Resveratrol: A multitargeted agent for age-associated chronic diseases

Abstract

Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g., NFκB, STAT3, HIF-1α, β-catenin and PPAR-γ), suppress the expression of antiapoptotic gene products (e.g., Bcl-2, Bcl-X L , XIAP and survivin), inhibit protein kinases (e.g., src, PI3K, JNK and AKT), induce antioxidant enzymes (e.g., catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating. Efforts are also underway to improve its activity in vivo through structural modification and reformulation. Our review describes various targets of resveratrol and their therapeutic potential.

Polyphenols from red wine are potent modulators of innate and adaptive immune responsiveness

“…In fact, RSV prevents or delays the onset of age-related diseases, such as diabetes, inflammation, Alzheimer's disease and CVD, also inducing neuroprotection and inhibiting neoplastic growth (69)(70)(71)(72)(73)(74)(75)(76)(77) . The therapeutic potential of RSV has been demonstrated by the extended lifespan and ameliorated motor function in mice fed a high-energy diet (78) .…”

High sensitivity to carcinogens in the brain of a mouse model of Alzheimer's disease

“…More than 20 epidemiologic surveys have consistently showed that common non-steroidal anti-inflammatory drugs may protect against the development of AD (Rogers, 2008) and, although mono-targeted therapies have proven so far ineffective in preventing AD, new agents that block several cellular pathways simultaneously are being analyzed (Harikumar and Aggarwal, 2008). It seems that amyloid-b peptide, which is derived from the longer amyloid precursor protein (APP), is the main stimulator of the inflammatory response found in the brain of AD patients (Sastre et al, 2008), resulting in the presence of activated microglia and astrocytes around neuritic plaques (Rodrigo et al, 2004) and increased levels of inflammatory mediators (Hoozemans et al, 2008).…”

Resveratrol: A miraculous natural compound for diseases treatment

“…The major RSV dietary sources are shown in Figure 1. This metabolite was initially recognized as an antibiotic produced in response to various environmental stresses, such as mechanical damage, microbial infection, UV radiation, heat, and pathogenic conditions (Harikumar & Aggarwal, 2008; Pervaiz, 2003). It was initially extracted from the roots of white hellebore ( veratrum grandiflorum O. Loes .)…”