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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.

Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice.\nOkano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, Nakagawa K.\nJ Biol Chem. 2008 Apr 25;283(17):11270-9. Epub 2007 Dec 14. \nPMID: 18083713 \ndoi: 10.1074/jbc.M702971200 \n\nOur results suggest that cerebral menaquinone-4 originates from phylloquinone intake and that there are two routes of accumulation, one is the release of menadione from phylloquinone in the intestine followed by the prenylation of menadione into menaquinone-4 in tissues, and another is cleavage and prenylation within the cerebrum.

Ikaria Lean Belly Juice Only $69/Bottle Limited Time Offer! Special Deal + Special 80% Discount Save $840+ 180 Days Money Back Guarantee lkaria Lean Belly Juice lkaria Lean Belly Juice Five Star Ikaria Lean Belly Juice is a powerful new formula that makes weight loss easier, faster and much more fun… Ikaria Lean Belly Juice is a powerful weight management complex that is 100% herbal and pure, which can aid in burning stubborn belly fat effectively and helps you lose weight naturally. Regular Price: $179/per bottle Only for: $69/per bottle Buy Now What Is Ikaria Lean Belly Juice? Ikaria Lean Belly Juice formula is different from other weight loss or diet pills. You might have never tried or seen something like or even close. Ikaria Lean Belly Juice for losing belly fat before. As the name suggests, this Ikaria belly fat-burning juice is based on a daily ritual of the healthiest part of the world, Ikaria. Researchers found that a number of natural ingredients, fruits, and plant extracts available on the island can help lose weight by eliminating toxic lipid molecules and reducing high uric acid levels in the human body. Ikaria Lean Belly Juice is an effective weight loss diet supplement that is made up of several effective, scientifically-proven ingredients that can help you lose weight. It aids in shedding belly fat and excess weight. This product has incredible health benefits to clients. The Ikaria Lean Belly Juice formula was created by a group of experts who wanted to help all those people who were struggling to lose weight. The formula of the supplement has been prepared under strict conditions in an FDA-registered facility, and its blend of natural ingredients like milk thistle supports weight loss incredibly. Each bottle comes with 30 days of servings that can be blended together with liquids. The powder's formula is produced in GMP-certified, FDA-approved labs to guarantee high-quality and safety. A lot of people have questions rega

LeanBiome™ About How it Works? Ingredients Order Now LeanBiome Hurry Up! Offer Expires in: 00 HOUR 23 MINUTE 57 SECOND LeanBiome Attention! Get Special 84% Discount Today Faster fat burning and weight loss Healthy cholesterol and sugar levels Boost energy levels Regular price: $129 Only for: 39$ Buy Now payment_intro What Is LeanBiome? LeanBiome Supplement LeanBiome is a natural dietary supplement available on the market by Lean for Good. This dietary supplement has been designed for women above 18 years of age to support weight loss. The LeanBiome formula is based on the latest Ivy Research and real-world results. It is made using beneficial gut bacteria strains, lean bacteria species, and Phytosome green tea extract. The LeanBiome weight loss formula is helpful in losing weight accumulated in different parts of your body, thus supporting a completely healthy body. The presence of beneficial bacteria in this formula makes it better than other weight loss supplements on the market as these healthy bacteria (good bacteria) help you lose weight, maintain proper gut health, and support healthy digestion through a healthy digestive system. How Does LeanBiome Work? If you're a woman above 18 years old struggling with weight loss, LeanBiome could be the supplement for you. It contains nine beneficial bacteria strains and natural green tea extract. The way LeanBiome operates is by first promoting a healthy stomach. When your stomach is healthy, it contains beneficial bacteria that aid in the digestion and absorption of nutrients from food. The presence of harmful bacteria in your stomach can cause weight gain. LeanBiome promotes the growth of beneficial bacteria and reduces harmful bacteria in your gut, leading to improved digestion and a healthier stomach.Next in the action line is Inulin - a prebiotic fiber that strides hand in hand with these probiotics. It nourishes the friendly bacteria in your gut, promoting better digestion and stable blood sugar levels.

Sunlight, vitamin D and the prevention of cancer: a systematic review of epidemiological studies. Rhee HV, Coebergh JW, Vries ED. Eur J Cancer Prev. 2009 Aug 26. [Epub ahead of print] PMID: 19730382 We, therefore, conclude that there is accumulating evidence for sunlight as a protective factor for several types of cancer. The same conclusion can be made concerning high vitamin D levels and the risk of colorectal cancer. This evidence, however, is not conclusive, because the number of (good quality) studies is still limited and publication biases cannot be excluded. The discrepancies between the epidemiological evidence for a possible preventive effect of sunlight and vitamin D and the question of how to apply the findings on the beneficial effects of sunlight to (public) health recommendations are discussed.

Nonalcoholic fatty liver disease is common and, for most people, causes no signs and symptoms and no complications. But in some people with nonalcoholic fatty liver disease, the fat that accumulates can cause inflammation and scarring in the liver. This more serious form of nonalcoholic fatty liver disease is sometimes called nonalcoholic steatohepatitis. At its most severe, nonalcoholic fatty liver disease can progress to liver failure.

Vitamin D deficiency is the cause of common obesity. Foss YJ. Med Hypotheses. 2009 Mar;72(3):314-21. Epub 2008 Dec 2. PMID: 19054627 doi:10.1016/j.mehy.2008.10.005 Common obesity and the metabolic syndrome may therefore result from an anomalous adaptive winter response. The stimulus for the winter response is proposed to be a fall in vitamin D. The synthesis of vitamin D is dependent upon the absorption of radiation in the ultraviolet-B range of sunlight. At ground level at mid-latitudes, UV-B radiation falls in the autumn and becomes negligible in winter. It has previously been proposed that vitamin D evolved in primitive organisms as a UV-B sensitive photoreceptor with the function of signaling changes in sunlight intensity. It is here proposed that a fall in vitamin D in the form of circulating calcidiol is the stimulus for the winter response, which consists of an accumulation of fat mass (obesity) and the induction of a winter metabolism (the metabolic syndrome). Vitamin D deficiency can account for the secular trends in the prevalence of obesity and for individual differences in its onset and severity. It may be possible to reverse the increasing prevalence of obesity by improving vitamin D status.

A new study in animals demonstrates that a diet rich in coconut oil protects against 'insulin resistance' (an impaired ability of cells to respond to insulin) in muscle and fat. The diet also avoids the accumulation of body fat caused by other high fat diets of similar calorie content. Together these findings are important because obesity and insulin resistance are major factors leading to the development of Type 2 diabetes. "

n-3 fatty acids and gene expression. Deckelbaum RJ, Worgall TS, Seo T. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1520S-1525S. Review. Erratum in: Am J Clin Nutr. 2006 Oct;84(4):949. PMID: 16841862 Accumulating evidence in both humans and animal models clearly indicates that a group of very-long-chain polyunsaturated fatty acids, the n-3 fatty acids (or omega-3), have distinct and important bioactive properties compared with other groups of fatty acids. n-3 Fatty acids are known to reduce many risk factors associated with several diseases, such as cardiovascular diseases, diabetes, and cancer. The mechanisms whereby n-3 fatty acids affect gene expression are complex and involve multiple processes. As examples, n-3 fatty acids regulate 2 groups of transcription factors, such as sterol-regulatory-element binding proteins and peroxisome proliferator-activated receptors, that are critical for modulating the expression of genes controlling both systemic and tissue-specific lipid homeostasis. Modulation of specific genes by n-3 fatty acids and cross-talk between these genes are responsible for many effects of n-3 fatty acids.

Arthritis has a cause: the toxins that have attacked your body. If not washed out, toxic wastes will continue accumulating until they damage your joint structure. In addition, inflammation strikes and you end up with disabling arthritis. Can you prevent this threat? Yes, by washing out of your system the toxins through an adequate diet.

Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator. Pereira CV, Machado NG, Oliveira PJ. Toxicol Sci. 2008 Oct;105(2):408-17. Epub 2008 Jul 3. PMID: 18599498 doi: 10.1124/jpet.107.128017 The data from the present work appear to show that berberine also presents some degree of toxicity to "nontumor" systems, which should be carefully understood. ANT inhibition in nontumor cells by berberine would be responsible for a decrease in energy production and could also result in MPT induction. To the best of our knowledge, no full toxicity assessment exists for berberine in humans, although its use in several commercially available supplements suggests that the compound may present a relatively wide safety interval. In fact, a study with patients with congestive heart failure treated with 1.2 g/day of oral berberine revealed low toxicity and resulted into an average plasma concentration of 0.11 mg/l which would translate into 0.3µM (Zeng and Zeng, 1999Go). Repeated cumulative treatments, alternative forms of formulation (e.g., topical application vs. injection) or more importantly, active mitochondrial accumulation due to its positive charge would be expected to increase its concentration in cells into the range of concentrations used in this study. Empirical data from nontraditional medicines plus the use of extensive clinical assays would allow the use of berberine as a promising antimelanoma agent while maintaining its safety for humans. In radial/vertical forms of melanoma, a possible topical application of berberine would also be possible, thus minimizing side effects on other organs. In conclusion, the present work identifies the ANT as an important target for berberine, with clear relevance for its proposed antitumor effects.

Losing belly fat is a dream of millions of people around the world. Belly fat is one of the most dangerous of all fats because the fat accumulates around your organs. According to Rob Poulos, a fitness author, people are trying to get rid of belly fat all the wrong way.

he good news for those whose bodies are loaded with a few unwanted and extra pounds of flab is that it is not all that difficult to lose weight with fatburners. Natural products are readily available and these can do the job quite effectively. These products are designed especially to help improve the metabolic rate in the body and in addition these products will also prevent further accumulation of flab in the body.