Abstract
Curcuma longa, also known as turmeric, has long been used as a medicinal herb with various biological effects. A hot water extract of C. longa (WEC) has been reported to show antioxidant and anti-inflammatory activity, but its effect on hepatic inflammation is poorly understood. In the present study, to investigate the effect of WEC on non-alcoholic steatohepatitis, C57BL/6J mice were fed a low-methionine, choline-deficient diet with 0·175% WEC (WEC group) or without WEC (control group) for 6 or 12 weeks. Although hepatic steatosis was similar in the WEC group and the control group, WEC suppressed the elevation of plasma aspartate aminotransferase and alanine aminotransferase, which are markers of hepatocellular damage. Compared with the control group, the WEC group had higher hepatic levels of reduced glutathione and superoxide dismutase, as well as a lower hepatic level of thiobarbituric acid-reactive substances. WEC also reduced hepatic expression of mRNA for inflammatory factors, including TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, F4/80 and CC motif chemokine receptor 2. Histological examination revealed that WEC suppressed hepatic recruitment of F4/80+ monocytes/macrophages and inhibited hepatic fibrosis. Furthermore, WEC inhibited hepatic expression of mRNA for molecules related to fibrosis, such as transforming growth factor-β, α-smooth muscle actin, type I collagen (α1-chain) and tissue inhibitor of matrix metalloproteinase-1. These findings suggest that dietary intake of WEC prevents the progression of non-alcoholic steatohepatitis by alleviating hepatic oxidative stress and inflammation.
Highlights
Curcuma longa, known as turmeric, has long been used as a medicinal herb with various biological effects
In contrast to the baseline group, body weight showed a significant decrease in the control group after 6 and 12 weeks on the LMCD diet, while the relative liver weight, hepatic TAG content and hepatic total cholesterol content all showed a significant increase at both times
In contrast to the baseline group, severe hepatic steatosis was observed in the control group and the water extract of C. longa (WEC) group after 6 weeks and 12 weeks (Fig. 2(A)) on the LMCD diet
Summary
Known as turmeric, has long been used as a medicinal herb with various biological effects. WEC inhibited hepatic expression of mRNA for molecules related to fibrosis, such as transforming growth factor-β, α-smooth muscle actin, type I collagen (α1-chain) and tissue inhibitor of matrix metalloproteinase-1 These findings suggest that dietary intake of WEC prevents the progression of non-alcoholic steatohepatitis by alleviating hepatic oxidative stress and inflammation. Despite attempts to treat NASH with various pharmacological agents, clinically meaningful improvement of outcomes has not been achieved[2] Both clinical and animal studies have revealed that oxidative stress and impairment of antioxidant defences contribute to liver injury and the development of fibrosis[2]. Accumulation of lipids in the liver leads to increased oxidation of NEFA Resident hepatic macrophages such as Kupffer cells (KC, F4/80+CC motif chemokine receptor 2 (CCR2)−) and inflammatory monocytes (F4/80+CCR2+) recruited to the liver from the bone marrow are known to have a key role in the development of NASH[6]. Activated KC produce monocyte chemoattractant protein-1 (MCP-1, known as CCL2), which attracts CCR2-expressing inflammatory monocytes[12] that amplify hepatocyte injury, inflammation and fibrosis by producing inflammatory cytokines and chemokines[13,14]
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