Genipin Ameliorates Carbon Tetrachloride-Induced Liver Injury in Mice via the Concomitant Inhibition of Inflammation and Induction of Autophagy

Abstract

Genipin, as the most effective ingredient of various traditional medications, encompasses antioxidative, anti-inflammatory, and antibacterial capacities. More recently, it is suggested that genipin protects against septic liver damage by restoring autophagy. The purpose of the current study was to explore the protective effect of genipin against carbon tetrachloride- (CCl4-) induced acute liver injury (ALI) and its underlying molecular machinery. Our results indicated that treatment with genipin significantly reduced CCl4-induced hepatotoxicity by ameliorating histological liver changes, decreasing the aspartate aminotransferase and alanine transaminase levels, alleviating the secretion of inflammatory cytokines, and promoting autophagic flux. Moreover, genipin effectively induced the conversion of LC3 and inhibition of p62 accumulation. The liver expressions of ATG5, ATG7, and ATG12 were significantly increased by genipin pretreatment in the ALI mice model. This protective effect may be mediated by the inhibition of mTOR and the activation of p38 MAPK signaling pathways. Meanwhile, genipin attenuated CCl4-induced inflammatory response by inhibiting the NF-κB and STAT3 signaling pathway. In addition, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or inhibition of p38 MAPK by SB203580 abolished the hepatoprotective effect of genipin. Taken together, our study implicates that genipin has a protective potential against CCl4-induced hepatotoxicity, which might be strongly associated with the induction of autophagy and the attenuation of inflammatory response.

Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice

“…Inflammation is an adaptive response to cellular or tissue damage, and the MAPK cascade signaling pathway controls the inflammatory response [ 17 ]. MAPK is responsible for the regulatory response of pro-inflammatory cytokine production and modulates various inflammatory mediators in most cells [ 11 , 13 ].…”

“…The nuclear factor-κB (NF-κB) activation and active forms of the mitogen-activated protein kinase (MAPK) pathway regulate the expression of pro-inflammatory cytokines [ 11 , 12 ]. Expression of TNF-α, IL-1β and IL-6 is induced by activation of NF-κB [ 13 ]. Extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 constitute MAPK, which is regulated by NF-κB through a variety of pathways [ 14 , 15 ].…”

Novel Findings regarding the Bioactivity of the Natural Blue Pigment Genipin in Human Diseases

“…Genipin (50 mg/kg) has also been found to decrease oxidative stress, including lipid peroxidation, and apoptosis in mice [ 20 ]. Similarly, based on a study of C57BL/6 mice, Wang et al [ 21 ] found that an intravenous injection of genipin (2.5 mg/kg) may protect against hepatotoxicity induced by carbon tetrachloride (CCl 4 ); this protection may be facilitated by attenuating the inflammatory response and inducing autophagy, which may be mediated by the mTOR (mechanistic target of rapamycin) and p38 MAPK (mitogen-activated protein kinase) signaling pathways. Seo et al [ 22 ] also note that 25, 50, and 100 mg/kg genipin seems to prevent D-galactosamine and LPS-induced hepatic injury in mice through suppression of necroptosis-mediated inflammasome signaling.…”

Regeneration of skeletal system with genipin crosslinked biomaterials

“… 150 Genipin has been found to diminish oxidative stress, and it is used to attenuate oxidative injury after chemotherapy. 151 – 153 However, no studies have explored the effects of genipin on OA or RA currently. In the previous study, our group constructed MSCs/hydrogel/porous titanium scaffolds to repair osteochondral defects and simultaneously ameliorate the RA inflammatory state, which is an example of the use of a bioactive material to simultaneously achieve tissue regeneration and symptomatic treatment.…”