Silymarin coated gold nanoparticles ameliorates CCl₄-induced hepatic injury and cirrhosis through down regulation of hepatic stellate cells and attenuation of Kupffer cells

Abstract

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 À1 ).Silymarin coated gold nanoparticles were administered intragastrically once per day for 14 weeks in a dose of 30 mg kg À1 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.

Glycogen–gold nanohybrid escalates the potency of silymarin

“…This method was adopted from Kabir et al with further modifications. 2 GNPs were also prepared without Sly for the confirmation of successful formation of SGNPs and for comparison with SGNPs in characterization techniques. To prepare the Gly-and Sly-tethered gold nanoparticles (GSGNPs), …”

“…Chemically inert biocompatible nanoparticles are exploited as functional drug carriers which were reported to reduce the toxic side effects of the drug candidate with increased potency and therapeutic index. 2 Being a physicochemically inert material with desirable stability and biocompatibility, bioactive molecule-conjugated GNPs hold promises for a wide range of biomedical therapeutic applications. 6 GNPs were reported to improve the hepatoprotective, antimicrobial, and anticancer efficacy of the therapeutic bioactive molecules upon conjugation.…”

“…6 GNPs were reported to improve the hepatoprotective, antimicrobial, and anticancer efficacy of the therapeutic bioactive molecules upon conjugation. 2,[7][8][9] Synthesis methods, templates, and reducing and stabilizing agents play a crucial role in the fabrication of GNPs with biocompatible attributes. Plant phytochemicals of tea leaves, Morinda citrifolia roots, and Pelargonium graveolens leaves were reported as green nano-factory for the synthesis of biocompatible GNPs and to be preferred over chemically or physically synthesized counterparts.…”

“…Attempts have been made to improve the bioavailability of Sly through nanoencapsulation, but further interventions are still required to fabricate the potent nanohybrids. [2][3][4] The present study was aimed to develop a nanohybrid system to improve the solubility, bioavailability, and potency of the Sly molecule. In this study, the inherent reducing capability of Sly was exploited for tethering the same on the gold nanoparticle (GNP) surface in the presence of glycogen (Gly).…”

“…Nanoparticulate Sly was reported to produce a pronounced increase in bioavailability and biological activity due to its increased solubility. 2,34 Previous reports suggested that functionalization of Sly on GNPs ameliorates the hepatic damage through downregulating the liver stellate cells and attenuating Kupffer cells. 2 Presence of Gly enhanced the gut permeation of the GSGNPs and guided toward the liver.…”