title: Ginger-derived nanoparticles protect against alcohol-induced liver damage.
abstract: Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)-mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant-derived nanoparticles.
authors.affiliation: James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Zhong-Bin
authors.initials: ZB
authors.lastname: Deng
authors.affiliation: James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.affiliation: James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Louisville, Louisville, KY, USA.|Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA.
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Louisville, Louisville, KY, USA.|Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA.|Robley Rex Louisville Veterans Administration Medical Center, Louisville, KY, USA.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.affiliation: James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA.|Robley Rex Louisville Veterans Administration Medical Center, Louisville, KY, USA; H0Zhan17@louisville.edu.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
keywords: Nrf2 detoxic effect; TLR4/TRIF pathway; alcoholic liver injury; ginger nanoparticles; shogaol