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Oswizle

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Biochim Biophys Acta. 2006 Sep 20;: 17049164


Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK.

Zhe Cheng , Tao Pang , Min Gu , An-Hui Gao , Chuan-Ming Xie , Jia Li , Fa-Jun Nan

Berberine is a plant alkaloid used in traditional Chinese medicine and has been reported to have antihyperglycemic activity in NIDDM patients. However, the molecular basis for this action is yet to be elucidated. Here we investigate the effects and signaling pathways of berberine on L6 rat skeletal muscles. Our study demonstrates that berberine stimulates glucose uptake in a time- and dose-dependent manner. Intriguingly, berberine-stimulated glucose uptake does not vary as insulin concentration increases, and could not be blocked by the PI 3-kinase inhibitor wortmannin. Berberine only weakly stimulates the phosphorylation of Akt/PKB, a key molecule in the insulin signaling pathway, but strongly promotes the phosphorylation of AMPK and p38 MAPK. The effects of berberine are not a result of pro-oxidant action, but a consequence of an increased cellular AMP:ATP ratio. Moreover, berberine-stimulated glucose uptake is inhibited by the AMPK inhibitor Compound C and the p38 MAPK inhibitor SB202190. Inhibition of AMPK reduces p38 MAPK phosphorylation, suggesting that AMPK lies upstream of p38 MAPK. These results suggest that berberine circumvents insulin signaling pathways and stimulates glucose uptake through the AMP-AMPK-p38 MAPK pathway, which may account for the antihyperglycemic effects of this drug.
 

Oswizle

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Diabetes. 2006 Aug ;55:2256-64 16873688

Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States.

Yun S Lee , Woo S Kim , Kang H Kim , Myung J Yoon , Hye J Cho , Yun Shen , Ji-Ming Ye , Chul H Lee , Won K Oh , Chul T Kim , Cordula Hohnen-Behrens , Alison Gosby , Edward W Kraegen , David E James , Jae B Kim

Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase-independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.
 

Oswizle

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NEW USES OF BERBERINE

A Valuable Alkaloid from Herbs for "Damp-Heat" Syndromes

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

BACKGROUND
Berberine is an isoquinoline alkaloid with a bright yellow color that is easily seen in most of the herb materials that contain any significant amount of this compound. Among Chinese herbs, the primary sources are phellodendron and coptis (similar isoquinoline alkaloids, in these herbs, such as jateorrhizine, coptisine, palmatine, and columbamine, also have a yellowish color). Berberine has long been used as a dye; it is currently known as "natural yellow 18," being one of about 35 yellow dyes from natural sources.


Chemical structure of berberine.
British booklet on berberine.

Coptis chinensis rhizomes (huanglian; literally "yellow thread") and related species used as its substitutes have about 4-8% berberine, while Phellodendron amurense bark (huangbo, literally "yellow bo," where bo is this particular type of tree) has about half as much, at 2-4% berberine. This compound is also found in the less commonly used Chinese herb sankezhen (B. sargentiana) and in the Japanese barberry (woody portion of Berberis thunbergii). All of these herbs are known as therapies for damp-heat syndromes, particularly for intestinal and lung infections, and they are used topically for various skin diseases. Several Western herbs also contain berberine, such as barberry root bark (Berberis vulgaris), Oregon grape root (Berberis aquifolium), and goldenseal root (Hydrastis canadensis). Berberine was isolated and used as an herbal drug in China 50 years ago (the drug forms are usually the hydrochloride or sulfate; the chloride, as used in the dye, may have the strongest antiseptic action). It has since become an ingredient in several Western herbal products, particularly for treatment of intestinal infections.

Coptis and phellodendron have been used in China for treating gastrointestinal diseases with reported success; applications have included acute gastroenteritis, cholera, and bacillary dysentery. So, the first applications of isolated berberine were for treatment of these conditions. Recent clinical trials have yielded conflicting results as to which of the disease organisms causing intestinal symptoms are responsive to berberine (1, 2). Tests of the antiseptic action of berberine against bacteria, yeasts, viruses, and amoebas have shown a range of activity levels from apparent potent action to mild suppression. Inhibition of giardia and of candida have been areas of considerable interest and initial positive research results have led to development of several herb products for those applications.


Whole coptis rhizomes.
Sliced coptis.

Soon after berberine was prepared as an isolated agent for clinical use, it was noted that berberine had other potential benefits; for example, it appeared to reduce high blood pressure at doses of about 1 gram per day (3). The hypotensive action of berberine has been confirmed in several pharmacology experiments, but follow-up clinical trials have been lacking. Still, this effect of berberine fortunately led to further testing of the compound for patients with cardiovascular disease risk factors, and evidence developed to demonstrate a lowering of cholesterol (and triglycerides) and of blood sugar. These new findings are the main focus of this brief report.

CHOLESTEROL
There has been increased interest in lowering blood cholesterol, and especially LDL-cholesterol, as a means of curtailing the high rates of heart attack and stroke. In addition to recommended dietary changes, many people are prescribed statin drugs for this goal. The statin drugs are powerful, frequently effective, and may have other benefits, though they also pose certain risks. During the 1990s, the Chinese herb material "red rice yeast" (Monascus purpureus) was sold in the U.S. as a natural supplement that contains, as one of its active ingredients, small amounts of lovastatin, one of the widely used statin drugs (it also contains several related compounds that contributed to the cholesterol lowering action). After prolonged legal disputes between the supplement providers, the drug companies, and the FDA about its content of the drug substance, the sale of red rice yeast and its extracts as natural cholesterol lowering agents was banned.

It was reported recently that berberine lowers cholesterol through a mechanism different than that of the statin drugs, suggesting potential use both as an alternative to the statins and as a complementary therapy that might be used with statins in an attempt to gain better control over cholesterol. In a controlled Chinese study (4), it was shown that berberine, administered 500 mg twice per day for 3 months, reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. The apparent mechanism is increasing the production of a receptor protein in the liver that binds the LDL-cholesterol, preparing it for elimination.

BLOOD SUGAR
Research on use of berberine for diabetes began with Ni Yanxi and his colleagues in Changchun (a large city in Jilin Province) with diabetes treatments. As an introduction to a 1995 English language publication on this subject (presenting their earlier clinical data from 1983-1987), they wrote (5): "It was found by accident that berberine had the therapeutic effect on the decrease of blood glucose when the authors used berberine to treat diarrhea in patients who suffered from diabetes."

Dietary therapy was first introduced to the patients for one month. For those who still had high fasting blood sugar, berberine was administered orally at a dose of 300, 400, or 500 mg each time, three times daily, adjusting the dosage according to the blood glucose levels; this treatment was followed for 1-3 months. A control group without diabetes was similarly treated, with no effect on blood sugar. For the diabetic patients, it was reported that patients had less thirst, consumed less water and urinated less, had improved strength, and had lower blood pressure; the symptoms declined in correspondence with declining blood glucose levels. Laboratory studies suggest that berberine may have at least two functions in relation to reducing blood sugar: inhibiting absorption of sugars from the intestine and enhancing production of insulin. As relayed by Ni in his review of the literature, clinical experience with berberine has shown that doses of 2 grams per day produced no side effects.

REFERENCES
Rabbani GH, et al., Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic E. coli and Vibrio cholerae, Journal of Infectious Diseases 1987; 155(5): 979-984.
Kaneda Y, et al., In vitro effects of berberine sulphate on the growth and structure of Entamoeba histolytica, Giardia lamblia, and Trichomonas vaginalis, Annals of Tropical Medicine and Parasitology 1991; 85(4); 417-425.
Chang HM and But PPH (editors), Pharmacology and Applications of Chinese Materia Medica, (volume 2), 1986 World Scientific, Singapore.
Kong Weijia, et al., Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins, Nature Medicine 2004; 10(12): 1344-1351.
Ni Yanxia, et al., Therapeutic effect of berberine on 60 patients with non-insulin dependent diabetes mellitus and experimental research, Chinese Journal of Integrated Traditional and Western Medicine 1995; 1(2); 91-95.
April 2005
 

Stupes

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Berberine is definatley one of them. What is the other active? It is an extract from some plant of the Lagerstroemia genus. Is it Banaba?
 

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Berberine is definatley one of them. What is the other active? It is an extract from some plant of the Lagerstroemia genus. Is it Banaba?
Berberine is definately a protion of the plant but not the entire active of the plant.
 

Stupes

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Berberine is definately a protion of the plant but not the entire active of the plant.
Haha - a mystery - I like it. Tannic acid has got to be the "Tannis complex" from Banaba. This acts on the Glut 4 and enhances Insulin receptors without feeding fat like insulin itslef does. Berberine does much of the same - activates Glut 4 and increases Insulin Recptor sensitivity. They both lower insulin levels though - which must be why you must take them with carbs. But what is the other active in the Phellodendron? And what does it do? And what are the dangers if these lower blood sugar levels? Or is that only in diabetics? A non-diabetic's body will naturally work to keep levels up I assume. I have alot of questions I have to research.........
 
Enigma76

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Haha - a mystery - I like it. Tannic acid has got to be the "Tannis complex" from Banaba. This acts on the Glut 4 and enhances Insulin receptors without feeding fat like insulin itslef does. Berberine does much of the same - activates Glut 4 and increases Insulin Recptor sensitivity. They both lower insulin levels though - which must be why you must take them with carbs. But what is the other active in the Phellodendron? And what does it do? And what are the dangers if these lower blood sugar levels? Or is that only in diabetics? A non-diabetic's body will naturally work to keep levels up I assume. I have alot of questions I have to research.........

Good questions about the lowered insulin levels. I am in no means related to USPlabs nor am I an expert on berberine/banaba, but I can say that I believe the lowered levels is a longterm thing from longterm supplementation. The method of action I assume is related to berberine/banaba increasing GLUT4; with more GLUT4, less insulin is needed to initiate transport of glucose into a cell.

Even if my assumptions are wrong, reducing circulating insulin is a beautiful thing; less insulin means less fat accumulation, less inflammation, and less of the host of negative problems associated with insulin insensitivity.
 
Mulletsoldier

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Good questions about the lowered insulin levels. I am in no means related to USPlabs nor am I an expert on berberine/banaba, but I can say that I believe the lowered levels is a longterm thing from longterm supplementation. The method of action I assume is related to berberine/banaba increasing GLUT4; with more GLUT4, less insulin is needed to initiate transport of glucose into a cell.

Even if my assumptions are wrong, reducing circulating insulin is a beautiful thing; less insulin means less fat accumulation, less inflammation, and less of the host of negative problems associated with insulin insensitivity.
Bingo, on both accounts.
 

stxnas

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Oooh, oooh, pick me :wave:

Mullet, that post that you replied "bingo" to seems to say in a round about way that AP could help reduce inflammation...???....Is this true or am I reading into this too much.

Cissus + AP would be my dream stack if that is true...not to mention that I could pretty much run them year around!
 
haiz69

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Oooh, oooh, pick me :wave:

Mullet, that post that you replied "bingo" to seems to say in a round about way that AP could help reduce inflammation...???....Is this true or am I reading into this too much.

Cissus + AP would be my dream stack if that is true...not to mention that I could pretty much run them year around!
Reduction in inflammation is definitely an effect of AP. My joints never felt better than during my YG log.
 

stxnas

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You must spread some Reputation around before giving it to haiz69 again.

Thanks for the feedback!
 

Oswizle

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Exp Mol Med. 2006 Dec 31;38 (6):599-605 17202835

Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte.

[My paper] Bong Hyuk Choi , In Ahn , Yu Hee Kim , Ji Won Park , So Young Lee , Chang Kee Hyun , Myoung Soo Do

Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological effects, yet its exact mechanism is unknown. In order to understand the anti-adipogenic effect of BBR, we studied the change of expression of several adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1 micrometer, 5 micrometer and 10 micrometer concentrations of BBR. We also measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1 cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-alpha, PPAR-gamma, fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was slightly decreased. Next, we measured the change of inflammation markers of 3T3-L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of inflammation markers such as TNF-alpha, IL-6, C- reactive protein and haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect seems to be due to the down-regulation of adipogenic enzymes and transcription factors.
 
prld2gr8ns

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That's good to know. :burger: :jaw:
 

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