Metformin or Berberine - For what conditions?

Part of me wants to to try out Berberine supplementation as Eliot made mention of it on one his videos where he talks about combatting excessive bile causing diarrhea. I was searching online and found this herbal antibiotic pop up a few times for remedying SIBO, which is what I reckon I have due to my constant burping.

Is there anybody here who can co-sign the herb for its effectiveness at balancing out the microbiome???
Justy a note that FDA released the following regarding Metformin:

The US Food and Drug Administration (FDA) announced on Thursday that five companies have now voluntarily recalled extended-release metformin drugs because of elevated levels of N-nitrosodimethylamine (NDMA), a potential carcinogen.

The five companies who were notified of the agency’s testing results and who are recalling their extended-release (ER) product, and specific labeling and lots recalled, are:
  • Apotex – all lots
  • Amneal – all lots
  • Marksans, branded as Time-Cap – one lot (XP9004)
  • Lupin – one lot (G901203)
  • Teva, branded as Actavis – 14 lots
While researching the many supplements I have started taking over these past few months I found this study published in early 2015:
I can't say I understand everything but berberine appears to help against skin disorders, like pigmentation disorders and "significantly inhibits melanogenesis in in B16F10 melanoma cells".


Berberine, an isoquinoline alkaloid, has a wide range of beneficial properties, including anti‑bacterial, anti‑inflammatory, anti‑cancer, and cholesterol‑lowering effects. Recently findings suggest that berberine improves glucose and lipid metabolism disorders. In the present study, we examined the mechanism underlying the inhibitory effect of berberine on α‑melanocyte‑stimulating hormone (α‑MSH)‑stimulated B16F10 melanoma cells. The results showed that berberine attenuated α‑MSH induction of the microphthalmia‑associated transcription factor (MITF) and tyrosinase in a dose‑dependent manner. To elucidate the mechanism underlying the inhibitory effect of berberine, we examined the effect of α‑MSH‑stimulated phosphorylation of PI3K/AKT, ERK, and GSK3β. The results showed that treatment with berberine resulted in a reduction in the phosphorylation of PI3K/AKT, ERK, and GSK3β. Taken together, the results suggested that berberine inhibits melanin synthesis and tyrosinase activity by downregulating the expression of MITF and tyrosinase. Thus, these findings may contribute to the potential application of berberine in the prevention and treatment of skin pigmentation disorders.
Found some new studies on berberine for those interested.
The first suggests berberine might be a helpful addition for those with arterial plaque/atherosclerosis:


Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR’s metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P < 0.05, n = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (*P < 0.05; *P < 0.05), and 37 and 35% in plasma (***P < 0.001; *P < 0.05), after 4 months on BBR. BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins.

That it interacts with the gut microbiota is interesting, further on this:


Berberine (BBR), an isoquinoline alkaloid, has been found in many plants, such as Coptis chinensis Franch and Phellodendron chinense Schneid. Although BBR has a wide spectrum of pharmacological effects, its oral bioavailability is extremely low. In recent years, gut microbiota has emerged as a cynosure to understand the mechanisms of action of herbal compounds. Numerous studies have demonstrated that due to its low bioavailability, BBR can interact with the gut microbiota, thereby exhibiting altered pharmacological effects. However, no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects. Here, we describe the direct interactive relationships between BBR and gut microbiota, including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota. In addition, the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed. Furthermore, we provide our viewpoint on future research directions regarding BBR and gut microbiota. This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.
From memory, gut microbiota can change insulin responses among many other things.

For a more comprehensive up to date dive on some of the well documented studies on berberines different uses, there is also the following:


Berberine is a quaternary ammonium salt and naturally occurring benzylisoquinoline alkaloid, present in numerous medicinal herbs’ roots and stem bark as an active constituent, especially in the genus Berberis. It contains many pharmacological properties such as antioxidant, antiviral, antidiabetic, antidepressant, antidiarrheal, antibacterial any many more. Since nature is the best healer, it has been traditionally used in Ayurvedic and Chinese medicine to mitigate several disease conditions. Besides the beneficial effects of berberine, some drawbacks such as its poor aqueous solubility and low oral bioavailability hinder its applications. Although it has been used for dietary supplements, despite its vast potential to evolve as a drug candidate, there are no approved pure berberine formulations available in market for any particular disease. Therefore, this review provides an overview to the reader by incorporating recent studies on berberine's sources, extraction techniques, chemistry, different Nano carriers and bioavailability enhancers for enhancing bioavailability, versatile applications, toxicological aspects and recent patents along with future perspectives. The accumulated evidence may broaden the horizon of drug designers, scientists, academicians, and researchers on berberine and help design and develop effective berberine formulations on a large scale for treating several diseases.
Although the above focuses on making it more bio-available, we can see from the other papers berberines effects appear to partially be because of it's poor bio-availability.
More on berberine (or barberry as called in my book Prescription for Herbal Healing by Phyllis A. Belch).

Benefits of barberry for specific health conditions include the following:
Cuts, scrapes, and abrasions; infections of the bladder, eyes, nails, reproductive tract, sinuses, skin, throat, and parasitic infection. In cell studies, berberine (a compound in barberry) kills a vast variety of germs - among them the parasites Leishmania and Plasmodium (the organism that causes malaria); Pseudomonas, Salmonella, Shigella, Staphylococcus, Streptococcus, and Vibrio bacteria; and various kinds of fungi - and is very active against a number of others. Some laboratory tests have found that berberine is a more potent antibiotic than the sulfa drugs against some kinds of infections. Berberine also is effective against come bacteria that have become antibiotic-resistant. But human data are unavailable to support its use in such cases. [the book was published in 2012].

Diarrhea. One study found that individuals suffering from cholera-induced diarrhea experienced significant relief from acute diarrhea after twenty-four hours with a dosage of 100 milligrams of barberry four times a day. [...]

Gastritis and peptic ulcers. Berberine kills Helicobacter pylori, a bacterium implicated in both ulcers and chronic gastritis. Animal studies have shown that the compounds in barberry can reduce muscle spasms, which might further explain their usefulness in gastrointestinal disorders. Alcohol extracts of barberry may help with heartburn and stomach cramps.

Here is another interesting article about berberine, it doesn't mention bio-availability, but it does say that berberine tinctures could be more effective and berberine in combination with alpha-lipoic acid and milk thistle could enhance its health benefits. Plus, according to an earlier post in this thread there is no problem with bio-availability.

There are many references to (non-Western?) studies.

  • About Berberine​

    Definition of Berberine:​

    Goldenseal, Oregon grape, and Chinese goldthread are just a few of the plants that contain the alkaloid Berberine. Traditional medicine has relied on its bright yellow hue and antibacterial, anti-inflammatory, and antioxidant capabilities for generations. Berberine has been the subject of numerous studies, and research (Han et al., 2021), has shown that it may have potential therapeutic uses for a variety of conditions, including type 2 diabetes, high cholesterol, and inflammation.

    Natural Sources of Berberine:​

    Berberine can be present in various plant species, including Berberis vulgaris (barberry), Berberis aristata (tree turmeric), Hydrastis canadensis (goldenseal), and Coptis chinensis (Chinese goldthread). Berberine is also present in various traditional medicinal herbs used in Ayurveda and Chinese medicine, such as Phellodendron amurense and Cortex Phellodendri (Vuddanda et al., 2010).

    Historical Uses Of Berberine In Traditional Medicine​

    Traditional Chinese medicine, Ayurvedic medicine, and Native American medicine have all employed Berberine for ages.
    According to a study (Cicero & Baggioni, 2016), Traditional medicine has employed Berberine to treat a wide range of conditions, such as digestive issues, lung infections, diarrhea, and dysentery. Berberine has been used to treat diabetes, excessive cholesterol, and hypertension in Chinese medicine. As a result of Berberine’s demonstrated hypoglycemic effects, blood sugar levels may be lowered. It has also been demonstrated to have lipid-lowering properties, indicating that it has the ability to decrease cholesterol. Moreover, berberine has been used to treat gastroenteritis brought on by bacteria.
    Another study published in Toxins (Och et al., 2020), found that, the biological effects of Berberine are diverse, and they include anti-inflammatory, antioxidant, and antibacterial characteristics. In Ayurveda medicine, Berberine has been used to alleviate inflammation and bacterial infections. By lowering inflammatory cytokine levels, Berberine has been proven to have anti-inflammatory benefits. Furthermore demonstrated to possess antioxidant effects, Berberine helps defend against oxidative damage.
    In Native American medicine, Berberine has been used as a general tonic to support overall health and wellbeing. A study published in Pharmacognosy Magazine (Wintola & Afolayan, 2011), found that Berberine has antioxidant properties, which can help to protect against oxidative stress. An imbalance between free radicals and antioxidants causes oxidative stress, which affects the body. Berberine has been shown to have a high level of antioxidant activity, which can help to protect against oxidative stress.
    Berberine has a lengthy history of use in traditional medicine, to sum up. It has been used to treat a number of illnesses, such as digestive issues, respiratory infections, diarrhea, and dysentery. Furthermore, diabetes, excessive cholesterol, and hypertension have all been treated using Berberine. It is a promising natural therapy for a number of medical disorders due to its wide range of biological activities, which include anti-inflammatory, antioxidant, and antibacterial characteristics.
  • Biological Effects of Berberine​

    Berberine’s Effects on Glucose Metabolism and Insulin Sensitivity​

    Berberine has been shown to have numerous health benefits, including improving glucose metabolism and insulin sensitivity.
    Berberine’s effects on glucose metabolism and insulin sensitivity have been studied extensively, both in animals and humans. Berberine significantly reduced fasting blood glucose, HbA1c, and insulin resistance in persons with type 2 diabetes, according to a comprehensive review and meta-analysis of 14 randomized controlled trials including 1068 participants (Dong et al., 2012).
    The enzyme AMP-activated protein kinase (AMPK), which controls glucose and lipid metabolism, is turned on by Berberine, supporting its function in metabolic regulation. (Lee et al., 2006). Activating AMPK can increase glucose uptake in muscle cells and improve insulin sensitivity (Hawley et al., 2010).
    Anti-inflammatory, antioxidant, and lipid-lowering properties, in addition to its effects on glucose metabolism and insulin sensitivity, have been demonstrated for Berberine (Imenshahidi & Hosseinzadeh, 2019). However, more research is needed to verify Berberine’s long-term safety and effectiveness in humans.

    Berberine’s Effects on Lipid Metabolism and Blood Lipid Levels​

    In recent years, researchers have become interested in the potential of Berberine to improve lipid metabolism and lower blood lipid levels.
    According to research, Berberine has been found to have positive impacts on lipid metabolism. One particular study discovered that Berberine could enhance the function of AMP-activated protein kinase (AMPK), which is an enzyme that is essential in controlling lipid metabolism in the liver and other parts of the body (Lee et al., 2006). As a result of the enhanced AMPK activity induced by Berberine, there could be an increase in the process of fat oxidation and a reduction in the production of lipids. This effect can potentially lead to an improvement in lipid metabolism and a decrease in the buildup of fat in the liver.
    Aside from its impact on AMPK, Berberine has demonstrated its ability to lower the expression of specific genes associated with lipid synthesis in the liver. These genes include fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) (Zhang et al., 2008). This can contribute to the reduction of lipid production in the liver, leading to potential enhancements in lipid metabolism.
    Numerous studies have explored the impacts of Berberine on blood lipid levels. An analysis that combined data from 11 randomized controlled trials discovered that the use of Berberine resulted in notable decreases in total cholesterol, triglycerides, and LDL cholesterol levels, while also leading to an elevation in HDL cholesterol levels (Ju et al., 2018). Additional research has indicated that Berberine can enhance lipid metabolism and decrease blood lipid levels among individuals diagnosed with nonalcoholic fatty liver disease (NAFLD) (Yan et al., 2015) (Y. Wang et al., 2017).
    The results of these studies highlight the promising potential of Berberine as a natural means to enhance lipid metabolism and lower blood lipid levels. Nevertheless, additional research is necessary to fully comprehend the mechanisms behind Berberine’s actions and to establish the most effective dosages and treatment schedules suitable for various patient groups.

    Berberine’s Effects on Inflammation and Oxidative Stress​

    The pharmacological properties of Berberine are diverse, with documented anti-inflammatory and antioxidant effects. To understand the means by which Berberine generates these effects, a number of investigations have been conducted.
    The process of inflammation is multifaceted, involving the stimulation of immune cells and the discharge of diverse inflammatory agents. Research indicates that Berberine can curb the activation of multiple inflammatory signaling pathways, such as NF-κB, MAPK, and NLRP3 inflammasome, resulting in diminished output of inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) (Jeong et al., 2009) (Zhang et al., 2011).
    Additionally, Berberine has been demonstrated to have a safeguarding impact on oxidative stress, which occurs due to the disproportionality between the generation of reactive oxygen species (ROS) and the body’s inherent antioxidant defenses. Research suggests that Berberine can heighten the effectiveness of antioxidant enzymes such as superoxide dismutase (SOD) and catalase, while concurrently curbing the generation of ROS in diverse cellular types (Y. Z. Wu et al., 2019) (Zhang et al., 2014).
    A randomized controlled trial that involved patients diagnosed with type 2 diabetes indicated that taking Berberine supplements resulted in decreased inflammation markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), and improved antioxidant status, which was evident by a decline in malondialdehyde (MDA) levels and an increase in superoxide dismutase (SOD) activity (Geng et al., 2016).
    A study Involving rats demonstrated that administering Berberine reduced the levels of inflammatory cytokines such as TNF-α and IL-1β, and augmented the activity of antioxidant enzymes such as SOD and glutathione peroxidase (GPx) in liver tissue (Yang et al., 2019).
    Based on the results of these studies, it can be inferred that Berberine can potentially serve as a therapeutic agent for the prevention and management of inflammatory and oxidative stress-related ailments, owing to its anti-inflammatory and antioxidant characteristics.

    Berberine’s Potential For Promoting Weight Loss​

    Berberine has recently gained attention in Western medicine for its potential to improve various aspects of metabolic health, including blood glucose levels, lipid profiles, and body weight.
    Studies suggest that Berberine may aid weight loss through multiple mechanisms. One such mechanism involves the activation of AMP-activated protein kinase (AMPK), which plays a crucial role in regulating energy metabolism and promoting fat burning. A study conducted about AMPK (Jin et al., 2017), found that Berberine treatment increased the activation of AMPK, which led to increased fat burning and weight loss in obese mice.
    Berberine may also affect gut microbiota, which has been linked to weight regulation. A study conducted by Zhang (Zhang et al., 2012), found that Berberine treatment altered the composition of gut microbiota in obese mice, resulting in improved glucose tolerance, decreased body weight, and reduced adipose tissue inflammation.
    Furthermore, Berberine may help to reduce inflammation, which is often associated with obesity and metabolic disorders. A study conducted by (Cao et al., 2021), found that Berberine treatment reduced inflammation markers and improved insulin sensitivity in overweight and obese individuals.
    Furthermore, Berberine is believed to enhance insulin sensitivity, a key factor in maintaining healthy blood glucose levels and facilitating weight loss. A study conducted (Yang et al., 2012), found that Berberine treatment can enhance insulin sensitivity and glucose metabolism in individuals with metabolic syndrome.
    Overall, the evidence suggests that Berberine may have potential for promoting weight loss by multiple mechanisms, including activation of AMPK, modulation of gut microbiota, reduction of inflammation, and improvement of insulin sensitivity.
  • Clinical Evidence of Berberine’s Effectiveness​

    Review of Recent Clinical Trials and Studies: Discussion of the Effectiveness of Berberine in Improving Various Health Conditions​

    Berberine has been studied in recent clinical trials and research for its potential to improve various health conditions such as hyperlipidemia, hypertension, metabolic syndrome, and type 2 diabetes.

    Type 2 Diabetes:​

    According to a meta-analysis of 14 randomized controlled trials involving 1068 participants, Berberine was found to have a significant effect on reducing fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels in comparison to placebo or other hypoglycemic agents. The study concluded that Berberine could be an effective and safe option for managing type 2 diabetes (Guo et al., 2021). A randomized controlled trial (RCT) conducted on 116 participants found that the combination of Berberine with lifestyle modifications was more effective than lifestyle modifications alone in improving glycemic control and lipid metabolism (Dong et al., 2012).


    A review of 11 randomized controlled trials with 874 participants found that Berberine resulted in a significant decrease in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and an increase in high-density lipoprotein cholesterol levels, compared to placebo or other lipid-lowering agents. The study concluded that Berberine could be an effective and safe option for managing hyperlipidemia (Guo et al., 2021).


    A review and meta-analysis of nine randomized controlled trials involving 1065 participants demonstrated that Berberine was effective in lowering systolic and diastolic blood pressure when compared to placebo or other antihypertensive medications. The study concluded that Berberine could be an effective and safe option for managing hypertension (Lan et al., 2015).

    Metabolic Syndrome:​

    One randomized controlled trial with 97 participants revealed that Berberine significantly enhanced lipid metabolism, inflammation, and insulin resistance in patients diagnosed with metabolic syndrome. Meanwhile, another randomized controlled trial with 48 participants showed that Berberine improved insulin resistance and liver function in patients with non-alcoholic fatty liver disease(NAFLD) (Och et al., 2022).
    In addition to the above health conditions, Berberine has also shown potential in improving cognitive function and reducing inflammation (Li Zhao, 2017). More research is required to validate these results.
    The studies discussed above indicate that Berberine may be a potential option for the management of health conditions such as type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. Additionally, the studies suggest that Berberine has good safety and tolerability profile, but it is noteworthy that some studies have reported gastrointestinal adverse effects, such as diarrhea, constipation, and nausea. Nevertheless, further research is necessary to validate these findings and establish the long-term safety and efficacy of Berberine as a therapeutic agent (Lin et al., 2020).
  • Safety and Side Effects of Berberine​

    Possible Side Effects of Berberine​

    Although Berberine is generally regarded as safe, it is essential to be aware of potential side effects, which may include:
    • Gastrointestinal Distress: Berberine is generally considered safe, but it can cause gastrointestinal discomfort in some individuals. Nausea, vomiting, diarrhea, and constipation are some of the reported side effects. A study on rats with hypertriglyceridemia showed that Berberine can alter the gut microbiota and increase the levels of short-chain fatty acids, which may cause gastrointestinal distress in some people (Li et al., 2014).
    • Interaction with Medications: Berberine has been found to interact with several medications, including antibiotics, antihistamines, and blood pressure medications. It can increase the effects of these medications or reduce their effectiveness, which can be harmful to your health. It is important to talk to your doctor before taking Berberine if you are currently taking any medications (Han et al., 2021).
    • Lowered Blood Pressure: Berberine may cause a decrease in blood pressure. A study conducted on rats found that when Berberine was combined with simvastatin, a cholesterol-lowering drug, it enhanced the drug’s ability to lower blood pressure (Shi-Jun Yue, 2019). While using Berberine, it is crucial to keep track of your blood pressure, particularly if you are taking any medication for hypertension.
    • Neurological Effects: Studies have indicated that Berberine may have therapeutic potential for treating central nervous system disorders like Alzheimer’s and Parkinson’s disease. However, high doses of Berberine have been found to cause cognitive impairment and neuronal damage in rats (L. Wu et al., 2019). Additional studies are required to establish the appropriate and safe dosages of Berberine that can be used for the treatment of neurological conditions.
    • Hypoglycemia: Berberine has the potential to lower blood sugar levels, which can cause hypoglycemia in individuals with type 2 diabetes, particularly if they are taking other medications to control their blood sugar. It is crucial to monitor blood sugar levels frequently while taking Berberine (Kong et al., 2008).
    • In conclusion, while Berberine has many potential health benefits, it is important to be aware of the possible side effects. If you are considering taking Berberine, it is important to talk to your doctor to determine if it is right for you and to monitor your health closely while taking it.
    • Discussion of interactions With Other Medications And Health Conditions
    In recent years, Berberine has gained attention for its potential benefits in managing various health (Wang et al., 2018)conditions. However, as with any supplement or medication, it is important to understand how Berberine may interact with other medications and health conditions.

    Interactions with Medications:​

    Berberine has been shown to interact with several medications, including antibiotics, blood thinners, and medications for diabetes and high blood pressure.
    • Antibiotics: Berberine has been shown to enhance the effects of certain antibiotics, including tetracycline and ciprofloxacin. This may be due to Berberine’s ability to increase the permeability of bacterial cell membranes, allowing antibiotics to more easily penetrate and kill the bacteria (Sadeghnia et al., 2017).
    • Blood thinners: Berberine may increase the effects of blood thinners, such as warfarin and aspirin, leading to an increased risk of bleeding. Patients taking these medications should consult with their healthcare provider before taking Berberine (Pérez-Rubio et al., 2013) (X. Wang et al., 2017).
    • Medications for diabetes: Berberine has demonstrated potential in improving glucose metabolism and insulin sensitivity, making it a promising option for treating diabetes. However, caution should be taken when using Berberine with other diabetes medications like metformin, as it may increase the risk of hypoglycemia(low blood sugar) (Wang et al., 2018).
    • Medications for high blood pressure: There is a possibility that Berberine may interact with medications that are commonly used to manage hypertension, such as calcium channel blockers and beta-blockers. Berberine has been shown to have a hypotensive effect, which may exacerbate the effects of these medications (Suadoni & Atherton, 2021).
    • Interactions With Health Conditions:​

    Berberine has been shown to have potential benefits for several health conditions, but it may also interact with certain conditions.
    • Liver disease: Berberine has been shown to have hepatoprotective effects, meaning it may protect the liver from damage (Liu et al., 2013). However, patients with liver disease should consult with their healthcare provider before taking Berberine, as it may interact with certain medications used to treat liver disease.
    • Pregnancy: There is limited research on the safety of Berberine during pregnancy. One study in rats found that high doses of Berberine during pregnancy led to fetal abnormalities, but more research is needed to determine the safety of Berberine during human pregnancy (Jahnke et al., 2006).
    • Importance of Consulting a Healthcare Provider Before Taking Berberine​

    Recently, Berberine has gained increasing popularity in Western countries due to its potential health benefits. However, it is crucial to consult with a healthcare provider before taking Berberine. This article will delve into the significance of seeking medical advice before using Berberine.

    Potential Side Effects​

    Although Berberine is considered safe for most people, it can cause side effects, especially when taken in high doses or for extended periods. Diarrhea, constipation, stomach cramps, and nausea are among the most frequently reported side effects of Berberine (Alolga et al., 2016) Berberine can potentially interact with some medications, such as anticoagulants and antihypertensive drugs. Therefore, it is essential to consult a healthcare provider to evaluate any potential risks and interactions.

    Medical Conditions​

    Berberine may have potential benefits for several medical conditions, but it is important to determine whether it is appropriate for individual health conditions. For example, Berberine has the potential to lower blood sugar levels, which could be advantageous for individuals with diabetes. However, it can also interact with diabetes medications, and people with low blood sugar or hypoglycemia should not take Berberine. Similarly, Berberine may interact with medications used to treat mental health conditions or liver diseases. Consulting a healthcare provider can help identify any potential risks.

    Dosage and Safety​

    Berberine supplements are available over the counter, and the dosage can vary significantly between products. The recommended dose is typically 500 mg to 1500 mg per day, divided into two or three doses. However, the optimal dose may vary depending on individual factors such as age, weight, and medical history. Consulting a healthcare provider can help determine the correct dose and ensure it is safe for individual use.

    Quality Control​

    The quality of Berberine supplements can vary significantly between products, and some may contain harmful contaminants or inadequate amounts of active ingredients. Therefore, it is essential to choose a reputable brand and consult a healthcare provider to ensure the product is safe and effective.
    In conclusion, Berberine has potential health benefits, but It is crucial to seek advice from a healthcare professional before considering it’s use. A healthcare provider can evaluate individual risks, interactions, and optimal dosage, and ensure that the product is safe and effective. It is crucial to remember that Berberine supplements are not a substitute for medical treatment, and individuals should always follow the advice of their healthcare provider.
  • Applications of Berberine in Health and Wellness​

    Discussion of the potential of Berberine as a natural remedy for various health conditions​

    The potential of Berberine to lower blood sugar levels in individuals with type 2 diabetes is one of the most extensively studied areas. In a study (Zhang et al., 2008), researchers found that Berberine was found to be equally effective as metformin, a drug commonly used to treat type 2 diabetes, in reducing blood sugar levels in individuals with the condition. Berberine appears to work by increasing insulin sensitivity and promoting the uptake of glucose into cells. Berberine’s ability to activate AMP-activated protein kinase (AMPK), an enzyme that regulates metabolism, may be responsible for its ability to lower blood sugar levels.
    Berberine has also been shown to have potential as a natural remedy for cardiovascular disease. In a 2019 study (Cao & Su, 2019), researchers found that Berberine supplementation significantly reduced the levels of LDL cholesterol, total cholesterol, and triglycerides in people with metabolic syndrome while increasing the levels of HDL cholesterol. Metabolic syndrome is a combination of risk factors that can lead to diabetes, heart disease, and stroke.
    Apart from its potential for diabetes and cardiovascular disease, Berberine has been researched for its potential as a natural remedy for other health conditions. For instance, a study was conducted on mood disorders (Fan et al., 2019), found that Berberine may have potential as a natural remedy for depression, due to its ability to modulate the levels of certain neurotransmitters in the brain. Berberine has also been shown to have antimicrobial properties, and may be effective against a variety of bacterial, viral, and fungal infections.

    Overview of different forms of Berberine Supplementation​

    Berberine has become a popular dietary supplement because of its potential health benefits. Different forms of Berberine supplementation are:

    Berberine Capsules​

    Berberine capsules are the most common form of Berberine supplementation. These capsules typically contain 500 mg of Berberine, and the recommended dosage is two capsules per day. Berberine capsules are convenient to use and are widely available online and in health food stores. However, Taking Berberine capsules may lead to gastrointestinal side effects, including but not limited to diarrhea, constipation, and abdominal pain.

    Berberine Powder​

    Berberine powder is another form of Berberine supplementation. This form of Berberine is usually sold in bulk and can be mixed with water or juice. Berberine powder may be more convenient for people who have difficulty swallowing capsules. However, Berberine powder has a bitter taste and may cause stomach upset if taken on an empty stomach.

    Berberine Tincture​

    Berberine tincture is an alcohol-based liquid extract of Berberine. This form of Berberine supplementation is typically used in herbal medicine and may not be as widely available as capsules or powder. Berberine tincture may be more effective than capsules or powder as the alcohol in the tincture may increase the absorption of Berberine. However, Berberine tincture may not be suitable for people who are sensitive to alcohol.

    Berberine Combined With Other Supplements​

    Berberine is often combined with other supplements, such as milk thistle or alpha-lipoic acid, to enhance its health benefits. These combination supplements may be more effective than Berberine alone, but more research is needed to determine their effectiveness. Additionally, combination supplements may be more expensive than Berberine alone.
  • Berberine’s Potential For Promoting Overall Health And Wellness​

    One of the primary benefits of Berberine is its ability to help regulate blood sugar levels. A study on randomized control trials (Li Wang, 2021), found that in individuals with type 2 diabetes, Berberine has been shown to lower blood glucose levels to a degree similar to that of metformin, a commonly prescribed medication for diabetes. Another study published in Experimental and Therapeutic medicine (Cao & Su, 2019), found that Berberine was effective in reducing insulin resistance and improving insulin sensitivity in overweight individuals with metabolic syndrome.
    Berberine may also have a positive impact on cardiovascular health. A study published in 2004 (Kong et al., 2004), found that in individuals with high cholesterol, Berberine was found to decrease total cholesterol levels and triglycerides. Another study published in the Journal of Medicinal Food (Alexander Bertuccioli, 2020), found that Berberine has been shown to effectively lower both total cholesterol and LDL cholesterol levels.
    In addition to its effects on blood sugar and cholesterol levels, Berberine may also have anti-inflammatory and antimicrobial properties. A study published in 2022 (Chen et al., 2022), found that Berberine was observed to decrease inflammation in rats that were suffering from acute lung injury. Another study published in 2015 (Peng et al., 2015), found that Berberine was effective in inhibiting the growth of several bacterial and fungal strains.
  • Conclusion​

  1. Summary of the Potential Benefits of Berberine​

    Berberine is a natural substance found in certain plants such as goldenseal, barberry, and Oregon grape, that has shown promise in providing several health benefits. One of its potential benefits is its ability to improve insulin sensitivity, which can result in the lowering of blood sugar levels in individuals with type 2 diabetes.
    • Reducing inflammation: Berberine has anti-inflammatory properties that may help reduce inflammation in the body.
    • Lowering cholesterol levels: Berberine has the ability to lower total cholesterol levels, as well as LDL (“bad”) cholesterol and triglycerides.
    • Improving heart health: Berberine may have a protective effect on the heart, potentially reducing the risk of heart disease.
    • Supporting weight loss: Berberine can help with weight loss by boosting metabolism and reducing fat accumulation.
    • Supporting gut health: Berberine has been shown to have antimicrobial properties that can help treat various gut infections, including diarrhea and small intestine bacterial overgrowth (SIBO).
    • Supporting brain health: Berberine may help improve cognitive function and reduce the risk of neurodegenerative diseases like Alzheimer’s.
    • Future Research Directions And Potential Applications Of Berberine In Improving Health And Wellness​

    • Metabolic Disorders: Berberine has demonstrated promise in improving glucose and lipid metabolism and has potential in managing metabolic conditions such as obesity, metabolic syndrome, and type 2 diabetes. Further studies could investigate the mechanisms underlying Berberine’s effects and evaluate the safety and effectiveness of long-term Berberine use in humans.
    • Cardiovascular Health: Berberine exhibits potential in lowering blood pressure and cholesterol levels, which can contribute to the prevention of cardiovascular diseases. Further research could examine the potential of Berberine in enhancing heart health by investigating its impact on blood vessel function, heart muscle health, and protection against heart attacks and strokes.
    • Gut Health: Studies have shown that Berberine possesses antimicrobial properties and may help maintain a healthy gut microbiome. Further research could explore its potential in treating gastrointestinal conditions such as inflammatory bowel disease and irritable bowel syndrome, as well as its overall impact on gut health.
    • Cancer Prevention: Research has suggested that Berberine has anti-cancer properties and has the potential to inhibit the growth and metastasis of cancer cells. Future studies could delve into the mechanisms by which Berberine accomplishes this and its viability as an adjuvant therapy for cancer treatment.
    • Brain Health: Research has suggested that Berberine has the potential to enhance cognitive function and prevent neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Further studies could be conducted to investigate the specific mechanisms through which Berberine influences brain function and to explore its potential as a treatment for various brain-related conditions.
I've taken berberine on and off and I wanted to mention that I think it does lower the blood pressure, not only long-term but almost immediately.

I have congenial low blood pressure and I noticed that when I take berberine I feel a bit dizzy afterwards because it seems that my blood pressure drops a bit. It isn't super serious, at least not for me, but I don't take it anymore because of that.

This doesn't mean that it is bad. I know I get this effect even when I drink green and black tea, which are known for lowering blood pressure, and I think is has to do with the fact that I live in high altitude (because green tea didn't have that effect when I lived in a lower altitude).

I guess what it means is that berberine really works ;-D and perhaps only those who are on the low blood pressure side can be just a bit cautious and keep track of that effect.
I've taken berberine on and off and I wanted to mention that I think it does lower the blood pressure, not only long-term but almost immediately.

I have congenial low blood pressure and I noticed that when I take berberine I feel a bit dizzy afterwards because it seems that my blood pressure drops a bit. It isn't super serious, at least not for me, but I don't take it anymore because of that.

This doesn't mean that it is bad. I know I get this effect even when I drink green and black tea, which are known for lowering blood pressure, and I think is has to do with the fact that I live in high altitude (because green tea didn't have that effect when I lived in a lower altitude).

I guess what it means is that berberine really works ;-D and perhaps only those who are on the low blood pressure side can be just a bit cautious and keep track of that effect.
fwiw I use to respond in the same way. Can't nail down what fixed it exactly - but I do know I still get 'low blood pressure' if my guts are inflamed. So something to calm them (bentonite/zeolite) and lower cortisol in the evening helps.
Getting enough salt/potassium, time restricted eating (because my 'blood pressure' could drop without 'sugar' fuelling me, see the last part on my nervous system/stress response) - eating in mornings and not afternoons, and exercise (weights/strength training). A balance between an over excitable/easily stressed nervous system and things that could stress it out (such as exercise and fasting) + plenty of B1. B1 being crucial.
It's likely the change in blood sugar caused by berberine wasn't compatible with a nervous system/body stuck in flight/stress mode (the inflamed guts being one side effect). The result being 'low blood pressure' rather than adaptation.

I put 'low blood pressure' in quotes, as low blood pressure and low blood sugar (and not being in ketosis) have the same symptoms for me from observation.
Dihydroberberine sounds to be a better option regarding side effects and has slow release effects on the body, possibly making it more tolerable.

Berberine and Its More Biologically Available Derivative, Dihydroberberine, Inhibit Mitochondrial Respiratory Complex I: A Mechanism for the Action of Berberine to Activate AMP-Activated Protein Kinase and Improve Insulin Action​

OBJECTIVE—Berberine (BBR) activates AMP-activated protein kinase (AMPK) and improves insulin sensitivity in rodent models of insulin resistance. We investigated the mechanism of activation of AMPK by BBR and explored whether derivatization of BBR could improve its in vivo efficacy.

RESEARCH DESIGN AND METHODS—AMPK phosphorylation was examined in L6 myotubes and LKB1−/−cells, with or without the Ca2+/calmodulin-dependent protein kinase kinase (CAMKK) inhibitor STO-609. Oxygen consumption was measured in L6 myotubes and isolated muscle mitochondria. The effect of a BBR derivative, dihydroberberine (dhBBR), on adiposity and glucose metabolism was examined in rodents fed a high-fat diet.

RESULTS—We have made the following novel observations: 1) BBR dose-dependently inhibited respiration in L6 myotubes and muscle mitochondria, through a specific effect on respiratory complex I, similar to that observed with metformin and rosiglitazone; 2) activation of AMPK by BBR did not rely on the activity of either LKB1 or CAMKKβ, consistent with major regulation at the level of the AMPK phosphatase; and 3) a novel BBR derivative, dhBBR, was identified that displayed improved in vivo efficacy in terms of counteracting increased adiposity, tissue triglyceride accumulation, and insulin resistance in high-fat–fed rodents. This effect is likely due to enhanced oral bioavailability.

CONCLUSIONS—Complex I of the respiratory chain represents a major target for compounds that improve whole-body insulin sensitivity through increased AMPK activity. The identification of a novel derivative of BBR with improved in vivo efficacy highlights the potential importance of BBR as a novel therapy for the treatment of type 2 diabetes.

Insulin resistance is a major metabolic abnormality leading to type 2 diabetes, and, as such, there is considerable interest in the discovery of insulin-sensitizing agents to aid in the treatment of this disease. AMP-activated protein kinase (AMPK), a heterotrimeric protein that plays a key role in regulation of whole-body energy homeostasis, is one attractive drug target. Two classes of commonly used insulin-sensitizing drugs, thiazolidinediones and biguanides, exert their beneficial effects, at least in part, by activating AMPK (1,2).
Natural products have been a rich resource for the development of novel therapeutics used to treat a variety of human diseases. We have recently reported that berberine (BBR) displays insulin-sensitizing properties in rodent models of insulin resistance and diabetes (3). BBR is commonly used as a nonprescription oral drug in China to treat gut infections and diarrhea with few side effects, and its therapeutic potential for the treatment of diabetes (4) and dyslipidemia (5) in humans has been reported. These beneficial effects are related in part to the ability of BBR to activate AMPK (3,6,7). Here we show that, similar to metformin and rosiglitazone, BBR activates AMPK via inhibition of respiratory complex I of the mitochondrion.
Despite its potent stimulation of AMPK in cell-based assays, an important issue arising from our previous work (3) is that considerably large oral doses (380–560 mg · kg−1 · day−1) of BBR were required for beneficial metabolic effects in rodents. Aiming to improve its therapeutic efficacy, we designed a number of BBR derivatives and show that one such derivative, dihydroberberine (dhBBR), has markedly improved in vivo efficacy in the treatment of insulin-resistant rodents.
Last edited by a moderator:
I have a particularly sensitive intestine and IBS, how can I take Berberine/Metformin and be sure to minimize the possibility of gastro-intestinal side-effects?
Don't take berberine in powder form for sure. I bought bulk berberine powder and tried that just once. I don't remember how it made my stomach feel because it has a somewhat oily texture and is so bitter that I could still taste it 16 hours later. Thankfully I have a pill machine so I started putting it in pills, but it stains EVERYTHING (it is historically used as dye too).

But I like how well it works so much that I'm considering getting a few acres of land and growing barberry or turmeric to produce it myself.
But I like how well it works so much that I'm considering getting a few acres of land and growing barberry or turmeric to produce it myself.
Nice. You can also make your own tinctures then. :-D

Another article I found about the benefits of berberine for the skin. I looked up dihydroberberine, but couldn't find anything on this site.

It is also used in skincare products like moisturisers, toners and masks.


Summary of the Potential Benefits Of Berberine In Improving Skin Health​

  • Anti-inflammatory properties: Berberine The inflammation and redness of the skin can be diminished by using berberine, which has powerful anti-inflammatory qualities. Anti-inflammatory and immune-modulatory effects of berberine on autoreactive T cell activation in autoimmune inflammation were reported in a study published in 2020 (Ehteshamfar et al., 2020).
  • Antioxidant properties: The skin can be protected from the oxidative stress induced by free radicals thanks to berberine’s potent antioxidant effects. Berberine has antioxidant effects, according to a 2014 study. (Li et al., 2014).
  • Anti-microbial properties: Because of its broad-spectrum antibacterial characteristics, berberine can be used to treat and prevent bacterial, fungal, and viral skin infections. The growth of numerous different bacteria, including Staphylococcus aureus and Escherichia coli, was found to be prevented by berberine in a study published in 2005 (Yu et al., 2005).
  • Wound healing properties: Berberine has been found to promote wound healing by stimulating the proliferation of skin cells and increasing the production of collagen. A study published in 2021 found that berberine enhanced the migration of human keratinocytes and fibroblasts, which are essential for wound healing (Zhou et al., 2021).
  • Acne treatment: By decreasing sebum production and blocking the growth of Propionibacterium acnes, a bacterium linked to acne, berberine has been shown to be an effective treatment. A study published in 2020 found that berberine reduced sebum production in human sebocytes and inhibited the growth of Propionibacterium acnes (Niu et al., 2020).

Future Research Directions and Potential Applications of Berberine in Skincare​

Anti-inflammatory Properties​

Acne, rosacea, and eczema are just some of the skin problems that can be triggered by inflammation, which is also a major factor in the aging process. The inflammation caused by these diseases can be alleviated with the use of berberine’s powerful anti-inflammatory capabilities.
Inflammatory cytokines like TNF- and IL-6 are known to contribute to the development of inflammatory skin disorders; one study found that berberine can effectively suppress their production (Ma et al., 2020). In addition, a different study discovered that berberine can suppress skin inflammation by blocking the NF-B signaling pathway (Naz et al., 2022).

Antimicrobial Properties​

Berberine has also been found to exhibit potent antimicrobial properties, making it effective against a range of bacterial, fungal, and viral infections that can affect the skin. For example, berberine has been found to be effective against various strains of acne-causing bacteria, including Propionibacterium acnes (Peng et al., 2015).
Furthermore, berberine has been found to exhibit antifungal properties and can effectively treat various fungal infections that affect the skin, including athlete’s foot and ringworm (da Silva et al., 2016). Additionally, berberine has been found to have antiviral properties, making it effective against viral skin infections like herpes simplex virus (HSV) (Warowicka et al., 2020).

Anti-aging Properties​

The anti-aging benefits of berberine have been studied extensively, and the results show that it can reduce the appearance of fine lines, wrinkles, and age spots. The skin’s suppleness is increased and fine lines and wrinkles are diminished because to berberine’s ability to stimulate collagen formation (Ai et al., 2021).
In addition to its anti-wrinkle effects, berberine has been shown to reduce the production of enzymes that damage collagen in the skin (Ai et al., 2015). Additionally, It has also been discovered that berberine contains antioxidant qualities, which can help prevent skin damage from free radicals and environmental stresses (Liu et al., 2021).

Future Research Directions​

Further study is needed to completely understand the mechanisms of action of berberine and to find the best concentration and formulation for usage in skincare products, although the prospective applications of berberine in skincare are promising. Investigating the efficacy of berberine against other skin conditions like psoriasis and dermatitis and exploring the potential synergistic effects of combining berberine with other skincare ingredients like vitamin C and retinol are both promising avenues for future study.

  1. Ai, F., Chen, M., Yu, B., Yang, Y., Xu, G., Gui, F., Liu, Z., Bai, X., & Chen, Z. (2015). Berberine regulates proliferation, collagen synthesis and cytokine secretion of cardiac fibroblasts via AMPK-mTOR-p70S6K signaling pathway. Int J Clin Exp Pathol, 8(10), 12509-12516.
  2. Ai, X., Yu, P., Peng, L., Luo, L., Liu, J., Li, S., Lai, X., Luan, F., & Meng, X. (2021). Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases. Front Pharmacol, 12, 762654. Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases
  3. Andoh, T., Yoshihisa, Y., Rehman, M. U., Tabuchi, Y., & Shimizu, T. (2021). Berberine induces anti-atopic dermatitis effects through the downregulation of cutaneous EIF3F and MALT1 in NC/Nga mice with atopy-like dermatitis. Biochem Pharmacol, 185, 114439. Redirecting
  4. Calvo, A., Moreno, E., Aldalur, I., Sanmartín, C., Larrea, E., González-Peñas, E., Irache, J. M., & Espuelas, S. (2022). Effect of topical berberine in murine cutaneous leishmaniasis lesions. J Antimicrob Chemother, 77(4), 1072-1081. Effect of topical berberine in murine cutaneous leishmaniasis lesions
  5. da Silva, A. R., de Andrade Neto, J. B., da Silva, C. R., Campos Rde, S., Costa Silva, R. A., Freitas, D. D., do Nascimento, F. B., de Andrade, L. N., Sampaio, L. S., Grangeiro, T. B., Magalhães, H. I., Cavalcanti, B. C., de Moraes, M. O., & Nobre Júnior, H. V. (2016). Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp. Antimicrob Agents Chemother, 60(6), 3551-3557.
  6. Ehteshamfar, S. M., Akhbari, M., Afshari, J. T., Seyedi, M., Nikfar, B., Shapouri-Moghaddam, A., Ghanbarzadeh, E., & Momtazi-Borojeni, A. A. (2020). Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation. J Cell Mol Med, 24(23), 13573-13588.
  7. Fouladi, R. F. (2012). Aqueous extract of dried fruit of Berberis vulgaris L. in acne vulgaris, a clinical trial. J Diet Suppl, 9(4), 253-261.
  8. Han, S., Yan, R.-B., Guan, S., Fan, W.-J., Chu, H.-C., & Liang, Y.-X. (2021). Current research progress in identifying the mechanism of berberine in pain regulation. Pharmacological Research – Modern Chinese Medicine, 1, 100019. Redirecting
  9. Kim, H. J., Kim, Y. J., & Park, W. (2021). Berberine modulates hyper-inflammation in mouse macrophages stimulated with polyinosinic-polycytidylic acid via calcium-CHOP/STAT pathway. Sci Rep, 11(1), 11298. Berberine modulates hyper-inflammation in mouse macrophages stimulated with polyinosinic-polycytidylic acid via calcium-CHOP/STAT pathway - Scientific Reports
  10. Li, Z., Geng, Y. N., Jiang, J. D., & Kong, W. J. (2014). Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evid Based Complement Alternat Med, 2014, 289264.
  11. Liu, Y., Long, S., Zhang, S., Tan, Y., Wang, T., Wu, Y., Jiang, T., Liu, X., Peng, D., & Liu, Z. (2021). Synthesis and antioxidant activities of berberine 9-O-benzoic acid derivatives. RSC Adv, 11(29), 17611-17621. Synthesis and antioxidant activities of berberine 9-O-benzoic acid derivatives
  12. Ma, J., Chan, C. C., Huang, W. C., & Kuo, M. L. (2020). Berberine Inhibits Pro-inflammatory Cytokine-induced IL-6 and CCL11 Production via Modulation of STAT6 Pathway in Human Bronchial Epithelial Cells. Int J Med Sci, 17(10), 1464-1473. Berberine Inhibits Pro-inflammatory Cytokine-induced IL-6 and CCL11 Production via Modulation of STAT6 Pathway in Human Bronchial Epithelial Cells
  13. More, N. V., Kharat, K. R., & Kharat, A. S. (2017). Berberine from Argemone mexicana L exhibits a broadspectrum antibacterial activity. Acta Biochim Pol, 64(4), 653-660. Berberine from Argemone mexicana L exhibits broadspectrum antibacterial activity | Acta Biochimica Polonica
  14. Naz, I., Masoud, M. S., Chauhdary, Z., Shah, M. A., & Panichayupakaranant, P. (2022). Anti-inflammatory potential of berberine-rich extract via modulation of inflammation biomarkers. J Food Biochem, 46(12), e14389.
  15. Neag, M. A., Mocan, A., Echeverría, J., Pop, R. M., Bocsan, C. I., Crişan, G., & Buzoianu, A. D. (2018). Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacol, 9, 557. Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders
  16. Niu, J., Yuan, M., Chen, C., Wang, L., Tang, Z., Fan, Y., Liu, X., Ma, Y. J., & Gan, Y. (2020). Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improving Skin Permeation and Retention. Int J Nanomedicine, 15, 9987-10005. Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improv | IJN
  17. Och, A., Podgórski, R., & Nowak, R. (2020). Biological Activity of Berberine-A Summary Update. Toxins (Basel), 12(11). Biological Activity of Berberine—A Summary Update
  18. Olleik, H., Yacoub, T., Hoffer, L., Gnansounou, S. M., Benhaiem-Henry, K., Nicoletti, C., Mekhalfi, M., Pique, V., Perrier, J., Hijazi, A., Baydoun, E., Raymond, J., Piccerelle, P., Maresca, M., & Robin, M. (2020). Synthesis and Evaluation of the Antibacterial Activities of 13-Substituted Berberine Derivatives. Antibiotics (Basel), 9(7). Synthesis and Evaluation of the Antibacterial Activities of 13-Substituted Berberine Derivatives
  19. Ozturk, M., Chia, J. E., Hazra, R., Saqib, M., Maine, R. A., Guler, R., Suzuki, H., Mishra, B. B., Brombacher, F., & Parihar, S. P. (2021). Evaluation of Berberine as an Adjunct to TB Treatment. Front Immunol, 12, 656419. Evaluation of Berberine as an Adjunct to TB Treatment
  20. Peng, L., Kang, S., Yin, Z., Jia, R., Song, X., Li, L., Li, Z., Zou, Y., Liang, X., Li, L., He, C., Ye, G., Yin, L., Shi, F., Lv, C., & Jing, B. (2015). Antibacterial activity and mechanism of berberine against Streptococcus agalactiae. Int J Clin Exp Pathol, 8(5), 5217-5223.
  21. Qureshi, M., Qadir, A., Aqil, M., Sultana, Y., Warsi, M. H., Ismail, M. V., & Talegaonkar, S. (2021). Berberine loaded dermal quality by design adapted chemically engineered lipid nano-constructs-gel formulation for the treatment of skin acne. Journal of Drug Delivery Science and Technology, 66, 102805.
  22. Reddi, K. K., Li, H., Li, W., & Tetali, S. D. (2021). Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα. Molecules, 26(16). Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα
  23. Song, Y. C., Lee, Y., Kim, H. M., Hyun, M. Y., Lim, Y. Y., Song, K. Y., & Kim, B. J. (2015). Berberine regulates melanin synthesis by activating PI3K/AKT, ERK and GSK3β in B16F10 melanoma cells. Int J Mol Med, 35(4), 1011-1016. Berberine regulates melanin synthesis by activating PI3K/AKT, ERK and GSK3β in B16F10 melanoma cells
  24. Wang, X., Feng, S., Ding, N., He, Y., Li, C., Li, M., Ding, X., Ding, H., Li, J., Wu, J., & Li, Y. (2018). Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis. Evid Based Complement Alternat Med, 2018, 5164314.
  25. Warowicka, A., Nawrot, R., & Goździcka-Józefiak, A. (2020). Antiviral activity of berberine. Arch Virol, 165(9), 1935-1945.
  26. Wojtyczka, R. D., Dziedzic, A., Kępa, M., Kubina, R., Kabała-Dzik, A., Mularz, T., & Idzik, D. (2014). Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative Staphylococcus strains in vitro. Molecules, 19(5), 6583-6596. Berberine Enhances the Antibacterial Activity of Selected Antibiotics against Coagulase-Negative Staphylococcus Strains in Vitro
  27. Xu, Z., Feng, W., Shen, Q., Yu, N., Yu, K., Wang, S., Chen, Z., Shioda, S., & Guo, Y. (2017). Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation. Aging Dis, 8(6), 760-777. Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation
  28. Xu, Z., Feng, W., Shen, Q., Yu, N., Yu, K., Wang, S., Chen, Z., Shioda, S., & Guo, Y. (2017). Rhizoma coptidis and berberine as a natural drug to combat aging and aging-related diseases via anti-oxidation and AMPK activation. Aging and disease, 8(6), 760.
  29. Yu, H. H., Kim, K. J., Cha, J. D., Kim, H. K., Lee, Y. E., Choi, N. Y., & You, Y. O. (2005). Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J Med Food, 8(4), 454-461.
  30. Zhai, L., Huang, T., Xiao, H. T., Wu, P. G., Lin, C. Y., Ning, Z. W., Zhao, L., Kwan, H. Y. A., Hu, X. J., Wong, H. L. X., Li, X. Q., & Bian, Z. X. (2020). Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity. Front Pharmacol, 11, 576496. Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium–Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity
  31. Zhao, Z., Guo, M., Xu, X., Hu, Y., Liu, D., Wang, C., Liu, X., & Li, Y. (2022). In Vitro Synergistic Inhibitory Activity of Natural Alkaloid Berberine Combined with Azithromycin against Alginate Production by Pseudomonas aeruginosa PAO1. Oxid Med Cell Longev, 2022, 3858500.
  32. Zhou, R., Xiang, C., Cao, G., Xu, H., Zhang, Y., Yang, H., & Zhang, J. (2021). Berberine accelerated wound healing by restoring TrxR1/JNK in diabetes. Clinical Science, 135(4), 613-627.
Berberine continues to amaze me! In my book Prescription for Herbal healing by Phyllis A. Balch I read that homeopathic preparations of barberry (Berberis Vulgaris) are also used for kidney stones. Berberine is a compound in barberry. See:

Berberine continues to amaze me!

Same here! I've been researching some herbs and supplements and found some amazing things about Berberine again.

I've found a couple of articles that review the antiviral activity of berberine. I seems that it might be effective against many difficult viral diseases, including HIV, which I mention just because it is a disease that is very difficult to cure, so it's quite amazing to see that berberine could be helpful in those cases too.

This study seems to be non-conclusive, but it's promising nonetheless:

Berberine is traditionally used to treat diarrhea, bacillary dysentery, and gastroenteritis in clinics, here our research shows that berberine is effective in inhibiting HIV-1 entry. [...] As a summary, these studies successfully identify compound berberine as a potential candidate drug for HIV-1 treatment. As a summary, antiviral activity of berberine in combination with its use in clinical practice, this medicine can be used as a potential clinically anti-HIV drug.

This one reviews other studies, I'll put just a few excerpts to give an idea:
(It's a bit long but I wanted to put here some of the info at least)

Activity of BBR against viruses of the family Flaviviridae

[...] Hong et al. have shown that BBR suppresses hepatitis C virus replication by targeting the viral E2 glycoprotein, specifically blocking HCV attachment and entry. Molecular docking studies have indicated that BBR interacts with the HCV E2 glycoprotein [47], suggesting that BBR could be a good candidate for the development of entry inhibitors for the prophylaxis and treatment of HCV infection. The antiviral effect of BBR does not seem to involve modulation of host cell functions such as the interferon response [47–49]. BBR also exhibits antiviral activity against dengue virus (DENV) and Zika virus (ZIKV) infections. Both of these viruses belong to the family Flaviviridae.

Activity of BBR against viral-borne respiratory syndromes

BBR has an inhibitory effect on the NF-κB signaling pathway and therefore might function as an antiviral agent against coronavirus infection [53, 54]. Recent studies have indicated that an extract from Coptidis rhizoma containing BBR and other protoberberine alkaloids might inhibit coronavirus RNA synthesis and viral assembly and release [55].

[...] During RSV infection, phosphorylation of p38 MAPK occurs at a very early stage of virus replication, and this phosphorylation can be reduced by BBR treatment. The precise molecular mechanism of this inhibition is still unknown, but recent studies have demonstrated that the effect of BBR is based on its direct interaction with a component of the TLR4 receptor complex. BBR can inhibit TLR4 activation and thus suppress p38 MAPK activation.

In addition, the production of interleukin 6 (IL-6) mRNA upon RSV infection is suppressed by BBR, which indicates its anti-inflammatory role during RSV infection [58]. It has been shown that BBR functions through several pathways, such as the NF-κB, ERK1/2 and p38 MAPK. As a consequence, these functions decrease the levels of several proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (Il-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2). BBR also inhibits the phosphorylation of NF-κB and IκBα) [59].

Anti-influenza activity

Yan et al. showed that BBR inhibits influenza virus replication in human pulmonary adenocarcinoma cells (cell line A549) and mouse lungs by suppressing the infection. This research confirmed that BBR inhibits the expression of TLR7 and NF-κB, both of which are upregulated in influenza-infected lung tissues [63].

[...] It has been shown that BBR modulates the generation of proinflammatory substances such as cytokines and stimulates the antiviral state in infected host cells. The potential therapeutic mechanism of BBR in influenza-associated viral pneumonia might be the result of both inhibition of the viral infection and modulation of the release of inflammatory factors [65, 66]. Other studies have shown that BBR and its derivatives also inhibit cytopathogenic effects and neuraminidase (NA) activity in vitro. Enkhtaivan et al. showed that the active site of the viral NA can be blocked by berberine derivatives (BDs) (Table 1) in the same way as it is blocked by the antiviral drug oseltamivir (a well-known NA inhibitor) [65]. The inhibition of viral NA was confirmed in a molecular docking study using BD and the neuraminidases of both influenza A and B viruses [67].

Using this example of the anti-influenza activity of BBR and its derivatives, we can see that BBR is multifunctional and acts through diverse mechanisms. It can attach to protein molecules at their active sites, hence directly blocking their activity, as is the case with the influenza virus NA protein [67], and it can activate different signaling pathways leading to antiviral activity, e.g., inhibition of the expression of TLR7 and NF-κB [64]. The regulatory effects of BBR on the TLR signaling pathway has also been shown to affect the process of intestinal mucosal damage in rats, but the exact molecular interactions between BBR and other molecules remain to be identified. However, based on the existing evidence, we might assume that they rely on binding of BBR to their active sites [68].

Anti-inflammatory properties of BBR

[...] The mechanism of the anti-inflammatory effect of BBR is complex. BBR can inhibit the binding activity NF-κB and activator protein 1 (AP1). AP1 and NF-κB are key transcription factors that are responsible for regulating the expression of many genes involved in inflammation [69]. Moreover, the anti-inflammatory properties of BBR also involve the modulation of MAPKs. BBR can inhibit generation of proinflammatory cytokines and moderate the inflammatory response. During RSV infection, BBR decreases interleukine-6 (IL-6) mRNA level. In influenza virus infection, BBR reduces the mRNA expression of TLR7 and NF-κB in lung tissue [70].

Anti-HPV effect

BBR also suppresses human papillomavirus (HPV) transcription
. HPVs are non-enveloped, epitheliotrophic viruses with a circular double-stranded DNA genome that belong to the family Papillomaviridae. Persistent infection with high-risk HPVs, such as HPV16 and HPV18, can lead to the development of cervical cancer. Cancer development and progression are driven by the expression of two oncogenes, E6 and E7. Their expression is mainly dependent on the viral E2 protein and on the availability of the host transcription factor activator protein 1 (AP1). HPV E6 and E7 interact with tumor suppressor proteins, p53 and Rb, respectively. E6 binds and induces ubiquitin-mediated degradation of p53, while E7 inactivates the Rb protein and alters additional cellular signaling pathways that are important for transformation. BBR can effectively target both the host AP1 and the viral oncoproteins E6 and E7. Inhibition of AP1 and blocking of viral E6 and E7 oncoprotein expression seem to be among the anti-HPV mechanisms of action of BBR [73].

Activity of BBR against members of the families Herpesviridae and Picornaviridae

Low (micromolar) concentrations of BBR can also suppress the replication of different HCMV strains that are resistant to known DNA polymerase inhibitors
. HCMV is a member of the family Herpesviridae and has a dsDNA genome. HCMV is responsible for life-threatening pneumonia, gastrointestinal diseases, retinitis, and other conditions after primary infection and in immunocompromised patients. [...] Lunganini et al. showed that BBR interferes with the transactivating function of the HCMV IE2 protein. IE2 plays a critical role in the progression of HCMV replication and in viral pathogenesis and reactivation from latency [74]. It is the most important HCMV regulatory protein and a strong transcriptional activator of viral and cellular gene expression. IE2 binds to DNA and has the ability to interact with cellular transcription factors, which is necessary for regulation of transcriptional activation of viral and host genes and cellular functions [75].

The inhibitory activity of BBR on the IE2-dependent transactivation of early genes depends on activation of MAPKs. BBR is active against human herpes simplex virus types 1 and 2 (HSV 1 and 2) and also against mouse cytomegalovirus (MCMV). HSV infection is characterized by small blisters on the skin or mucous membranes of the mouth, often called “cold sores” or “fever blisters”, and can cause a sore throat. It has been reported that BBR inhibits DNA synthesis by intercalating into DNA. BBR also inhibits the synthesis of both HSV-1 and HSV-2 late genes and proteins [76]. Inhibitory activity of BBR has also been observed against different genotypes of enterovirus 71 (EV71), which belongs to the family Picornaviridae and has a positive-sense RNA genome.

Anti-HIV activity

BBR and berberrubine along with 9-substituted derivatives of berberine have demonstrated antiviral activity against HIV [80], probably due to inhibition of reverse transcriptase (RT) activity
. The use of 20 µg of BBR per reaction resulted in 94% inhibition of HIV-1 RT. An improved therapeutic effect was observed when berberine-9-0 esters were used [80] (Table 1). BBR might therefore have a potential application as a complimentary therapeutic agent against HIV infection.

Sounds quite amazing! I guess we should have some berberine around just in case :-)
Top Bottom