RNA-Seq Analysis of Protection against Chronic Alcohol Liver Injury by Rosa roxburghii Fruit Juice (Cili) in Mice

Abstract

Rosa roxburghii Tratt. fruit juice (Cili) is used as a medicinal and edible resource in China due to its antioxidant and hypolipidemic potentials. The efficacy of Cili in protecting alcohol-induced liver injury and its underlying mechanism was investigated. C57BL/6J mice received a Lieber-DeCarli liquid diet containing alcohol to produce liver injury. After the mice were adapted gradually to 5% alcohol, Cili (4 mL and 8 mL/kg/day for 4 weeks) were gavaged for treatment. The serum enzyme activities, triglyceride levels, histopathology and Oil-red O staining were examined. The RNA-Seq and qPCR analyses were performed to determine the protection mechanisms. Cili decreased serum and liver triglyceride levels in mice receiving alcohol. Hepatocyte degeneration and steatosis were improved by Cili. The RNA-Seq analyses showed Cili brought the alcohol-induced aberrant gene pattern towards normal. The qPCR analysis verified that over-activation of CAR and PXR (Cyp2a4, Cyp2b10 and Abcc4) was attenuated by Cili. Cili alleviated overexpression of oxidative stress responsive genes (Hmox1, Gsta1, Gstm3, Nqo1, Gclc, Vldlr, and Cdkn1a), and rescued alcohol-downregulated metabolism genes (Angptl8, Slc10a2, Ces3b, Serpina12, C6, and Selenbp2). Overall, Cili was effective against chronic alcohol liver injury, and the mechanisms were associated with decreased oxidative stress, improved lipid metabolism through modulating nuclear receptor CAR-, PXR-and Nrf2-mediated pathways.

Transcriptome Analysis of Protection by Dendrobium nobile Alkaloids (DNLA) against Chronic Alcoholic Liver Injury in Mice

“…The Lieber–DeCarli alcohol diet-induced alcoholic liver injury involves mild liver damage characterized by steatosis and mild inflammation [ 6 , 21 ], which is different from acute CCl 4 -induced liver injury with marked elevation of serum enzymes, hepatocyte necrosis, lipid peroxidation, mitochondrial dysfunction, and oxidative damage [ 15 , 16 ]. In the present study, increases in serum enzyme activities were mild with foci of apoptosis/necrosis, rendering a serum triglyceride increase and lipid accumulation in the liver the major pathologies.…”

“…Similarly, Cyp2a5 -null mice exhibited enhanced alcoholic liver injury and hyperglycemia [ 4 ]. Thus, appropriate activation of CAR and PXR is beneficial as an adaptive response to alcohol exposure within the threshold range, but their overaction could aggravate the liver injury [ 6 , 25 ].…”

“…Combination therapy options including the use of traditional medicine [ 5 , 6 ] towards multiple targets will eventually be required for ALD [ 7 ]. Dendrobium species have been widely used as Chinese medicines; they have many beneficial effects [ 8 ].…”

“…Other than stopping drinking, there are limited therapeutic strategies to reverse alcoholic liver injury. Therefore, discovering therapeutic candidates for the treatment of alcoholic liver injury from Chinese herbal medicine would be significant [ 5 , 6 , 18 , 19 , 20 ] and of clinical significance. In this study, a chronic liver injury model was induced by the Lieber–DeCarli liquid diet containing 5% alcohol [ 21 ], and the effects of DNLA intervention were evaluated after 28 days of treatment.…”

The Synergistic Action of Metformin and Glycyrrhiza uralensis Fischer Extract Alleviates Metabolic Disorders in Mice with Diet-Induced Obesity

“…Liver and epididymal WAT were fixed in paraformaldehyde/phosphate-buffered saline (PBS) (10% v / v ) and stained with hematoxylin and eosin and oil red O; epididymal WAT paraffin-embedded sections were stained using hematoxylin and eosin [ 39 ]. For fatty liver detection, liver tissue was embedded in optimal cutting temperature (OCT) compound and stored at −80 °C [ 40 ]. The OCT-embedded samples were sectioned to obtain 4 μm thick slices and stained with oil red O for the evaluation of fat droplets.…”