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.
Aim. Citrus unshiu peel has been used to treat various diseases in traditional East Asian medicine including Korea, and many studies have been reported regarding inflammatory diseases including ulcerative colitis (UC). However, the underlying mechanism by which Citrus unshiu peel modulates inflammation in UC remains unclear. Therefore, this study aimed to evaluate the therapeutic effect and underlying mechanism of Citrus unshiu peel water extract (CUP) for UC. Methods. The experiment for UC was conducted with 8-week-old male Balb/c mice. After 1 week of adaptation, acute colitis was induced in all groups except the normal group by 5% DSS dissolved in drinking water for 1 week. Balb/c mice were divided into 5 groups (n = 8/group): control group (Control), distilled water-treated group (DSS), 100 mg/kg sulfasalazine-treated group (SASP), 100 mg/kg CUP-treated group (CUPL), and 200 mg/kg CUP-treated group (CUPH). The efficacy of CUP on UC was evaluated by biochemical analyses such as ROS and MPO in serum and MDA in tissues, and expression of proteins related to inflammation and apoptosis was evaluated through Western blot. Results. As a result of confirming the macroscopic changes and H&E staining in colon tissues to confirm the preventive and therapeutic effects of CU, decrease in colon length and inflammatory lesions were inhibited in the CUP-treated group compared to the DSS group. In addition, as a result of serum ROS and tissue MDA analysis and oxidative stress-related protein analysis, it was significantly decreased in the CUP-administered group compared to the control group. In addition, treatment with CUP not only inactivated MAPK, p-IκBα, and NF-κBp65 by blocking the PI3K/Akt pathway but also significantly reduced the expression of inflammatory cytokines. Conclusion. These results show that CUP not only suppresses oxidative stress in UC but also regulates inflammation-related proteins and apoptotic proteins by regulating the PI3K/Akt signaling pathway, suggesting that it has the potential as a material for developing new natural therapeutic agents for UC.
This study was conducted to evaluate the effect of Chaenomelis Fructus (CF) extract on thioacetamide (TAA)-induced liver fibrosis in mice. The mice were divided into four groups for examination: Normal group (Normal, n=9), group with liver fibrosis administered distilled water (Control, n=9), group with liver fibrosis administered silymarin 100 mg/kg (Silymarin, n=9), group with liver fibrosis administered CF 200 mg/kg (CF, n=9). Liver fibrosis was established in the mice via an injection of TAA (1 week 100 mg/kg B.W., 2∼3 weeks 200 mg/kg B.W., 4∼8 weeks 400 mg/kg B.W., three times a week, I.P) for 8 weeks and they were administered silymarin and CF extract (every day, P.O) with the TAA. After the autopsy, we analyzed the expression of inflammation-related proteins and fibrosis-related factors in the liver tissue by the western blot test. The results of the experiment showed that the administration of CF regulated the expression of phosphorylated AMPK (p-AMPK) and Sirtuin 1 (SIRT1) and inhibited the expression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. In addition, the expressions of matrix metalloproteinase-2 (MMP-2), TIMP metallopeptidase inhibitor 1 (TIMP-1), ɑ-smooth muscle actin (ɑ-SMA), and collagen Ⅰ related to fibrosis were suppressed. These results suggest that the progression of liver fibrosis may be alleviated by regulating the AMPK/SIRT1/NF-κB pathway, as well as the expression of fibrosis-related factors.
Objectives: The aim of the current study was to investigate the effect of Sosiho-tang on thioacetamide (TAA)-induced liver fibrosis in mice and to elucidate its underlying mechanisms.Methods: The mice were divided into 4 groups: Normal mice (Normal), TAA-induced control mice (Control), TAA-induced and silymarin-treated (50 mg/kg) mice (Silymarin), and TAA-induced and Sosiho-tang treated (200 mg/kg) mice (SSHT). Liver fibrosis was induced via intraperitoneal injection of TAA three times a week for 8 weeks. Silymarin and Sosiho-tang were concomitantly administered for 8 weeks. Serum and liver tissues were then collected and the anti-oxidant and inflammatory protein levels in the liver tissues were evaluated using western blotting.Results: SSHT administration significantly reduced the levels of AST, ALT, ammonia, and MPO in the serum. SSHT also significantly down-regulated liver NADPH oxidase and regulated the Nrf2/Keap1 signaling pathway. SSHT treatment downregulated the liver NF-κB levels and suppressed inflammatory cytokines. SSHT treatment also decreased bile acid-related factors, such as CYP7A1 and NTCP, and fibrosis-related factors, such as α-SMA and Collagen Ⅰ.Conclusions: Taken together, these data suggest that SSHT administration suppressed the progression of liver fibrosis by activating the Nrf2/Keap1 pathway and inhibiting NF-κB.
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