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How Berberine Fights Oxidative Stress, Inflammation And Diabetes

By Max Cerquetti April 22, 2021

How_Berberine_Fights_Oxidative_Stress_Inflammation_And_Diabetes

Berberine is a natural botanical compound, which is found in a number of plants, including Oregon grape, Phellodendron, greater celandine, European barberry, goldenseal, and Chinese goldthread, among others. This compound, which is in the alkaloid category, has a long and highly regarded use in traditional Chinese, as well as Indian Ayurvedic medicine as an anti-diarrheal and anti-infective, and was also used as the source of a brilliant yellow dye for wool, leather, and wood.

Alkaloids as a chemical group are quite interesting and contain a huge number of compounds, all of which have at least one nitrogen atom in their structural makeup. A great many of these nitrogen-containing alkaloids have strong biological effects on the human body and have already provided a great many beneficial medicines, including the potent opioid pain reliever morphine and the leukemia chemotherapy agent vincristine. One of the properties that make these alkaloid compounds so attractive to medical research is that they are water-soluble in acidic conditions and fat (lipid) soluble in more neutral or alkaline conditions, giving them the ability to actually cross cellular membranes in their more neutral form. 

Included of course in this renewed interest in the alkaloids is berberine, and hundreds of new studies on this compound are making their way into the scientific journals yearly. One of the most frequently investigated properties of berberine is its therapeutic effects on cardiovascular as well as metabolic diseases, as these are the leading causes of death globally and new therapeutic agents are urgently needed. 

 

Oxidative Stress, Inflammation And The Development of Diabetes

One of the most promising therapeutic uses of berberine is its effect on oxidative stress, the imbalance that occurs between the production of damaging free radicals and the body’s ability to neutralize those free radicals with antioxidants. Free radicals are a natural byproduct of metabolism, produced when oxygen atoms are split into single atoms that have unpaired electrons. But because these free radicals don’t like to remain unpaired, they are constantly scavenging the body looking for other electrons with which to pair. 

 

In the process of this scavenging for other electrons, these free radicals cause damage to proteins, cell membranes, and even to DNA itself by effectively “stealing” their electrons through a process known as oxidation. This process of oxidative stress plays a major role in the development of a wide range of disease processes, including among others, cardiovascular disease, diabetes, cancer, stroke, neurodegenerative diseases such as dementia, and chronic inflammation. In addition to the damage caused by these scavenging free radicals, the consumption of rancid fats (mostly in the form of industrial cooking oils) in the diet as well as a deficiency in antioxidant status also both initiates and propagates this oxidative damage. 

 

Although the exact mechanisms through which type 2 diabetes comes about is not completely known, it’s now clearly recognized that oxidative stress plays a large role in its development, principally by generating noxious reactive oxygen species such as superoxide anions and hydrogen peroxides. These compounds are thought to directly damage the specialized islet cells in the pancreas which produce insulin. 

 

Oxidative Stress And Berberine

The development of diabetes is closely related to the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a family of enzymes found in cell membranes that functions to catalyze the production of superoxide free radicals known as superoxides. These superoxides, among other roles, serve to protect the body by destroying various viral and bacterial pathogens when needed. Normally, these NADPH oxidase enzymes are dormant in resting cells, but if overactivated can produce damaging levels of reactive oxygen species (ROS). In vascular (blood vessel) cells, an imbalance in ROS can lead to hypertension (high blood pressure), myocardial infarction (heart attack), atherosclerosis (the accumulation of fatty plaques in arterial walls), and stroke.


There have been quite a large number of animal model studies showing berberine’s potent antioxidant activity. Berberine acts to reduce oxidative stress through a number of different routes, including the direct scavenging of superoxide free radicals. Berberine also directly inhibits the expression of NADPH oxidase, which as explained above, is one of the key originators of reactive oxygen species. 

 

Berberine-neuroprotection-and-antioxidant-activity

 

Inflammation, Obesity And Berberine

 

Inflammation is also directly involved in the development of type 2 diabetes through several complex chemical pathways which lead to the production of highly inflammatory cytokines, ultimately resulting in increased insulin resistance and further pancreatic islet cell dysfunction. There is a very strong association between the development of inflammation and oxidative stress and it also bears emphasizing that berberine’s role in the suppression of inflammation is a very complex one that involves multiple pathways which overlap with its antioxidant pathways.

One of these overlapping pathways involves AMPK (adenosine monophosphate-activated protein kinase). Many researchers believe that it is berberine’s influence on this AMPK pathway that explains much of its impact on human health. AMPK serves as a sort of central “control switch” which helps to regulate how much energy the body both produces and uses. When these multiple AMPK regulated pathways become dysfunctional and AMPK is turned off, blood sugar, as well as blood lipid (fat) abnormalities, can result, which can lead to diabetes and even metabolic syndrome, a dangerous combination of increased abdominal fat accumulation and increased blood pressure in addition to the elevated levels of blood sugar and blood lipids. AMPK activation has also been shown to actually reduce aging. 

There are only a handful of known chemical compounds that activate AMPK, including the commonly prescribed diabetes drug metformin. Berberine is also one of these compounds. In fact, berberine activates AMPK to a similar degree as metformin. 


Berbeine AMPK activation


Berberine not only activates AMPK but also increases glycolysis, the metabolic pathway that converts glucose (sugar) into energy and also leads to a reduction in gluconeogenesis (the production of new glucose) in the liver. This same mechanism is also thought to underlie berberine’s positive effects on weight loss and its anti-obesity effects. Berberine has not only been used successfully to treat experimentally induced type 2 diabetes in mice but it has also been used in human trials to treat type 2 diabetes. Interestingly, berberine’s antidiabetic properties seem in part to be its effect on the human gut microbiome, promoting gut microbial balance.  

In summary, berberine is a natural plant-derived compound that has potent antioxidant and anti-aging effects and works through multiple biological chemical pathways to ameliorate the damaging effects of free radicals, suppress inflammation and regulate glucose production. Through these same mechanisms, berberine also works to exert positive effects on weight loss and helps to regulate blood sugar. And while it’s beyond the scope of this article, berberine also has shown great promise in the suppression of certain types of cancer. 

 

Certainly, this powerful supplement should be considered by anyone who is looking for a natural way to receive these anti-aging, anti-inflammatory, and anti-obesity benefits. You can find complete information on our quality berberine supplement here, specially formulated with piperine (derived from black pepper) to increase absorption and for maximum bioavailability.

 

 

References:

 

1. Zahra Ilyas, Simone Perna, Salwa Al-thawadi, Tariq A. Alalwan, Antonella Riva, Giovanna Petrangolini, Clara Gasparri, Vittoria Infantino, Gabriella Peroni, Mariangela Rondanelli,The effect of Berberine on weight loss in order to prevent obesity: A systematic review,Biomedicine & Pharmacotherapy, Volume 127, 2020, 110137, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2020.110137.

2. Waller G.R., Nowacki E.K. (1978) The Role of Alkaloids in Plants. In: Alkaloid Biology and Metabolism in Plants. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-0772-3_5

3. Sack RB, Froehlich JL. Berberine inhibits intestinal secretory response of Vibrio cholerae and Escherichia coli enterotoxins. Infect Immun. 1982 Feb;35(2):471-5. doi: 10.1128/IAI.35.2.471-475.1982. PMID: 7035365; PMCID: PMC351064.

4. Feng X, Sureda A, Jafari S, et al. Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics. Theranostics. 2019;9(7):1923-1951. Published 2019 Mar 16. doi:10.7150/thno.30787

5. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717. doi:10.1016/j.metabol.2008.01.013

6. Antero Salminen, Kai Kaarniranta. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network, Ageing Research Reviews, Volume 11, Issue 2, 2012, Pages 230-241, ISSN 1568-1637, https://doi.org/10.1016/j.arr.2011.12.005.

7. Zhang, Y., Gu, Y., Ren, H. et al. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun 11, 5015 (2020). https://doi.org/10.1038/s41467-020-18414-8

8. Zahra Ilyas, Simone Perna, Salwa Al-thawadi, Tariq A. Alalwan, Antonella Riva, Giovanna Petrangolini, Clara Gasparri, Vittoria Infantino, Gabriella Peroni, Mariangela Rondanelli,The effect of Berberine on weight loss in order to prevent obesity: A systematic review,Biomedicine & Pharmacotherapy, Volume 127, 2020, 110137, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2020.110137.


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