Hepatoprotective Effects of Albumin-Encapsulated Nanoparticles of a Curcumin Derivative COP-22 against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Injury in Mice

Abstract

Acute liver injury (ALI) is a severe syndrome and can further develop into acute liver failure (ALF) which can lead to high mortality and cause irreversible liver injuries in the clinic. Liver transplantation is the most common treatment; however, liver donors are lacking, and the progression of ALF is rapid. Nanoparticles can increase the bioavailability and the targeted accumulation of drugs in the liver, so as to significantly improve the therapeutic effect of ALI. Curcumin derivative COP-22 exhibits low cytotoxicity and effective anti-inflammatory activity; however, it has poor water solubility. In this study, COP-22-loaded bovine serum albumin (BSA) nanoparticles (22 NPs) were prepared and characterized. They exhibit effective hepatoprotective effects by inhibiting inflammation, oxidative stress, and apoptosis on Lipopolysaccharide/D-Galactosamine-induced acute liver injury of mice. The anti-inflammatory activity of 22 NPs is related to the regulation of the NF-κB signaling pathways; the antioxidant activity is related to the regulation of the Nrf2 signaling pathways; and the apoptosis activity is related to mitochondrial pathways, involving Bcl-2 family and Caspase-3 protein. These three cellular pathways are interrelated and affected each other. Moreover, 22 NPs could be passively targeted to accumulate in the liver through the retention effect and are more easily absorbed than 22.HCl salt in the liver.

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

“…In addition, some mono-carbonyl curcumin derivatives were designed to improve curcumin’s biological activities, namely, metabolic stability, high lipid solubility, and bioavailability. For instance, ortho-substituted mono-carbonyl curcumin derivatives (2-methoxy- and 2-trifluoromethoxy- derivatives and 2-methoxy- and 2-trifluoromethoxy-substituted derivatives) demonstrated the ability to inhibit the production of RNS and ROS against oxidative and nitrosative stress in a mouse colitis model [ 176 , 177 , 178 ]. Furthermore, the benzene ring in these derivatives can be substituted by other rings, namely, the pyridine ring, furan ring, naphthalene ring, and lactam ring, and has been used to prevent and treat various diseases [ 179 , 180 ].…”

Domino hepatocyte transplantation using explanted human livers with metabolic defects attenuates D-GalN/LPS-induced acute liver failure

“…Previous studies have shown that the molecular mechanisms of acute liver injury are related to glutathione depletion, oxidative stress, and mitochondrial dysfunction, excessive inflammatory response, and apoptosis. Therefore, novel therapeutic options improving mitochondrial functions, targeting to maintain bioenergetic status, or exerting cellular antioxidant capacity also represent potential therapeutic approaches in the treatment of ALF [ 33 ].…”

Natural Products for Acetaminophen-Induced Acute Liver Injury: A Review

“…Additionally, studies have demonstrated that CMN suppresses APAP and causes apoptosis in liver cells by reducing the expression of the pro-apoptotic genes Bax and Caspase-3, inducing anti-apoptotic genes such as Bcl-x1, and increasing the Bcl2/Bax ratio [120]. CMN also exhibits functions such as restoring liver enzymes, inhibiting lipid peroxidation, preventing NF-κB activation, and reducing the secretion of inflammatory cytokines [121], thereby alleviating APAP-induced liver injury. Moreover, it can enhance the protective effects of NAC when used in combination, allowing for a reduction in the therapeutic dose of NAC [122].…”