Recent findings reveal that the antidepressant effects of berberine result from the activation of the 5-HT2 receptor by its impact on the brain-derived neurotrophic factor-cAMP response element, the binding protein, and the eukaryotic elongation factor 2 pathways. Berberine is an alkaloid you can find in several plants, including barberry, goldenseal, and Oregon grape. Zhang et al. Ayati S.H., Fazeli B., Momtazi-borojeni A.A., Cicero A.F.G., Pirro M., Sahebkar A. Several studies among people with type 2 diabetes have shown that taking 600-2,700 mg of berberine daily may lower fasting and long-term blood sugar levels by up to 20% and 12%, respectively . Xie W., Gu D., Li J., Cui K., Zhang Y. The Homeostasis Model in the San Antonio Heart Study. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, Systolic blood pressure and diastolic blood pressure in mmHg, Alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, gamma-glutamyltransferase, total protein, and albumin, Berberine was safe with no serious adverse events, No differences in triglycerides, thromboxane A2, blood pressure, BMI, or waist-to-hip ratio [, A significant reduction in total cholesterol and LDL-C at week 4, No significant changes in the concentrations of HDL-C, fasting glucose, and serum triglycerides in any of the groups, Percentage change from baseline of total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and Triglycerides (Tg) plasma concentrations, Significant reduction in the homeostasis model assessment of insulin resistance (HOMA-IR index), Significant decrease in total and low-density lipoprotein cholesterol, Triglycerides, high density lipoprotein cholesterol, and oral glucose tolerance test (OGTT) were not affected, Significant reductions in blood glucose and insulin after the standard mixed meal, Increase in flow-mediated dilation (FMD) and a significant reduction in arterial systolic blood pressure [, Change from baseline in circulation endothelial microparticles, Significant reduction in total and LDL cholesterol, LDL cholesterol change was positively associated with hsCRP and EMP changes, hsCRP and EMP changes were associated with each other [, Change in LDL cholesterol, triglycerides, and HDL cholesterol, Difference in the LDL Cholesterol, triglycerides, and HDL cholesterol, Change in inflammatory cytokines (IL-1, IL6, IL-10, hsPCR, and TNF-), Difference in the inflammatory cytokine values, Change in the hormone profile (glucagon, active GLP-1, and GIP), Significant correlation between baseline level of non-HDL-C and the reduction observed after 12 weeks of treatment, Significant reduction in LDL-C and apolipoprotein (Apo) B, No changes were observed between treatment arms in HDL-C, triglycerides, fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), waist circumference, and body mass index, Differences in ApoB/ApoA ratio did not reach statistical significance [, Levels of triglycerides and cholesterol high-density lipoprotein (HDL-C), The ratios of ApoB-100/ApoA-1 were reduced, No statistically significant changes were observed in TG and HDL-C levels, The weight loss observed in the AP consumption group had no significant impact on LDL-C reduction, Apo B-100, TC/HDL-C ratio, or on the ApoB/ApoA1 ratio, Non-significant contribution of weight-loss to LDL-C reduction [, Effects on lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides), Effects on metabolic indexes (glucose levels), Effects on metabolic indexes (insulin plasma levels and insulin sensitivity index (HOMA index)), Reduced LDL cholesterol below 130 mg/dL in 56.5% of patients (Combination A), Reduced plasma levels of triglycerides, total and LDL cholesterol, and increased HDL cholesterol. Hsu W.-H., Hsieh Y.-S., Kuo H.-C., Teng C.-Y., Huang H.-I., Wang C.-J., Yang S.-F., Liou Y.-S., Kuo W.-H. Berberine Induces Apoptosis in SW620 Human Colonic Carcinoma Cells through Generation of Reactive Oxygen Species and Activation of JNK/P38 MAPK and FasL. suggests that berberine has different effects on testosterone in men than in women. Berberine is a bitter-tasting and. Berberine Mitigates High Glucose-Induced Podocyte Apoptosis by Modulating Autophagy via the MTOR/P70S6K/4EBP1 Pathway. The levels of these proteins have been reported to increase after their exposure to berberine, while the levels of Bcl-X, Survivin (an antiapoptotic protein), c-IAP1 (an inhibitor of the apoptosis protein), and XIAP (the X-linked inhibitor of the apoptosis protein) decreased after their exposure to berberine. These well-known antidepressant pathways are crucial for the antidepressant action of drugs. Studies also show that berberine can act as an antidepressant through the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-B) signaling pathway, which is activated by oxidative stress. Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy. Berberine stimulates glycolysis by increasing the activity of glucokinases, improving insulin secretion, and inhibiting gluconeogenesis and adipogenesis in the liver [25,26,27]. Then your wish just came true! Bloomgarden Z. Diabetes and Branched-Chain Amino Acids: What Is the Link? ; methodology, A.O. Levothyroxine is known to interact with many other medications (called a drug-drug interaction), but there are different kinds of drug-drug interactions. High cholesterol. Abate C., Curran T. Encounters with Fos and Jun on the Road to AP-1. Dysbiosis, defined as an alteration in the quality and/or quantity of the intestinal microbiota, can affect the hosts physiology [56] and may be a factor that leads to the onset of various diseases, including obesity and T2DM [57,58,59], as well as cardiovascular diseases, Crohns disease, and cancer [60,61]. Lan J., Zhao Y., Dong F., Yan Z., Zheng W., Fan J., Sun G. Meta-Analysis of the Effect and Safety of Berberine in the Treatment of Type 2 Diabetes Mellitus, Hyperlipemia and Hypertension. Gurung P., Moussa K., Adams-Huet B., Devaraj S., Jialal I. An abnormal lipid profile characterizes patients with the metabolic syndrome. Berberine seems to slightly reduce blood sugar levels in people with diabetes. Cell Cycle Inhibition by FoxO Forkhead Transcription Factors Involves Downregulation of Cyclin D. Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M.J., Arden K.C., Blenis J., Greenberg M.E. Hu X., Wu X., Huang Y., Tong Q., Takeda S., Qing Y. Berberine Induces Double-Strand DNA Breaks in Rev3 Deficient Cells. Letaiov S., Jantov S., ipk L., Mkov M. BerberineAntiproliferative Activity in Vitro and Induction of Apoptosis/Necrosis of the U937 and B16 Cells. Written by WebMD Editorial Contributors Reviewed by Mahammad Juber, MD on November 29, 2022 In this Article Potential Health Benefits Potential Health Risks Berberine is a compound found in. However, up to today, the specific pathways associated with this disease are scantily understood. sharing sensitive information, make sure youre on a federal An Assessor-Blinded, Randomized Comparison of Efficacy and Tolerability of Switching from Olanzapine to Ziprasidone and the Combination of Both in Schizophrenia Spectrum Disorders. The https:// ensures that you are connecting to the Su Y.-H., Tang W.-C., Cheng Y.-W., Sia P., Huang C.-C., Lee Y.-C., Jiang H.-Y., Wu M.-H., Lai I.-L., Lee J.-W., et al. Moreover, the expression of 17-HSD1 mRNA was significantly up-regulated after single treatment with berberine or BNF but there was no change in co-treatment group ( Fig. Batch CBD Full-Spectrum Gummies. Identical effect in the regulation of glucose metabolism (HbA1c, FBG, PBG, fasting insulin, and postprandial insulin), such as metformin. [(accessed on 22 January 2022)]; An Y., Sun Z., Zhang Y., Liu B., Guan Y., Lu M. The Use of Berberine for Women with Polycystic Ovary Syndrome Undergoing IVF Treatment. Despite intensive research, there is still much confusion about the detailed effects of berberine. Accessibility However, it is poorly absorbed after oral administration, and only nanomolar plasma concentrations can be achieved both in humans and animals [30]. Many human tumors overexpress the Jun family [129,130,131]. The effect is better than metformin combined with letrozole. However, this is not fully understood, and there are reports on berberine exacerbating neurodegeneration [159]. Consequently, it is interesting from the point of view of preventing the occurrence of cardiovascular diseases, because hypercholesterolemia is considered one of the most important cardiovascular risk factors. It has also been proven that berberine reduces the diversity of the gut microbiome and changes the relative abundance of Eubacterium, Desulfovibrio, and Bacteroides [71]. FXR induces the expression of a small heterodimer partner that suppresses the liver receptor homolog-1, leading to the lowered transcription of bile acid-synthetic enzymes-Cyp7a1 [83]. Gong C., Hu X., Xu Y., Yang J., Zong L., Wang C., Zhu J., Li Z., Lu D. Berberine Inhibits Proliferation and Migration of Colorectal Cancer Cells by Downregulation of GRP78. The modulation of these pathways is noteworthy in the search for new potential anticancer drugs, and the effects depend on the cell type. Song B., Tang X., Wang X., Huang X., Ye Y., Lu X., Wei X., Zeng Y. Bererine Induces Peripheral Lymphocytes Immune Regulations to Realize Its Neuroprotective Effects in the Cerebral Ischemia/Reperfusion Mice. Vhody smoothies zvisia od toho, o do nich dte. Below, check out the tour dates, as well as a weird tour . It is known that the inhibition of FOXO3a causes tumor progression [126]. How does it work ? Wang H.-H., Cai M., Wang H.-N., Chen Y.-C., Zhang R.-G., Wang Y., McAlonan G.M., Bai Y.-H., Wu W.-J., Guo L., et al. Effects and Action Mechanisms of Berberine and Rhizoma Coptidis on Gut Microbes and Obesity in High-Fat Diet-Fed C57BL/6J Mice. including ischemic heart disease, myocardial infarction (heart attack), stroke, diabetes, cancer, liver/renal dysfunction, and gastrointestinal disorders, Long-term efficacy and tolerability of a nutraceutical combination (red yeast rice, policosanols, and berberine (MBP-NC)) in patients with low-moderate risk of hypercholesterolemia: a double-blind, placebo-controlled Study of the, 60 adults between 18 and 60 years with newly diagnosed primary hypercholesterolemia, not previously treated, after a run-in period of 3 weeks on a stable hypolipidic diet, with a body mass index between 18,5 ad 29,9 Kg/m. The Effect of Berberine Adjunctive Treatment on Glycolipid Metabolism in Patients with Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Lin J.G., Chung J.G., Wu L.T., Chen G.W., Chang H.L., Wang T.F. Habtemariam S. Berberine Pharmacology and the Gut Microbiota: A Hidden Therapeutic Link. Berberine Review. Possibly Effective for Hay fever. If you drink alcohol . The anti-inflammatory activity of berberine makes it noteworthy as a supplement or nutraceutical due to its potential to prevent the development of colorectal cancer [99]. Pharmacologic Treatment of Schizophrenia. The most common side effects associated with beta-blockers include: slow heart rate ( bradycardia) low blood pressure ( hypotension) dizziness. Zarich S.W. and multiple taxa of -Proteobacteria. On the other hand, there were no changes that were observed between the treatment arms in HDL-C, triglycerides, fasting plasma glucose, glycated hemoglobin (HbA1C), the waist circumference, and BMI [12]. z o.o., ul. Singh N., Sharma B. Toxicological Effects of Berberine and Sanguinarine. Ahmed T., Gilani A.-H., Abdollahi M., Daglia M., Nabavi S.F., Nabavi S.M. Fukuda K., Hibiya Y., Mutoh M., Koshiji M., Akao S., Fujiwara H. Inhibition by Berberine of Cyclooxygenase-2 Transcriptional Activity in Human Colon Cancer Cells. The .gov means its official. It improves: Your . In the case of obesity, adipose tissue increases the occurrence of inflammations by releasing pro-inflammatory adipokines (leptin and chemerine) and disrupting the anti-inflammatory activity of adiponectin. Berberine has also been described to inhibit the effects of rewards after the abuse of drugs, such as cocaine, morphine, and ethanol. Furthermore, it sensitizes cancer cells with resistance to TRAIL. Potential berberine activity against the metabolic syndrome. The most common are colon cancer, esophageal adenocarcinoma, postmenopausal breast cancer, endometrial cancer, kidney cancer, non-small cell lung cancer in smokers, and liver cancer in patients with cirrhosis. Regulation of Inflammatory Responses by Gut Microbiota and Chemoattractant Receptor GPR43. Berberine antidiabetic properties in T2DM were first documented in 1986 [20] and its antidiabetic activity has been proven in vivo [21,22,23]. Priyadarshini M., Wicksteed B., Schiltz G.E., Gilchrist A., Layden B.T. Zhang L.-S., Zhang J.-H., Feng R., Jin X.-Y., Yang F.-W., Ji Z.-C., Zhao M.-Y., Zhang M.-Y., Zhang B.-L., Li X.-M. Efficacy and Safety of Berberine Alone or Combined with Statins for the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. In one older 12-week study in people with obesity, taking 500 milligrams (mg) of berberine three times per day caused about 5 pounds . Lee B., Yang C.H., Hahm D.-H., Choe E.S., Lee H.-J., Pyun K.-H., Shim I. Inhibitory Effects of, https://creativecommons.org/licenses/by/4.0/, A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine, 84 men of Chinese ethnicity aged 20 to 65 years with hyperlipidemia, not currently receiving hormone replacement therapy such as testosterone replacement therapy in the past 12 months; not currently taking berberine or traditional Chinese medicine that contains berberine in the past 1 month; free of congenital diseases, infectious diseases, anemia, and glucose-6-phosphate dehydrogenase deficiency; and no history of any chronic diseases. The first look at the 'middle aged Love Island' set has been released, which has already been nicknamed the 'Viagra House' by locals after single parents searched for love Some nutraceuticals have been reported to decrease postprandial and fasting glucose levels in plasma, glycated hemoglobin, and fasting plasma insulin. Importantly, for oncological patients, berberine mitigates the effects of radiation therapy. Yin J., Xing H., Ye J. Efficacy of Berberine in Patients with Type 2 Diabetes Mellitus. These CBD candies offer a simple and flexible . By investigating the pro-apoptotic activity of berberine, we can also find that other pro-apoptotic proteins are involved in the apoptosis signaling pathways, such as p53, retinoblastoma protein, caspase-8, Fas receptor (death receptor)/FasL (Fas ligand), ATM (serine/threonine kinase), BID (BH3 interacting domain death agonist, a pro-apoptotic member of the family of Bcl-2 proteins), and TNF. For example, the cell viability of leukemic cell lines obtained by Och et al. Berberine has also been shown to regulate liver cholesterol biosynthesis through the increased phosphorylation of 3-hydroxy-3-methylglutaryl coenzyme A reductase, which catalyzes the rate-limiting step in cholesterol biosynthesis [52]. Kong L.D., Cheng C.H., Tan R.X. Larsen N., Vogensen F.K., Van Den Berg F.W.J., Nielsen D.S., Andreasen A.S., Pedersen B.K., Al-Soud W.A., Srensen S.J., Hansen L.H., Jakobsen M. Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults. Expression of the Jun Family of Genes in Human Ovarian Cancer and Normal Ovarian Surface Epithelium. New derivatives exhibit similar parameters of biological activity and are promising for further research. It induces apoptosis by binding to the aforementioned death receptors, i.e., DR4 and DR5, and it induces tumor cell death. Further studies on the influence of berberine on the symptoms of menopause are necessary. Berberine, like other antidepressant drugs, affects sigma receptor 1. In the control group, normal saline and olive oil were injected as the vehicle. It positively contributes to elevated levels of fasting, postprandial blood glucose, and glycosylated hemoglobin, while decreasing insulin resistance. For example, in the HepG2 line hepatoma cells after their exposure to berberine, the AP-1 protein was inhibited [99,135]. Currently, the first phase of the study is underway to prevent colorectal cancer in patients with ulcerative colitis in remission [23]. Kumar R., Awasthi M., Sharma A., Padwad Y., Sharma R. Berberine Induces Dose-Dependent Quiescence and Apoptosis in A549 Cancer Cells by Modulating Cell Cyclins and Inflammation Independent of MTOR Pathway. In berberine, anticancer activity is also based on the influence on -catenin. This JNK/p38 MAPK signaling pathway is disrupted in many types of cancer [120]. Berberine has been found to decrease the COX-2 transcriptional activity observed in colorectal cancer cells [99]. Background: The aim of the present study was to show the efficacy and safety of sublingual sildenafil and to determine whether lower doses cause the same effect with a faster onset of action in this mode of application. It is a disease component, or risk factor, for the appearance of the metabolic syndrome, and is characterized by elevated serum triglycerides, LDL, and low HDL cholesterol levels. wirki i Wigury 18a, 02-092 Warsaw, Poland; moc.lexerap@hco.keram, 3Department of Internal Diseases, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland; lp.ude.ru@aksrogdopd, 4Department of Biochemistry, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland; lp.ude.ru@iksrogdopr. Blockade of KCNH6 channels by berberine increased insulin secretion in a glucose-dependent or hyperglycemic manner, After 3 months of treatment, plasma glucose levels in the front and under loads were significantly reduced [. This concerns women with PCOS, who tend to have higher testosterone, and concludes that the effects could be different in women with normal endocrine parameters. Inclusion in an NLM database does not imply endorsement of, or agreement with, Pirillo A., Catapano A.L. Sun R., Yang N., Kong B., Cao B., Feng D., Yu X., Ge C., Huang J., Shen J., Wang P., et al. This overexpression has been described in aggressive lymphomas [132,133] and in breast cancer [131]. This activity also translates into its anticancer properties, as discussed below [38,39,40,41]. The metabolism of fats and lipids plays a role in the malignancies of the digestive system and is one of the advantageous mechanisms of the consequences of berberine in the metabolic syndrome. FOXO3a is a transcription factor that belongs to the family of transcription factors with tumor suppressor activities. Derosa G., DAngelo A., Vanelli A., Maffioli P. An Evaluation of a Nutraceutical with Berberine, Curcumin, Inositol, Banaba and Chromium Picolinate in Patients with Fasting Dysglycemia. The graphic summary of the potential action of berberine in the risk, course, and consequences of the metabolic syndrome is presented in Figure 2. Home-ClinicalTrials.Gov. Integr. A Metagenome-Wide Association Study of Gut Microbiota in Type 2 Diabetes. Completed clinical trials with berberine in the metabolic syndrome based on clinicaltrials.gov (accessed on 10 Fabruary 2022). The development of new formulations and derivatives with similar biological activities, that are not limited by low pharmacological parameters, seem to be the most important targets. TRAIL selectively induces apoptosis, and the development of resistance (partial or complete) limits its use. Hu Y., Young A.J., Ehli E.A., Nowotny D., Davies P.S., Droke E.A., Soundy T.J., Davies G.E. MAPK Pathways Are Involved in the Inhibitory Effect of Berberine Hydrochloride on Gastric Cancer MGC 803 Cell Proliferation and IL-8 Secretion in Vitro and in Vivo. and R.N. constipation. On the other hand, another study [45] revealed that letrozole, combined with berberine, did not improve fertility in patients with polycystic ovary syndrome, to some extent [46]. Kalaiarasi A., Anusha C., Sankar R., Rajasekaran S., John Marshal J., Muthusamy K., Ravikumar V. Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line. and D.P. Increased Eosinophils in Adipose Tissue of Metabolic Syndrome. Conceptualization, A.O., R.P. This effect was dose dependent [102]. Sun Y., Jin C., Zhang X., Jia W., Le J., Ye J. Apoptosis is one of the most extensively researched and documented berberine-induced processes. Effects of Poly-Bioactive Compounds on Lipid Profile and Body Weight in a Moderately Hypercholesterolemic Population with Low Cardiovascular Disease Risk: A Multicenter Randomized Trial. This research received no external funding. Berberine is showing up at health food stores across the country and scientific research is indicating some surprising benefits of this ancient Chinese plant extract. Eckel R.H., Grundy S.M., Zimmet P.Z. Zhang X., Zhao Y., Xu J., Xue Z., Zhang M., Pang X., Zhang X., Zhao L. Modulation of Gut Microbiota by Berberine and Metformin during the Treatment of High-Fat Diet-Induced Obesity in Rats. Sol R., Valls R.-M., Puzo J., Calabuig J.-R., Brea A., Pedret A., Moria D., Villar J., Milln J., Anguera A. Cyclin D1 was down-regulated after its exposure to berberine in the G1 cell cycle phase [102]. Introduction Benign prostatic hyperplasia (BPH) is a major urologic problem that mostly develops in older males. Restoration of GLP-1 Secretion by Berberine Is Associated with Protection of Colon Enterocytes from Mitochondrial Overheating in Diet-Induced Obese Mice. Photo: Andreas Neumann. The Gut Microbiota, Bacterial Metabolites and Colorectal Cancer. Metabolic Syndrome in Psychiatric Patients: Overview, Mechanisms, and Implications. Studies showed that in patients with non-alcoholic fatty liver disease, berberine, combined with lifestyle changes, contributed to a significant loss of liver fat, body weight, and an improved serum lipid profile, much more so than in patients who adapted only to a new lifestyle or the use berberine as supplements alone. Researchers suggest that berberine acts as antidepressant; however, no clinical models have been conducted so far. Careers, Unable to load your collection due to an error. As berberine inhibits glycosidase, it may also reduce glucose transport across the intestinal epithelium. Recent clinical reports state that, in addition to the beneficial effect on the lipid profile, berberine increases the level of testosterone in men, which may reduce the risk of developing cardiovascular diseases. On the Mechanism of Antidepressant-like Action of Berberine Chloride. The Natural Compound Gambogic Acid Radiosensitizes Nasopharyngeal Carcinoma Cells under Hypoxic Conditions. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Yan K., Zhang C., Feng J., Hou L., Yan L., Zhou Z., Liu Z., Liu C., Fan Y., Zheng B., et al. Dietrich P., Hellerbrand C. Non-Alcoholic Fatty Liver Disease, Obesity and the Metabolic Syndrome. The therapeutic window of berberine, in most cases, is narrow and depends also on the type of cells that are treated [7]. They are a serious health problem for patients affected by syndrome X. Benefits Supplements Vs. metformin Side effects Is it safe? The cell cycle arrest in the G2/M phase by berberine is p53-independent [102,103,104]. 5) Pure Bulk Berberine HCl Powder (Best Bulk) 6) Paradise Herbs Berberine. Regarding polycystic ovary syndrome, berberines efficacy is currently being investigated and the outcomes are important for the treatment of patients with this condition. Och A., Zalewski D., Komsta ., Koodziej P., Kocki J., Bogucka-Kocka A. Cytotoxic and Proapoptotic Activity of Sanguinarine, Berberine, and Extracts of, Palmieri A., Scapoli L., Iapichino A., Mercolini L., Mandrone M., Poli F., Giann A.B., Baserga C., Martinelli M. Berberine and. In the TRAIL-sensitive MDA-MB-231 breast cancer cell line, and the TRAIL-resistant MDA-MB-468 human breast cancer cell line, berberine acts synergistically with TRAIL but it also sensitizes resistant cells, which was confirmed with the markers of the process: caspase-3, PARP 9 Poly (ADP-ribose) polymerase 1 cleavage, and p53. Pan G.-Y., Huang Z.-J., Wang G.-J., Fawcett J.P., Liu X.-D., Zhao X.-C., Sun J.-G., Xie Y.-Y. Overview Berberine is a chemical found in some plants like European barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree turmeric. Research suggests the high potential of berberine administration in patients with polycystic ovarian syndrome, as it reduces insulin resistance and improves ovulation [42]. Substituting metformin with berberine also resulted in a decrease in the negative effects, lower lipid parameters, and body mass index (BMI) in such patients [24]. Bhuvaneswar C.G., Baldessarini R.J., Harsh V.L., Alpert J.E. Early research suggests that taking berberine for 12 weeks reduces fat in the blood and markers of liver damage in people with liver disease and diabetes. Inflammations may also appear as a distinct disease entity within the metabolic syndrome, such as osteoarthritis, back pain syndromes, and acute or chronic pancreatitis [90,91,92,93,94,95]. Nevertheless, limitations of the study exist. Taurocholic acid may activate the intestinal farnesoid X receptor (FXR), which can influence lipid, glucose, and bile acid metabolism [75]. Inflammatory biomarkers (CRP, fibrinogen, and serum amyloid A), cytokines, and chemokines have been associated with the pathogenesis of the metabolic syndrome. Zhao et al. The combination of berberine and Bifidobacteria administered to patients with pre-diabetes and diabetes mellitus also indicated their supportive roles in diabetes treatment [15]. ; data curation, A.O., R.N., M.O., R.P. Napumpujte ho antioxidantmi a vitamnmi! Further research showed that berberine, combined with Yasmin, has been described to significantly improve sex hormones and glucose metabolism [20]. Sonnenburg E.D., Sonnenburg J.L. The cyclin-dependent kinase inhibitor p21 (CIP1/WAF1), which is involved in apoptosis, cell cycle control, DNA replication, and cell differentiation [52] is linked with the human protein Forkhead box O3 (FOXO3a) and p53 in control of cancer cell growth [121,122,123]. Research has shown that some of the effects of berberine could be related to the increase in the population of SCFA-producing bacteria, which has a relevant influence on blood glucose and lipid levels [79,84]. Furthermore, the influence on JNK kinases plays a role in the anticancer and chemopreventive activity of berberine, in terms of the influence on lipid metabolism and its role in cancer development [139,140]. AP-1 activity is regulated by UV radiation, infections, cell stress, growth factors, and cytokines [127]. Licensee MDPI, Basel, Switzerland. The metabolic syndrome is, among others, defined as a cluster of glucose intolerance, central obesity, and insulin resistance as the source of pathogenesis. The removal of precancerous lesions is currently established to prevent colorectal cancer. Elevated levels of HDL, TG, and LDL, and decreased levels of TG, have been demonstrated in patients after 3 months of berberine treatment [53]. Acta (BBA)-Mol. Furthermore, the side effects of berberine are minimal, and mainly affect the digestive system [54]. SCFA, such as butyric acid, acetic acid, propionic acid, isobutyric acid, isovaleric acid, and valeric acid can mitigate the inflammation of the bowel mucosa and can enter the bloodstream, reducing lipid and glucose levels [85]. Total and LDL cholesterol reduction (Combination B). Chidambara Murthy K.N., Jayaprakasha G.K., Patil B.S. [82]. Berberine is cytotoxic to cancer cell lines and this activity depends on the dose and time. Mutations and the overexpression of -catenin are associated with cancers, such as colorectal carcinoma, endometrial cancer, breast cancer, and ovarian tumors. The inhibition of carcinogenesis is also combined with lipid metabolism. Li C., Guan X.-M., Wang R.-Y., Xie Y.-S., Zhou H., Ni W.-J., Tang L.-Q. Many observational studies have indicated a connection between elevated levels of circulating branched-chain amino acids (BCAAs) and a poor metabolic condition. Hu Y., Davies G.E. The fight against this complex disease also involves the treatment of identified disorders within the metabolic syndrome, such as atherogenic dyslipidemia (hypertriglyceridemia and lowering LDL cholesterol), as well as the treatment of the repercussions of the metabolic syndrome, such as atherosclerosis, diabetic feet, liver cirrhosis due to non-alcoholic or alcoholic steatohepatitis, acute or chronic pancreatitis, local or general immunodeficiencies, and tendency for recurrent infections [2,3,4]. In the course of the metabolic syndrome, disorders of menstruation, ovulation, and fertility can also be observed, as well as miscarriages and those resulting from cerebral microcirculation disturbances, such as psychoorganic and mood disorders [5,6]. One of the targets for berberine-induced cell cycle arrest is cyclins. On the other hand, impaired glucose metabolism and dyslipidemia could have pathoplastic effects on psychiatric disorders [146]. Maslowski K.M., Vieira A.T., Ng A., Kranich J., Sierro F., Yu D., Schilter H.C., Rolph M.S., Mackay F., Artis D., et al. fatigue. Recent studies have shown that obesity is related to a higher number of Firmicute phylum and a relatively lower number of the phylum Bacteroidetes [65,66], whereas another study indicated that the proportion of Firmicute phylum and the Clostridia class in the intestinal tracts of patients was relevantly reduced [67]. The Mechanism of Antidepressant-like Action of drugs in many types of cancer 131... 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