-
Current Atherosclerosis Reports Jan 2000The purpose of this review article is twofold. It seeks to present an overview of research studies conducted on the many effects of probucol, and it demonstrates the... (Review)
Review
The purpose of this review article is twofold. It seeks to present an overview of research studies conducted on the many effects of probucol, and it demonstrates the interest in pursuing studies on probucol"s multiple specific actions and its future as a therapeutic agent. Within this article, the results of animal studies, experimental human studies, and clinical human studies are detailed, as is information on toxicology studies and on the side effects of the drug.
Topics: Animals; Anticholesteremic Agents; Antioxidants; Apolipoproteins E; Arteriosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Coronary Disease; Disease Models, Animal; Disease Progression; Humans; Hypercholesterolemia; Insulin Resistance; Myocardial Infarction; Probucol; Rabbits; Rats; Vascular Resistance
PubMed: 11122724
DOI: 10.1007/s11883-000-0094-0 -
Current Opinion in Lipidology Aug 2015Probucol is a potent antioxidative drug that has been used for prevention and treatment of atherosclerotic cardiovascular diseases and xanthoma. Probucol has been used... (Review)
Review
PURPOSE OF REVIEW
Probucol is a potent antioxidative drug that has been used for prevention and treatment of atherosclerotic cardiovascular diseases and xanthoma. Probucol has been used as a lipid-lowering drug for a long time especially in Japan, although Western countries quitted its use because of the reduction in serum HDL-cholesterol (HDL-C). This review highlights both basic and clinical studies that provide new insights into the pleiotropic effects of probucol.
RECENT FINDINGS
Recently, the mechanisms for the pharmacologic actions of probucol have been elucidated at the molecular level with a special focus on HDL metabolism and its functions. Probucol enhances plasma cholesteryl ester transfer protein activity and hepatic scavenger receptor class B type I, causing a decrease in HDL-C. It also accelerates the antioxidative function of HDL via increase in paraoxonase 1 activity. Recent retrospective analyses of probucol-treated patients with heterozygous familial hypercholesterolemia and those after coronary revascularization demonstrated a strong beneficial effect of probucol on secondary prevention of cardiovascular events and mortality.
SUMMARY
Probucol has pleiotropic and beneficial therapeutic effects on cardiovascular system. Although statins are effective for lowering LDL-cholesterol (LDL-C) and reducing coronary heart disease risk, probucol should be considered as an option in case statins are not effective.
Topics: Animals; Biological Transport; Cardiovascular System; Cholesterol; Humans; Probucol
PubMed: 26125504
DOI: 10.1097/MOL.0000000000000199 -
Mini Reviews in Medicinal Chemistry 2023With the development of the social economy over the last 30 years, non-alcoholic fatty liver disease (NAFLD) is affected by unhealthy living habits and eating styles and... (Review)
Review
With the development of the social economy over the last 30 years, non-alcoholic fatty liver disease (NAFLD) is affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. It is very important to investigate the pathogenesis and treatment of NAFLD for the development of human health. Probucol is an antioxidant with a bis-phenol structure. Although probucol is a clinically used cholesterol-lowering and antiatherosclerosis drug, its mechanism has not been elucidated in detail. This paper reviews the chemical structure, pharmacokinetics and pharmacological research of probucol. Meanwhile, this paper reviews the mechanism of probucol in NAFLD. We also analyzed and summarized the experimental models and clinical trials of probucol in NAFLD. Although current therapeutic strategies for NAFLD are not effective, we hope that through further research on probucol, we will be able to find suitable treatments to solve this problem in the future.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Probucol; Antioxidants; Cholesterol; Liver
PubMed: 36967462
DOI: 10.2174/1389557523666230324092842 -
Journal of Clinical Pharmacology Jan 1990Increased levels of cholesterol, LDL-cholesterol, and VLDL-cholesterol are known risk factors for the development of atherosclerotic vascular disease. Probucol is an... (Review)
Review
Increased levels of cholesterol, LDL-cholesterol, and VLDL-cholesterol are known risk factors for the development of atherosclerotic vascular disease. Probucol is an orally active agent that can reduce total cholesterol and LDL-cholesterol. The drug also reduces HDL-cholesterol. However, it may modify the lipoprotein in such a way that removal of cholesterol from peripheral tissues is still enhanced. Probucol also has antioxidant activity, which may inhibit the oxidative modification of LDL that contributes to lipid deposition in blood vessel walls. Probucol is a well tolerated agent. However, its ability to prolong life in human subjects still needs to be determined.
Topics: Animals; Arteriosclerosis; Humans; Phenols; Probucol
PubMed: 2406299
DOI: 10.1002/j.1552-4604.1990.tb03431.x -
Free Radical Biology & Medicine Jan 1993Recently, interest has increased in the hypothesis that low-density lipoprotein (LDL) modified by oxidation may lead to the initiation and to the development of... (Review)
Review
Recently, interest has increased in the hypothesis that low-density lipoprotein (LDL) modified by oxidation may lead to the initiation and to the development of atherosclerosis. In vitro studies of cellular interactions with LDL have revealed that various cells, including endothelial cells and smooth muscle cells, can oxidize LDL. The biochemical changes in LDL may further enhance its atherogenic potential. In addition to these in vitro studies, there is in vivo evidence for oxidized LDL in atherosclerotic lesions and for circulating antibodies against oxidized LDL. Probucol, 4,4'-(isopropylidenedithio)bis(2,6-di-tert-butylphenol), is a widely used cholesterol-lowering drug. Recently, there has been accumulating evidence for other mechanisms of probucol's antiatherogenic effects apart from cholesterol-lowering action. Attention has especially focused on probucol's antioxidant action in the mechanism of antiatherogenesis. In the present article, we will summarize the antiatherogenic and antioxidant actions of probucol.
Topics: Animals; Antioxidants; Arteriosclerosis; Cell Membrane; Cholesterol; Free Radicals; Humans; Lipoproteins, HDL; Oxidation-Reduction; Probucol
PubMed: 8454225
DOI: 10.1016/0891-5849(93)90510-2 -
Nihon Rinsho. Japanese Journal of... Mar 2001
Review
Topics: Angioplasty, Balloon, Coronary; Animals; Antioxidants; Arteriosclerosis; Clinical Trials as Topic; Coronary Artery Disease; Foam Cells; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins; Probucol; Secondary Prevention
PubMed: 11347145
DOI: No ID Found -
Atherosclerosis Nov 2009Probucol has a long history of clinical application with established efficacy and safety profiles. Probucol is a potent anti-oxidant drug that has been in clinical use... (Review)
Review
Probucol has a long history of clinical application with established efficacy and safety profiles. Probucol is a potent anti-oxidant drug that has been in clinical use during the past few decades for the treatment and prevention of cardiovascular diseases. Here we review the current status of knowledge on the pharmacology, clinical benefits, and the mechanism of actions of this unique drug. Probucol has diverse pharmacological properties with therapeutic effects on the cardiovascular systems. Its mechanism of pharmacologic actions at the molecular level has recently been elucidated with the new concept of HDL metabolism associated with cholesteryl ester transfer protein (CETP) or scavenger receptor class B type I (SR-BI). HDL-C reduction may not be a "side effect" but it most likely might reflect a mechanism of action of probucol. Probucol could be reconsidered as an option at least in case statins, which are known to be effective in lowering low-density lipoproteins (LDL) and coronary artery disease (CAD) risk, are not effective. In particular, a marked CAD risk reduction has been recently reported in long-term probucol treatment of patients with heterozygous familial hypercholesterolemia (FH) in Japan. Therefore, probucol could be a more common therapeutic drug for the treatment of patients with FH as well. There is more than enough reason to believe that this old drug has much more to offer than hitherto known.
Topics: Animals; Anticholesteremic Agents; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Evidence-Based Medicine; History, 20th Century; Humans; Hyperlipoproteinemia Type II; Probucol; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 19457483
DOI: 10.1016/j.atherosclerosis.2009.04.002 -
British Journal of Pharmacology Oct 2023Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide, yet pharmacotherapies for TBI are currently lacking. Neuroregeneration is important...
BACKGROUND AND PURPOSE
Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide, yet pharmacotherapies for TBI are currently lacking. Neuroregeneration is important in brain repair and functional recovery. In this study, probucol, a cholesterol-lowering drug with established safety profiles, was examined for its therapeutic effects and neuroregenerative actions in TBI.
EXPERIMENTAL APPROACH
Male mice were subjected to the controlled cortical impact model of TBI, followed by daily administration of probucol. Neurological and cognitive functions were evaluated. Histological analyses of the neocortex and hippocampus were performed to detect the lesion, dendritic degeneration (microtubule-associated protein 2), synaptic density (synaptophysin), neurogenesis (doublecortin), brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) activation. Involvement of BDNF/TrkB pathway in probucol-mediated effects was examined in primary cultures of cortical neurons.
KEY RESULTS
Probucol reduced brain lesion volume, enhanced the recovery of body symmetry, improved motor function and attenuated memory dysfunction after TBI. Meanwhile, probucol promoted post-injury dendritic growth and synaptogenesis and increased hippocampal proliferating neuronal progenitor cells, along with the formation as well as the survival of newborn neurons. Moreover, probucol enhances BDNF expression and TrkB activation. In vitro, probucol promoted neurite outgrowth, which was inhibited by a selective TrkB antagonist ANA-12.
CONCLUSIONS AND IMPLICATIONS
Probucol enhanced functional restoration and ameliorated cognitive impairment after TBI by promoting post-injury neuronal remodelling and neurogenesis. Increased activation of BDNF/TrkB pathway by probucol, at least in part, contributed to the neuroregenerative effects of probucol. Together, it may be promising to repurpose probucol for TBI.
Topics: Mice; Animals; Male; Receptor, trkB; Probucol; Tropomyosin; Brain-Derived Neurotrophic Factor; Brain Injuries, Traumatic; Nerve Regeneration
PubMed: 37263748
DOI: 10.1111/bph.16157 -
Translational Neurodegeneration Jan 2024Neurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative... (Review)
Review
Neurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative stress, neuroinflammation and compromised blood-brain barrier (BBB) integrity. Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies. Emerging research indicates that probucol, a historic lipid-lowering medication, offers substantial potential in the realm of neurodegenerative disease prevention and treatment. Preclinical investigations have unveiled multifaceted cellular effects of probucol, showcasing its remarkable antioxidative and anti-inflammatory properties, its ability to fortify the BBB and its direct influence on neural preservation and adaptability. These diverse effects collectively translate into enhancements in both motor and cognitive functions. This review provides a comprehensive overview of recent findings highlighting the efficacy of probucol and probucol-related compounds in the context of various neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and cognitive impairment associated with diabetes.
Topics: Humans; Neurodegenerative Diseases; Probucol; Alzheimer Disease; Parkinson Disease; Blood-Brain Barrier
PubMed: 38247000
DOI: 10.1186/s40035-024-00398-w -
General Pharmacology 1988Over 15 yr of clinical experience with probucol seems to indicate that the drug is a safe and moderately effective hypocholesterolemic drug even in long-term treatment.... (Review)
Review
Over 15 yr of clinical experience with probucol seems to indicate that the drug is a safe and moderately effective hypocholesterolemic drug even in long-term treatment. Adverse effects are infrequent and usually tolerable. Probucol prolongs QT-interval but this does not seem to be connected with harmful effects in man. Its hypocholesterolemic action is not sufficient in all patients but this can be substantially improved by combining other hypolipidemic drugs with different mode of action. Interference with lipoprotein structure may contribute to the hypocholesterolemic action of probucol, and despite the lowering of HDL cholesterol probucol has been shown to regress peripheral cholesterol deposits. There is also tentative evidence that the drug may protect from CHD in primary prevention. The newly-discovered antioxidant property of probucol preventing harmful LDL modification in vitro might partly explain the favorable effects of probucol independently of its effects on LDL- or HDL-cholesterol levels.
Topics: Animals; Humans; Hypercholesterolemia; Phenols; Probucol; Time Factors
PubMed: 3046993
DOI: 10.1016/0306-3623(88)90023-7