Silymarin coated gold nanoparticles ameliorates CCl 4 -induced hepatic injury and cirrhosis through down regulation of hepatic stellate cells and attenuation of Kupffer cells† Nurul Kabir, a Hamid Ali, a Muhammad Ateeq, b Massimo F. Bertino, c Muhammad Raza Shah * b and Louis Franzel c Silymarin coated gold nanoparticles with a mean size of 20 nm were synthesized and functionalized in one pot using silymarin as a reducing and stabilizing agent. Conjugation of gold with silymarin was confirmed with FT-IR and UV-visible techniques. The aim of this study was to investigate the hepatoprotective and antifibrotic potential of Silymarin coated gold nanoparticles. For this purpose oxidative liver damage was induced in Wistar rats by intraperitoneal injection of CCl 4 dissolved in olive oil (1 : 1 v/v, 1 ml kg 1 ). Silymarin coated gold nanoparticles were administered intragastrically once per day for 14 weeks in a dose of 30 mg kg 1 of body weight. Hepatoprotective and antifibrotic activities of silymarin coated gold nanoparticles were assessed in terms of reduction in serum enzymes (ALT, AST, ALP), through histopathology and immunohistochemistry techniques. It also reduced the CCl 4 -induced damaged area as well as fibrotic area to 0% as assessed by histopathology. The Alpha SMA and Kupffer cells were also reduced in number around the portal traid area by the silymarin coated gold nanoparticles. These hepatoprotective and antifibrotic effects were better than the positive control silymarin. Our results suggest the therapeutic effect of silymarin coated gold nanoparticles in CCl 4 -induced liver injury and cirrhosis by promoting extracellular matrix degradation, hepatic stellate cells inactivation with strong enhancement of hepatic regenerative capacity. Silymarin coated gold nanoparticles could be administered for up to 14 weeks without inducing side effects or alterations of the histological structure of kidneys, heart, pancreas and lungs. 1. Introduction Metal and oxide nanoparticles are currently being considered for a wide array of medical applications, including sensing, 1–5 photodynamic therapy, 6 drug delivery, 7 imaging 8 and hyper- thermia. 9 In most cases, chemically inert nanoparticles are employed to minimize toxicity and side effects. For example, Au nanoparticles are oen employed for drug delivery 10 and pho- tothermal therapy, 11 and Fe oxide nanoparticles are employed for MRI 12 and hyperthermia. 13 Chemically reactive materials are seldom employed, typically only as biocides for external appli- cation. For example, Ag nanoparticles have been employed for millennia as antibacterials and can now be found in commercial detergents 14 and in clothing. 15 Cu nanoparticles, another well-known biocide, are being employed as antifungals and antibacterials for clothing. 16 Several reports have also shown 17–21 that the antibacterial activity of several biocides can be amplied by conjugation to Ag nanoparticles. These results are not completely surprising, since the conjugates couple two biocides, one organic (the capping agents) and one inorganic (the Ag nanoparticles). These two biocides can affect different metabolic pathways of the targeted organisms and can thus be more effective than each component taken individually. Recent reports, however, have suggested that nanoparticles of chemi- cally inert materials can also enhance the potency of certain molecules. For example, the group of Kotov showed that leukemia cells were killed more efficiently by conjugation of 6- mercaptopurine to Au nanoparticles. 22 Jin and He 23 showed that the antibacterial activity of nisin increased when MgO was added to a culture of food borne pathogens such as E. coli, and our own group 24 showed that conjugation to Au nanoparticles increased by up to three times the antibacterial, antifungal, insecticidal and cytotoxic activity of the biocide 2–4, dihy- droxybenzene carbodithioic acid (DHT). The latter results, a Dr Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, Pakistan b H.E.J Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan c Department of Physics, Virginia Commonwealth University, Richmond, VA, USA. E-mail: raza.shah@iccs.edu † Electronic supplementary information (ESI) available. See DOI: 10.1039/c3ra46093b Cite this: RSC Adv. , 2014, 4, 9012 Received 24th October 2013 Accepted 21st January 2014 DOI: 10.1039/c3ra46093b www.rsc.org/advances 9012 | RSC Adv. , 2014, 4, 9012–9020 This journal is © The Royal Society of Chemistry 2014 RSC Advances PAPER Published on 21 January 2014. Downloaded by University of Malaya on 08/05/2014 04:25:05. View Article Online View Journal | View Issue