Guggulsterone Manages Bile Export While Lowering LDL

Byron's Comments:

Help for clearing excess fat and cholesterol from the liver.

Study Title:

The hypolipidemic agent guggulsterone regulates the expression of human bile salt export pump: dominance of transactivation over farsenoid X receptor-mediated antagonism.

Study Abstract:

Conversion of cholesterol to bile acids in the liver is initiated by the rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1) and excretion of bile acids from the liver is mediated by the bile salt export pump (BSEP). The expression of CYP7A1 and BSEP is coordinately regulated by a negative feedback and positive feed-forward mechanism, respectively, through bile acid-mediated activation of farsenoid X receptor (FXR). It is well established that hypolipidemic agent guggulsterone is an FXR antagonist and down-regulates FXR target genes. In this study, however, we have demonstrated that guggulsterone synergistically induced the expression of BSEP in cells treated with FXR agonist bile acids. A dissection study located in the BSEP promoter an activating protein (AP)-1 site supporting the action of guggulsterone. Deletion or mutation of the AP-1 element was diminished, whereas insertion of the AP-1 element into a heterologous promoter enhanced activation of the promoter by guggulsterone. Selective c-Jun N-terminal kinase and extracellular signal-regulated kinase inhibitors markedly decreased the transactivation, suggesting an involvement of AP-1 activation pathway in the up-regulation of BSEP by guggulsterone. Consistent with its FXR antagonism, guggulsterone antagonized bile acid-mediated transactivation of BSEP promoter when the AP-1 element was disrupted. In conclusion, guggulsterone regulates BSEP expression through composite mechanisms, and the transactivation through the AP-1 element is dominant over the FXR-mediated antagonism. The up-regulation of BSEP expression by guggulsterone without activating FXR pathway as an FXR agonist to suppress CYP7A1 expression represents a possible mechanism for guggulsterone-mediated hypolipidemic effect.

Study Information:

Deng R, Yang D, Radke A, Yang J, Yan B. The hypolipidemic agent guggulsterone regulates the expression of human bile salt export pump: dominance of transactivation over farsenoid X receptor-mediated antagonism. J Pharmacol Exp Ther. 2007 March 320(3):1153-62
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Fogarty Hall, 41 Lower College Road, Kingston, RI 02881, USA.

Full Study:

http://jpet.aspetjournals.org/content/320/3/1153.long


Related Entries: Protect and Energize Your Immune System
GMOs, Roundup, and Sunscreen Linked with Diminished Brain Resiliency
Signs of Concussions and Mild Traumatic Brain Injury
Sleep – Molecular Clean Up Time for the Brain
Artificial Sweeteners Provoke High Risk for Diabetes
Hypothyroidism, Brain Stress, and Season Changes
Alcohol, Adolescents, and Young Adults – A Neurological Disaster Waiting to Happen
GABA: Managing Brain Stimulation, Anxiety, and Other Consequences
Brain Fatigue: Fundamental Solutions
Brain Fatigue 101
Astonishing Benefits of Cranberries
Summer Heat Stress – More Than Just Dehydration
Chronic Active Epstein Barr Virus: Additional Tools for the Battle
Pine Nut Oil Reduces Inflammation, Clotting Risk, and Fatty Liver Congestion
New Findings with Epstein Barr Virus: The Sleeping Giant
Type 1 Diabetes: Risk Factor Alert
Disrupted Gut Clocks Linked with IBS, GERD, Obesity, and Other GI Concerns
Body Clocks and Weight Management – It’s All About Timing
Saturated Fat Myth – Debunked Again
Powerful Nutrition for Common Chemical Exposures
Endocrine Disruptor Compounds and Natural Solutions
Endocrine Disruptor Compounds and Your Hormones
Low Blood Pressure Linked with Brain Atrophy
Vitamin K, Leptin, AGEs, and Arthritis
Advanced Solutions for Osteoarthritis
Osteoarthritis: Good Oils versus Bad Oils and Inflammation
High Levels of Omega 6 Fatty Acids Found in Bones of Osteoarthritis Patients Worsens Joint Breakdown
Lipoic Acid Protects the Heart and Immune System from Acute Emotional Stress
Whiplash, Thyroid, and Adrenals
Brain Inflammation Now Documented in Chronic Fatigue Syndrome
Brain Protective Effects of Proathocyanidins
Nutrient Highlight: Discover the Best Form of Folate
Lutein and Zeaxanthin Offset Gene Weaknesses that Cause Macular Degeneration
Lycopene Builds Its Anti-Prostate Cancer Case
Carotenes Improve the Quality of Semen
Vitamin B12 as Methylcobalamin Repairs Nerves & Lowers Pain
Folic Acid Activates Neural Stem Cells for Brain Rejuvenation
Chromium Improves Insulin Function & Reduces Binge Eating
How Fiber and Niacin Protect Against Colon Inflammation and Cancer
Berries Have Anti-Aging Impact on Immune System
Strawberries Reduce Cardiovascular Risk
Friendly Flora Improves Fatty Liver Disease
Flavonoid Intake Improves Cardio Health in At-Risk Men
Polyphenols and Essential Fatty Acids Reduce Cardio Risk in Overweight People
Vitamin C Reduces the Risk for Hemorrhagic Stroke
Testosterone Therapy Increases Heart Attack Risk
Magnesium Intake Linked to Lower Cardiovascular Inflammation
Q10 Boosts Energy, Nerves, Muscles & Metabolism
Coenzyme Q10 Remarkably Improves Circulation
Tyrosine Helps Maintain Mental Ability Under Stress
Green Tea Extract Lowers Blood Pressure, Cholesterol, Blood Sugar & Inflammation
Poor Flexibility is a Sign of Stiff Arteries
A Sluggish Lymph System Causes Snoring & Sleep Apnea
DHA is Vital to Cardiovascular Wellness
Magnesium Supplements Lower Blood Pressure, Prevent Calcification
Magnesium for the Prevention of Heart Disease
Pomegranate Protects HDL Cholesterol from Damage
Pomegranate Blocks Flu Replication
Tocotrienols:  Twenty Years of Dazzling Cardiovascular and Cancer Research
Is Resveratrol the Fountain of Youth?
Grape Seed Extract Lowers Blood Pressure
Scientists Tout Resveratrol as a Primary Nutrient for Cardio Health
Leptin, Thyroid, and Weight Loss
Excess Appetite Causes Abdominal Fat
Low Energy? Detect Thyroid Related Fatigue
Curcumin Boosts AMPK Activation, Prevents Fatty Liver
Quercetin Activates Mitochondrial Biogenesis
Quercetin Guards Against Inflammation-Induced Bone Loss
Head Injuries Double or Triple the Risk of Early Death
Fatty Fish Consumption Lowers the Risk of Type 2 Diabetes by 33%
Flavonoids Continue to Show Potent Diabetes Prevention
Vitamin K2 Decreases Bone Loss in Postmenopausal Women
Cissus Quadrangularis Enhances Fracture Healing
Cissus Quadrangularis Reduces Exercise-Related Joint Pain
Nobiletin and Tangeretin Help Protect Against Bone Loss
Nobiletin and Tangeretin Inhibit Respiratory Virus
Oregano Oil Inhibits Biofilm Formation
Bromelain Helps Chronic Sinus Inflammation
Curcumin Demonstrates Potent Anti-Flu Properties
Quercetin Protects Brain and Body from Low Oxygen Stress
Ubiquinol Q10 Protects Against Magnified Tissue Injury
Ubiquinol Q10 Protects Eyes of Diabetic Patients
Limonene Promotes Healing of Digestive Lining
Magnesium Intake Reduces Mortality
Fiber is Vital for Cardio Health
Friendly Flora Boosts Weight Loss in Obese Women
Tocotrienols Help Correct Fatty Liver in Humans
Vitamin E Boosts Quality of Life for Alzheimer’s Patients
Astaxanthin Demonstrates Brain Protection & Rejuvenation
Top 10 Health Stories of 2013
Resveratrol’s Amazing Anti-Aging Effect on Circulation
Grape Seed Extract Normalizes Blood Pressure in Mild Hypertension Patients
Don’t Let Bacterial Infections Set Up Shop
Viral Replication Fueled by Sugar
Anti-Vitamin Propaganda Hits a Fever Pitch
Antacid Medications Cause Vitamin B12 Deficiency, Speed Aging
Men Should Take Folic Acid Prior to Conception to Prevent Birth Defects
Exercise Potently Reduces the Risk for Diseases of Aging
Fisetin Demonstrates Potent Bone Protection Properties


Most Popular News:


Connect with Wellness Resources:

Connect on Facebook Follow us on Twitter Wellness Resources on Pinterest Wellness Resources YouTube Channel Get RSS News Feeds
Telecourse
bookstore
Thyroid and Metabolism
podcast
autoship