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      Regulatory effect of a Chinese herbal medicine formula on non-alcoholic fatty liver disease

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          Abstract

          BACKGROUND

          Non-alcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease. The Chinese herbal medicine (CHM) Dachaihu decoction (DCHD) has been proved to treat NAFLD with good efficacy in previous studies. Based on the TCM principle of formula formation, we divided DCHD into soothing liver part, invigorating spleen part, and dredging intestine part. Marshall officially proposed the concept of “intestinal-hepatic axis”, which systematically explains the interactions between the intestine and liver. We hypothesized that the effect of CHM on NAFLD is achieved by regulating the liver and intestine. Thus, we aimed to investigate the possible effect of a CHM formula on NAFLD in a rat model.

          AIM

          To investigate the effects of a CHM formula (a decoction of Chinese thorowax root, scutellaria root, and white peony root) on NAFLD and its regulatory effect on the “intestinal-liver” axis.

          METHODS

          Sixty rats were randomly divided into control, model, pioglitazone hydrochloride (PH), and CHM (a decoction of Chinese thorowax root, scutellaria root, and white peony root) groups. An NAFLD rat model was established using a high-fat high-fructose diet for 16 wk. From the 13th week, rats were administered with PH or a decoction of Chinese thorowax, scutellaria, and white peony root (CHM group) for 4 wk. Rats in the control group and model group were administered with an equal volume of distilled water. At the end of the study, blood was collected via the abdominal aorta. Liver tissues were harvested and any morphological changes were observed by hematoxylin-eosin (HE) staining, Oil red O staining, and Masson staining. In addition, blood lipids, liver function markers, and triglyceride (TG) in liver tissues were analyzed. The levels of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), Toll-like receptor-4 (TLR4), and nuclear factor-kappa B (NF-кB) in liver tissues and secreted immunoglobulin A (sIgA) in intestinal tissues were analyzed by ELISA, and protein and mRNA expression of occludin and zonula occludens-1 (ZO-1) in the intestine were measured using Western blot and reverse transcription-quantitative polymerase chain reaction, respectively. The endotoxin level in plasma was detected by endpoint chromogenic assay.

          RESULTS

          Compared to the normal control group, the liver coefficient, serum TG, total cholesterol (TC), low density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-β, NF-kB, and TLR4 in liver tissues increased significantly in the model group, while serum high density lipoprotein (HDL), intestinal sIgA, and protein and mRNA expression of occludin and ZO-1 decreased significantly in the model group ( P < 0.01). PH and CHM attenuated the elevated liver coefficient, serum TG, TC, LDL, AST, and ALT, blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-β, NF-kB, and TLR4 in liver tissues and increased serum HDL levels compared to the model group ( P < 0.01). Intestinal sIgA and the protein and mRNA expression of intestinal occludin and ZO-1 were significantly increased in the PH group compared to the model and CHM groups ( P < 0.01).

          CONCLUSION

          The decoction of Chinese thorowax root, scutellaria root, and white peony root is beneficial in regulating lipid metabolism and liver function, which indicates that it has a good effect on the liver. To a certain extent, this CHM formula can affect both the liver and intestine, while its effect on the liver is superior to that on the intestine.

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          Most cited references19

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          Degree of polymerization of inulin-type fructans differentially affects number of lactic acid bacteria, intestinal immune functions, and immunoglobulin A secretion in the rat cecum.

          This study examined the role of degree of polymerization (DP) of inulin-fructans in modulating the interaction between lactic acid bacteria and IgA cecal secretion. Rats were fed a control diet or a diet containing one of the fructans with different DP. Consuming fructans increased the cecal IgA concentrations in the order DP4 > DP8 > DP16. Cecal lactobacilli counts were higher in DP4, DP8, and DP16, whereas bifidobacteria were higher in DP8, DP16, and DP23. Cecal IgA concentrations were correlated with cecal lactobacilli counts (P < 0.01). DP4, DP8, and DP16, but not DP23, significantly increased IgA-producing plasma cells in the cecal mucosa. IFN-γ and IL-10 production in the cecal CD4(+) T cells was enhanced solely in DP4. The results show that fructans with lower DP enhance cecal IgA secretion and increase the plasma cells and suggest that the increased lactobacilli may contribute to the stimulation of cecal IgA secretion.
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            Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague–Dawley rats

            Background In humans and animal models, excessive intake of dietary fat, fructose and cholesterol has been linked to the development of non-alcoholic fatty liver disease (NAFLD). However, the individual roles of the dietary components remain unclear. To investigate this further, we compared the effects of a high-fat diet, a high-fructose diet and a combination diet with added cholesterol on the development of NAFLD in rats. Methods Forty male Sprague–Dawley rats were randomized into four groups receiving either a control-diet (Control: 10% fat); a high-fat diet (HFD: 60% fat, 20% carbohydrate), a high-fructose diet [HFr: 10% fat, 70% carbohydrate (mainly fructose)] or a high-fat/high-fructose/high-cholesterol-diet (NASH: 40% fat, 40% carbohydrate (mainly fructose), 2% cholesterol) for 16 weeks. Results After 16 weeks, liver histology revealed extensive steatosis and inflammation in both NASH- and HFD-fed rats, while hepatic changes in HFr-rats were much more subtle. These findings were corroborated by significantly elevated hepatic triglyceride content in both NASH- (p < 0.01) and HFD-fed rats (p < 0.0001), elevated hepatic cholesterol levels in NASH-fed rats (p < 0.0001), but no changes in HFr-fed rats, compared to Control. On the contrary, only HFr-fed rats developed dyslipidemia as characterized by higher levels of plasma triglycerides compared to all other groups (p < 0.0001). Hepatic dysfunction and inflammation was confirmed in HFD-fed rats by elevated levels of hepatic MCP-1 (p < 0.0001), TNF-alpha (p < 0.001) and plasma β-hydroxybutyrate (p < 0.0001), and in NASH-fed rats by elevated levels of hepatic MCP-1 (p < 0.01), increased hepatic macrophage infiltration (p < 0.001), and higher plasma levels of alanine aminotransferase (p < 0.0001) aspartate aminotransferase (p < 0.05), haptoglobin (p < 0.001) and TIMP-1 (p < 0.01) compared to Control. Conclusion These findings show that dietary fat and cholesterol are the primary drivers of NAFLD development and progression in rats, while fructose mostly exerts its effect on the circulating lipid pool.
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              Gut-liver axis and microbiota in NAFLD: insight pathophysiology for novel therapeutic target.

              There is increasing evidence for a correlation between intestinal microbiota, bacterial translocation and hepatic steatosis. Intestinal microbiota affects nutrient absorption and energy homeostasis. Altered intestinal permeability may favor the passage of bacteriaderived compounds into systemic circulation, causing a systemic inflammatory state, characteristic of the metabolic syndrome. The interaction between intestinal permeability and luminal bacteria is involved in the pathogenesis and evolution of non-alcoholic liver disease. Microbiota pharmacological modulation could be a promising tool for a new therapeutical approach to non-alcoholic fatty liver disease.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                14 September 2019
                14 September 2019
                : 25
                : 34
                : 5105-5119
                Affiliations
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China. liyuhang@ 123456bucm.edu.cn
                Author notes

                Author contributions: Li YH carried out the research and designed the experiments; Yang JM analyzed the data and wrote the manuscript; Wang M, Zhang XL, Zhang SJ, Gao YS, Chen L, Wu MY, Zhou L, Zhou YM, and Wang Y contributed to drug preparation and experimental manipulation; Sun Y and Zheng FJ contributed to experimental instruction and data acquisition.

                Supported by the National Natural Science Foundation of China, No. 81673868.

                Corresponding author: Yu-Hang Li, PhD, Professor, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11, East Beisanhuan Road, Chaoyang District, Beijing 100029, China. liyuhang@ 123456bucm.edu.cn

                Telephone: +86-10-64287503 Fax: +86-10-53912004

                Article
                jWJG.v25.i34.pg5105
                10.3748/wjg.v25.i34.5105
                6747291
                31558860
                3ce119a8-696e-4a47-bc1a-fd99d988cf5a
                ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 12 April 2019
                : 14 June 2019
                : 19 July 2019
                Categories
                Basic Study

                non-alcoholic fatty liver disease,chinese herbal medicine,liver function,intestinal-hepatic axis

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