Abstract
Aim Acute liver injury (ALI) can occur for various reasons by induced inflammation and apoptosis of liver cells including hepatocytes, Kupffer cells, and hepatic stellate cells. Thioacetamide (TAA), which is a classic hepatotoxin, causes oxidative stress, membrane damage, and accumulation of lipid droplets and subsequently provokes consecutive liver injury. In the current study, we tested whether Paeoniae Radix Alba (PR) could alleviate TAA-induced ALI. Methods Thirty-five male rats were equally separated into five groups. The first group was the normal group, which received distilled water only. The remaining four groups received intraperitoneal TAA (200 mg/kg) for 3 days to induce ALI. The four groups were divided into the control group (no treatment), silymarin-treated, 100 mg/kg PR-treated, and 200 mg/kg PR-treated. The efficacy of PR against hepatotoxicity was evaluated in terms of the serum biochemical index and protein expression associated with inflammation and apoptosis. Moreover, the dissected livers were analyzed by hematoxylin and eosin stain. Results PR alleviated liver dysfunction as evidenced by decreased levels of aspartate aminotransferase, alanine aminotransferase, and ammonia. Phosphorylated AMP-activated protein kinase (AMPK) and Sirtuin 1 (Sirt1) levels were obviously decreased in the TAA control group, whereas PR reversed these changes. PR also prevented deteriorative effects through inhibition of inflammation and apoptosis via nuclear transcription factor-kappa Bp65 (NF-κBp65) inactivation. Moreover, we found that the hepatoprotective effect of PR pretreatment was mediated by restoration of histopathological changes. Conclusion PR efficiently blocked both the inflammatory response and apoptosis through activating the AMPK/Sirt1/NF-κBp65 pathway. Therefore, PR is considered a potential therapeutic agent against ALI.
Highlights
Acute liver injury (ALI) is characterized by a rapid loss of liver function without preexisting liver disease and is frequently life-threatening
Bi et al [4] reported that Paeoniae Radix Alba (PR; the root of the plant Paeonia lactiflora Pallas, Bai Shao) reduced toxicity via the degradation of toxic alkaloids and enhanced efficacy associated with cytochromes P450 (CYP450)
Paeoniflorin, a glucoside of PR, has been used to treat hepatic inflammatory disease including liver ischemia/reperfusion injury [24]. ese studies indicate that PR possesses potent pharmacological activity associated with liver diseases. erefore, using PR, a natural plant, we studied the mechanism of action of PR on liver damage that was different from studies reported so far, and we aimed to study the development of a natural therapeutic agent for liver damage based on PR
Summary
Acute liver injury (ALI) is characterized by a rapid loss of liver function without preexisting liver disease and is frequently life-threatening. A variety of causes of ALI have been identified, including infections, neoplasms, toxic factors, and drugs [1]. Emerging evidence suggests that oxidative stress (OS) is involved in the development of liver injury [2]. Ioacetamide (TAA) converts into a highly toxic reactive intermediate, thioacetamide S-dioxide, by cytochromes P450 (CYP450) enzymes. CYP450 yields OS and participates in drug-induced liver damage. Thioacetamide S-dioxide toxicity will be partially blocked by CYP450 inhibitors [3]. PR has been used as a medicinal herb in traditional Chinese medicine and is named “White Paeony.”. PR has been used more widely than Radix Paeoniae Rubra (Red Paeony) [5] PR has been used as a medicinal herb in traditional Chinese medicine and is named “White Paeony.” Recently, PR has been used more widely than Radix Paeoniae Rubra (Red Paeony) [5]
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