The potential of natural products for targeting PPAR α

Abstract

Peroxisome proliferator activated receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone) are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this “hot” target.

Amelioration of experimental metabolic syndrome induced in rats by orlistat and Corchorus olitorius leaf extract; role of adipo/cytokines

“…Treatment of HFD‐fed rats with C. olitorius extract or orlistat resulted in decreased fasting blood glucose, serum insulin, and HOMA‐IR index. This finding coincides with many studies reporting that phytol and terpenes have potential roles in the management of insulin resistance and metabolic disorders that accompany diabetes and/or obesity …”

“…This finding coincides with many studies reporting that phytol and terpenes have potential roles in the management of insulin resistance and metabolic disorders that accompany diabetes and/or obesity. [25,26] The serum of the obese control rats in this study showed that there were significant increases in concentrations of TC, triglyceride (TG), LDL-C and FFA, along with decreased of HDL-C. Eight weeks administration of 30 mg/kg orlistat, 300 mg/kg or 400 mg/kg C. olitorius extract in obese rats decreased significantly the lipid profile, AI along with significant increases in HDL-C.…”

The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer’s Disease and Other Neurodegenerative Disorders

“…Unfortunately, a lot of clinical trials with agonists of PPARs in neurodegenerative diseases are controversial, due to the fact, that there are studies suggesting their ineffectiveness. Some other last data indicate promising, positive effect of PPARs agonists [127][128][129][130][131][132][133][134][135]. Overall it seems that personalized gene-related therapy or personalized combination Reduces Aβ production [48] Decreases Aβ plaque accumulation Improves learning memory [55] Decreases Aβ accumulation and reverses memory deficits and anxiety symptoms [132] WY-14643 Decreases tau protein and inflammation markers Increases ability in Moris water test [37] GW7647 Regulates APP amyloidogenic processing Decreases the expression of sAPPβ and ability of BACE1 Reduces Aβ release and Aβ production [50] Fenofibrate Regulates oxidative stress accumulation [133] Fenofibrate Parkinson's disease Protects against the damaging effect of MPTP in a rat model Decreases inflammation [94,134] Cerebral injury Reduces suspectibility to stroke in apolipoprotein E-deficient animals Decreases cerebral infarct volume [135] of specific pharmacological compounds should be more efficient.…”

Exogenously Applied Ascorbic Acid-Mediated Changes in Osmoprotection and Oxidative Defense System Enhanced Water Stress Tolerance in Different Cultivars of Safflower (Carthamus tinctorious L.)

“…Ascorbic acid is commonly known as vitamin C and it is well known to regulate stress tolerance in plants as reported in a number of studies, e.g., pea [12], canola [13] and maize [14] etc. Furthermore, it acts as a co-factor for enzymes that work in various metabolic pathways [15]. Moreover, exogenously applied ascorbic acid is believed to be very effective in protecting proteins and lipids in plants exposed to water deficit and higher saline regimes [11,16].…”