The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats

Abstract

The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from Potentilla Chinensis against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid signi cantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid signi cantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP + /NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of the caspase and Bcl-2 families. Moreover, Asiatic acid could regulate the Keap1/Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and in ammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid regulated the gene expression of Gpat4 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Keap1/Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis.

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics

“…Cholestasis is closely related to metabolic disorders. Metabolomics can reveal the changes in the spectrum of endogenous metabolites in the body and further analyze the overall biological status and functional regulation of the body (S. Chen et al, 2022 ; Lin et al, 2020 ). After CR treatment, 45 metabolites in the serum were regulated.…”

Untargeted metabolomics reveals dynamic changes in metabolic profiles of rat supraspinatus tendon at three different time points after diabetes induction

“…However, high phosphatidylcholine levels were associated with a low risk of type 2 diabetes ( 20 ). The key metabolic pathway associated with these metabolites is glycerophospholipid metabolism, a type of lipid metabolism, and abnormal lipid metabolism is directly associated with oxidative stress and inflammatory responses ( 53 ). Compared to the T2DM-12w group, some LysoPC decreased in the T2DM-24w group, although the related mechanism needs to be explored further.…”

Neuroprotective mechanisms of Asiatic acid

“…In addition, it has a wide range of biological activities, such as anti-inflammatory, antioxidant, anti-infective, and anti-tumor effects [ 8 ]. Intensive studies in the past decades have revealed that AA plays a crucial role in myocardial injury [ [9] , [10] , [11] ], hepatitis [ 12 , 13 ], osteoporosis [ 14 , 15 ], tumors [ [16] , [17] , [18] , [19] ], bacterial and fungal infection [ 20 , 21 ], skin diseases [ 22 , 23 ], wound healing [ 24 ], and diabetes [ 25 , 26 ]. Furthermore, it has great potential in treating various neurological diseases such as spinal cord injury (SCI), neural tumors, traumatic brain injury (TBI), epilepsy, cerebral ischemia, Alzheimer's disease (AD), and Parkinson's disease (PD).…”