Ginsenoside Rg1 ameliorates aging‑induced liver fibrosis by inhibiting the NOX4/NLRP3 inflammasome in SAMP8 mice. 2021

Yan Li, and Duoduo Zhang, and Lan Li, and Yuli Han, and Xianan Dong, and Liu Yang, and Xuewang Li, and Weizu Li, and Weiping Li
Key Laboratory of Anti‑Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Aging is often accompanied by liver injury and fibrosis, eventually leading to the decline in liver function. However, the mechanism of aging‑induced liver injury and fibrosis is still not fully understood, to the best of our knowledge, and there are currently no effective treatment options available for liver aging. Ginsenoside Rg1 (Rg1) has been reported to exert potent anti‑aging effects due to its potential antioxidant and anti‑inflammatory activity. The present study aimed to investigate the protective effect and underlying mechanism of action of Rg1 in aging‑induced liver injury and fibrosis in senescence‑accelerated mouse prone 8 (SAMP8) mice treated for 9 weeks. The histopathological results showed that the arrangement of hepatocytes was disordered, vacuole‑like degeneration occurred in the majority of cells, and collagen IV and TGF‑β1 expression levels, that were detected via immunohistochemistry, were also significantly upregulated in the SAMP8 group. Rg1 treatment markedly improved aging‑induced liver injury and fibrosis, and significantly downregulated the expression levels of collagen IV and TGF‑β1. In addition, the dihydroethylene staining and western blotting results showed that Rg1 treatment significantly reduced the levels of reactive oxygen species (ROS) and IL‑1β, and downregulated the expression levels of NADPH oxidase 4 (NOX4), p47phox, p22phox, phosphorylated‑NF‑κB, caspase‑1, apoptosis‑associated speck‑like protein containing a C‑terminal caspase recruitment domain and the NLR family pyrin domain containing 3 (NLRP3) inflammasome, which were significantly upregulated in the liver tissues of elderly SAMP8 mice. In conclusion, the findings of the present study suggested that Rg1 may attenuate aging‑induced liver injury and fibrosis by reducing NOX4‑mediated ROS oxidative stress and inhibiting NLRP3 inflammasome activation.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D008297 Male Males
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002681 China A country spanning from central Asia to the Pacific Ocean. Inner Mongolia,Manchuria,People's Republic of China,Sinkiang,Mainland China
D000071199 NLR Family, Pyrin Domain-Containing 3 Protein An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME. Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000074663 NADPH Oxidase 4 An NADPH oxidase that is strongly expressed in the kidney. It forms a complex with CYBA-P22PHOX and produces intracellular SUPEROXIDES that may regulate cellular signaling in APOPTOSIS; BONE RESORPTION; and NF-KAPPA B activation. Nox4 Protein,Renal NAD(P)H Oxidase,Renox NAD(P)H Oxidase,Oxidase 4, NADPH
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous

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