Berberine Alkaloid:

The History and Role of Berberine as a Global Medicine

Global Health Concepts

Copyright: Anthony Musso- All Rights Reserved- 2011

Index

Chapter 1: Berberine History and Synopsis

Chapter 2: Use in Diabetes Treatments

Chapter 3: Use in Cholesterol Reduction

Chapter 4: Use in Dysentery (Diarrhea)

Chapter 5: Use in Bacterial Infection

Chapter6: Use in Liver Function Treatment

Chapter 7: Use in Critical Disease: Malaria and Dengue

Chapter 8: Fever Reduction Combination Therapy

Chapter 9: Artemisinin, Berberine Plus Other Compounds

A. Summary

B. Global Distribution Information

C. Reference List of Clinical Evidence

D. Certificates of Analysis

E. Botanical Ingredient Chemistry Data

History and Synopsis of Berberine Alkaloid

Note to Readers: I have been working with Berberine Alkaloid for almost 6 years while based out of Asia. I have been the first person to combine it with Artemisinin which is another powerful plant concentrate (Artemisia Annua Botanical) used to treat severe fever in Mainland China for over 2000 years. Both Berberine and Artemisinin concentrates have extensive use historically as individual concentrates or simply in raw plant form soaked in water and used for drinking in tea form but always consumed for medical benefit purposes. I created this free E Book for people from the over 220 countries who need a self-medication type treatment that is safe and works while using it for major medical problems ranging from Diabetes to Dysentery, Malaria and Dengue Fever.. The fact is that I have had so many requests for information on Berberine and its potential uses and combinations that I believe it is now mandatory for me to divulge this important information and have it disseminated and readily available to the general public and medical practitioners who are interested in unique, safe natural cures and remedies that work. This will be available online and in a downloadable free mobile application shortly.

Any questions or comments or requests please email to: anthonymusso@gmail.com

Chapter 1: History and Synopsis

Berberine has a long history in many countries due to the fact that it is scattered over the planet in most geographical regions in a few different plant forms and can be easily visible in those plants due to its extreme yellow color and bitter taste. My belief is that it was long ago used as a dye and coloring agent first and then accidently secondarily discovered when it spilled on an open infection and clearly revealed ONE of its many healing qualities.

It is published worldwide that Berberine was known to be used both as a preventative and a remedy as far back as ancient Egypt for treating serious medical conditions such as Plague and Hepatitis. It has been used effectively in China and Europe for over 2500 years.

Synopsis of General And Technical Information:

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.

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 medicine 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.

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 has limited distribution and availability..

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.

Berberine Indications

For treatment and cure of fungus infections and yeast infections, especially systemic, chronic, or recurrent fungus infection and yeast infection caused by Candida albicans intestinal yeast overgrowth (Candidiasis). For treatments addressing the symptoms of Candida albicans intestinal yeast infection. In men and women for addressing underlying causes of fungus and yeast-related disorders including oral yeast infection (thrush), vaginal yeast infection (vaginitis) and male yeast infection (jock itch). For treatment and supportive therapy of intestinal disorders commonly associated with Candida albicans yeast overgrowth (Candidiasis) including Irritable Bowel Syndrome (IBS), leaky gut syndrome, intestinal parasite infections, and intestinal bacterial infections.

Berberine Source & Availability:

Berberine is a natural, herbal, botanical dietary supplement commonly available in pill, tablet, or capsule form. Berberine is an alkaloid found in various plants, including goldenseal, barberry, Oregon grape, and goldthread. Berberine exhibits a broad spectrum of antibiotic activity in test-tube, animal, and human studies.

Berberine Medicinal Value;

Berberine-containing plants are used medicinally in virtually all traditional medical systems, and have a history of usage in Ayurveda (Hindu) and Chinese medicine dating back at least 3,000 years. Berberine has demonstrated significant antimicrobial activity against bacteria, fungi, yeast, protozoans (Giardia, etc.), viruses, helminthes

(worms) and chlamydia. In addition, Berberine's actions include: antagonism of the

effects of cholera and E. coli toxin, inhibition of intestinal ion secretion, inhibition of smooth muscle contraction (spasms), and reduction of inflammation. Berberine's most common clinical uses include: bacterial diarrhea and intestinal parasites.

Chapter 2: Use in Diabetes Treatments

The quest for an effective, permanent cure for Diabetes is still ongoing despite huge funding and corporate and personal commitments from organizations and individuals worldwide in order to find a remedy. There has been some advancement and improvement with medicines however the disease and the massive side effects it produces still takes its toll every year.

Detecting signs and symptoms of the disease as early as possible is paramount in a first stage management of the disease. The next best action to take is to thoroughly familiarize oneself with the compound Berberine Alkaloid and start taking it as a remedy.

For over 2000 years the Chinese Traditional Doctors have been using Berberine as a potent remedy to treat the various forms of Diabetes. Berberine has the effect to prevent the absorption of sugars from the intestine and it increases the production of insulin. Yet it does not produce negative side effects even when taking over 2 grams (2000 milligrams) of the concentrate per day.

Studies of Berberine Alkaloid for Diarrhea treatment showed blood glucose levels going significantly lower on the patients who had Diabetes and that is how it was first recognized formally that it worked for Diabetics. One can easily find, through a scan on the internet, all the research reports and studies which are still ongoing on this amazing compound’s effectiveness for Diabetes. One can notice a significant physical difference in energy fro, the body’s conversion of carbohydrates in sugars for energy when taking Berberine. If you are a Diabetic then it is necessary to check blood sugar more regularly since it will change immediately after taking the compound in pill or powder form. Usually the result is a significant lowering of any medicines or insulin requirement within a short amount of time of taking Berberine.

Chapter 3: Use in Cholesterol Reduction

Recently is has been discovered that Berberine Alkaloid is extremely effective in dramatically reducing Cholesterol levels in human beings. Clinical studies have shown its effectiveness and potential use in place of statin drugs. It works from a different principal. Dosage is extremely important and results are witnessed with the first 30 days but after 90 days of continuous use the cholesterol reductions are obvious.

Specific studies have shown a decrease over three months of use with correct dosages of a 40% reduction of Serum Cholesterol and a 42 % reduction of LDL Cholesterol and an over three-fold hepatic LDLR Expression increase. These are substantial results and one can test this for themselves simply by consuming the tablets or pills twice daily for 30 to 90 days.

Chapter 4: Use in Treating Dysentery (Diarrhea)

Probably the most extensive global use of Berberine

Alkaloid is for the prevention and control of Diarrhea

ranging from mild to severe forms.

One can see quite rapidly how effective Berberine is for

healing Diarrhea within 30 minutes to 3 hours of taking an

adequate dose. It appears to directly treat the underlying

causes of the condition unlike the over the counter drugs and

synthetic medicines that only mask the problem and provide

moderate or no comfort. GI tract and gas pains are rapidly

diminished and dehydration is stopped. Many clinical studies have been completed simply because the obvious physical effectiveness of the compound has excited so many researchers and scientists over

many decades of use in many countries, especially Asia since it is processed on an industrial scale in China. Relatively little is known in the USA or Europe about Berberine and its practical uses due to the fact that the Pharmaceutical companies have a stronghold on the information and distribution of products used to treat Diarrhea. Nurses are especially shocked to see how well it works on so many disease states and how simple it is to apply as a non-toxic substance.

For Globe Trotting Travelers, Berberine and certain proprietary combinations including Artemisinin can be a miracle treatment in an emergency away from home. There is nothing worse than having your vacation time destroyed by rampant Diarrhea. I advise world travelers to take the Berberine combination compounds starting on the day they leave on their trip. It is an excellent preventative.

Acid Reflux Treatment

Acid Reflux and extreme chronic heartburn usually indicates a proliferation of the H.Pylori (Helicobacter Pylori) in the upper gut. This condition can be very severe and painful so that it requires immediate attention since it also can easily lead to ulceration and make a more complicated condition for healing. Berberine Alkaloid by itself has been known to neutralize and clear an infestation of this parasite quite rapidly. It compares as effective as the drug ranitidine and it can even stimulate the healing of ulcers. It is known to have faster clearance of the Parasite.

The combination of multiple compounds of Artemisinins and Berberine can also be used for effective Acid Reflux condition treatment. These combinations offer one the most effective known anti-parasite medicine used through the ages.

Chapter 5: Use in Bacterial Infections

Another significant use of Berberine Alkaloid in in the use

of treating bacterial infections ranging from Eye Infections

including Conjunctivitis, Ear Infections, Tooth Infections

and Urinary Tract Infections. Clinical studies have verified the usefulness of Berberine Alkaloid to treat infections.

Chapter 6: Use for Liver Function

Over the last ten years Berberine Alkaloid has been studied in depth to uncover both its preventive and curative benefits regarding liver disease and toxicity. These studies have shown positive and dramatic healing benefits from liver toxicity through the ingestion of Berberine and have also concluded that Berberine can be used as a preventive agent for the liver from various toxicities that would otherwise permanently impair positive liver function which is so vital to good health.

Chapter 7: Use in Critical Disease: Malaria and Dengue

As mentioned earlier the first Artemisinin Combination Therapy (ACT) to use Berberine as the second ingredient in combination with the compound Artesunate (a concentrated and chemically modified Artemisinin used for Malaria) was ActRX Brand produced in Mainland China. Other ACTS typically use Quinine in a synthetic form or variation as the second ingredient. However, synthetic Quinine has become extremely ineffective in fighting Malaria over the last 20 years and is also known to be extremely toxic and even deadly in just 1 extra dose consumed.

Berberine appears to be the best combination with Artemisinin and/or Artesunate for other critical diseases such as Dengue Fever and Typhoid Fever. Thus far the evidence is anecdotal but nevertheless it is worth using since with Dengue Fever there is no known cure or remedy that works at all. Patients showing up with Dengue Fever around the world’s hospitals and clinics are shocked to find out there is no known medicine to treat it and they just can only hope for good results while being managed for the deadly disease.

Chapter 8 : Fever Fixer Blend

Berberine Alkaloid and Artemisinin can be combined with an anti-inflammatory such as Ibuprofen to effectively reduce fever and infection within a few days and give Quick relief as a simple over the counter remedy that is easy to use and safe for all ages. Knowledge of dosages is necessary to get optimum results as all of the compounds are weight based.

Chapter 9: Artemisinin and Berberine Combinations

As one of the handful of people on the planet experienced in the use of combinations of Artemisinin and Berberine Alkaloid with other synergistic plant concentrates and even some synthetics I feel it mandatory to discuss the potential of these plant medicines and the potent results one can obtain from their usage in combination.

Some of the combinations I have experienced results with are:

A. Artemisia Annua concentrate and/or Artesunate with Berberine AlkaloidB. Artemisinin combined with Berberine Alkaloid and Type 1 Collagen PowderC. Artemisinin Annua Concentrate and/or Artesunate with Berberine Alkaloid

and Ibuprofen.D. Artemisia Annua and Berberine Alkaloid combined with other known Anti-

Parasitic compounds as a proprietary formula.

Summary

ON a personal note, the first question I normally get from new

acquaintance I meet when they ask what do I do and after explaining about these amazing herbal concentrates and remedies is: Do you use these formulas ?

Even if they do not answer I inform them quite definitively that I would not let anyone in my family travel to another country without taking these substances with them and also I educate them in their use. My children take these products regularly when fever shows up or they have the possibility of some disease such as Dysentery, Dengue or Malaria while traveling and living in Asian countries like the Philippines.

I recommend everyone carry these ingredients in pill, capsule or powder form in their medicine cabinets and first aid kits like I do everywhere I travel. Even eating first class Sushi restaurant is quite risky as I found out one time in Boston, Mass.

Note: There are well over 500 studies done on Berberine

Alkaloid. The following is a sampling of those studies.

Many more are in process due to the extreme significance of

this compound and its effectiveness in so many areas of

health and wellness. It is worth your while to read any

relevant studies on conditions you are interested in knowing

about.

References:

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22. Hsu WH, Hsieh YS, Kuo HC, Teng CY, Huang HI, Wang CJ, Yang SF, Liou YS, Kuo WH: Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL. Arch Toxicol 2007, 81:719 728.

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32. Kim HR, Min HY, Jeong YH, et al. Cytotoxic constituents from the whole plant of Corydalis pallida. Arch Pharm Res 2005;28(11):1224-1227.

33. Kim KW, Ha KT, Park CS, Jin UH, Chang HW, Lee IS, Kim CH: Polygonum cuspidatum, compared with baicalin and berberine, inhibits inducible nitric oxide synthase and cyclooxygenase-2 gene expressions in RAW 264.7 macrophages. Vascul Pharmacol 2007, 47:99-107.

34. Kim JS, Tanaka H, Shoyama Y. Immuno quantitative analysis for berberine and its related compounds using monoclonal antibodies in herbal medicines. Analyst 2004;129(1):87-91.

35. Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 2004;10(12):1344-1351.

36. Kuo CL, Chi CW, Liu TY: The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett 2004, 203:127-137.

37. Kuo CL, Chi CW, Liu TY. Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells. In Vivo 2005;19(1):247-252.

38. Lee DU, Kang YJ, Park MK, Lee YS, Seo HG, Kim TS, Kim CH, Chang KC : Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-alpha, iNOS, and IL-12 production in LPS-stimulated macrophages. Life Sci 2003, 73:1401-1412.

39. Letasiova S, Jantova S, Cipak L, Muckova M: Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells. Cancer Lett 2006, 239:254-262.

40. Li F, Wang HD, Lu DX, Wang YP, Qi RB, Fu YM, Li CJ: Neutral sulfate berberine modulates cytokine secretion and increases survival in endotoxemic mice. Acta Pharmacol Sin 2006, 27:1199-1205.

41. Lin CC, Kao ST, Chen GW, et al. Berberine decreased N-acetylation of 2-aminofluorene through inhibition of Nacetyltransferase gene expression in human leukemia HL-60 cells. Anticancer Res 2005;25(6B):4149-4155.

42. Lin CC, Kao ST, Chen GW, et al. Apoptosis of human leukemia HL-60 cells and murine leukemia WEHI-3 cells induced by berberine through the activation of caspase-3. Anticancer Res 2006;26(1A):227-242.

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47. Mantena SK, Sharma SD, Katiyar SK: Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP. Carcinogenesis 2006, 27:2018-2027.

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49. Nair KP. Giardiasis in children. Pediatric Clinics India 1970;5:45.

50. Peng PL, Hsieh YS, Wang CJ, Hsu JL, Chou FP: Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Toxicol Appl Pharmacol 2006, 214:8-15.

51. Pereira GC, Branco AF, Matos JA, Pereira SL, Parke D, Perkins EL, Serafim TL, Sardao VA, Santos MS, Moreno AJ, et al: Mitochondrially targeted effects of berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium] on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions. J Pharmacol Exp Ther 2007, 323:636-649.

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53. Recknagel RO, Glende EA, Dolak JA, Waller RL: Mechanism of carbon tetrachloride toxicity. Pharmacol Ther 1989, 43:139-154.

54. Sack RB, Froelich JL. Berberine inhibits intestinal secretory response of Vibrio cholera and Escherichia coli enteroxins. Infect Immin 1982;35:471-475.

55. Scazzocchio F, Cometa MF, Tomassini L, Palmery M: Antibacterial activity of Hydrastis canadensis extract and its major isolated alkaloids. Planta Med 2001, 67:561-564.

56. Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J: Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line. Cancer Chemother Pharmacol 2008, 61:1007-1018.

57. Shitan N, Tanaka M, Terai K, Ueda K, Yazaki K: Human MDR1 and MRP1 recognize berberine as their transport substrate. Biosci Biotechnol Biochem 2007, 71:242-245.

58. Sun D, Abraham SN, Beachey EH. Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli. Antimicrob Agents Chemother 1988;32:1274-1277.

59. Sun X, Zhang X, Hu H, Lu Y, Chen J, Yasuda K, Wang H: Berberine inhibits hepatic stellate cell proliferation and prevents experimental liver fibrosis. Biol Pharm Bull 2009, 32:1533-1537.

60. Swabb EA, Tai YH, Jordan L. Reversal of cholera toxin-induced secretion in rat ileum by luminal berberine. Am J Physiol 1981;241:G248- G252.

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62. Wang YX, Yao XJ, Tan YH. Effects of berberine on delayed afterdepolarizations in ventricular muscles in vitro and in vivo. J Cardiovasc Pharmacol 1994;23:716-722.

63. Wu JF, Liu TP. Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion. Yao Hsueh Hsueh Pao 1995;30:98-102.

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