Ginsenoside Rg3 ameliorates acetaminophen-induced hepatotoxicity by suppressing inflammation and oxidative stress.
OBJECTIVES
Improper usage of acetaminophen (APAP) leads to morbidity and also mortality secondary to liver damage. Ginseng could suppress APAP-induced hepatotoxicity and ginsenoside Rg3 is a kind of major component in ginseng against liver damage. Herein, we intended to estimate the beneficial function and molecular mechanism of Rg3 on APAP-caused hepatotoxicity and identified hepatoprotection.


METHODS
A total of 50 C57BL/6J mice were divided into five random groups, and each contains 10 mice as the control, acetaminophen (350 mg/kg) and Rg3 (5, 10 and 20 mg/kg) + acetaminophen (350 mg/kg) groups. These mice were intragastric administration a single dose of acetaminophen by oral treatment behind pre-administered with several doses of ginsenoside Rg3 for six hours.


KEY FINDINGS
According to our data, the injection of APAP (350 mg/kg) enhanced the basal levels of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and lactic dehydrogenase. However, these abnormal added were alleviated by Rg3. Moreover, Rg3 treatment obviously relieved APAP-caused inflammation and oxidant in liver tissues. The depletion of glutathione, glutathione peroxidase, total antioxidant capacity and generation of malondialdehyde induced by APAP treatment were reduced by Rg3. By H&E staining, Rg3 effectively reduced APAP-caused apoptosis and inflammatory infiltration. Moreover, Rg3 attenuated APAP-caused hepatic damage in part by regulating the pro-inflammatory and anti-inflammatory cytokines. Moreover, we found that Rg3 could bind to NLRP3 suggesting the anti-inflammatory effects of Rg3 by molecular docking study.


CONCLUSIONS
In summary, Rg3 showed hepatic protective function in APAP-induced hepatotoxicity as evidenced by a reduction of the oxidant and the inflammatory reply, relieve of hepatocellular damage, showing potential in Rg3 as a potential therapeutic medicine to prevent hepatic injury.
['Gao|Yan|Y|', 'Yan|Jiaqing|J|', 'Li|Juntong|J|', 'Li|Xun|X|', 'Yang|Songwei|S|', 'Chen|Naihong|N|', 'Li|Lin|L|', 'Zhang|Lan|L|']
D000082:Acetaminophen D000818:Animals D000893:Anti-Inflammatory Agents D000975:Antioxidants D017209:Apoptosis D056486:Chemical and Drug Induced Liver Injury D016207:Cytokines D004305:Dose-Response Relationship, Drug D036145:Ginsenosides D007249:Inflammation D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D062105:Molecular Docking Simulation D018384:Oxidative Stress
ginsenoside Rg3 acetaminophen hepatic damage molecular docking Luminex analysis