title: Resveratrol nanoparticle system improves dissolution properties and enhances the hepatoprotective effect of resveratrol through antioxidant and anti-inflammatory pathways.
abstract: Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection. Unfortunately, RES is restricted in clinical application due to poor dissolution property and adsorption. In addition, red wine as a supplement for preventing disease is not recommended for patients with alcohol-related disorders. To address these limitations, we successfully developed a novel RES nanoparticle system (RESN) and demonstrated that RESN could circumvent the physicochemical drawbacks of raw RES with respect to dissolution, such as the reduction of particle size, amorphous transformation, and hydrogen-bond formation. In addition, we employed an animal model of CCl₄-induced hepatotoxicity to estimate the potential of the nanoparticle formulation to improve the hepatoprotective effect of orally administered RES. Our results demonstrated that RESN can diminish liver function markers (aspartate aminotransferase and alanine aminotransferase) by decreasing hepatocyte death due to CCl₄-induced hepatotoxicity in rats, when compared with RES administration. The effect was achieved by reducing oxidative stress (decreased reactive oxygen species and lipid peroxidation) and lowering inflammatory cytokines (decreased tumor necrosis factor-α and interleukin 1β) and protein expression (cyclooxygenase-2, inducible nitric oxide synthase, cytosolic phospholipase A2, and caspase-3). In conclusion, enhancement of the dissolution of RES through a nanoparticle engineering process can result in increased hepatoprotective effects mediated by antioxidant and anti-inflammatory activities. Consequently, we suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver diseases.
authors.affiliation: Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan.
authors.forename: Chiang-Wen
authors.initials: CW
authors.lastname: Lee
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Yen
authors.forename: Haw-Wei
authors.initials: HW
authors.lastname: Huang
authors.forename: Tzu-Hui
authors.initials: TH
authors.lastname: Wu
authors.forename: Horng-Huey
authors.initials: HH
authors.lastname: Ko
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Tzeng
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016503:Drug Delivery Systems; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012995:Solubility; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol