberine is an Anti-Depressant INDEX

Berberine acts as an antidepressant by increasing levels of key neurotransmitters in the hippocampus and frontal cortex of the brain.

Specifically, Berberine inhibits monoamine oxidase A (MAO-A), an enzyme that breaks down Serotonin.

Animal studies indicate that Berberine may also be useful for alleviating the depression and anxiety that often follow morphine addictions.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/18585703

Reference: http://www.sciencedirect.com/science/article/pii/S0024320507005796

Reference: http://www.ncbi.nlm.nih.gov/pubmed/17585901

Reference: http://www.ncbi.nlm.nih.gov/pubmed/11270727

Reference: http://www.ncbi.nlm.nih.gov/pubmed/23269899

Berberine Treats Inflammation INDEX

Berberine shows anti-inflammatory activity both in the lab and in living organisms.

It reduced inflammation from dust mite allergens in a Chinese study using mice.
Berberine lessens inflammation of the airways caused by inhalation of cigarette smoke.
Inflammation of the blood vessels was improved in a rat study.
Berberine reduced inflammation of the liver and the fat tissues in an animal model of non-alcoholic fatty liver disease.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/14732220

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26275466

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26309516

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26027825

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26936230

Berberine Improves Blood Sugar Balance INDEX

Overview:
Berberine is an ideal treatment for type 2 diabetes, working differently from drugs like Metformin.
It works through increasing insulin, regenerating the pancreatic cells, promoting antioxidant enzyme activity, and decreasing damage to cells. Berberine reduces fasting blood glucose, triglycerides, apo b, LDL-C, and total cholesterol while improving glucose tolerance.

Berberine addresses blood sugar imbalances in a number of different ways:
• Delays the breakdown of carbohydrates into simple sugars.
• Mimics insulin action by increasing the ability of the body to take up glucose.
• Additionally, lowers blood sugar by
  • Decreasing glucose transport through the intestinal lining.
  • Increasing insulin receptor expression.
  • Enhancing glucagon secretion.
  • Inhibiting dipeptidyl peptidase IV (DPP IV) enzyme.
  • Increasing adiponectin, a protein which helps regulate blood sugar levels (through AMPK) .
  • Directly increasing AMPK, which stimulates glucose uptake in muscle cells and helps balance high blood sugar.
    It is also a major player in regulating metabolism.
  • Acutely activating the blood sugar transport activity of Glucose transporter 1 (GLUT1).
  • Activating the fatty acid receptor GPR40.

Improves insulin resistance through:
• Inhibiting NF-kappaB (NF-kB).
• Increasing insulin receptor expression (via protein kinase C).
• Inhibiting production of glucose in the liver.
• Improving the gut microbiota.

Berberine protects the pancreas against cell death from exposure to excess fat.

1. Reference: http://www.ncbi.nlm.nih.gov/pubmed/20868663

2. Reference: http://www.ncbi.nlm.nih.gov/pubmed/23118793

3. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19800084

4. Reference: http://www.ncbi.nlm.nih.gov/pubmed/15066220

5. Reference: http://www.ncbi.nlm.nih.gov/pubmed/20515652

6. Reference: http://www.ncbi.nlm.nih.gov/pubmed/12898419

7. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19800084

8. Reference: http://www.ncbi.nlm.nih.gov/pubmed/18996945

9. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19640223

10. Reference: http://www.ncbi.nlm.nih.gov/pubmed/21536037

11. Reference: http://www.ncbi.nlm.nih.gov/pubmed/17049164

12. Reference: http://www.dezedr.com/editor_new/uploadfile/
    20101215024656644.pdf?phpMyAdmin=b9425pjb2rciothp5vqk881rl2

13. Reference: http://www.ncbi.nlm.nih.gov/pubmed/16873688

14. Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464622

15. Reference: http://circres.ahajournals.org/content/100/3/328.full

16. Reference: http://www.ncbi.nlm.nih.gov/pubmed/21545824

17. Reference: http://www.ncbi.nlm.nih.gov/pubmed/20658575

18. Reference: http://www.ncbi.nlm.nih.gov/pubmed/18198644

19. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19059538

20. Reference: http://www.ncbi.nlm.nih.gov/pubmed/21304897

21. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22880019

22. Reference: http://www.ncbi.nlm.nih.gov/pubmed/20414047

Berberine Promotes Weight Loss INDEX

Berberine improves insulin sensitivity by inhibiting fat storage.

Berberine inhibits the production of body fat through up-regulation of C/EBP inhibitors, CHOP and DEC2.

In a human study of berberine on weight loss, 500 mg berberine was given to obese patients 3 times daily for 12 weeks. Results included a weight loss average of 5 pounds, as well as a significant improvement of triglyceride and cholesterol stats.

Another 3-month study of obese patients with metabolic syndrome used just 300 mg of berberine three times a day.
At the end of the trial, the patients’ body mass index (BMI) went down from 31.5 to 27.4 and they lost fat around the middle.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22474499

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21893041

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22739410

Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310165/

Reference: https://www.selfdecode.com/disease/metabolic-syndrome-x/

Berberine is Anti-Cancer INDEX

Berberine shows promise as a general anti-cancer agent, killing cancer cells and blocking proliferation.

It shows potential as an alternative medicine for tumor chemotherapy.

Berberine can also work synergistically with conventional cancer treatments as it has been shown in lab experiments to sensitize many different types of cancer cells to the effects of the conventional chemotherapy drug doxorubicin.

1. Brain Cancer:
   Berberine induces cell death in human brain cancer (glioblastoma) cells.
   Studies show it to have a potent anti-tumor effect on Glioblastoma multiforme (GBM), which is the most common type of malignant brain cancer and known to be a grim diagnosis.

2. Breast Cancer:
   Coptis extracts (which contain berberine) enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells. The effect of Berberine on the growth of anoikis-resistant breast cancer cells was greater than treatment with doxorubicin, a drug commonly used to treat breast cancer.

3. Cervical Cancer:
   Berberine is a potentially promising compound for the treatment of cervical cancer associated with HPV.
   Berberine induces cell death in human cervical cancer cells.

4. Colon Cancer:
   Berberine induces cell death in colon tumor cells (through activation of an apoptosis-inducing factor).
   Derivatives of Berberine are even stronger against colon cancer than the original compound.

5. Liver Cancer:
   Berberine induces cell death in liver cancer cells.
   Berberine can inhibit Aspergillus flavus, a common fungal infection that produces cancer-causing compounds in the liver.

6. Lymphoma:
   A Berberine derivative inhibits lymphoma in a Chinese study.
   Berberine as a whole shows potential as an anti-tumor agent for Primary effusion lymphoma (PEL), associated with AIDS.

7. Oral Cancer:
   Berberine induces cell death in human oral cancer cells.

8. Spinal Cancer:
   Berberine induces cell death in tumor cells that develop in the spine, according to rat studies.

9. Thyroid Cancer:
   Berberine inhibits thyroid cancer cells.

1. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22842630

2. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19704371

3. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22783430

4. Reference:http://www.ncbi.nlm.nih.gov/pubmed/20930370

5. Reference: http://www.ncbi.nlm.nih.gov/pubmed/25504754

6. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19000652

7. Reference: https://www.ncbi.nlm.nih.gov/pubmed/19800775

8. Reference: http://www.ncbi.nlm.nih.gov/pubmed/10463599

9. Reference: http://www.ncbi.nlm.nih.gov/pubmed/17970084

10. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22574158

11. Reference: http://www.ncbi.nlm.nih.gov/pubmed/25045712

12. Reference: http://www.ncbi.nlm.nih.gov/pubmed/20830746

13. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22690956

14. Reference: http://www.ncbi.nlm.nih.gov/pubmed/18674916

15. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22320346

16. Reference: http://www.ncbi.nlm.nih.gov/pubmed/17970083

17. Reference: http://www.ncbi.nlm.nih.gov/pubmed/25634589

18. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19424587

19. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22318822

20. Reference: http://www.ncbi.nlm.nih.gov/pubmed/26307103

Berberine Improves Cholesterol Stats INDEX

Berberine promotes proper cholesterol balance.

In combination with other nutraceuticals, berberine lowers high total cholesterol, high LDL, and insulin resistance.

The lipid-lowering effects also result in moderate weight-loss.

Berberine has potential as an alternative to statins.

The ability of Berberine to lower LDL comes through:

    Increasing activity at the LDL receptor in the liver. 
    Reducing Hepatocyte nuclear factor 1alpha. 
    Inhibiting lipid synthesis through activation of AMPK.

1. Reference: http://www.ncbi.nlm.nih.gov/pubmed/17341006

2. Reference: http://www.ncbi.nlm.nih.gov/pubmed/15531889

3. Reference: http://www.ncbi.nlm.nih.gov/pubmed/23087140

4. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22113535

5. Reference: http://www.ncbi.nlm.nih.gov/pubmed/16890192

6. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19782362

7. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22739410

8. Reference: http://www.ncbi.nlm.nih.gov/pubmed/15531889

9. Reference: http://www.ncbi.nlm.nih.gov/pubmed/17767919

10. Reference: http://www.ncbi.nlm.nih.gov/pubmed/19687008

11. Reference: https://selfhacked.com/blog/natural-ampk-activators/

12. Reference: http://www.ncbi.nlm.nih.gov/pubmed/16508037

Berberine Lowers Blood Pressure INDEX

Berberine lowers blood pressure and dilates blood vessels, showing it to be a good candidate as a treatment for high blood pressure.

Berberine blocks the human platelet alpha-adrenoceptors causing blood vessels to dilate, relaxing muscles, healing ulcers (through antisecretory action in the stomach), causing a sedative effect. It inhibits ACE and directly releases NO/cGMP in blood vessels, causing a blood pressure-lowering effect.

Berberine derivatives inhibit acetylcholinesterase, resulting in increased levels and prolonged action of the neurotransmitter acetylcholine.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/1359895

Reference: http://www.ncbi.nlm.nih.gov/pubmed/15934023

Reference: http://www.ncbi.nlm.nih.gov/pubmed/1649363

Reference: http://www.sciencedirect.com/science/article/pii/S1537189103000053

Reference: http://www.ncbi.nlm.nih.gov/pubmed/20880702

Reference: https://selfhacked.com/blog/acetylcholine/

Berberine Prevents Heart Disease INDEX

Berberine shows potential for multiple aspects of cardiovascular health, including arrhythmias, enlarged hearts, heart attacks, heart rate, and especially atherosclerosis by:

Reducing the formation of plaque in the arteries by reducing foam cell formation and preventing the plaque from breaking off.

Reducing oxidative stress and inflammation of the blood vessels.

Berberine also demonstrates a protective effect on heart muscle cells injured by the return of blood flow after blood flow restriction –as after a stroke.

Berberine increased the quality of life and decreased death rates for patients with congestive heart failure.

1. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22188769

2. Reference: http://berberine%20demonstrates%20a%20protective%20effect%20on%20heart%20muscle%20cells
   %20injured%20by%20the%20return%20of%20blood%20flow%20after%20blood%20flow%20restriction%20(r)./

3. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22387061

4. Reference: http://www.ncbi.nlm.nih.gov/pubmed/21168503

5. Reference: http://www.ncbi.nlm.nih.gov/pubmed/23241897

6. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22796454

7. Reference: http://www.ncbi.nlm.nih.gov/pubmed/22140092

8. Reference: http://www.ncbi.nlm.nih.gov/pubmed/21980456

9. Reference: http://www.ncbi.nlm.nih.gov/pubmed/12910687

10. Reference: http://www.ncbi.nlm.nih.gov/pubmed/12860219

Berberine Prevents Alzheimer's Disease INDEX

Berberine inhibits beta-amyloid and amyloid plaque accumulation that is characteristic of Alzheimer’s Disease.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/17125739

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22152059

Berberine Helps Arthritis INDEX

Berberine helps with osteoarthritis and rheumatoid arthritis in animal models.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21108488

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21676922

Reference: http://www.ncbi.nlm.nih.gov/pubmed/24803296

Berberine Protects the Liver INDEX

Berberine protects against rat liver fibrosis induced by multiple agents toxic to the liver.

It also protected against infection-related liver damage in mice.

Berberine improves non-alcoholic fatty liver disease in humans in a study of 184 patients.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/17973934

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26288557

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26288557

Berberine Prevents and Arrests Colitis/IBD INDEX

Berberine is a key anti-inflammatory agent in a Traditional Chinese Medicine formula which is prescribed for ulcerative colitis.

Berberine demonstrates the ability to inhibit both the development and perpetuation of inflammatory bowel disease (IBD).

Some of the methods by which it does this are by inhibiting lipid peroxidation, intestinal bacterial growth and NF-?B inflammation.

Reference:http://www.ncbi.nlm.nih.gov/pubmed/20969848

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21922249

Reference: http://www.ncbi.nlm.nih.gov/pubmed/22173918

Reference: http://www.ncbi.nlm.nih.gov/pubmed/20932871

Reference: http://www.ncbi.nlm.nih.gov/pubmed/20828550

Berberine is Anti-Bacterial INDEX

Berberine shows effectiveness against a variety of microbes:

S. aureus, P. aeruginosa, E. coli, Candida albicans,

Others:

• S. cerevisiae,
• A. pullulans (black + white),
• T. viride (brown),
• M. gypseum,
• B. subtilis,
• Z. ramigera,
• A. niger,
• F. nivale,
• P. chrysogenum and
• T. viride (green).

Reference: http://www.ncbi.nlm.nih.gov/pubmed/12422513

Reference: https://selfhacked.com/blog/s-cerevisiae/

Reference: https://selfhacked.com/blog/b-subtilis/

Reference: https://selfhacked.com/blog/treat-cure-candida/

Berberine is Anti-Parasitic INDEX

Berberine shows anti-parasitic effects on anaerobic protozoa.

It is effective against Trichomonas vaginalis in lab experiments, as well as dog roundworm (Toxocara canis).

Berberine combined with pyrimethamine was effective against malaria in human studies.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/2131648

Reference: http://www.ncbi.nlm.nih.gov/pubmed/11775115

Reference: http://www.ncbi.nlm.nih.gov/pubmed/12499659

Reference: http://www.ncbi.nlm.nih.gov/pubmed/9337003

Berberine is Anti-Viral INDEX

Berberine may be useful for the treatment of infections with influenza A virus.

Berberine acts against the Herpes Simplex Virus.

Berberine is anti-HIV.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21683808

Reference: http://www.ncbi.nlm.nih.gov/pubmed/24913175

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21295891

Berberine Heals Canker Sores INDEX

A topical application of Berberine gelatin may be an effective treatment for canker sores (aphthous stomatitis).

Reference: http://www.ncbi.nlm.nih.gov/pubmed/23246229

Berberine Treats Diabetic Nephropathy INDEX

Berberine can relieve injury to the kidneys in diabetic rats with nephropathy.

Berberine reduces fibronectin and collagen accumulation in rat kidney cells exposed to high blood sugar.

Berberine works by inhibiting NF-?B and by inhibiting aldose reductase and oxidative stress in kidney cells.

Reference:http://www.ncbi.nlm.nih.gov/pubmed/23266672

Reference: http://www.ncbi.nlm.nih.gov/pubmed/26531813

Reference: http://www.ncbi.nlm.nih.gov/pubmed/19142714

Reference: https://selfhacked.com/blog/nuclear-factor-kappa-beta/

Reference: http://www.ncbi.nlm.nih.gov/pubmed/20674665

Reference: http://www.ncbi.nlm.nih.gov/pubmed/18471986

Berberine Improves Mitochondrial Function INDEX

Berberine creates new mitochondria by increasing SIRT1 and the NAD+/NADH ratio.

Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366688/

Reference: https://selfhacked.com/blog/nad-important-increase/

Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366688/

Drug Interactions INDEX

Repeated doses of berberine inhibit cytochromes P450 in humans, altering the normal breakdown of drugs.

Reference: http://www.ncbi.nlm.nih.gov/pubmed/21870106

Adverse Effects INDEX

Mild adverse digestive effects were observed among a few subjects in studies:
abdominal discomfort (nausea, distension, diarrhea) was relieved by taking Berberine after meals.
Constipation was ameliorated by reducing the dose.

Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478874/#B10

Buying Berberine INDEX

Start with one capsule a day.
Here are some options:

Reference: http://www.iherb.com/
Thorne-Research-Berberine-500-60-Veggie-Caps/46113?rcode=coh780

Dangers: Berberine in Health. INDEX
https://en.wikipedia.org/wiki/Berberine
LINK 2: https://liftmode.com/blog/berberine-benefits/
LINK 3: https://liftmode.wordpress.com/2017/03/16/
taking-berberine-look-out-for-these-3-side-effects-and-3-great-stacks/

The bioavailability of berberine is low.

Cautions include -- Do NOT use if
• pregnant,
• breastfeeding,
• have kidney disorder,
• have blood pressure problems,
• have a heart condition,
• experiencing respiratory problems.

Adverse Symptoms
• nausea,
• vomiting,
• drop in blood pressure,
• difficulty breathing,
• bronchial constriction,
• stimulated intestinal smooth muscle.

How to Improve Berberine Absorption

The Berberine herb has a multitude of potential benefits.
The one problem that some people have with Berberine is that they sometimes experience issues with Berberine absorption.

Enzymes in your gut and stomach lining break down Berberine rapidly.
But the main problem that people have is that Berberine is not always ‘pumped’ into your bloodstream properly.
Berberine is affected by a protein called ‘P-Glycoprotein’ (P-gp). This protein is found in the cell membrane of most cells. P-glycoprotein affects how many medications work, by inhibiting their entry into the cells.

Researchers have found that natural P-gp inhibitors may help to increase Berberine’s absorption, thereby increasing its effects. One study used P-gp inhibitors extracted from the HIV virus. The protein inhibitors dramatically increased the absorption levels of Berberine into cells.

Interestingly, scientists have recently found that the bacteria in your gut play an important role in helping your body to absorb Berberine. Scientists from China discovered that your gut microbes transform Berberine into a slightly different form to help it be absorbed better. You might want to think of using Berberine with probiotics to help improve absorption!

Article: Berberine enhances the Antibacterial activity of ... Antibiotics. INDEX
Berberine Enhances the Antibacterial activity of selected Antibiotics
against Coagulase-Negative Staphylococcus strains in Vitro
Molecules 2014, 19, 6583-6596; doi:10.3390/molecules19056583
http://www.mdpi.com/1420-3049/19/5/6583/pdf

Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococcus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study ... the most noticeable effects were observed for

S. haemolyticus ATCC 29970, 
S. epidermidis ATCC 12228, 
S. capitis subsp. capitis ATCC 35661, 
S. galinarium ATCC 700401, 
S. hominis subsp. hominis ATCC 27844, 
S. intermediusATCC 29663 and 
S. lugdunensis ATCC 49576. 

The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin.

The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

The widespread abuse of antibiotics for the treatment of bacterial infections has led to the emergence and spread of drug resistant strains. The rise in the rate of infections from multi-drug resistant (MDR) bacteria is recognized worldwide as a major health crisis. A recent joint technical report of the European Centre for Disease Prevention and Control (ECDC) and the European Medicines Agency (EMA) in collaboration with Action on Antibiotic Resistance (ReAct) estimated that at least 25,000 patients die each year in the EU from infections due to multidrug resistant bacteria.

Antibiotic resistant staphylococci strains are the major public health concern since the bacteria can circulate in the environment without difficulty. Coagulase-negative staphylococci (CoNS) colonize different parts of the human skin and mucous membranes. Notably, every species of CoNS that has been characterized as a resident in humans (S. epidermidis, S. capitis, S. cohnii, S. haemolyticus, S. hominis, S. lugdunensis, S. saccharolyticus, S. saprophyticus, S.warneri), may also be responsible for nosocomial infections, particularly in immunocompromised patients. What is more, CoNS have become the leading cause of infections related to medical devices such as vascular catheters, prosthetic joints and artificial heart valves.

Plants are known to produce a variety of compounds as defenses against a wide range of microorganisms.
Berberine is an isoquinoline-type alkaloid isolated from many kinds of medicinal plants such as

• Berberis aristata,
• Berberis aquifolium,
• Berberis vulgaris,
• Coptis chinensis,
• Coptis japonica,
• Hydrastis canadensis,
• Phellodendron amurense,
• Phellodendron chinense schneid and
• other species.

Berberine has antidiabetic, antidiarrhoeal, antimicrobial, immuno-stimulating, hypotensive and anti-inflammatory properties. ... It has been reported that berberine has weak activity against Gram-negative bacteria and is more active against Gram-positive bacteria including S. aureus and S. epidermidis. Moreover, the toxicity and mutagenicity of berberine to human cells were relatively low in both in vitro and in vivo experiments. ...

It has been shown that pharmacological treatment by some phytochemicals is an inexpensive, readily applicable approach in the chemotherapy and management of various infections. Due to the multi-drug resistance problem the use of combinations of antibiotics with the different mechanisms of action is often necessary for the treatment of severe staphylococcal infections. The augmented action of antibiotics along with natural substances may have positive synergistic effects toward specific, drug resistant microorganisms which are difficult to eradicate, particularly in hospital settings.

... 4. Conclusions
The antimicrobial effect of berberine chloride in combination with various anti-staphylococcal drugs on reference CoNS strains varied greatly depending on the bacterial strain and drug used. The most significant synergistic effects towards CoNS strains were noted when berberine was combined with linezolid, cefoxitin and erythromycin. Our data showed a synergy of berberine and antibiotics in the antimicrobial action against some reference CoNS strains in vitro, what seems to suggest a potential role of berberine as a compound capable of augmenting the action of common antibiotics in vivo. Future work is necessary to precisely assess the effects of berberine in the treatment of CoNS infections, which may result in the development of efficient new therapeutic strategies for persistent staphylococcal infections.

Research: Berberine enhances Chemosensitivity & Induces apoptosis... INDEX
http://www.jcancer.org/v08p1679.pdf

Breast cancer is the most common malignancy in women, accounting for 31% of all female cancers around the world. Although chemotherapy is effective in reducing the size of the primary tumor before surgery, long-term chemotherapy not only caused adverse effects in about half of breast cancer patients, but also inevitably induced multi-drug resistance. A growing amount of evidence suggests that the extrusion of drugs by cell membrane pumps, apoptosis resistance, modification of drug-targeting molecules and drugs redistribution of the intracellular accumulation play crucial roles on chemotherapeutic resistance. However, the molecular mechanisms underlying the multidrug resistance of breast cancer are still ill-defined.

Therefore, a better understanding of the chemoresistance is of great importance to develop novel therapeutic strategies for improving the poor prognosis. Reprogramming cellular energy metabolism is recently accepted to be one of the main hallmarks of cancer. Cancer cells, especially drug-resistant cancer cells, unlike their normal counterparts, employ exacerbated aerobic glycolysis rather than mitochondrial oxidative phosphorylation for maintaining their energy homeostasis, which called the ‘Warburg effect’. It has been suggested that the characteristic of energy metabolism shift facilitates cancer cell survival and contributes the drug resistance to conventional cancer chemotherapy and radiotherapy. ...

Berberine (BER), an isoquinoline alkaloid purified from the Berberis species, has exhibited multiple pharmacological activities, including antibacterial, anti-hypertensive, and anti-arrhythmic effects. It has also been reported that low doses of berberine enhance radiosensitivity in colon cancer by inhibiting P-gp expression, while high doses of berberine can directly inhibit tumor growth in lung cancer through activating, but there are few reports about whether berberine could enhance chemotherapy sensitivity and relative molecular mechanisms. ...

... high-dose berberine could overcome breast cancer drug resistance by directly inducing apoptosis.
p53 is the most commonly mutated tumor suppressor gene, and a lack of functional p53 is associated with an increased risk of the development of drug resistance. Furthermore, it has been reported that the treatment of A549 cells (expressing wild-type p53) are more sensitive than human lung cancer cells H1299 (p53-deficient) after berberine treatment. ... high-dose berberine could significantly activate p53 rather than the low dose, which was regulated by phosphorylated AMPK. It is reported that AMPK activation is associated with the phosphorylation of p53 at Ser15 and Ser20. AMPK inhibitor Compound C reduced the p53 expression and decreased apoptosis. ... high-dose berberine induced apoptosis by activating the AMPK–p53 pathway with the independence of HIF-1a.

In summary, ... low-dose berberine could enhance DOX sensitivity on drug-resistant breast cancer in vivo and in vitro through the AMPK-HIF-1a-P-gp pathwayy. High-dose berberine directly induced apoptosis on drug-resistant breast cancer by activating the AMPK-p53 pathway.

Summary: more Facts and Info. INDEX
https://examine.com/supplements/berberine/
Kurtis Frank, https://examine.com/user/KurtisFrank/

Berberine is supplemented for its anti-inflammatory and anti-diabetic effects.
It can also improve intestinal health and lower cholesterol.
Berberine is able to reduce glucose production in the liver.

Human and animal research demonstrates that 1500 mg of berberine, taken in 3 doses of 500mg each, is equally effective as taking 1500 mg of Metformin or 4 mg glibenclamide, two pharmaceuticals for treating type II diabetes. Effectiveness was measured by how well the drugs reduced biomarkers of type II diabetes.

Berberine may also synergize with anti-depressant medication and help with body fat loss.
Both of these benefits need additional evidence behind them before berberine can be recommended specifically for these reasons.

Berberine’s main mechanism is partly responsible for its anti-diabetic and anti-inflammatory effects.
Berberine is able to activate an enzyme called Adenosine Monophosphate-Activated Protein Kinase (AMPK) while inhibiting Protein-Tyrosine Phosphatase 1B (PTP1B).

Berberine has a high potential to interact with a medications, and some interactions may be serious.

Berberine is one of the few supplements in the Examine.com database with human evidence that establishes it to be as effective as pharmaceuticals.

Do Not Confuse With
Piperine (Black Pepper extract), Berberol (Brand name), Berberrubine (Metabolite)

Due to AMPK inhibition, berberine is normoglycemic (reduces blood sugar only if elevated).
However, the reduction in blood sugar from berberine may make other hypoglyemics more likely to cause reduced blood sugar.

High doses of berberine taken acutely, due to their poor intestinal uptake rate, may cause cramping and diarrhea; for this reason, berberine should be taken in multiple doses throughout the day.

Berberine is known to inhibit CYP2D6, CYP2C9, and CYP3A4, which can lead to a host of drug interactions, some of which can be serious.

Berberine is known to induce the protein concent of P-glycoprotein.

Berberine interacts with organic anion transporter proteins, which may limit tissue uptake of Metformin.

Berberine may interact with microlide antibiotics such as azithromycin and clarithromycin at hERG channels on the heart, leading to serious cardiotoxicity.

Does NOT go well with:
Phosphodiesterase inhibitors (can attenuate but not abolish the increase in cAMP that PDE inhibitors result in, and may reduce their fat-burning effects).

DOSAGE:
The standard dose of berberine is 900-2,000 mg a day, divided into three to four doses.

Berberine should be taken with a meal, or shortly after, to take advantage of the blood glucose and lipid spike associated with eating.

Too much berberine at once can result in stomach upset, cramping, and diarrhea.

EDITOR's COMMENTS:
Kurtis Frank, https://examine.com/user/KurtisFrank/

The increase in AMPK will inherently suppress muscle hypertrophy in muscle cells.
You can attenuate this by inducing PGC-1a (happens with intense workouts) but this also sort of suppresses AMPK in these tissues (AMPK will still be active in the liver and fat cells, so those tissue effects would be preserved). Pairing Berberine with intense exercise that contracts your muscle cells would be prudent and may reverse the muscle suppressing effects of Berberine. Another reason to lift weights or do powerful aerobic exercise like rowing I guess

P-Glycoprotein inhibition seems central to increase absorption of Berberine (kinda like how Curcumin needs piperine for absorption). I'm trying to find a list of P-Glycoprotein inhibitors on Examine, and what I can find are Milk Thistle (little bit skeptical), Ecdysteroids and Capsicum Carotenoids (not sure about these two to be honest), Chrysin (might be smart, since Chrysin itself is not well absorbed) and Schizandra Chinensis lignans. Pick and choose what you want to use as combination therapy I guess, or just have some Coconut oil for the capric acid content.

Human Effect Matrix:
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects berberine has on your body, and how strong these effects are.

(GO to the website by the page LINK, above, and view the CHART and Comments indicating a perspective on the possible strength of the findings of selected research papers/studies/reports. )

SOURCES:
Berberine (2,3-methylenedioxy-9,10-dimethoxy-protoberberine) has been used historically in Ayurveda and Traditional Chinese medicine (vicariously through herbs which contain it) as an anti-microbial, anti-protozoal, and anti-diarrheal agent.

It has shown efficacy against various bacteria strains such as cholera, giardia, shigella, and salmonella; potentially also staphylococcus, streptococcus, and clostridium.

Its actions against protozoa extend to Giardia lamblia, Trichomonas vaginalis, Leishmania donovani, and Malaria.

Surprisingly, crude extracts are more potent than isolated berberine in these anti-protozoan effects suggesting synergistic or additive effects with other compounds in these plants.

Berberine Complexes
Berberine can complex at a 1:1 ratio with the flavonoid baicalin (and to a degree, wogonoside), the complex of which can be formed when Radix Scutellariae and Rhizoma Coptidis (sources of Baicalin and Berberine, respectively) are mixed which occurs in a few Traditional Chinese Medicine combination therapies. It is thought that these complexes (and another Berberine–glycyrrhizin complex) enhance absorption through forming ion-pairs and enhancing fat solubility, where the glucuronide of Baicalin has its carboxylate ion bind to the quaternary ammonium ion of Berberine.

Absorption
Overall bioavailability of Berberine is quite low at 'less than 5%. ...

Berberine appears to be subject to P-Glycoprotein mediated efflux from the intestines and liver.
In the intestines, P-Glycoprotein is responsible for approximately 90% reduced transportation of Berberine and Berberine has been further demonstrated to actually induce (increase) the activity of P-Glycoprotein transporters in the intestine which have caused reduced absorption of other compounds subject to P-gp, such as Ciprofloxacin (demonstrated with 25-50mg/kg Berberine in rats; 4-8mg/kg human equivalent).

... pairing Berberine with compounds that are known to inhibit P-Glycoprotein (Milk Thistle, ketoconazole, or d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) enhances the biological activity of Berberine.

Sodium Caprate, an ester of Capric Acid (Decanoic Acid; a constituent of milk fat at 2-3% and Coconut Oil at 10%) appears to enhance absorption via reversibly widening the gaps between intestinal cells and allowing passive diffusion. ...

Due to low intestinal uptake rate, large doses (1g) are associated with constipation.
This constipative effect is also due to some properties of berberine in the colon, and can be useful to reducing watery diarrhea at 400mg, four 100mg doses.

... Adenosine Mono-phosphate Kinase (AMPK) is a nutrient sensor protein that is central to the actions of various anti-diabetic drugs (Metformin), and appears to be a central lever point for the actions of Berberine. Berberine activates AMPK in a dose and time-dependent manner. ...

... activation of AMPK extends to adipocytes (fat cells), skeletal myocytes (skeletal muscle cell), and the liver; ....

Neurology.
... Has been shown to increase dopamine concentration in some areas of the brain following oral administration.

... A reduced rate of diabetes-induced memory loss has been noted elsewhere with 25-100 mg/kg Berberine twice daily (total dose 50-200 mg/kg) for 30 days in diabetic rats, which was credited to anti-oxidant effects secondary to AMPK activation (mimicked by both Metformin and high dose Vitamin C supplementation). ...

Cardiac Tissue.
Ischemia-Reperfusion injury in cardiac tissue may be alleviated by Berberine. ...
1.2-2g Berberine daily in persons with cardiomyopathy (in addition to standard therapy) increases Left Ventrical Ejection Fraction and improves quality of life more than placebo. ...

Triglycerides.
... LDL cholesterol has been shown to be reduced by 25% in hypercholesterolemic persons over 3 months of Berberine ingestion. Beyond modifying the expression of the receptor, activating ERK can also preserve the constitution of the receptor and stabilize it; leading to a prolongation of the time the LDL receptor can uptake LDL-C into liver cells. ... Triglycerides have been noted to be reduced 16% following 1g of Berberine ingestion for 4 weeks and 1500mg daily for 12 weeks in otherwise healthy obese persona has noted a reduction of 23%. ...

Blood Flow.
Berberine is a known vasorelaxant in animals and has been used with success in humans. ...
It is known that berberine works on the endothelium itself and underlying smooth muscle (mostly the former) and it is thought that berberine may work via ACE enzyme inhibition of the NO-cGMP axis or through a1-adrenergic receptor blocking. One study has noted that berberine at 25-200µM is able to inhibit ephedrine and histamine induced aortic contractions in a reversible manner yet failed to inhibit contractions from high potassium or caffeine.

Mechanisms (Glucose Related).
Berberine has been found to partly normalize the decrease of glucose uptake induced by palmatate (a fatty acid), which is through anti-inflammatory effects in inhibiting increased activity of IKKß and NF-kB; which subsequently increase IRS-1 and reduce glucose uptake via the insulin receptor.[164] This anti-inflammatory effect has been noted elsewhere when measuring cytokines, and fatty-acid induced insulin resistance has also been replicated elsewhere related to NF-kB.

Interventions
One study in persons with newly diagnosed metabolic syndrome noted that 300 mg Berberine thrice a day (900mg total) for 12 weeks was associated with a significant reduction of BMI from 31.5+/-3.6 to 27.4+/-2.4 (average 13% decrease) with a significant decrease in waist circumference by 5.5%; lean mass and fat mass were not measured. Otherwise healthy but obese persons taking 500 mg Berberine thrice daily (1500 mg total) for 12 weeks without adjustments to exercise noted reduction in body weight of approximately 5 lbs (2.3% body weight; 3.6% body fat); food intake was not changed overall, but two subjects reported a decrease in appetite.

Another trial in humans with nonalcoholic fatty liver disease who were given either lifestyle interventions alone, or lifestyle interventions plus 15 mg pioglitazone daily or 0.5 mg berberine thrice daily for 16 weeks found a significant reduction in BMI of 1.51 in the berberine group compared to a 0.72 reduction in BMI with lifestyle interventions alone; pioglitazone had a reduction similar to lifestyle interventions alone.

Virology
A study using the virological strain PR/8/34 (Influenza A) and WS/33 (H1N1) noted that its replication in macrophages (immune cells) was suppressed with 25 uM Berberine, which extended to A549 human epithelial cells (potent suppression) but not MDCK cells. The suppression with Berberine had IC50 values of 0.01 µM and 0.44 µM for these respective viral strains, which outperformed the reference drug amantadine.

Lipid Peroxidation
In an ex vivo assay of lipid peroxidation, Berberine inhibited lipid peroxidation directly with an IC50 of 72 µM, and was found to be active in TNBS-induced colitis in reducing lipid peroxidation in the colon. Lipid peroxidation has also been shown to be reduced in the ß-cells of the pancreas following oral ingestion of 150-300 mg/kg bodyweight.

Cancer Metabolism

14.1. Mechanisms (General)

Multiple targets exist which may explain anti-cancer effects of berberine.
Berberine is known to directly bind to DNA, which is one mechanism by which it can cause cell cycle arrest in multiple human cell cancer lines in vitro, although upregulation of GADD153, a transcription factor involved in apoptosis, may also play a role and has been seen to accompany cell cycle arrest and apoptosis in a human cervical cancer cell line. This mechanism has been observed in one case to occur through downregulating death-domain-associated protein, a key protein which regulates pathways related to cell survival, by binding to its promoter region, which led triggered a cascasde ultimately leading to cancer cell death. Berberine also has been seen to interfere with DNA synthesis in growing ovarian cancer cells by inhibiting two key enzymes in this pathway, dihydrofolate reductase and thymidylate synthase.

Berberine also seems to suppress the expression of certain proteins which are anti-apoptotic in cancer cells, such as Mcl-1. Berberine can also affect telomerase activity through multiple mechanisms as well, including the downregulation of the chaperone protein nucleophosmin, through inhibition of human telomerase reverse transcriptase, an essential component of human telomerase, or perhaps even through direct interaction with telomeric DNA.

Another possible mechanism of berberine's effect on cancer is via JAK3 selective inhibition, as at least one study has noted that berberine could decrease viability in cancer cell lines overexpressing active JAK3 (Ba/F3-JAK3V674A and L540) while not having a significant effect in other cell lines (HDLM-2 and DU145) at the same concentration of 3uM.

14.3. Migration and Metastasis
The migration of a human tongue squamous cell carcinoma line has been shown to be reduced by berberine in vitro, and involved the inhibition of several proteins including NF-?B, MMP-2, and MMP-9. Similar effects have been seen in a human lung cancer cell line.

14.4. Autophagy
Autophagy is the process a cell undergoes to degrade cellular components and to produce energy, usually under times of nutrient deficiency. Its relationship to cancer is complex, as a loss of the ability of Autophagy could make cells cancerous by knocking out caspase-independent autophagic, or type II, cell death; parodoxically, however, autophagy may also promote tumor survival by giving cancer cells a growth advantage.

Berberine has been shown in vitro to induce autophagic cell death in human liver cancer cells through the distinct increase in Beclin-1, which is one of the main proteins involved in this pathway, as well as an inhibition of mTOR (through MAPK activation and AKT inhibition), which is one of the main regulators of this pathway. Berberine, at least when combined with radiation, has been shown to induce autophagic cell death in lung carcinoma cells, which also led to tumor shrinkage in a xenograft mouse model.

14.5. Adjunct Therapy Potential
Berberine has been found to enhance the cytotoxicity of Doxorubicin (a chemotherapeutic agent), where cytotoxicity of Doxorubicin was enhanced with a Combination Index of 0.61-0.73, denoting synergism. This study noted that the IC50 values on growth inhibition with Doxorubicin were enhanced from 3.1 and 16.7 uM (A549 and HeLa cells) to 1.7 and 1.9 uM despite Berberine being relatively weak. Berberine (60 mg/kg) has also been found to reduce the hepatotoxicity of Doxorubicin in rats, attenuating the increase in ALT and AST and reducing Doxorubicin-induced liver necrosis by 28%.

14.6. Brain
Berberine has been seen to inhibit the growth of human neuroblastoma cells which express p53 at concentrations of 5 µM-100 µM in vitro, with cells not expressing this protein being much less sensitive (IC50 > 100 µM), suggesting that p53-induced apoptosis in these cells. Berberine also induced apopotosis in glioblastoma cells in vitro with an IC50 of 134 µg/mL through the mitochondrial apoptotic pathway.

14.7. Breast
Berberine induces apoptosis in breast cancer cells in vitro at 25 µM through the mitochodrial/caspase-dependent pathway.

14.8. Liver
In HepG2 cells and metastatic liver cells MHCC97-L (as well as nasopharyngeal carcinoma cell lines HONE1 and HK1) appears to induce cytotoxicity with IC50 values at 100 uM (HepG2) and 250 uM (MHCC97-L) via autophagy, as abolishing Atg5 attenuates cytotoxicity. Berberine was noted to dose-dependently increase staining for autolysosomes and autophagosomes, which may be due to induction of Beclin-1 (which binds to and sequesters Bcl-2, a mitochondrial membrane protection protein; reducing Bcl-2 indirectly promotes autophagy) and lead to cancer cell death via mitochondrial capsase release. ...

14.10. Thyroid
Berberine has been found to inhibit thyroid cancer cells growth in vitro using the cell lines 8505C and TPC1 (anaplastic and papillary, respectively). This study noted dose-dependent reductions in cell proliferation with an IC50 of 10 uM, and was involved with inducing apoptosis at G2/M and G0/G1 for 8505C and TPC1 cells, respectively, modulated by increased expression of P27.

14.11. Colon
In two tested colon cancer cell lines (HT-29 and IMCE) as well as a normal cell line (YAMC), Berberine at 50 µM is able to suppress over half the cancer cell growth with further inhibition at 100 µM and these doses induced apoptosis in cancer cells; suggesting anti-cancer potential of Berberine in colon cancer cells. Apoptosis was only induced in normal colon cells at 200 µM, suggesting that cancer cells are sensitized to the effects of Berberine; the cell death is mediated by oxidation (ROS) inducing AIF release from the mitochondria and accumulation in the nucleus and is caspase independent.

14.12. Prostate
Berberine inhibits the growth of p53-expressing prostate cancer cells in vitro at concentrations of 30-100 µM, but has a weaker effect against prostate cancer cells lacking p53 (PC-3 cells) (IC50 > 100 µM), as the main mechanism by which berberine operates in this cell line seems to be by inducing p53-dependent apoptosis. Another study on PC-3 cells, however, did find that berberine indeed induces apoptosis in these cells through the mitochondrial/caspase-dependent pathway, and is dependent on the generation of reactive oxygen species.

14.13. Immunological Cancers
A human lymphoma cell line (U937) has been seen to undergo apopoptosis when exposed to 50-75 µM berberine in vitro through a mitochondrial/caspase-dependent mechanism. Human HL-60 leukemia cells have also been seen to undergo apoptosis induced by berberine exposure above 30 µM, alongside an increase in the production of reactive oxygen species.

17.5. Skin
Berberine has interactions with the skin and has potential to be used as a topical agent, as it suppresses lipid synthesis from sebaceus glands and acts like a surfactant in that it increases skin permeability to polar drugs. If used as a skin agent, however, excessive sunlight should be avoided due to berberine's potential to form free radicals when used externally.

17.6. Penis
In isolated corpus cavenosum smooth muscle cells, Berberine at 10-1000 uM concentration was able to concentration-dependently reduce oxidative damage induced by H2O2 and preserve both nitric oxide (NO) and SOD content. Lower concentrations of 1-3uM Berberine was able to concentration-dependently increase the expression of eNOS by 40% and 66% with no influence on iNOS and this was shown to increase penile relaxation (a pro-erectile effect) after direct injections of Berberine into rabbit penises. This study noted a dose-dependent (1-5mg/kg) relaxation in phenylephrine precontracted penile strips with 5 mg/kg increasing intracavernous pressure (ICP) by 399%. The mechanism of action of Berberine is direct (non-neuronal) and NO dependent ...

(A study) noted that Paparvine (Papaver somniferum) as active control was more potent acutely, but Berberine appeared to increase penile tumescence for a longer duration of time.

18.1. Polycystic Ovarian Syndrome
Polycystic Ovarian Syndrome (PCOS) is a condition affecting women that is commonly associated with insulin resistance, where Metformin is a common pharmaceutical to control side-effects. One trial alongside standard therapy (antiandrogens and estrogen) that compared Berberine and Metformin (both at 1500 mg in three doses) against placebo over 3 months noted that Berberine was associated with the largest reduction in waist circumference (despite no significant differences in weight) yet no significant differences existed between measures of insulin resistance, blood glucose, or insulin with both being better than placebo.

18.2. Liver Disorders with concurrently High Glucose
Berberine appears to be safe and effective for reducing triglycerides in persons with liver cirrhosis or hepatitis according to preliminary evidence, and a later study using 1g Berberine for 2 months in persons with Hepatitis C (n=18) or Hepatitis B (n=17) with high blood glucose that there were

reductions in fasting blood glucose (13.4-17.1%), triglycerides (17.6-19%) and
reduced the elevation of liver enzymes (ALT and AST).

19.2. statins
Berberine by itself is implicated in reducing cholesterol levels by up to 25% in persons with high cholesterol, which is thought to be through upregulating and preserving the expression of the LDL receptor (which takes up LDL from the blood into tissues). Berberine has been implicated in attenuating increases of PCSK9 (a protein that suppresses expression of the LDL receptor) which may disconnect the side effect of high cholesterol from conditions that induce PCSK9 activity; this includes inflammation (leading to it being referred to as 'the next statin' by some and statin drugs, where the induction of PCSK9 appears to limit the statin's own ability to reduce cholesterol. and as such the combination of statin drugs and berberine for the purpose of lipid and cholesterol reduction appears to be synergistic.

19.3. Policosanol and Red Yeast Extract
The combination of Berberine (usually 500 mg), Red Yeast Extract (3mg) and Policosanol (10mg) has been used in a few trials in humans together, and has been implicated in

weight loss in persons with metabolic syndrome (2kg over 18 weeks),
• decreases in blood pressure,
• reductions in insulin resistance,
• reductions in total cholesterol, LDL-C, and
• improved blood flow.

At least one study noted that 18 weeks of supplementation in persons with metabolic syndrome resulted in less ventricular mass and an improvement in the E/A ratio (from 1.00 ± 0.43 to 1.12 ± 0.30 over 18 weeks), indicative of better heart health.

Despite this combination being used very frequently, the one study to compare the combination against Berberine in isolation suggest that most benefit is secondary to Berberine rather than a possible synergistic relationship.

19.4. Sodium Caprate
Sodium Caprate (decanoic acid or capric acid, bound to sodium) a fatty acid found in coconut oil and other sources, has been demonstrated to enhance the absorption of Berberine when both are simultaneously fed to rats. This enhancement has been repeated elsewhere, where absorption was increased 1.49-3.49 fold depending on where the absorption was measured in the intestines (greater enhancement in the ileum, less in the jujenum). Neither of these studies noted damage to the intestinal mucosa.

20.2. Contraindications
Due (partially) to inhibition of the CYP3A4 enzyme, berberine can adversely interact with Cyclosporin A and increase bioavailability of the latter, which necessitates a lower dosage. Berberine can also adversely interact with warfarin, thiopental, and tolbutamide by displacing them from their sites of action and increasing blood toxicity potential. Macrolide antibiotics such as azithromycin and clarithromycin may also interact with berberine and may lead to serious heart problems.

It also displaces bilirubin from albumin at a very high rate, which may be a factor for reported green stools alongside berberin's natural coloration as yellow. Because of the former reactions, however, it should not be used in jaundiced neonates and pregnant women.

Product: Berberine, Thorne Research. INDEX
https://www.thorne.com/products/dp/berberine-500
Retail: C$47.00 -- USA $33.55
LINK 2: https://www.amazon.com/
Thorne-Research-Berberine-500-Botanical-Metabolism/dp/B009LI7VRC
Amazon: USA $33.55 -- Special: USA $31.87
Link 3: https://well.ca/products/thorne-research-berberine-500_141056.html
Regular: C$23.99 --- 60 Vegetarian Capsules
500 mg -- 60 caps

a versatile botanical compound with wide application
• 500 mg Berberine HCl per capsule
• higher amount to help maintain healthy blood sugar metabolism*
• supports healthy lipid levels*
• provides cardiovascular support*
• a constituent of many herbs, including barberry (the source in this product), Oregon grape, goldenseal, and Coptis

Berberine is an alkaloid that is present in a number of plants, including

• Berberis vulgaris (barberry),
• Berberis aristata (tree turmeric),
• Berberis aquifolium (Oregon grape),
• Hydrastis canadensis (goldenseal), and
• Coptis chinensis (goldthread).

This important plant extract demonstrates important benefits for

• glucose metabolism,
• maintenance of healthy lipid levels,
• insulin sensitivity,
• cardiac support,
• weight management,
• gastrointestinal health,
• immune modulation, and
• cognitive support.

FEEDBACK:
• Ok, so this supplement was a complete blessing in disguise!
  I originally ordered this to help with my acne and inflammation.
  While it didn't do anything for my acne initially (I took two bottles worth) it DID expel parasites from my body!
  After taking this I started to get stomach distress which it indicates on the bottle can happen. I started to bloat too. Then after almost three weeks I started to expel round worms and pin worms in my stool! Little did I know that this stuff does in fact kill parasites!!
  
  

• This has been a miracle drug to the person for whom I purchased it because they are insulin resistant (apparently many people are who do not know it). The person lost an incredible amount of weight as a direct result of taking this version of berberine. The only side effect seems to be a more active bowel movement schedule. Not diarrhea, just more and looser BMs.

  If you are having an insulin resistance problem i.e. you can't lose weight no matter how much you exercise and cut calories you (could) consider looking into whether you are insulin resistant and taking berberine. ...
  
  

• As a woman with PCO/Insulin Resistance, everyday is a constant struggle to feel good and not gain 50 lbs from eating ... well, ANYTHING. After years of metformin and then thyroid medication, I really felt like I was never going to be in good shape & health, no matter how much I worked out and ate well.

  Then my Naturopath told me about Thorne's Berberine.
  About 4 weeks into taking this natural miracle, I'm effortlessly fitting into my ridiculously skinny jeans and feel better than I have in maybe forever.

Product: Berberis Formula, Genestra. INDEX
https://well.ca/products/genestra-berberis-formula_116278.html
Regular: $81.89 --- 180 Vegetable Capsules

Dosage:
For persons over 19 years of age --- 1 capsule two times daily, with food.

Genestra Berberis Formula is a blend of barberry, goldenseal and Oregon grape extracts that are traditionally used in Herbal Medicine to help maintain gastrointestinal health. The main bioactive ingredient in these extracts is berberine.

Traditionally used in Herbal Medicine as a bitter to aid digestion, to help relieve digestive disturbances such as dyspepsia, and as a mild laxative.

Ingredients: 
    200 mg -- Barberry root & stem extract 
    200 mg -- Oregon Grape extract 
     50 mg -- Goldenseal root extract 
     25 mg -- Barberry root bark 
     25 mg -- Oregon Grape root 

 : INDEX

DEFINITIONS.

apoptosis
A natural process of self-destruction by degradative enzymes in certain cells, such as epithelial cells and erythrocytes, that are genetically programmed to have a limited lifespan or are damaged, as by irradiation or toxic drugs. Also called programmed cell death.

aldose
one of the two main types of monosaccharide sugars;
those that contain an aldehyde group (-CHO), such as glucose, galactose, OR mannose.

An aldose, like a ketose, is a monosaccharide (a simple sugar), which have a carbon backbone chain with many alcohol (hydroxy groups) and an aldehyde. They are polar molecules and very soluble in water due to the many -OH groups they possess. Monosaccharides are a type of carbohydrate, organic structures which can be thought of as having the ingredients for many water (H2O) molecules attached to the carbons in the chain, hence the 'hydrate" of carbohydrate. For most organisms, carbohydrates are an important source of energy that is taken in as food, and broken down in a series of processes called metabolism. Aldoses feature prominently in two metabolic regimes, glycolysis which is the break down of sugars, and gluconeogenesis which is the opposite.

AMPK
Acronym: Adenosine Monophosphate-Activated Protein Kinase
AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 and SnRK1 in yeast and plants, respectively. It consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle.

The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, and modulation of insulin secretion by pancreatic beta-cells.

autophagy
The process of self-digestion by a cell through the action of enzymes originating within the same cell.
the nutrition of the body by its own tissues, as in dieting. Autophagy allows the orderly degradation and recycling of cellular components. Autophagy has roles in various cellular functions. One particular example is in yeasts, where the nutrient starvation induces a high level of autophagy. This allows unneeded proteins to be degraded and the amino acids recycled for the synthesis of proteins that are essential for survival.

cytokines
soluble messenger molecules, e.g. lymphokines (produced by lymphocytes) and interleukins (made by other white blood cells) that facilitate communication between different compartments of the immune system; examples include interferons, tumour necrosis factor-alpha (TNF-a), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF); these cause biological effects in destination cell populations (e.g. activation, division or migration of destination cells) and often trigger inflammation.

A general term for a range of proteins of low molecular weight that exert a stimulating or inhibiting influence on the proliferation, differentiation and function of cells of the immune system.

ketoconazole
a synthetic imidazole that is a broad-spectrum antifungal agent used for treatment of chronic mucocutaneous candidiasis and systemic fungal infections due to species of Candida, Epidermophyton, Microsporum, Trichophyton, and others.

lignans
chemicals derived from flaxseeds, pumpkin seeds, cranberries, tea, and whole grains;
have phytoestrogenic properties and are used as chemopreventives, to lower blood cholesterol, and to treat atherosclerosis.
Precaution advised for those at risk for developing hormone-dependent cancers.

MDCK cells
Acronym: Madin-Darby Canine Kidney Cells (virus tissue culture)
Madin-Darby Canine Kidney (MDCK) cells are a model mammalian cell line used in biomedical research.
MDCK cells are used for a wide variety of cell biology studies including cell polarity, cell-cell adhesions (termed adherens junctions), collective cell motility, as well as responses to growth factors. It is one of few cell culture models that is suited for 3D cell culture and multicellular rearrangements known as branching morphogenesis.

statins
Drugs of the hydroxymethyl glutaryl coenzyme A reductase inhibitor class (HMG-CoA reductase inhibitors).
These drugs block the liver's production of cholesterol by competitive inhibition of the reductase coenzyme that catalyzes the rate-limiting step of cholesterol synthesis. They can lower the levels of low-density lipoproteins (LDLs) by 25 - 45 per cent and a number of major trials have shown their benefits in preventing heart attacks and other effects of ATHEROSCLEROSIS. They reduce the risk of sepsis and fatal sepsis in people with cardiovascular disease, and it has been established that intensive statin treatment after heart attacks provides greater protection against death than does a standard regimen.

This growing drug class includes atorvastatin (Lipitor), cerivastatin (Liponay), fluvastatin (Lescol), pravastatin (Lipostat), rosuvastatin (Crestor) and simvastatin (Zocor). Note that the root ‘statin’ has proved popular with pharmacological neologists so, unfortunately, there are many other drugs, not in the HMG-CoA reductase inhibitor class, with ‘statin’ in their names.

telomeres
region at the ends of EUKARYOTIC CHROMOSOMES, enabling the cell to distinguish between natural ends and unnatural ends, caused by chromosome breakage. The telomeric DNA comprises of hundreds of copies of a repeated sequence, to which specific proteins, called ‘telomere binding proteins’ (TBPs) bind to regulate the length of the chromosome.

A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes.

During chromosome replication, the enzymes that duplicate DNA cannot continue their duplication all the way to the end of a chromosome, so in each duplication the end of the chromosome is shortened (this is because the synthesis of Okazaki fragments requires RNA primers attaching ahead on the lagging strand). The telomeres are disposable buffers at the ends of chromosomes which are truncated during cell division; their presence protects the genes before them on the chromosome from being truncated instead. The telomeres themselves are protected by a complex of shelterin proteins, as well as by the RNA that telomeric DNA encodes (TERRA).

Over time, due to each cell division, the telomere ends become shorter; Shortened telomeres are considered synonymous with aging.

TNBS
Acronym: Trinitrobenzene sulfonic acid; 2,4,6-Trinitrobenzene sulfonic acid.
Its primary usage is primarily to neutralize peptide terminal amino groups in scientific research.
It is also used to induce Crohn's Disease in the colon of laboratory animals in order to model Inflammatory Bowel Disease.

Due to its extreme oxidative properties, if mixed with reducing agents including hydrides, sulfides, and nitrides, it may begin a vigorous reaction that culminates in almost immediate detonation. The aromatic nitro compounds may explode in the presence of a base such as sodium hydroxide or potassium hydroxide even in the presence of water or organic solvents because of the explosive tendencies of aromatic nitro compounds which increase in the presence of multiple nitro groups.

INDEX