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Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. - Nat Med. 2004 Dec;10(12):1344-51.
Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins.
Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD.
Nat Med. 2004 Dec;10(12):1344-51. Epub 2004 Nov 7.
PMID: 15531889
doi:10.1038/nm1135
We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs. -
Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine -- Zhang et al. 93 (7): 2559 -- Journal of Clinical Endocrinology & Metabolism
Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine.
Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, Huo L, Wang M, Hong J, Wu P, Ren G, Ning G.
J Clin Endocrinol Metab. 2008 Jul;93(7):2559-65. Epub 2008 Apr 8.
PMID: 18397984
doi:10.1210/jc.2007-2404
Conclusions: Berberine is effective and safe in the treatment of type 2 diabetes and dyslipidemia. -
Powerful Advances in Natural Cancer Prevention - Life Extension
Scientists have known that cruciferous vegetables contain a host of chemopreventive agents that act in many different ways to block cancer development.2 Key among these products are indole-3-carbinol (I3C) and sulforaphane.1,3
Cancer cells need a brisk blood supply to support their rampant growth and reproduction. Preliminary studies in vitro and in vivo have found that apigenin inhibits blood vessel growth (angiogenesis) in human ovarian cancer cells, blocking production of two main signaling molecules required to stimulate vessel growth.20,21 Scientists confirmed this effect in ovarian cancer cells, also finding that apigenin strongly inhibits cell proliferation.22
Apigenin and BITC: Complementary Cancer Protection
Cancer cells also need energy to support their frenetic reproductive activity. Researchers applied apigenin to human pancreatic cancer cells in culture and studied the cells’ uptake of glucose.14 Astonishingly, they found that apigenin deprived energy-hungry cancer cells of glucose to support their voracious appetites and aggressive growth. It did this by down-regulating vital glucose-transporting proteins in cancer cells. This approach could effectively starve deadly cancer cells and stop them in their tracks.
Another cruciferous vegetable component receiving rave reviews is the sulfur-containing molecule benzyl isothiocyanate, or BITC (pronounced “bitsy”). As with apigenin, population studies have shown that higher intakes of BITC correlate with reduced risk of cancers of the lung, breast, and colon30 while blocking cancer development in a host of different ways.
BITC induces breast cancer cell death by apoptosis (programmed cell death), interfering with cancer cells’ energy utilization and causing them to die off before they can contribute to tumor growth.31,32 In human ovarian cancer cells, BITC induces apoptosis by a different mechanism. It stimulates “signaling” molecules that tell cancer cells it’s time to close up shop. -
Berberine - wellness.com
"Berberine is a bitter-tasting, yellow, plant alkaloid with a long history of medicinal use in Chinese and Ayurvedic medicine. Berberine is present in the roots, rhizomes and stem bark of various plants including Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). Berberine has also been used historically as a dye, due to its yellow color.
Clinical trials have been conducted using berberine. There is some evidence to support its use in the treatment of trachomas (eye infections), bacterial diarrhea, and leishmaniasis (parasitic disease). Berberine has also shown antimicrobial activity against bacteria, viruses, fungi, protozoans, helminths (worms), and chlamydia (STD). Future clinical research is warranted in these areas, as well as cardiovascular disease, skin disorders, and liver disorders.
Berberine has been shown to be safe in the majority of clinical trials. However, there is a potential for interaction between berberine and many prescription medications, and berberine should not be used by pregnant or breastfeeding women, due to potential for adverse effects in the newborn." -
Berberine, dosing and safety - wellness.com
Side Effects and Warnings
Berberine has been reported to cause nausea, vomiting, hypertension (high blood pressure), respiratory failure and paresthesias (abnormal sensations such as numbness or tingling); however, clinical evidence of such adverse effects is not prominent in the literature. Rare adverse effects including headache, skin irritation, facial flushing, headache, bradycardia (slowed heart rate) have also been reported with the use of berberine. Use cautiously when taking berberine for longer than eight weeks due to theoretical changes in bacterial gut flora.
Use cautiously in individuals with diabetes, as both human and animal studies indicate that berberine may decrease blood sugar levels. Also use cautiously in individuals with hypotension (low blood pressure), as berberine may have antihypertensive effects.
Patients with cardiovascular disease should also use caution as berberine has been associated with the development of ventricular arrhythmias in subjects with congestive heart failure.
Although not well studied in humans, berberine may also theoretically cause delays in small intestinal transit time or increase the risk of bleeding.
Berberine may cause abortion, eye or kidney irritation, nephritis (inflamed kidneys), dyspnea (difficulty breathing), flu-like symptoms, giddiness, lethargy, or liver toxicity.
Patients with leukopenia (abnormally low white blood cell count) should use cautiously due to the potential for development of leukopenia symptoms.
When injected under the skin, berberine may cause hyperpigmentation in the arm. Use berberine cautiously in individuals with high exposure to sunlight or artificial light due to potential for adverse phototoxic reactions.
Avoid in newborns due to potential for increase in free bilirubin, jaundice, and development of kernicterus (brain damage caused by severe newborn jaundice). Use berberine cautiously in children due to a lack of safety information.
Pregnancy and Breastfeeding
Berberine is not recommended in pregnant or breastfeeding women due to a -
Developmental toxicity evaluation of berberine in rats and mice. Gloria D. Jahnke. 2006; Birth Defects Research Part B: Developmental and Reproductive Toxicology - Wiley InterScience
Developmental toxicity evaluation of berberine in rats and mice.
Jahnke GD, Price CJ, Marr MC, Myers CB, George JD.
Birth Defects Res B Dev Reprod Toxicol. 2006 Jun;77(3):195-206.
PMID: 16634078
DOI: 10.1002/bdrb.20075
BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health-related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice.
METHODS: Berberine chloride dihydrate was administered in the feed to timed-mated Sprague-Dawley (CD) rats (0, 3625, 7250, or 14,500 ppm; on gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3500, 5250, or 7000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1313 mg/kg/day (rats) and 0, 569, 841, and 1155 mg/kg/day (mice).
RESULTS:There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1000 mg/kg/day was conducted in both species.
CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7250 ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL was raised to 1000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5-6% with no change in live litter size. The maternal toxicity LOAEL remained at 5250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1000 mg/kg/day BCD based on decreased fetal body weight. -
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 - JPET
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.
Pereira GC, Branco AF, Matos JA, Pereira SL, Parke D, Perkins EL, Serafim TL, Sardão VA, Santos MS, Moreno AJ, Holy J, Oliveira PJ.
J Pharmacol Exp Ther. 2007 Nov;323(2):636-49. Epub 2007 Aug 17.
PMID: 17704354
doi: 10.1124/jpet.107.128017
The present work shows that berberine is accumulated by mitochondria of a mouse melanoma cell line, leading to mitochondrial fragmentation and dysfunction, accompanied by decreased cellular energy charge. When the effect was compared with the results obtained on isolated mitochondrial fractions, it is observed that regardless of the system used, berberine is toxic for mitochondria. One major limitation of the present study (as in many others) is the lack of knowledge of the real concentration of berberine that reaches mitochondria in intact cells. Although we do not possess data regarding this aspect, it is wise to speculate that mitochondrial berberine concentrations will be much higher than in the bulk cytosol due to electrophoretic accumulation. We believe that the range of berberine concentrations accumulated by mitochondria in intact cells is within the range of concentrations used on isolated mitochondrial fractions in the present study. The present work not only provides insights on the mechanism by which berberine interferes with tumor cell proliferation, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of berberine as a nontoxic “natural” over-the-counter medication. -
Berberine Inhibits Metastasis of Nasopharyngeal Carcinoma 5-8F Cells by Targeting Rho Kinase-mediated Ezrin Phosphorylation at Threonine 567 - JBC
Berberine inhibits metastasis of nasopharyngeal carcinoma 5-8F cells by targeting Rho kinase-mediated Ezrin phosphorylation at threonine 567.
Tang F, Wang D, Duan C, Huang D, Wu Y, Chen Y, Wang W, Xie C, Meng J, Wang L, Wu B, Liu S, Tian D, Zhu F, He Z, Deng F, Cao Y.
J Biol Chem. 2009 Oct 2;284(40):27456-66. Epub 2009 Aug 3.
PMID: 19651779 -
Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells — Mol Cancer Ther
Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells.
Mantena SK, Sharma SD, Katiyar SK.
Mol Cancer Ther. 2006 Feb;5(2):296-308.
PMID: 16505103
doi: 10.1158/1535-7163.MCT-05-0448
The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy.
The evaluation of ancient herbal medicines may indicate novel strategies for the treatment of prostate cancer, which remains the leading cause of cancer-related deaths in American men (1). In our present investigation, we show that a naturally occurring isoquinoline alkaloid, berberine, significantly inhibits the proliferation and reduces the viability of DU145 and PC-3 as well as LNCaP cells (Fig. 1), which suggests that berberine may be an effective chemotherapeutic agent against both androgen-sensitive and androgen-insensitive prostate cancer cells. Importantly, we found that berberine did not exhibit toxicity to nonneoplastic human prostate epithelial cells under the conditions used, except for a moderate reduction in cell viability at higher concentrations when cells were treated in vitro for an extended period of time.
In conclusion, the results of the present study indicate that berberine inhibits proliferation and induces G1-phase arrest and apoptosis in human prostate cancer cells but not in normal human prostate epithelial cells. In addition, we provide mechanistic evidence that berberine-induced apoptosis in prostate carcinoma cells, particularly hormone-refractory prostate carcinoma cells, is mediated through enhanced expression of Bax, disruption of the mitochondrial membrane potential, and activation of caspase-3. -
Jonathan Treasure - Herbological.com
"This site provides information on herbal medicine (as distinct from herbal medicines) sometimes also called phytotherapy.
Herbological.com is maintained by Jonathan Treasure, a medical herbalist with professional qualifications in both conventional medical sciences and herbal medicine from the UK, now located in Southern Oregon, USA. (See bio and consulting pages for further details) " -
Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-κB, u-PA and MMP-2 and -9
Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9.
Ho YT, Yang JS, Li TC, Lin JJ, Lin JG, Lai KC, Ma CY, Wood WG, Chung JG.
Cancer Lett. 2009 Jul 8;279(2):155-62. Epub 2009 Feb 28.
PMID: 19251361
doi:10.1016/j.canlet.2009.01.033
There is increasing evidence that urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) play an important role in cancer metastasis and angiogenesis. Inhibition of u-PA and MMPs could suppress migration and invasion of cancer cells. Berberine, one of the main constituents of the plant Rhizoma coptidis, is a type of isoquinoline alkaloid, reported to have anti-cancer effects in different human cancer cell lines. There is however, no available information on effects of berberine on migration and invasion of human tongue cancer cells. Here, we report that berberine inhibited migration and invasion of human SCC-4 tongue squamous carcinoma cells. This action was mediated by the p-JNK, p-ERK, p-p38, IκK and NF-κB signaling pathways resulting in inhibition of MMP-2 and -9 in human SCC-4 tongue squamous carcinoma cells. Our Western blowing analysis also showed that berberine inhibited the levels of urokinase-plasminogen activator (u-PA). These results suggest that berberine down-regulates u-PA, MMP-2 and -9 expressions in SCC-4 cells through the FAK, IKK and NF-κB mediated pathways and a novel function of berberine is to inhibit the invasive capacity of malignant cells. -
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 -- Mantena et al. 27 (10): 2018 --
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.
Mantena SK, Sharma SD, Katiyar SK.
Carcinogenesis. 2006 Oct;27(10):2018-27. Epub 2006 Apr 18.
PMID: 16621886
doi:10.1093/carcin/bgl043
In the present investigation, we show that berberine, which is present abundantly in Berberis plant species, significantly inhibits the viability, proliferation and induces cell death in human epidermoid carcinoma A431 cells (Figure 1), but this effect was not found in normal human epidermal keratinocytes under the identical conditions, except for a non-significant reduction in cell viability at higher concentrations of berberine (50 and 75 µM) and treatment of cells for a longer period of time (72 h). These data suggested that berberine may be examined as an effective chemotherapeutic agent against non-melanoma skin cancers.
In conclusion, our study indicates that berberine inhibits growth, induces G1 arrest and apoptotic cell death of human epidermoid carcinoma A431 cells. We also provide mechanistic evidences that berberine-induced apoptosis in human epidermoid carcinoma cells is mediated through disruption of mitochondrial membrane potential and activation of caspase 3 pathway, although other pathways may have a role and that require further investigation. Moreover, further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the prevention of non-melanoma skin cancers. -
Berberine : Information on Uses, Dosage & Side Effects on Healthline.com
"Berberine is a bitter-tasting, yellow, plant alkaloid with a long history of medicinal use in Chinese and Ayurvedic medicine. Berberine is present in the roots, rhizomes and stem bark of various plants including Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). Berberine has also been used historically as a dye, due to its yellow color.
Clinical trials have been conducted using berberine. There is some evidence to support its use in the treatment of trachomas (eye infections), bacterial diarrhea, and leishmaniasis (parasitic disease). Berberine has also shown antimicrobial activity against bacteria, viruses, fungi, protozoans, helminths (worms), and chlamydia (STD). Future clinical research is warranted in these areas, as well as cardiovascular disease, skin disorders, and liver disorders. -
Berberine health benefit and side effects : by Ray Sahelian, M.D.
"Berberine is a plant alkaloid isolated from the roots and bark of several herbs. Some of these herbs include:
Barberry (Berberis vulgaris), Berberis integerrima. Berbamine and berberine are found in the plant barberry.
Coptis chinensis or Berberis aristata
Goldenseal (Hydrastis canadensis)
Oregon Grape (Berberis aquifolium)
Phellodendron Amurense
Yerba mansa (Anemopsis californica).
The berberine alkaloid can be found in the roots, rhizomes, stem, and bark of the plants. Berberine-containing plants are used medicinally in many traditional medical systems, including Ayurvedic herbal and Chinese herbal medicine.
Coptis chinensis rhizome -- Golden Thread -- Huang Lian -- Intense yellow color most likely due to high content of berberine, which is very bitter in taste" -
A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. - Anti-Cancer Drugs
A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs.
Sun Y, Xun K, Wang Y, Chen X.
Anticancer Drugs. 2009 Oct;20(9):757-69.
PMID: 19704371 -
Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations - ScienceDirect - Journal of Ethnopharmacology
Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations.
Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y.
J Ethnopharmacol. 2009 Oct 29;126(1):5-17. Epub 2009 Aug 15.
PMID: 19686830
doi:10.1016/j.jep.2009.08.009
Conclusions
The modern evidences of treating cancer with Huanglian and berberine have a strong linkage with traditional concept and rules of using Huanglian in CM practice. As anticancer candidates with low toxicity, berberine and its altered structure, as well as Huanglian and its formulae, will attract scientists to pursue the potential anticancer effects and the mechanisms by using technologies of genomics, proteomics and other advanced approaches. On the other hand, relatively few in vivo studies have been conducted on anticancer effects of Huanglian and berberine. The clinical application of berberine or Huanglian as novel cancer therapeutic agents requires in vivo validations and further investigations of their anticancer mechanisms. -
Berberine - Wikipedia, the free encyclopedia
"Berberine is a quaternary ammonium salt from the group of isoquinoline alkaloids. It is found in such plants as Berberis, goldenseal (Hydrastis canadensis), and Coptis chinensis, usually in the roots, rhizomes, stems, and bark. Berberine is strongly yellow colored, which is why in earlier times berberis species were used to dye wool, leather and wood. Wool is still today dyed with berberine in Northern India
Berberine (BBR) is a natural compound with up-regulating activity on both low-density-lipoprotein receptor (LDLR) and insulin receptor (InsR). This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome.[12] Berberine has been tested and used successfully in experimental[13] and human diabetes mellitus.[14][15][16] Berberine has been shown to lower elevated blood glucose as effectively as metformin.[17] The mechanisms include inhibition of aldose reductase,[18] inducing glycolysis,[19] preventing insulin resistance[20] through increasing insulin receptor expression[14] and acting like incretins.
Berberine has drawn extensive attention towards its antineoplastic effects.[43][44] It seems to suppress the growth of a wide variety of tumor cells including breast cancer,[45] leukemia, melanoma,[46] epidermoid carcinoma, hepatoma, oral carcinoma, tongue carcinoma,[47] glioblastoma, prostate carcinoma, gastric carcinoma.[48][49] Animal studies have shown that berberine can suppress chemical-induced carcinogenesis, tumor promotion, tumor invasion,[50][51][52][53][54] prostate cancer,[55][56][57][58] neuroblastoma,[59][60] and leukemia.[34][61] It is a radiosensitzer of tumor cells but not of normal cells -
New antioxidant compounds have been identified in foods such as olive oil, honey and nuts
"Scientists at the University of Granada have identified and characterized for the first time different antioxidant compounds from foods such as olive oil, honey, walnuts and a medicinal herb called Teucrium polium. They have used two new techniques, capillary electrophoresis and high resolution liquid chromatography, that have enabled them to identify and quantify a great part of the phenolic compounds contained in these foods."
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A New Sugar Substitute Joins a Street Fight - NYTimes.com
The Food and Drug Administration agreed in December that rebaudioside A, an extract from the leaves of the stevia plant, is safe to add to food and drinks.
Stevia has one distinct advantage over all the rest. Because it comes from a plant, marketers can call it a natural sweetener. And that allows companies that have invested millions in new stevia products to tap into two powerful markets at once: natural ingredients and low-calorie products.
Two of the biggest backers, Cargill and Whole Earth Sweetener Company, earlier this year began rolling out packets of stevia-based sweeteners, called Truvia and PureVia respectively. The extract is in the companies’ drinks, too. Among the new stevia products marketed as naturally sweetened are Sprite Green from Coca-Cola and Trop50, from the PepsiCo subsidiary Tropicana. It’s essentially half water and half orange juice doctored with stevia. -
Stevia, Sweetener, Artificial Sweeteners - Dr. Weil
Stevia comes from an herb in the chrysanthemum family called Stevia rebaudiana. It is native to Paraguay, also grows in Brazil and Argentina, and is cultivated in China. The leaves have been used for centuries by native peoples to make sweet teas, or to sweeten other foods, with no evidence of harm. It is available in the United States, and the European Union as a dietary supplement and is sold here in whole-leaf form or as stevioside, the extracted sweet principle, sold as a granular white powder. The powder has very few calories but is so sweet that to use it, you must dissolve it in water, then dispense the solution by drops. A teaspoon of the liquid is equivalent in sweetness of a whole cup of sugar. Stevia is safe for diabetics and is widely used as a nonnutritive sweetener around the world.
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