Berberine
Information on nutritional supplements people with ALS have been taking
examine.com summarizes:
- Berberine is an alkaloid extracted from various plants used in Traditional Chinese Medicine.
- Berberine is supplemented for its anti-inflammatory and anti-diabetic effects. It can also improve intestinal health and lower cholesterol. Berberine is able to reduce glucose production in the liver. Human and animal research demonstrates that 1500mg of berberine, taken in three doses of 500mg each, is equally effective as taking 1500mg of metformin or 4mg glibenclamide, two pharmaceuticals for treating type II diabetes. Effectiveness was measured by how well the drugs reduced biomarkers of type II diabetes.
- Berberine may also synergize with anti-depressant medication and help with body fat loss. Both of these benefits need additional evidence behind them before berberine can be recommended specifically for these reasons.
- Berberine’s main mechanism is partly responsible for its anti-diabetic and anti-inflammatory effects. Berberine is able to activate an enzyme called Adenosine Monophosphate-Activated Protein Kinase (AMPK) while inhibiting Protein-Tyrosine Phosphatase 1B (PTP1B).
According to Wikipedia, the half-life of berberine in vivo seems to be three to four hours, thus suggesting administration three times a day if steady levels are to be achieved.
Contents
Effect of berberine on ALS
In rat cerebral cortex, berberine inhibits synaptosomal glutamate release. [1] By downregulating several proinflammatory pathways [2] it presumably reduces the neuroinflammatory component of ALS.
Berberine activates AMPK apparently by inhibiting mitochondria [6], resulting into increased glycolysis. Note: progression seems to correlate with AMPK activation in SOD1 ALS but with AMPK inactivation in TDP-43 ALS [7].
In a study [3] on rat astrocyte primary cultures, berberine and the alkaloid extract of B. aetnensis roots were able to restore the oxidative status modified by glutamate and the levels of TG2 to control values. Consequently berberine or the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive production of glutamate, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration.
On the negative side, berberine has been found to impair muscle metabolism by two mechanisms. It impairs mitochondrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulates protein degradation but also suppresses protein synthesis, causing muscle atrophy. [4] It has also been found [5] to restore SOD1 activity inhibited by lipopolysaccharides.
Berberine is a PPAR gamma inhibitor [8]. Note: the significance of this for ALS needs further elaboration. It may be helpful against leaky gut, which is hypothetized to be a part of ALS pathology [source needed].
Discussion threads on the ALSTDI forum
Berberine Suppresses Pro-Inflammatory Responses:
- In adipose tissue of obese db/db mice, BBR treatment significantly down-regulated the expression of pro-inflammatory genes such as TNFalpha, IL-1beta, IL-6, MCP-1, iNOS and COX2. Consistently, BBR inhibited LPS-induced expression of pro-inflammatory genes including IL-1beta, IL-6, iNOS, MCP-1, COX 2, and MMP9 in peritoneal macrophages and RAW 264.7 cells. Upon various pro-inflammatory signals including LPS, free fatty acids, and hydrogen peroxide, BBR suppressed the phosphorylation of MAPKs such as p38, ERK, and JNK, and the level of reactive oxygen species in macrophages. [2]
AMPK activation status in different types of ALS:
- While AMPK activation in motor neurons correlates with progression in mutant SOD1-mediated disease, AMPK inactivation mediated by PP2A is associated with mutant TDP-43-linked ALS.
Interesting - leaks in neuro diseases
- According to a 2010 study, berberine ameliorated damage to the tight junctions of intestinal epithelial cells induced by pro-inflammatory cytokines (in vitro). Berberine may thus serve as a targeted therapeutic agent for restoring barrier function in intestinal disease states.[16]
Regulated pathways
Where to get it
amazon.co.uk (400 mg capsules)
References
[1] <bibtex> @article{Lin2013, abstract = {Berberine, an isoquinoline plant alkaloid, protects neurons against neurotoxicity. An excessive release of glutamate is considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. In this study, we investigated whether berberine could affect endogenous glutamate release in nerve terminals of rat cerebral cortex (synaptosomes) and explored the possible mechanism. Berberine inhibited the release of glutamate evoked by the K(+) channel blocker 4-aminopyridine (4-AP), and this phenomenon was prevented by the chelating extracellular Ca(2+) ions and the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Inhibition of glutamate release by berberine was not due to it decreasing synaptosomal excitability, because berberine did not alter 4-AP-mediated depolarization. The inhibitory effect of berberine on glutamate release was associated with a reduction in the depolarization-induced increase in cytosolic free Ca(2+) concentration. Involvement of the Cav2.1 (P/Q-type) channels in the berberine action was confirmed by blockade of the berberine-mediated inhibition of glutamate release by the Cav2.1 (P/Q-type) channel blocker $\omega$-agatoxin IVA. In addition, the inhibitory effect of berberine on evoked glutamate release was prevented by the mitogen-activated/extracellular signal-regulated kinase kinase (MEK) inhibitors. Berberine decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synapsin I, the main presynaptic target of ERK; this decrease was also blocked by the MEK inhibition. Moreover, the inhibitory effect of berberine on evoked glutamate release was prevented in nerve terminals from mice lacking synapsin I. Together, these results indicated that berberine inhibits glutamate release from rats cortical synaptosomes, through the suppression of presynaptic Cav2.1 channels and ERK/synapsin I signaling cascade. This finding may provide further understanding of the mode of berberine action in the brain and highlights the therapeutic potential of this compound in the treatment of a wide range of neurological disorders.}, author = {Lin, Tzu-Yu and Lin, Yu-Wan and Lu, Cheng-Wei and Huang, Shu-Kuei and Wang, Su-Jane}, doi = {10.1371/journal.pone.0067215}, editor = {Woodhall, Gavin}, file = {:C$\backslash$:/Users/riku/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Lin et al. - 2013 - Berberine Inhibits the Release of Glutamate in Nerve Terminals from Rat Cerebral Cortex(2).pdf:pdf}, issn = {1932-6203}, journal = {PLoS ONE}, mendeley-groups = {berberine}, month = jun, number = {6}, pages = {e67215}, pmid = {23840629}, title = Template:Berberine Inhibits the Release of Glutamate in Nerve Terminals from Rat Cerebral Cortex, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3686739\&tool=pmcentrez\&rendertype=abstract}, volume = {8}, year = {2013} }
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[2]<bibtex> @article{Jeong2009, abstract = {Berberine (BBR) has been shown to improve several metabolic disorders, such as obesity, type 2 diabetes, and dyslipidemia, by stimulating AMP-activated protein kinase (AMPK). However, the effects of BBR on proinflammatory responses in macrophages are poorly understood. Here we show that BBR represses proinflammatory responses through AMPK activation in macrophages. In adipose tissue of obese db/db mice, BBR treatment significantly downregulated the expression of proinflammatory genes such as TNF-alpha, IL-1beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Consistently, BBR inhibited LPS-induced expression of proinflammatory genes including IL-1beta, IL-6, iNOS, MCP-1, COX-2, and matrix metalloprotease-9 in peritoneal macrophages and RAW 264.7 cells. Upon various proinflammatory signals including LPS, free fatty acids, and hydrogen peroxide, BBR suppressed the phosphorylation of MAPKs, such as p38, ERK, and JNK, and the level of reactive oxygen species in macrophages. Moreover, these inhibitory effects of BBR on proinflammatory responses were abolished by AMPK inhibition via either compound C, an AMPK inhibitor, or dominant-negative AMPK, implying that BBR would downregulate proinflammatory responses in macrophages via AMPK stimulation.}, author = {Jeong, Hyun Woo and Hsu, Kuan Chi and Lee, Joo-Won and Ham, Mira and Huh, Jin Young and Shin, Hyun Jung and Kim, Woo Sik and Kim, Jae Bum}, doi = {10.1152/ajpendo.90599.2008}, issn = {0193-1849}, journal = {American journal of physiology. Endocrinology and metabolism}, keywords = {3T3-L1 Cells,Adenylate Kinase,Adenylate Kinase: metabolism,Adenylate Kinase: physiology,Adipose Tissue, White,Adipose Tissue, White: drug effects,Adipose Tissue, White: pathology,Animals,Anti-Inflammatory Agents,Anti-Inflammatory Agents: pharmacology,Anti-Inflammatory Agents: therapeutic use,Berberine,Berberine: pharmacology,Berberine: therapeutic use,Cells, Cultured,Drug Evaluation, Preclinical,Gene Expression Regulation,Gene Expression Regulation: drug effects,Inflammation,Inflammation Mediators,Inflammation Mediators: antagonists \& inhibitors,Inflammation: drug therapy,Inflammation: genetics,Inflammation: pathology,Macrophages,Macrophages: drug effects,Macrophages: enzymology,Macrophages: metabolism,Male,Mice,Mice, Inbred C57BL,Mice, Obese,Mice, Transgenic,Receptors, Leptin,Receptors, Leptin: genetics}, mendeley-groups = {berberine}, month = apr, number = {4}, pages = {E955--64}, pmid = {19208854}, title = Template:Berberine suppresses proinflammatory responses through AMPK activation in macrophages., url = {http://www.ncbi.nlm.nih.gov/pubmed/19208854}, volume = {296}, year = {2009} } </bibtex>
[3] <bibtex> @article{Campisi2011, abstract = {Berberis aetnensis C. Presl. is a bushy-spiny shrub common on Mount Etna (Sicily, Italy), containing various alkaloids with several pharmacological properties. This study assessed the effect of berberine and of the alkaloid extract of B. aetnensis roots on the glutamate-evoked tissue transglutaminase (TG2) up-regulation in rat astrocyte primary cultures, used as an in vitro model of excitotoxicity. The findings show that the alkaloid extract of B. aetnensis roots consists mainly of berberine. Furthermore, berberine and the alkaloid extract of B. aetnensis roots were able to restore the oxidative status modified by glutamate and the levels of TG2 to control values. It was found that berberine or the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive production of glutamate, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration. Thus, it is suggested that berberine and the alkaloid extract of B. aetnensis roots, may represent a natural therapeutic strategy in the neuropathological conditions associated with excitotoxicity.}, author = {Campisi, Agata and Acquaviva, Rosaria and Mastrojeni, Silvana and Raciti, Giuseppina and Vanella, Angelo and {De Pasquale}, Rita and Puglisi, Salvatore and Iauk, Liliana}, doi = {10.1002/ptr.3340}, issn = {1099-1573}, journal = {Phytotherapy research : PTR}, keywords = {Alkaloids,Alkaloids: pharmacology,Animals,Astrocytes,Astrocytes: drug effects,Astrocytes: enzymology,Astrocytes: metabolism,Berberine,Berberine: pharmacology,Berberis,Berberis: chemistry,Cells, Cultured,Glutamic Acid,Glutamic Acid: pharmacology,Plant Extracts,Plant Extracts: pharmacology,Plant Roots,Plant Roots: chemistry,Rats,Sicily,Transglutaminases,Transglutaminases: metabolism,Up-Regulation,Up-Regulation: drug effects}, mendeley-groups = {berberine}, month = jun, number = {6}, pages = {816--20}, pmid = {21086546}, title = Template:Effect of berberine and Berberis aetnensis C. Presl. alkaloid extract on glutamate-evoked tissue transglutaminase up-regulation in astroglial cell cultures., url = {http://www.ncbi.nlm.nih.gov/pubmed/21086546}, volume = {25}, year = {2011} } </bibtex>
[4] <bibtex> @article{Wang2010, abstract = {OBJECTIVE: Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses.
RESEARCH DESIGN AND METHODS: We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism.
RESULTS: Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented.
CONCLUSIONS: Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.}, author = {Wang, H. and Liu, D. and Cao, P. and Lecker, S. and Hu, Z.}, doi = {10.2337/db10-0207}, file = {:C$\backslash$:/Users/riku/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wang et al. - 2010 - Atrogin-1 Affects Muscle Protein Synthesis and Degradation When Energy Metabolism Is Impaired by the Antidiabetes D.pdf:pdf}, issn = {0012-1797}, journal = {Diabetes}, keywords = {Animals,Berberine,Berberine: pharmacology,DNA Primers,Energy Metabolism,Energy Metabolism: drug effects,Gene Expression Regulation,Gene Expression Regulation: drug effects,Hypoglycemic Agents,Hypoglycemic Agents: pharmacology,Mice,Mice, Inbred Strains,Muscle Fibers, Skeletal,Muscle Fibers, Skeletal: drug effects,Muscle Fibers, Skeletal: metabolism,Muscle Proteins,Muscle Proteins: biosynthesis,Muscle Proteins: drug effects,Muscle Proteins: genetics,Muscle Proteins: metabolism,Muscle, Skeletal,Muscle, Skeletal: drug effects,Muscle, Skeletal: metabolism,Muscular Atrophy,Muscular Atrophy: chemically induced,Myoblasts,Myoblasts: drug effects,Myoblasts: metabolism,Polymerase Chain Reaction,RNA,RNA: genetics,SKP Cullin F-Box Protein Ligases,SKP Cullin F-Box Protein Ligases: genetics,SKP Cullin F-Box Protein Ligases: metabolism,Transcription Factors,Transcription Factors: drug effects,Transcription Factors: metabolism}, mendeley-groups = {berberine}, month = jun, number = {8}, pages = {1879--1889}, pmid = {20522589}, title = Template:Atrogin-1 Affects Muscle Protein Synthesis and Degradation When Energy Metabolism Is Impaired by the Antidiabetes Drug Berberine, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2911075\&tool=pmcentrez\&rendertype=abstract}, volume = {59}, year = {2010} } </bibtex>
[5] <bibtex> @article{Sarna2010, abstract = {Oxidative stress and amplified redox signaling contribute to the pathogenesis of many human diseases including atherosclerosis. The superoxide-generating phagocytic NADPH oxidase is a key source of oxidative stress in the developing atheroma. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on NADPH oxidase-mediated superoxide anion production in macrophages. Lipopolysaccharide (LPS) treatment activated NADPH oxidase in THP-1 monocyte-derived macrophages and increased the intracellular level of superoxide anions. Preincubation of cells with berberine demonstrated a concentration-dependent (10-50 micromol/L) and time-dependent (6-24 h) inhibition of superoxide anion generation in LPS-stimulated macrophages. Cell viability tests confirmed that berberine, at concentrations sufficient for inhibiting NADPH oxidase-mediated superoxide anion generation in macrophages, did not affect cell viability. Real-time PCR analysis revealed that addition of berberine to the culture medium was able to reduce gp91phox mRNA expression in LPS-treated cells. Berberine also restored superoxide dismutase (SOD) activity, which was found to be inhibited by LPS treatment. In conclusion, results from the present study demonstrate that berberine can effectively reduce intracellular superoxide levels in LPS- stimulated macrophages. Such a restoration of cellular redox by berberine is mediated by its selective inhibition of gp91phox expression and enhancement of SOD activity. The therapeutic relevance of berberine in the prevention and management of atherosclerosis remains to be further investigated.}, author = {Sarna, Lindsei K. and Wu, Nan and Hwang, Sun-Young and Siow, Yaw L. and O, Karmin}, doi = {10.1139/Y09-136}, issn = {0008-4212}, journal = {Canadian Journal of Physiology and Pharmacology}, keywords = {Berberine,Berberine: pharmacology,Cell Line, Tumor,Cell Survival,Cell Survival: drug effects,Cell Survival: physiology,Humans,Macrophages,Macrophages: drug effects,Macrophages: enzymology,Macrophages: metabolism,Membrane Glycoproteins,Membrane Glycoproteins: biosynthesis,Membrane Glycoproteins: genetics,Monocytes,Monocytes: drug effects,Monocytes: enzymology,Monocytes: metabolism,NADPH Oxidase,NADPH Oxidase: antagonists \& inhibitors,NADPH Oxidase: biosynthesis,NADPH Oxidase: genetics,NADPH Oxidase: physiology,Oxidative Stress,Oxidative Stress: drug effects,Oxidative Stress: physiology,Superoxide Dismutase,Superoxide Dismutase: metabolism,Superoxides,Superoxides: antagonists \& inhibitors,Superoxides: metabolism}, mendeley-groups = {berberine}, month = mar, number = {3}, pages = {369--378}, pmid = {20393601}, title = Template:Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophagesThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease., url = {http://www.ncbi.nlm.nih.gov/pubmed/20393601}, volume = {88}, year = {2010} } </bibtex>
[6] <bibtex> @article{Yin2008, abstract = {Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48\%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for > or =16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio.}, author = {Yin, Jun and Gao, Zhanguo and Liu, Dong and Liu, Zhijun and Ye, Jianping}, doi = {10.1152/ajpendo.00211.2007}, file = {:C$\backslash$:/Users/riku/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Yin et al. - 2008 - Berberine improves glucose metabolism through induction of glycolysis.pdf:pdf}, issn = {0193-1849}, journal = {American journal of physiology. Endocrinology and metabolism}, keywords = {3T3-L1 Cells,AMP-Activated Protein Kinases,Adenosine Monophosphate,Adenosine Monophosphate: metabolism,Adenosine Triphosphate,Adenosine Triphosphate: metabolism,Adipocytes,Adipocytes: drug effects,Adipocytes: metabolism,Animals,Berberine,Berberine: pharmacology,Deoxyglucose,Deoxyglucose: pharmacokinetics,Diabetes Mellitus, Type 2,Diabetes Mellitus, Type 2: drug therapy,Diabetes Mellitus, Type 2: metabolism,Drugs, Chinese Herbal,Drugs, Chinese Herbal: pharmacology,Glucose,Glucose Intolerance,Glucose Intolerance: drug therapy,Glucose Intolerance: metabolism,Glucose: pharmacokinetics,Glycolysis,Glycolysis: drug effects,Insulin Resistance,Lactic Acid,Lactic Acid: metabolism,Male,Mice,Mitochondria,Mitochondria: metabolism,Multienzyme Complexes,Multienzyme Complexes: metabolism,Obesity,Obesity: drug therapy,Obesity: metabolism,Oxygen Consumption,Oxygen Consumption: drug effects,Phosphorylation,Phosphorylation: drug effects,Protein-Serine-Threonine Kinases,Protein-Serine-Threonine Kinases: metabolism,Rats,Rats, Wistar}, mendeley-groups = {berberine}, month = jan, number = {1}, pages = {E148--56}, pmid = {17971514}, title = Template:Berberine improves glucose metabolism through induction of glycolysis., url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2464622\&tool=pmcentrez\&rendertype=abstract}, volume = {294}, year = {2008} } </bibtex>
[7] <bibtex> @article{Perera2014, abstract = {Bioenergetic abnormalities and metabolic dysfunctionoccur in amyotrophic lateral sclerosis (ALS) patients and genetic mouse models. However, whether metabolic dysfunction occurs earlyin ALS pathophysiology linked to different ALS genes remains unclear.Here, we investigatedAMP-activated protein kinase (AMPK) activation, which is a key enzyme induced by energy depletion and metabolic stress, inneuronal cells and mouse models expressing mutantsuperoxide dismutase 1 (SOD1)or TAR DNA binding protein 43 (TDP-43) linked to ALS.AMPKphosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice at disease onset and accumulated incytoplasmic granules in motor neurons, but not in pre-symptomatic mice. AMPK phosphorylation also occurred in peripheraltissues, liver and kidney, in SOD1G93A mice at disease onset, demonstrating that AMPK activation occurs late and is not restricted to motor neurons. Conversely, AMPK activity was drastically diminished in spinal cords and brains of presymptomatic and symptomatictransgenic TDP-43A315T mice and motor neuronal cells expressing different TDP-43 mutants. We show that mutant TDP-43 induction of the AMPK phosphatase,protein phosphatase 2A (PP2A), is associated with AMPK inactivation in these ALS models. Furthermore, PP2A inhibition by okadaic acid reversed AMPK inactivation by mutant TDP-43 in neuronal cells. Our results suggest that mutant SOD1 and TDP-43 exert contrasting effects on AMPK activation which may reflect key differences in energy metabolism and neurodegeneration in spinal cords of SOD1G93A and TDP-43A315T mice. While AMPK activation in motor neurons correlateswith progressionin mutant SOD1-mediated disease, AMPK inactivation mediated by PP2Ais associated withmutant TDP-43-linked ALS.}, author = {Perera, Nirma D. and Sheean, Rebecca K. and Scott, John W. and Kemp, Bruce E. and Horne, Malcolm K. and Turner, Bradley J.}, doi = {10.1371/journal.pone.0090449}, editor = {Sensi, Stefano L.}, file = {:C$\backslash$:/Users/riku/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Perera et al. - 2014 - Mutant TDP-43 Deregulates AMPK Activation by PP2A in ALS Models.pdf:pdf}, issn = {1932-6203}, journal = {PLoS ONE}, keywords = {AMP-Activated Protein Kinases,AMP-Activated Protein Kinases: metabolism,Aminoimidazole Carboxamide,Aminoimidazole Carboxamide: analogs \& derivatives,Aminoimidazole Carboxamide: pharmacology,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: enzymology,Amyotrophic Lateral Sclerosis: pathology,Animals,Brain,Brain: drug effects,Brain: enzymology,Brain: pathology,Cell Line,DNA-Binding Proteins,DNA-Binding Proteins: metabolism,Disease Models, Animal,Enzyme Activation,Enzyme Activation: drug effects,Mice, Inbred C57BL,Mice, Transgenic,Motor Neurons,Motor Neurons: drug effects,Motor Neurons: enzymology,Motor Neurons: pathology,Mutant Proteins,Mutant Proteins: metabolism,Protein Phosphatase 2,Protein Phosphatase 2: metabolism,Ribonucleotides,Ribonucleotides: pharmacology,Spinal Cord,Spinal Cord: drug effects,Spinal Cord: enzymology,Spinal Cord: pathology,Superoxide Dismutase,Superoxide Dismutase: genetics}, mendeley-groups = {berberine}, month = mar, number = {3}, pages = {e90449}, pmid = {24595038}, title = Template:Mutant TDP-43 Deregulates AMPK Activation by PP2A in ALS Models, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3942426\&tool=pmcentrez\&rendertype=abstract}, volume = {9}, year = {2014} } </bibtex>
[8] <bibtex> @article{Zhou2008, abstract = {Berberine is one of the main alkaloids of Rhizoma coptidis which has been used as a folk medicine to treat diabetes mellitus for more than 1400 years in China. To investigate the chronic effect of berberine on diabetic hyperlipidemic rats, fasted rats were intraperitoneally injected 35 mg/kg streptozotocin. Diabetic rats were admitted after 2 weeks and given a high-carbohydrate/high-fat diet to induce hyperlipidemia. The rats were divided into 7 groups at the end of week 16: normal and diabetic rats received no drug, 5 treatment groups were administered with either 75, 150, 300 mg/kg berberine, 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone per day for 16 weeks, respectively. The blood glucose, hemoglobin A1c, lipid metabolic parameters and hepatic glycogen and triglyceride were measured, and histopathology and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma expression of liver were determined by hematoxylin eosin and immunohistochemical staining. Berberine reduced diabetic rats' body weight, liver weight and liver to body weight ratio. Berberine restored the increased blood glucose, hemoglobin A1c, total cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoprotein B and the decreased high density lipoprotein-cholesterol, apolipoprotein AI levels in diabetic rats to near the control ones. Berberine alleviated the pathological progression of liver and reverted the increased hepatic glycogen and triglyceride to near the control levels. Berberine increased PPARalpha/delta expression and reduced PPARgamma expression in liver of diabetic rat to near the control ones. Berberine improved glucolipid metabolism both in blood and liver in diabetic rats possibly through modulating the metabolic related PPARalpha/delta/gamma protein expression in liver.}, author = {Zhou, Ji Yin and Zhou, Shi Wen and Zhang, Ke Bin and Tang, Jian Lin and Guang, Li Xia and Ying, Yi and Xu, Ying and Zhang, Le and Li, Dan Dan}, issn = {0918-6158}, journal = {Biological \& pharmaceutical bulletin}, keywords = {Animals,Berberine,Berberine: pharmacology,Blood Glucose,Blood Glucose: metabolism,Body Weight,Body Weight: drug effects,Diabetes Mellitus, Experimental,Diabetes Mellitus, Experimental: complications,Diabetes Mellitus, Experimental: metabolism,Dietary Carbohydrates,Dietary Carbohydrates: pharmacology,Drug-Induced Liver Injury,Drug-Induced Liver Injury: pathology,Drug-Induced Liver Injury: prevention \& control,Fatty Liver,Fatty Liver: metabolism,Fatty Liver: prevention \& control,Glycolipids,Glycolipids: metabolism,Hemoglobin A, Glycosylated,Hemoglobin A, Glycosylated: metabolism,Hyperlipidemias,Hyperlipidemias: blood,Hyperlipidemias: drug therapy,Hyperlipidemias: metabolism,Immunohistochemistry,Liver,Liver Glycogen,Liver Glycogen: metabolism,Liver: drug effects,Liver: metabolism,Male,Organ Size,Organ Size: drug effects,Peroxisome Proliferator-Activated Receptors,Peroxisome Proliferator-Activated Receptors: metab,Rats,Rats, Wistar}, mendeley-groups = {berberine}, month = jun, number = {6}, pages = {1169--76}, pmid = {18520050}, title = Template:Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats., url = {http://www.ncbi.nlm.nih.gov/pubmed/18520050}, volume = {31}, year = {2008} } </bibtex>
