Berberine

What is berberine?

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids discovered in such plants as berberis, such as 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 typically found in the roots, roots, stems, and bark.

Due to its yellow color, berberis species were utilized to dye wool, leather, and wood.under ultraviolet light, berberine shows a strong yellow fluorescence, making it useful in histology for staining heparin in mast cells. As a natural color, berberine has a color index.

Biosynthesis of berberine

The alkaloid berberine has a tetracyclic skeleton originated from a benzyltetrahydroisoquinoline system with the incorporation of an additional carbon atom as a bridge. Formation of the berberine bridge is rationalized as an oxidative procedure in which the n-methyl group, supplied by s-adenosyl methionine (sam), is oxidized to an iminium ion, and a cyclization to the fragrant ring happens by virtue of the phenolic group.

Reticuline is known as the immediate precursor of protoberberine alkaloids in plants.berberine is an alkaloid originated from tyrosine. L-dopa and 4-hydroxypyruvic acid both come from l-tyrosine. Although two tyrosine particles are utilized in the biosynthetic pathway, just the phenethylamine fragment of the tetrahydroisoquinoline ring system is formed via dopa, the staying carbon atoms originate from tyrosine through 4-hydroxyphenylacetaldehyde. L-dopa loses carbon dioxide to form dopamine 1. Likewise, 4-hydroxypyruvic acid also loses co2 to form 4-hydroxyphenylacetaldehyde 2. Dopamine 1 then reacts with 4-hydroxy-phenylacetaldehyde 2 to form (s)- norcolaurine 3 in a response comparable to the mannich response. After oxidation and methylation by sam, (s)- reticuline 4 is formed. (s)- reticuline works as a critical intermediate to other alkaloids. Oxidation of the tertiary amine then happens and an iminium ion is formed 5. In a mannich-like response the ortho position to the phenol is nucleophilic, and electrons are pressed to form 6. Item 6 then goes through keto– enol tautomerism to form (s)- scoulerine, which is then methylated by sam to form (s)- tetrahydrocolumbamine 7. Item 7 is then oxidized to form the methylenedioxy ring from the ortho-methoxyphenol, through an o2-, nadph- and cytochrome p450-dependent enzyme, giving (s)- canadine 8. (s)- canadine is then oxidized to offer the quaternary isoquinolinium system of berberine. This occurs in 2 different oxidation steps, both needing molecular oxygen, with h2o2 and water produced in the successive procedures. (1 ).

Overview

Berberine is a chemical discovered in some plants like european barberry, goldenseal, goldthread, oregon grape, phellodendron, and tree turmeric.

Berberine is a bitter-tasting and yellow-colored chemical. It might help reinforce the heartbeat, which might benefit people with particular heart conditions. It may likewise eliminate bacteria, aid regulate how the body utilizes sugar in the blood, and help in reducing swelling.

Individuals most frequently use berberine for diabetes, high levels of cholesterol or other fats in the blood, and high blood pressure. It is likewise utilized for burns, canker sores, liver illness, and lots of other conditions but there is no good clinical proof to support a number of these uses. (2 ).

History

Berberine is a cationic alkaloid that was first separated in 1917 from goldenseal (hydrastis canadensis), a north american herb of the buttercup household. It is found in the roots, roots, stems, and bark of numerous other plants, including berberisspp. (worldwide), yellowroot (southwestern united states), and the amur cork tree (east asia). It usually exists as the chloride, however t. Kametani and colleagues reported the overall synthesis as the iodide in 1969.

Berberine’s strong yellow color and yellow fluorescence made it an extensively used dye in early days of the industry. It is still utilized in india as a wool dye, and its fluorescence makes it beneficial as a histology stain.

But berberine’s main use is as a herbal dietary supplement. It has antibiotic, anti-inflammatory, and antineoplastic residential or commercial properties, and it is being investigated as a treatment for diabetes, cancer, hyperlipidemia, heart disease, and hiv. The us food and drug administration has actually not yet approved berberine for any prescription or non-prescription drug use, and it has sent out notices of violation to business that have actually made drug claims on their web sites. Clinical trials show that berberine is usually safe, however it has actually revealed drug interactions and is contraindicated for pregnant and breast-feeding females. (3 ).

Mechanism of action

Berberine is known as an amp-activated protein kinase (ampk) activator. Its insulin-independent hypoglycemic result is related to inhibition of mitochondrial function, stimulation of glycolysis and activation of ampk pathway. Additionally, berberine may also function as an α-glucosidase inhibitor. In the newly-diagnosed type 2 diabetic patients, berberine has the ability to lower blood insulin level via improving insulin sensitivity. However, in patients with poor β-cell function, berberine may enhance insulin secretion through resuscitating exhausted islets. In addition, berberine may have additional beneficial effects on diabetic cardiovascular complications due to its cholesterol-lowering, anti-arrhythmias and nitric oxide (no) causing properties. The antioxidant and aldose reductase inhibitory activities of berberine might be useful in reducing diabetic nephropathy. Although evidence from animal and human studies regularly supports the healing activities of berberine, massive multicenter trials are still necessary to assess the effectiveness of berberine on diabetes and its associated problems. (4 ).

Benefits of berberine

A compound called berberine is among the most efficient natural supplements readily available.

It has extremely impressive health benefits, and affects your body at the molecular level.

Berberine has actually been revealed to lower blood sugar level, cause weight loss and enhance heart health, to name a few.

It is one of the few supplements shown to be as efficient as a pharmaceutical drug.

This is a comprehensive review of berberine and its health results.

It triggers a significant reduction in blood sugar level levels

Type 2 diabetes is a severe illness that has actually ended up being incredibly common in recent years, causing countless deaths every year.

It is characterized by elevated blood glucose (glucose) levels, either brought on by insulin resistance or absence of insulin.

With time, high blood sugar levels can harm the body’s tissues and organs, causing various health issue and a reduced life expectancy.

Many studies show that berberine can significantly reduce blood sugar levels in individuals with type 2 diabetes.

In fact, its effectiveness is comparable to the popular diabetes drug metformin (glucophage).

It appears to work via numerous different mechanisms:.

  • Decreases insulin resistance, making the blood sugar reducing hormonal agent insulin more reliable.
  • Increases glycolysis, assisting the body break down sugars inside cells.
  • Reduction sugar production in the liver.
  • Slows the breakdown of carbs in the gut.
  • Increases the number of useful bacteria in the gut.

In one study of 116 diabetic patients, 1 gram of berberine daily lowered fasting blood sugar level by 20%, from 7.0 to 5.6 mmol/l (126 to 101 mg/dl), or from diabetic to typical levels.

It likewise lowered hemoglobin a1c by 12% (a marker for long-lasting blood sugar level levels), and likewise enhanced blood lipids like cholesterol and triglycerides.

According to a big review of 14 research studies, berberine is as efficient as oral diabetes drugs, consisting of metformin, glipizide and rosiglitazone.

It works very well with lifestyle adjustments, and also has additive impacts when administered with other blood sugar level lowering drugs.

If you take a look at discussions online, you frequently see individuals with sky-high blood sugar level literally stabilizing them just by taking this supplement.

This things actually works, in both the studies and the real life.

Bottom line:

Berberine is really effective at reducing blood sugar level and hba1c, which are elevated in individuals with diabetes. It works along with some pharmaceutical drugs.

Berberine might assist you slim down

Berberine might likewise be effective as a weight loss supplement.

So far, 2 research studies have actually taken a look at the results on body weight.

In a 12-week research study in overweight individuals, 500 mg taken 3 times each day triggered about 5 pounds of weight-loss, typically. The individuals also lost 3.6% of their body fat (14 ).

Another more remarkable study was conducted in 37 males and females with metabolic syndrome. This study went on for 3 months, and the participants took 300 mg, 3 times per day.

The individuals dropped their body mass index (bmi) levels from 31.5 to 27.4, or from obese to obese in only 3 months. They likewise lost stomach fat and enhanced lots of health markers.

The scientists believe that the weight-loss is triggered by better function of fat-regulating hormonal agents, such as insulin, adiponectin and leptin.

Berberine also appears to hinder the development of fat cells at the molecular level.

However, more research is required on the weight-loss results of berberine.

Bottom line:

Two research studies have actually revealed that berberine can trigger considerable weight reduction, while enhancing all sorts of other health markers at the same time.

It reduces cholesterol and might minimize your risk of heart disease

Cardiovascular disease is presently the world’s most common reason for premature death.

Numerous aspects that can be measured in the blood are connected with an increased risk of cardiovascular disease.

As it turns out, berberine has actually been shown to enhance a lot of these elements.

According to a review of 11 studies, it can:.

  • Lower overall cholesterol by 0.61 mmol/l (24 mg/dl).
  • Lower ldl cholesteroltrusted source by 0.65 mmol/l (25 mg/dl).
  • Lower blood triglycerides by 0.50 mmol/l (44 mg/dl).
  • Raise hdl cholesterol by 0.05 mmol/l (2 mg/dl).

It has actually also been revealed to lower apolipoprotein b by 13-15%, which is a really crucial risk factor.

According to some research studies, berberine works by inhibiting an enzyme called pcsk9. This causes more ldl being gotten rid of from the blood stream.

Remember that diabetes, high blood sugar levels and obesity are also significant danger factors for heart disease, all of which seem to be improved with this supplement.

Given the beneficial results on all these danger aspects, it promises that berberine might considerably lower the danger of heart problem.

Bottom line:

Studies reveal that berberine decreases cholesterol and triglyceride levels, while raising hdl (the “excellent”) cholesterol. It may decrease the risk of heart problem in the long-lasting.

Other health benefits

Berberine may also have many other health benefits:.

  • Depression: rat studies reveal that it might help combat anxiety.
  • Cancer: test tube and animal research studies have actually shown that it can decrease the development and spread of various different kinds of cancer.
  • Antioxidant and anti-inflammatory: it has actually been revealed to have potent antioxidant and anti-inflammatory effects in some studies.
  • Infections: it has actually been revealed to fight damaging microbes, including germs, viruses, fungis and parasites.
  • Fatty liver: it can minimize fat build-up in the liver, which need to assist secure against non-alcoholic fatty liver illness (nafld).
  • Cardiac arrest: one study revealed that it drastically enhanced signs and reduced risk of death in cardiac arrest clients.
  • Much of these benefits require more research study before firm suggestions can be made, but the present evidence is really promising.

Bottom line:

Preliminary studies reveal that berberine may have advantages versus anxiety, cancer, infections, fatty liver and cardiac arrest. It also has potent anti-oxidant and anti-inflammatory results. (5 ).

Further more

Scientific research and research studies with isolated berberine have actually shown significant success in the treatment of severe diarrhea, irritable bowel syndrome, type 2 diabetes, hypertension, raised blood lipids, alzheimer’s illness and cancer. Here’s more about how research suggests that berberine can help in dealing with these conditions.

Berberine for intense diarrhea

Berberine has been discovered to be efficient against diarrheas brought on by a number of organisms. These outcomes show that berberine seems effective in dealing with the majority of typical gastrointestinal infections with results similar to basic antibiotics for the most part. In fact, results were much better in several studies.

The benefit of berberine over traditional prescription antibiotics is that it exerts selective antimicrobial action as it targets a wide variety of disease-causing organisms including candida albicans, yet puts in no action against health-promoting bacterial species such as lactobacilli and bifidobacter species.

Berberine for sibo and ibs

Berberine has actually been revealed to be reliable in treating irritable bowel syndrome (ibs) and numerous preliminary studies suggest it may also be effective in attending to little intestinal overgrowth (sibo). Ibs is connected with some combination of:.

  • Abdominal discomfort or distension
  • Altered bowel function, irregularity, or diarrhea
  • Hypersecretion of colonic mucous
  • Dyspeptic signs (flatulence, queasiness, anorexia)
  • Varying degrees of anxiety or depression

Sibo frequently displays other associated symptoms consisting of:.

  • Brain “fogginess”
  • Fatigue
  • Joint pain
  • Skin issues such as acne, eczema, rashes or rosacea
  • Weight reduction

In a 2015 research study, clients with diarrhea-predominant ibs were randomized to get either berberine or a placebo twice a day for 8 weeks. The berberine group reported significant enhancement in diarrhea and less seriousness and frequency in defecation. The berberine group likewise experienced a 64.6 percent reduction in abdominal pain compared with initial ratings at the end of the study.

Berberine enhances the general ibs sign score, stress and anxiety score and depression rating. Finally, and not surprisingly, it was associated with an increased lifestyle score in clients while no such change was seen in the placebo group. (6 ).

Berberine and pcos

Berberine can use many advantages to females with pcos, consisting of improved fertility, support with weight reduction, and decreased risk for metabolic complications connected with the condition.

Berberine can offer an emotional lifeline to females who understand the problems pcos can create during pregnancy, consisting of:

  • Miscarriage
  • Gestational diabetes
  • Preeclampsia
  • Cesarean section (c-section)

Taking berberine in no chance guarantees that a lady will conceive. However it might help her feel more proactive and unwinded about the prospect. And some research study recommends a link between stress and annoyed efforts at conceiving.

Improving fertility

At least 2 research studies reveal the promise between berberine and fertility. In one pilot study, 98 anovulatory females (ladies who do not ovulate) with pcos took berberine. Ovulation enhanced by an average of 25% after 4 months.

A study published in medical endocrinology revealed that ladies with pcos who were randomly selected to take berberine had greater pregnancy rates than those who took metformin (an insulin-sensitizing medication) or placebo.

They also felt fewer side effects 12 weeks prior to in vitro fertilization (ivf) treatment. (7 )

Why it might be advantageous for gut health?

” one manner in which berberine works is that it [might assist] the body achieve a healthier mix of gut plants,” foroutan states. While more human research studies require to be performed to show this connection, numerous clinical studies, including this one released in the journal drug metabolism and personality, have actually revealed this in mice. Specifically, the study discovered that when bacteria from mice’s lower intestinal tract was exposed to berberine it “not just transformed bacterial physiology but also changed bacterial neighborhood structure and function.”.

Once again, there mainly seem to be mouse or in vitro (aka research studies not on living subjects) studies to support this benefit, so take the claims with a grain of salt. However foroutan says berberine’s potential for improving gut health is the number one factor it’s utilized by health specialists. “it’s a natural antimicrobial, implying it helps to keep gut microbes in balance,” she says. Having balanced and healthy gut plants can affect so many other elements about health, she adds, like general swelling, state of mind, immune function, and chronic illness risk. (8 ).

Adverse effects of berberine

The nationwide center for complementary and integrative health (nccih) trusted source notes that if adults take goldenseal, which consists of berberine, by mouth it is not likely to cause serious adverse results in the short-term. Nevertheless, there is inadequate info to show that long-term usage is safe.

Berberine can cause digestion side effects, such as:.

  • Upset stomach
  • Irregularity
  • Nausea

It can also cause a rash or headache in some people.

In animal research studies, researchers have noticed the following results, depending on the kind of animal, how much they took in, and for how long:.

  • Diarrhea
  • Vomiting
  • Nausea
  • Muscle trembling
  • Gastric ulcers
  • Liver and kidney augmentation
  • A decrease in leukocyte

It is essential to speak with a medical professional before taking berberine or other supplements, as they may not be safe or appropriate for everyone to utilize. Anyone who establishes an allergy to any organic item need to stop utilizing it at the same time.

The nccih recommends individuals not to use goldenseal, which consists of berberine, during pregnancy or while breastfeeding. They add that offering goldenseal to a newborn might trigger or aggravate jaundice and increase the danger of kernicterus, a possibly harmful condition. (9 ).

Dosage

The recommended dose of berberine is based upon analyses of the offered scientific literature. The results of berberine are obvious at relatively high dosages due to its low absorption in the digestion tract. Just how much berberine should you take per day? It is recommended to take in between 900 and 1500 mg of berberine.

The length of berberine intake depends on the result you wish to achieve. Analysis of scientific studies on berberine supplements offers some concept after for how long the outcomes of using berberine will show up. The result of preparations with berberine is observed:.

  • In insulin resistance after 2-4 months of use from 900 to 1500 mg of berberine each day;
  • In dyslipidemia, with high blood cholesterol levels after 6-24 months of use 600 to 1500 mg berberine daily;
  • In hypertension after 2 months of taking 900 mg of berberine per day;
  • In polycystic ovary syndrome after 3-6 months of taking 1500 mg of berberine daily;
  • In obesity after 3 months of 900 to 1500 mg berberine each day. (10 )

Interactions

  • Cyclosporine (neoral, sandimmune) interaction rating: major do not take this mix.
  • The body breaks down cyclosporine (neoral, sandimmune) to get rid of it. Berberine might decrease how fast the body breaks down cyclosporine (neoral, sandimmune). Cyclosporine (neoral, sandimmune) may develop in the body and might possible cause side effects.
  • Medications for diabetes (antidiabetes drugs) interaction ranking: major do not take this combination.
  • Berberine may lower blood sugar. Diabetes medications are likewise utilized to lower blood sugar. Taking berberine along with diabetes medications may trigger your blood glucose to go too low. Screen your blood sugar closely. The dose of your diabetes medication might need to be changed.
  • Some medications utilized for diabetes consist of glimepiride (amaryl), glyburide (diabeta, glynase prestab, micronase), insulin, pioglitazone (actos), rosiglitazone (avandia), and others.
  • Dextromethorphan (robitussin dm, and others) interaction rating: moderate be cautious with this combination.talk with your health company.
  • The body breaks down dextromethorphan (robitussin dm, others) to eliminate it. Berberine may reduce how rapidly the body breaks down dextromethorphan (robitussin dm, others). Taking berberine while taking dextromethorphan (robitussin dm, others) may increase the results and negative effects of dextromethorphan (robitussin dm, others).
  • Losartan (cozaar) interaction score: moderate be cautious with this combination.talk with your health supplier.
  • The liver activates losartan (cozaar) to make it work. Berberine may decrease how rapidly the body breaks down losartan (cozaar). Taking berberine while taking losartan (cozaar) might reduce the impacts of losartan.
  • Medications changed by the liver (cytochrome p450 2c9 [cyp2c9] substrates) interaction score: moderate beware with this combination.talk with your health company.
  • Some medications are changed and broken down by the liver. Berberine might decrease how rapidly the liver breaks down some medications. Taking berberine in addition to some medications that are broken down by the liver can increase the results and negative effects of some medications. Prior to taking berberine, talk to your doctor if you are taking any medications that are changed by the liver.
  • Some medications altered by the liver consist of celecoxib (celebrex), diclofenac (voltaren), fluvastatin (lescol), glipizide (glucotrol), ibuprofen (advil, motrin), irbesartan (avapro), losartan (cozaar), phenytoin (dilantin), piroxicam (feldene), tamoxifen (nolvadex), tolbutamide (tolinase), torsemide (demadex), and s-warfarin (coumadin).
  • Medications altered by the liver (cytochrome p450 2d6 [cyp2d6] substrates) interaction rating: moderate beware with this combination.talk with your health supplier.
  • Some medications are altered and broken down by the liver. Berberine may decrease how quickly the liver breaks down some medications. Taking berberine together with some medications that are broken down by the liver can increase the results and negative effects of some medications. Prior to taking berberine, speak with your doctor if you are taking any medications that are altered by the liver.
  • Some medications changed by the liver consist of amitriptyline (elavil), codeine, desipramine (norpramin), flecainide (tambocor), haloperidol (haldol), imipramine (tofranil), metoprolol (lopressor, toprol xl), ondansetron (zofran), paroxetine (paxil), risperidone (risperdal), tramadol (ultram), venlafaxine (effexor), and others.
  • Medications changed by the liver (cytochrome p450 3a4 [cyp3a4] substrates) interaction ranking: moderate beware with this combination.talk with your health company.
  • Some medications are altered and broken down by the liver. Berberine may reduce how quickly the liver breaks down some medications. Taking berberine in addition to some medications that are broken down by the liver can increase the impacts and side effects of some medications. Prior to taking berberine, talk to your doctor if you are taking any medications that are changed by the liver.
  • Some medications altered by the liver consist of cyclosporin (neoral, sandimmune), lovastatin (mevacor), clarithromycin (biaxin), indinavir (crixivan), sildenafil (viagra), triazolam (halcion), and lots of others.
  • Medications for high blood pressure (antihypertensive drugs) interaction ranking: moderate be cautious with this combination.talk with your health supplier.
  • Berberine may decrease high blood pressure in some individuals. Taking berberine together with medications utilized for lowering high blood pressure may trigger your blood pressure to go too low. However, it’s not known if this is a huge issue. Do not take too much berberine if you are taking medications for high blood pressure.
  • Some medications for hypertension consist of include captopril (capoten), enalapril (vasotec), losartan (cozaar), valsartan (diovan), diltiazem (cardizem), amlodipine (norvasc), hydrochlorothiazide (hydrodiuril), furosemide (lasix), and numerous others.
  • Medications that slow blood clot (anticoagulant/ antiplatelet drugs) interaction rating: moderate beware with this combination.talk with your health provider.
  • Berberine might slow blood clot. Taking berberine in addition to medications that also sluggish clotting might increase the chances of bruising and bleeding.
  • Some medications that slow blood clotting consist of aspirin, cilostazol (pletal), clopidogrel (plavix), dalteparin (fragmin), enoxaparin (lovenox), heparin, ticlopidine (ticlid), and others.
  • Midazolam (versed) interaction rating: moderate be cautious with this combination.talk with your health company.
  • The body breaks down midazolam (versed) to get rid of it. Berberine can reduce how quickly the body breaks down midazolam (versed). Taking berberine together with midazolam (versed) may increase the impacts and negative effects of midazolam (versed).
  • Sedative medications (cns depressants) interaction ranking: moderate be cautious with this combination.talk with your health service provider.
  • Berberine may trigger drowsiness and sleepiness. Medications that triggers drowsiness are called sedatives. Taking berberine together with sedative medications might cause too much sleepiness.
  • Some sedative medications consist of benzodiazepines, pentobarbital (nembutal), phenobarbital (luminal), secobarbital (seconal), thiopental (pentothal), fentanyl (duragesic, sublimaze), morphine, propofol (diprivan), and others. (11 )

Safety measures:

Before taking berberine, talk with your doctor if you dislike it or any other medications associated with it. The item can consist of some inactive components which can cause some serious allergies and other serious issues. Berberine has a high risk of disrupting drugs, and some of these reactions might be extreme. When high doses are used, gastrointestinal upset might happen, and because of its ability to lower blood glucose, it can increase the danger of hypoglycemia. (12 ).

Conclusion

Berberine and its derivatives have comprehensive pharmacological actions. In this evaluation, their anti-tumor effects and underlying mechanisms were systemically detailed based on systems pharmacology. This review also revealed the effectiveness and potential mechanism of action of berberine and its derivatives when used in the treatment of complex cancers at the molecular, cellular, and organism levels. Furthermore, several signaling paths were also detailed. However, there are restrictions in the research study of berberine, as its anti-tumor system has yet to be totally illuminated. More significantly, there have actually only been a few in vivo and pre-clinical studies assessing berberine. However, extensive examinations on the efficacy of berberine and its derivatives are continuous, and a growing number of research studies have actually begun focusing on the possible anti-tumor role of berberine, perhaps moderated through immune policy. The capability of berberine to increase chemosensitivity and lower the negative effects of chemosensitizers has actually likewise been stressed. Berberine and its derivatives may be promising drugs in cancer therapy, perhaps enhancing medical effectiveness and security. (13 ).

Referrals

  1. Https://en.wikipedia.org/wiki/berberine
  2. Https://www.webmd.com/vitamins/ai/ingredientmono-1126/berberine
  3. Https://www.acs.org/content/acs/en/molecule-of-the-week/archive/b/berberine.html#:~:text=berberine%20is%20a%20cationic%20alkaloid,many%20other%20plants%2c%20including%20berberisspp.
  4. Https://www.sciencedirect.com/science/article/pii/s2211383512000871#:~:text=berberine%20is%20known%20as%20an,as%20an%20%ce%b1%2dglucosidase%20inhibitor.
  5. Https://www.healthline.com/nutrition/berberine-powerful-supplement#toc_title_hdr_4
  6. Https://www.pharmaca.com/projectwellness/a-quick-guide-to-berberine/
  7. Https://www.verywellhealth.com/pcos-and-berberine-4136324#:~:text=berberine%20can%20offer%20numerous%20benefits,complications%20associated%20with%20the%20condition.
  8. Https://www.wellandgood.com/benefits-of-berberine/
  9. Https://www.medicalnewstoday.com/articles/325798#side-effects
  10. Https://ostrovit.com/en/blog/berberine-use-dosage-and-effects-1619512157.html?lang=eng
  11. Https://www.rxlist.com/berberine/supplements.htm#interactions
  12. Https://www.medicoverhospitals.in/medicine/berberine#:~:text=before%20taking%20berberine%2c%20talk%20with,reactions%20and%20other%20serious%20problems.
  13. Https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/full
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