The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome.
For thousands of years, natural medicines have played an important role in treating and preventing human diseases worldwide. Natural products offer large structural diversity, and modern techniques for separation, structure elucidation, screening and combinatorial synthesis have led to revitalization of plant products as sources of new drugs. The number of people with cardiometabolic syndrome is increasing worldwide. This is expected to increase the prevalence of potentially harmful distortions of lipid distribution and thus intensify the need for appropriate intervention. With increasing evidence of the pathophysiological importance of the dyslipidaemia associated with type 2 diabetes mellitus, hypertension and insulin resistance, a more aggressive approach to lipid management is required. Nuclear receptors are an attractive and promising target for drug development. Functioning as transcription factors and thereby controlling cellular processes at the level of gene expression, modulation of nuclear receptor activity produces selective alterations in downstream gene expression. These characteristics, combined with their involvement in significant diseases, make nuclear receptors a key target for the development of disease-specific therapy. This review examines natural product libraries as a rich source of ligands for nuclear receptors and their potential as promising therapeutic agents for clinical practice. Continual evolution in drug discovery from plants remains an important source of new pharmaceuticals. Furthermore, by uncovering the regulatory mechanisms and transcriptional targets of the PPARs and other related receptors, it will be possible to provide a comprehensive insight into the pathogenesis of metabolic disease and, at the same time, offer valuable information for rational drug design, ultimately leading to a reduction in the chronic microvascular complications of cardiometabolic syndrome.
Huang
Tom Hsun-Wei
TH
Herbal Medicines Research and Education Centre, Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia. thwh@yahoo.com
Teoh
Aik Wei
AW
Lin
Bei-Lun
BL
Lin
Diana Shu-Hsuan
DS
Roufogalis
Basil
B
D000818:Animals; D055808:Drug Discovery / Q000639:trends; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008024:Ligands; D024821:Metabolic Syndrome / Q000188:drug therapy*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors
D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear