YOUR DOCTOR DOESN’T KNOW

The Botanical

DIABETESCURE

Dr. Glenn Rothfeld’s

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Dr. Glenn Rothfeld’s

The Botanical Diabetes Cure Your Doctor Doesn’t Know 2

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The Botanical Diabetes Cure Your Doctor Doesn’t Know 3

The Botanical Diabetes Cure Your Doctor Doesn’t Know

Long used as an effective natural antibiotic, there has since been a virtual explosion of new scientific research on the botanical ex-

tract berberine.

The November 2010 issue explained that ber-berine has emerged as an incredibly effective nat-ural treatment for controlling blood sugar and lipids. In fact, research found that it performs just as well metformin, the #1 patent medication for type-2 diabetes.

Berberine doesn’t disappoint in the real world either. In case after case it has lived up to its re-search reputation in clinical observations at Tahoma Clinic. In fact, it turns out that in most of the cases where type-2 diabetes didn’t respond to berberine the patients were misdiagnosed before they came to us. Careful testing of their insulin responses to sugar revealed that they were actually type-1 diabetics.

Since 2008, there’s been a virtual avalanche of scientific research on berberine. But you may be surprised to find out that the research hasn’t only focused on type-2 diabetes and pre-diabetes or metabolic syndrome. Studies have revealed that the extract’s abilities reach far beyond blood sugar control.

In fact, research has found that berberine could play an important role in fighting cancer, guard-ing against Alzheimer’s, lowering cholesterol and triglycerides in non-diabetics, speeding recovery from strokes, and stimulating nerve cells and in-jured nerves. But before we cover the details on those findings let’s “re-cap” some berberine basics.

Berberine is known scientifically as an “isoquino-line alkaloid.” It has been used by our ancestors for centuries. Berberine occurs naturally in the stem, bark, and roots, of a variety of plants, including goldenseal (“Hydrastis canadensis”), Oregon grape (Berberis aquifolium), barberry (Berberis vulgaris),

goldenthread (Coptis chinensis) and tree turmeric (Berberis aristata).1

Help in the fight against bacterial blindness

Western medicine has generally ignored berber-ine. But the little attention the mainstream has given to the botanical has focused on its ability to treat infections, particularly gastrointestinal conditions. Berberine is an anti-fungal and anti-inflammatory and has been used in the treatment of bacterial and parasitic causes of diarrhea.

In “underdeveloped” countries, berberine is known as an effective treatment for trachoma, the #1 cause of infectious blindness and visual impair-ment world-wide, caused by the Chlamydia tra-chomatis. It’s estimated that 40 million people are infected by this bacteria, and 8 million of them are visually impaired or blind.

Dramatic results seen with type-2 diabetes in mere months

Berberine isn’t well absorbed by our intestinal tracts because it isn’t very soluble in water. This has led researchers to look for alternative ways of delivering it if it’s needed in non-intestinal areas of the body.2 Its poor absorbability is due, at least in part, to a molecule called a “P-glycoprotein.”3 Since milk thistle is a natural inhibitor of P-glycoprotein, researchers at the National University of Singapore felt pairing it with berberine may improve the oral absorption of the extract.4 They put their theory to the test with some diabetes research.

The twenty-six research volunteers in this study were already taking a variety of patent medicines, which included metformin, sulfonylureas, oral glitazones, and injected insulin. Despite all these treatments, their type-2 diabetes was still poorly controlled.

The Botanical Diabetes Cure Your Doctor Doesn’t Know 4

These volunteers took a combination product, “Berberol®,” which contained 500 milligrams of berberine from Berberis aristata and 105 milli-grams of milk thistle (for the technically inclined, S. marianum containing 60% flavolignans) per cap-sule. They were asked to take two capsules at night on an empty stomach, for ninety days. Twenty-two of the original group completed the three months.

Those volunteers who had successfully com-pleted the 90 days were rewarded for their efforts. They saw significant reductions in key markers related to glucose control: HgA1c, fasting insulin, triglycerides, total cholesterol and LDL cholesterol, and a measurement of insulin resistance (“HOMA-IR”). The researchers reported that “Berberol®” in these amounts was safe and well tolerated.5

Resisting insulin resistance Berberine has clearly shown great promise

against type-2 diabetes. This success led many…including me…to assume that berberine could im-prove, or even reverse, the signs and symptoms of “metabolic syndrome,” the “precursor state” for type-2 diabetes. But in science, assumptions are just that—assumptions—until they’re proven.

However, further research has now proven this hypothesis correct. Berberine does in fact help im-prove metabolic syndrome. In one double-blind, placebo-controlled study, sixty-four individuals with metabolic syndrome ate a nearly identical diet (it was adjusted only according to each person’s ideal weight). Each of the volunteers also took ei-ther a combination of berberine (500 milligrams), policosanol (10 milligrams), and red yeast rice (3 milligrams, a very small dose) or a placebo after dinner each day for eighteen weeks.

At the end of the study, those taking the ber-berine and other botanicals had significant im-provements in measurements of insulin resistance (“HOMA-IR”) when compared to those who took the placebo. In addition, the botanical users had better fasting and “two-hours-after-eating” blood sugar and insulin levels. Their systolic blood pres-sure, total cholesterol, and LDL cholesterol were all significantly improved as well.6

Other researchers also concluded that berberine can effectively treat metabolic syndrome and insu-

lin resistance, and help prevent them from proceed-ing inevitably to type-2 diabetes.7,8,9

Revealing the PCOS connectionWomen with polycystic ovarian syndrome

(“PCOS”) suffer from an unusually high incidence of insulin resistance. In addition, approximately 75% of women with PCOS have significantly higher levels of testosterone and other androgens than other women. Berberine may be able to help here as well. Research in China revealed that ber-berine can help relieve some of the troubling symp-toms of this condition.

Eighty-nine women with PCOS who were al-ready taking an anti-androgenic patent medicine took one of three additional treatments for three months.10 Thirty-one took berberine, thirty took the patent medicine metformin, and twenty-eight took placebo.

When compared with the metformin group, the berberine group had a significant decrease in waist circumference, waist-to-hip ratio, total cholesterol, triglycerides, and LDL-cholesterol. In addition the berberine users saw a significant increase in their HDL cholesterol and sex hormone binding globu-lin (SHGB) levels.

When compared with placebo, berberine again came out on top. The berberine users had even more significant improvement for all these param-eters, plus a significant improvement in fasting blood sugar and insulin, insulin resistance measure-ment, and “area under the curve” of insulin.

Berberine and your bonesDiabetic osteopathy is a complication of diabe-

tes. In normal bone, there’s a balance between new bone building done by bone cells called “osteo-blasts” and older bone destruction done by bone cells called “osteoclasts.” In addition, there’s a balance between two parathyroid gland hormones, called “calcitonin” which promotes bone build-ing, and “parathyroid hormone” which promotes bone degradation. But, in contrast, in diabetic os-teopathy the activity of bone-building osteoblasts is inhibited, and the activity of bone-degrading para-thyroid hormone is increased.

Research has shown that berberine can de-

The Botanical Diabetes Cure Your Doctor Doesn’t Know 5

crease the bone destruction done by osteoclasts, and inhibit the promotion of bone degradation by parathyroid hormone.11 Of course, it also helps by lowering the insulin resistance and blood sugar lev-els that stimulate these problems in the first place.

Berberine may be one of your brain’s best friends

Researchers are exploring berberine’s potential for the treatment of neurodegenerative disorders as well as its potential protective effects against depres-sion, schizophrenia, and anxiety.12 Although there are no controlled studies completed yet, the fact that berberine is a known inhibitor of the brain enzyme “cholinesterase” makes it a natural for treatment of Alzheimer’s disease.13 This is the same enzyme delib-erately targeted by patent medicines “approved” by los federales for Alzheimer’s disease treatment.

Even though studies of berberine’s effect on human Alzheimer’s aren’t yet reported, one animal study has already found that berberine suppresses brain cell’s inflammatory response to beta amy-loid, a major factor in Alzheimer’s dementia.14 A second animal study—done with mice genetically engineered to develop human-style Alzheimer’s disease—found that berberine reduced both the damage caused by beta amyloid, and the amount of cognitive impairment.15 These animal studies were building on earlier research that had already shown berberine significantly reduces beta-amyloid production in cultured human brain cells.16

Other animal studies have found that berberine may also help repair peripheral nerve damage. Ani-mals with sciatic nerve damage were given berberine by injection; within a month, there was a noticeable regrowth of the damaged sciatic nerve.17 In the same publication, the researchers reported that berberine stimulated increased growth of “dendrites,” the very thin extensions branching out from the main body of a nerve cell which transmit “information” in and out.

As berberine research continues we’re finding out that it really is one of the most versatile plant substances for supporting human health. It not only kills many micro-organisms, research has also found that it could significantly improve type-2 diabetes, and may even help to prevent it, too. Ber-berine has shown promise in fighting Alzheimer’s

disease, and, most recently, its anticancer actions have been the subject of considerable research.18

However, all these novel uses are really only new to “Western” science. Chinese medicine has long used an herbal remedy known as “huanglian.” Huanglian, derived from Coptidis rhizome, is pri-marily made up of berberine. The remedy is used for the treatment of many diseases, including cancer.19

Could berberine stop the spread of cancer? Although powerful on its own, research has

found that Berberine can give some medications a boost. For example, it’s been shown to increase the sensitivity “in vitro” (that is in cell cultures, not liv-ing animals or humans) of two cancer cell types…A549 and HeLa…to doxorubicin, an anti-cancer patent medicine.20 And it has been studied for its ability to inhibit breast cancer cell metastasis.21

Berberine has been found to have its own cyto-toxic effect on cancer cells. It was shown to have the ability to kill cancer cells in a specific breast cancer cell line known as MCF-7. Researchers speculate that the herb may be able to serve as a naturally occurring treatment for breast cancer therapy.22

But berberine doesn’t stop with breast cancer. It turns out that melanoma, or skin cancer, may be susceptible to berberine treatment as well. One group of researchers found that the botanical inhib-ited cancer on the cellular level keeping two types of melanoma cells from metastasizing or spread-ing around the body. This is particularly important since this is typically how melanoma kills.23

Berberine’s cancer-fighting prowess doesn’t even end there. It reportedly has beneficial effects against oral cancer, and helps stop the development and spread of tumors of the colon.25 And the herbal has been shown to inhibit prostate cancer cell growth in mice.26 (See page 7 for more details on berber-ine’s prostate cancer fighting prowess.)

Keep your cholesterol under controlBerberine isn’t only a friend to diabetic cholesterol

control, it can lower cholesterol in non-diabetics, too. One study tracked thirty-two people with high cholesterol who took berberine for three months. By the end of the study, total cholesterol levels were re-duced 29%, triglycerides were reduced by 35%, and

The Botanical Diabetes Cure Your Doctor Doesn’t Know 6

LDL-cholesterol was reduced by 25%. The same group of researchers28 (as well as another group29) demonstrated that berberine lowers cholesterol in a different way than “statin” patent medicines.

Another group of researchers investigated the pos-sibility of using berberine as a treatment for obesity and elevated cholesterol and triglycerides. Ten indi-viduals participated in the twelve week pilot study, taking 500 milligrams of berberine three times daily. Seven of ten completed the study; of these, four ex-perienced an average weight loss of 5 pounds and the other three did not lose or gain weight. However, there was an average 12.2% decrease in total choles-terol and an average 23% decrease in triglycerides.

In addition, the researchers observed an increase of calcitriol (a bone-building parathyroid hormone) levels in all ten volunteers during the study, sug-gesting berberine may also aid in the prevention of osteoporosis. These same authors also conducted a rat study that found a significant decline in total cholesterol and triglycerides at the end of a twelve-week berberine protocol.30

Improved heart function in just 8 weeksBerberine improves heart function in chronic

congestive heart failure. One hundred fifty-six in-dividuals with congestive heart failure were taking conventionally prescribed therapy of ACE inhibi-tors, digoxin, nitrates, and diuretics. Seventy-nine of the group also took 1200 to 2000 milligrams of berberine daily, while seventy-seven took a placebo.

When symptoms and heart function were com-pared at eight weeks and two years later, the pa-tients who took berberine showed significantly better heart function, better exercise capacity, and significantly less fatigue than the placebo group. There were thirteen deaths in the placebo group, but only seven in the berberine group.31

Berberine has also been found to be useful in the treatment of congestive heart disease and for ar-rhythmias.32 And the herb has been shown to sig-nificantly lower homocysteine (a cardiovascular risk factor) in experimental animals, while at the same time lowering lipids.33

In a study of stroke caused by blocking an artery to the brain in experimental animals, administra-

tion of berberine within twenty-four hours signifi-cantly improved recovery time, and reduced the overall area of dead brain cells.34

The natural antibioticYou read earlier that berberine was first used as a

natural antibiotic and it still has much to offer in this area. The list of micro-organisms berberine works against is a long one, including staphylococcus, streptococcus, chlamydia, diphtheria, salmonella, vibrio cholerae, diplococcus penumoniae, pseudo-monas, gonorrhea, candida (technically a fungus) and others.

Berberine also works against parasites, includ-ing Giardia lamblia, Trichomonas vaginalis, Ent-amoeba histolytica, and Leishmania donovani. In one study comparing the effects of berberine to the patent medicine, metronidazole (Flagyl®) just half a dose of berberine was nearly as effective against parasites as metronidzole at full dose.35

Berberine’s therapeutic effects go beyond just killing germs. The botanical can help fight the sometimes fatal diarrhea caused by a few of them. That’s right, death from intense diarrhea! Less than two centuries ago here in America, and even re-cently in “third world countries,” the majority of the population of small towns and villages, could be wiped out by the intense diarrhea caused by the nasty parasite Vibrio cholera. Vibrio cholera se-cretes a toxin which causes tremendous water loss from the internal intestinal walls.

In cases of cholera and other diarrhea-causing bacteria, berberine’s poor absorbability is actually an advantage, since the majority of it stays within the inner walls of the intestines directly killing the germs lurking there.36 In a separate diarrhea-com-bating action berberine reduces the intestinal re-lease of water and electrolytes caused by the cholera toxin.37 The botanical then adds a third layer of pro-tection against diarrhea by reducing abnormal gut permeability.38

Showing promise against MRSA In 21st century America, the “most-feared” bacte-

rial infection is methicillin-resistant staphylococcus aureus, also known as MRSA or “flesh-eating bac-teria.” It’s possible that berberine may help against

The Botanical Diabetes Cure Your Doctor Doesn’t Know 7

this deadly micro-organism, too. Research has shown that berberine alone inhibited some strains of MRSA. Combining the botanical with particu-larly nasty antibiotics azithromycin or levofloxacin inhibited 90% of all MRSA strains tested.39

Berberine’s germ-killing ability could also be the answer to four seemingly unrelated problems: low platelet counts (for the technically inclined, “id-iopathic thrombocytopenic purpura”, or “ITP”), gastric hypochlorhydria (low stomach acid), peptic ulcers, and some cases of ischemic (lack of blood flow) stroke.

How can this be? The answer may lie in berber-ine’s ability to kill the germ “helicobacter pylori.”

Helicobacter pylori are associated with ITP, and while the exact way the bacteria lead to the con-dition is unknown, it’s believed that they trigger auto-immunity. Researchers have reported that, in test tubes, a very low concentration of berberine (12 micrograms per milliliter) inhibits the growth of helicobacter.40

Canadian researchers completed a systematic review of the existing literature on the effect of helicobacter pylori eradication therapy on people diagnosed with ITP. The studies compared the platelet response of those infected with H. pylori to people not infected. (It’s a bit of a mystery why helicobacter eradication therapy would even be tried in individuals who didn’t have helicobacter, but perhaps it’s because it’s the only treatment ever found to be effective in ITP.)

Eleven studies were included in the review. In those, a total of two hundred individuals were di-agnosed with ITP and 282 patients received heli-cobacter pylori eradication therapy. Two hundred five were helicobacter pylori-positive and seventy seven were helicobacter pylori-negative. Over 52% of the helicobacter-positive individuals had a signif-icantly improved platelet count, while only 8.8% of the helicobacter-negative saw a significant im-provement in platelet count.

Putting these two studies together, it appears that berberine treatment—rather than harsh conven-tional “triple antibiotic” treatment—should be tried first in helicobacter-positive individuals with ITP.

The digestion connectionIt may seem strange at first glance that berber-

ine could treat both peptic ulcers and low stomach acid. That’s because of the mistaken impression that these two conditions are opposites. It’s true that for nearly the entire 20th century Western med-ical dogma said that peptic ulcers were caused by too much stomach acid, despite the finding by Jap-anese researchers in 1919 that spiral bacteria (he-licobacter are spiral-shaped) caused gastric ulcers, as well as the discovery of helicobacter in human stomachs by an American researcher in 1939.

After that, a number of physicians cured peptic peptic ulcers with antibiotics, including penicillin. (A Greek physician was actually fined for curing ulcers with antibiotics!) In the 1980s Australian researcher Barry Marshall famously gave himself a peptic ulcer by swallowing—you guessed it—a big dose of helicobacter pylori. He and fellow re-searcher Robin Warren also cured peptic ulcer pa-tients with antibiotics.

But as “Wikipedia” politely writes: “an extensive effort was required to convince the medical commu-nity of the relevance of their work.” (It appears that some things never change…) Marshall and Warren were finally awarded the Nobel Prize in Medicine and Physiology in 2005 for this discovery.

So, as the majority of peptic ulcers are caused by helicobacter pylori, and berberine inhibits he-licobacter, the connection is clear. Now, for low stomach acid…

In 2000, Japanese researchers reported on the results of acid secretion tests done on two hundred eighty individuals. They concluded: “In the popu-lation studied, advancing age had no influence on gastric acid secretion in helicobacter pylori-nega-tive subjects. Gastric acid secretion decreases with age in helicobacter pylori-positive subjects because of the increasing prevalence of FAG [fundal gastric atrophy] with age.”41 (The “fundus” of the stom-ach is—a bit loosely—the upper part.)

In other words, the presence or absence of H. pylori corresponded to the presence or absence of low stomach acid. So it’s a reasonable conclusion that the helicobacter caused the hypochlorhydria as time went by (“with age”), and not that advanc-

The Botanical Diabetes Cure Your Doctor Doesn’t Know 8

ing age causes helicobacter infection. And it’s also reasonable to conclude that, if caught before the damage is too great, berberine might reverse hy-pochlorhydria, maybe even returning things all the way back to normal!

Lastly, there’s the type of stroke that’s caused by lack of blood flow, called “ischemic stroke.” A Japanese research team reported that in a group of sixty-two first time stroke sufferers, chronic helico-bacter pylori infection was significantly associated with a higher risk of stroke due to small artery oc-clusion (for the technically inclined, p <0.001).42 Since berberine inhibits helicobacter….well, you see where I’m going here.

Oops, that wasn’t “lastly,” because I mustn’t leave off the research connecting some cases of coronary atherosclerosis with helicobacter pylori. Because we’re running out of space, and still have one important question to answer, I’ll just repro-duce part of the title of one of the many research articles proving the association: “The detection of H. pylori specific DNA in human coronary athero-sclerotic plaque.”43 Yup, H. pylori are implicated in the hardening of arteries too. And of course, as we learned earlier, the best form of berberine for bac-teria found outside of the gut would be the better absorbed berberine with milk thistle combination.

Berberine’s effect on “friendly” bacteriaWith all the anti-bacterial and anti-parasite ef-

fects associated with berberine, there’s been (until recently) one unanswered question. Does berberine act like “regular” antibiotics in your body…killing off all the “friendly” bacteria in your gut along with the “bad guy” types? In other words, if you’re tak-ing the botanical for a long period of time do you also need to be taking probiotics to counteract the “number” it’s doing on your gut? The answer from

a preliminary research study appears to be “no.”

This study was done on rats, so even though it’s very likely the same results would be seen in humans, it’s not for certain. It demonstrated two separate but (as the researchers wrote) likely in-ter-related effects. First, berberine prevented diet-caused insulin resistance and obesity. Secondly, using very sophisticated genomic testing, the re-searchers found beneficial changes in the rat’s gut bacteria. Even though there was less “diversity” of gut bacteria after berberine administration, the over two hundred bacterial species which disappeared were thought to be “antigenic” and “pro-inflam-matory,” while the remaining bacteria produced significantly more “short-chain fatty acids,” which have anti-inflammatory effects. So, in other words, it appears that berberine mostly targeted the bad guys leaving the good guys alone.

The researchers concluded that the changes in gut bacteria may be at least partly responsible for the ef-fects in preventing obesity and in-sulin resistance.44

No, this isn’t a definitive answer to whether ber-berine will ultimately be found to be in the same category as oregano and garlic, which discourage “unfriendly” bacteria while promoting the growth of good ones. So it can’t hurt to use probiotics. But—in my opinion—when this research is done in humans it will come to the same conclusion: Berberine targets the bad germs while leaving our “friendly” bacteria alone.

In fact, as research continues to pour in, I think it will not only be confirmed that berberine is good for us in all the ways both proven and hinted at in this article, but in many other ways that have yet to be discovered as well.

Thank you to Ronald Steriti N.D. for finding nearly all the research papers used in this review, and to Lauren Russel N.D. for her skill in organizing them.

The Botanical Diabetes Cure Your Doctor Doesn’t Know 9

1. Berberine. Alternative Medicine Review. 2000; 5(2): 175-177.

2. Tan W, Li Y, Chen M, Wang Y. Berberine hydrochloride: an-ticancer activity and nanoparticulate delivery system. Int J Nanomedicine. 2011; 5:1773-1777.

3. Pan GY, Wang GJ, Liu XD, Fawcett JP, Xie YY. The involve-ment of P-glycoprotein in berberine absorption. Pharmacol. Toxicol. 2002; 91(4): 193-197.

4. Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glyco-protein. Drug Metab Rev. 2004; 36(1): 57-104.

5. Di Pierro F, Villanova N, Agostini F, Marzocchi R, Soverini V, Marchesini G. Pilot study on the additive effects of ber-berine and oral type 2 diabetes agents for patients with sub-optimal glycemic control.Diabetes Metab Syndr Obes. 2012; 5: 213-7.

6. Affuso F, Mercurio V, Ruvolo Am Pirozzi C, Filomena M et al. A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome. World J Cardiol. 2012. March 26; 4(3): 77-83.

7. Zhang M, Lu X, Li J, Meng Z et al. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis. Molecular and Cellular Endocrinol-ogy. 2012. 363(1-2): 133-30.

8. Choi BH, Hn IS, Kin YH. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-LI adipocyte. Experimental and Molecular Medicine. 2006. 38(6): 599-605.

9. Yang J, Yin J, Gao H, Xu inxin, Wang Y, Xu L, Li M. Ber-berine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evidence-Based Complemen-tary and Alternative Medicine.2012:1-9.

10. Wei W, Zhao H, Wang A, Sui M, Liang K, Deng H, Ma Y, Zhang Y, Zhang H, Guan Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. Eur J Endocrinol. 2012 Jan;166(1):99-105.

11. Rahigude AB, Kaulaskar SV, Bhutada PS. Possible thera-peutic potential of berberine in diabetic osteopathy. Med Hy-potheses. 2012; 79(4): 440-4.

12. Kulkarni SK, Dhir A. Berberine: a plant alkaloid with thera-peutic potential for central nervous system disorders. Phyto-ther Res. 2010. 24(3): 317-24.

13. Ji HF, Shen L. Berberine: a potential multipotent natural product to combat Alzheimer’s disease. Molecules. 2011; 16(8): 6732-40.

14. Jia L, Liu J, Song Z, Pan X, Chen L, Cui X, Wang M. Berber-ine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappa B and mito-gen-activated protein kinase signaling pathways. J Pharm Pharmacol 2012. 64(10): 1510-21.

15. Durairajan SS, Liu LF,Lu JH, Chen LL. Berberine amelio-rates beta-amyloid pathology, gliosis, and cognitive impair-ment in an Alzheimer’s disease transgenic mouse model. Neurobiol Aging. 2012; 3(12): 2903-19.

16. Asai M et al. Berberine alters the processing of Alzheim-er’s amyloid precursor protein to decrease Ab secretion. Biochemical and Biophysical Research Communications 2007;352:498-502

17. Han A, Heo H, Kwon Y Berberine Promotes Axonal Regen-eration in Injured Nerves of the Peripheral Nervous System. J Med Food 2012;15(4):413-417

18. Tillhon M, Ortiz L, Lombardi P, Scovassi A. Berberine: new perspectives for old remedies. Biochemical Pharmacology. 2012. Article in press.

19. Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y. Ber-berine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J Ethnopharmacol. 2009; 126(1): 5-17.

20. Tong N, Zhang J, Chen Y, Li Z, Luo Y et al. Berberine sensi-tizes multiple human cancer cells to the anticancer effects of doxorubicin in vitro. Oncology Letters. 2012; 3: 1263-1267.

21. Kuo HP, Chuang TC, Tsai SC, Tseng HH, Hsu SC, Chen YC, Kuo CL et al. Berberine, an isoquinolone alkaloid, inhibits the metastatic potential of breast cancer cells via Akt path-way modulation. J Agric Food Chem. 2012, Sep 5 (Epub ahead of print)

22. Ibid.

23. Singh T, Vaid M, Katiyar N, Sharma S, Katiyar SK. Berber-ine, an isoquinolone alkaloid, inhibits melanoma cancer cell migration by reducing the expressions of cyclooxygenase-2, prostaglandin E, and prostaglandin E receptors. Carcinogen-esis. 2011. 32(1): 86-92.

24. Kuo C, Chi C, Liu T. The anti-inflammatory potential of ber-berine in vitro and in vivo. Cancer Letterss. 2004. 203(2): 127-137.

25. Park JJ, Seo SM, Kang SB, Kim EG, Lee YJ et al. Berberine inhibits human colon cancer cell migration via AMP-activat-ed protein kinase-mediated downregulation of integrin B1 signaling. Biochem Biophys Res Commun. 2012. Aug 25. (Epub ahead of print).

26. Wang Y, Liu Q, Liu Z, Li B, Sun Z, Zhou H, Zhang X, Gong Y, Shao C. Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells. Mutat Res. 2012. 734(1-2): 20-9.

27. Bhattacharjee B et al. Computer aided screening of inhibitors to 5-a reductase type 2 for prostate cancer. Bioinformation 2011;6(7):262-265

28. Kong W, Wei J, Abidi P, Lin M, Inaba S et al. Berberine is a nov-el cholesterol-lowering drug working through a unique mecha-nism distinct from statins. Nat Med. 2004. 10(12): 1344-51.

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The Botanical Diabetes Cure Your Doctor Doesn’t Know 10

29. Brusq JM, Ancellin N, Grondin P, Guillard R, Martin S, Sain-tillan Y, Issandou M. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J Lipid Res. 2006 47(6): 1281-8.

30. Hu Y, Ehli E, Kittelsrud J, Ronan P, Munger K et al. Lip-id-lowering effect of berberine in human subjects and rats. Phytomedicine. 2012; 19(10): 861-7.

31. Zeng XH, Zeng XJ, Li YY. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idio-pathic dilated cardiomyopathy. Am J Cardiol. 2003. 92(2): 173-6.

32. Lau CW, Yao XQ, Chen ZY, Ko WH, Huang Y. Cardiovascu-lar actions of berberine. Cardiovasc Drug Rev. 2001. 19(3): 234-44.

33. Chang X, Yan H, Xu Q, Xia M, Bian H et al. The effects of berberine on hyperhomocysteinemia and hyperlipidemia in rats fed with a long-term high-fat diet. Lipids in Health and Disease. 2012; 11:86.

34. Zhang X, Zhang Xi, Wang C, Li Y, Dong L. Neuroprotec-tion of early and short-time applying berberine in the acute phase of cerebral ischemia: Up-regulated pAkt, pGSK, and pCREB, down-regulated NF-kB expression, ameliorated BBB permeability.

35. Choudry VP, Sabir M, Bhide VN. Berberinein giardiasis. In-dian Pediatrics. 1972; 9: 143-146.

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References