Pien Tze Huang Gan Bao ameliorates carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats

Abstract

Liver damage results from a variety of insults, including hepatitis and chemical toxicity from alcohol, drugs and other toxins. The present study evaluated the hepatoprotective effects and potential mechanisms of action of the Traditional Chinese Medicine Pien Tze Huang Gan Bao (GB) in a rat model of carbon tetrachloride (CCl4)-induced liver injury. Sixty male Sprague-Dawley rats were randomly divided into six different groups: i) Control, ii) CCl4 injury model and groups treated with iii) silymarin as a positive drug control, iv) 150 mg/kg GB, v) 300 mg/kg GB and vi) 600 mg/kg GB. Control rats received no treatment, while the remaining ones were intraperitoneally injected with CCl4 (2 ml/kg) to induce acute liver disease. Silymarin or GB was orally administered prior to CCl4 treatment in various treatment groups for 7 days. Animals were sacrificed 24 h post-CCl4 injection. It was revealed that GB significantly reduced serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase and total bilirubin levels in the serum induced by CCl4. BG also prevented CCl4-induced changes in liver tissues, as revealed by histopathological analysis. CCl4-induced reductions in endogenous liver antioxidant enzyme activities of superoxide dismutase, glutathione and glutathione peroxidase as well as increases in malondialdehyde and thiobarbituric acid reactive substances were inhibited by GB treatment. Activated NF-κB in liver tissues was also significantly increased by CCl4, which was attenuated by GB as indicated by immunohistochemical and PCR analysis. Furthermore, CCl4-mediated increases in the inflammatory factors tumor necrosis factor-alpha and interleukin-1β secretion into the serum and their expression in liver tissues were reversed following GB treatment, as revealed by ELISA and PCR, respectively. These findings suggested that GB protects against CCl4-induced hepatic injury, inflammation and oxidative damage in rats and may be useful in future clinical application of liver injury and disease.

Quantitative Profiling of Oxylipin Reveals the Mechanism of Pien-Tze-Huang on Alcoholic Liver Disease

“…In the present study, we showed that PZH could improve hepatic steatosis and injury in ALD mice, consistent with previous studies. In addition, PZH reduced the level of MDA and increased the activity of GSH-PX, ultimately ameliorating oxidative stress, which is consistent with a previous study [31]. rough the analysis of oxylipin profiling, we found that PZH promoted the levels of 17-HETE, 15-HEPE, 5,6-dihydroxy-8Z, 11Z, 14Z, 17Z-eicosatetraenoic acid, 9-HOTrE, and 13-HOTrE, and reduced PGE2 levels, further activating the AMPK pathway.…”

“…Through the analysis of oxylipin profiling, we found that PZH promoted the levels of 17-HETE, 15-HEPE, 5,6-dihydroxy-8Z, 11Z, 14Z, 17Z-eicosatetraenoic acid, 9-HOTrE, and 13-HOTrE, and reduced PGE2 levels, further activating the AMPK pathway. Previous studies have also shown that PZH can reduce tumor necrosis factor-alpha and interleukin-1 β secretion to ameliorate hepatic inflammation [ 31 ] and can ameliorate hepatic injury by inhibiting the PERK/eIF2 α pathway [ 22 ]. In addition, PZH could also ameliorate hepatic fibrosis by suppressing the NF-kappa B pathway [ 21 ].…”

Bicyclol Attenuates Acute Liver Injury by Activating Autophagy, Anti-Oxidative and Anti-Inflammatory Capabilities in Mice

“…its similarities with chemical liver damage in humans (Hamdy and El-Demerdash, 2012;Ma et al, 2014). Although it has been proved that the oxidative damage and inflammatory response play a critical role in this model (Tsai et al, 2017;Zhao et al, 2017), other molecular mechanisms are not fully understood.…”

“…Given CCl 4 could result in liver injury through extensive inflammatory response (Zhao et al, 2017), several inflammatory cytokines were determined in livers of mice that were CCl 4 -challenged using real-time PCR and Milliplex. As shown in Figure 5 and Table 2, CCl 4 noticeably stimulated the mRNA expression and serum levels of IL-1b, IL-6, IL-18, and TNF-a compared to the control group, whereas bicyclol treatment decreased these inflammatory cytokine production, suggesting that bicyclol retained effective anti-inflammatory activity.…”

Pien Tze Huang (PZH) as a Multifunction Medicinal Agent in Traditional Chinese Medicine (TCM): a review on cellular, molecular and physiological mechanisms

“…Moreover, it also provides a new way of exploring the prevention and treatment of NAFLD. Other studies have also shown that PZH can significantly inhibit the expression of key genes involved in the metabolism of glycolipids, in acute or chronic alcoholic liver injury models, including PPAR-gamma, SREBP2, HMGCR, IL-β, and MCP-1 [59]. In addition, PZH can exert a hepatoprotective effect in an alcoholic and HFD in vivo model [56].…”