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Rhubarb is widely popular in North America as an ingredient in pie. Meanwhile, the rhubarb cultivation area in the United States and Canada is approximately 7 times the cultivated area of Europe. Moreover, the cultivated area of rhubarb in some Nordic countries is approximately 60 hectares. In addition to being used as a laxative in Europe, rhubarb is frequently used in food as a vegetable or in the production of desserts, jams, and fruits. Most of them are used to reduce blood lipids and lose weight. In the list of health care products published by the State Food and Drug Administration of China in 2016, 66 kinds contain rhubarb, 253 kinds contained aloe, 440 species contain Semen casssiae, and 282 species contain Polygonum multiflorum. In China, approximately 10% (800) of more than 8,000 proprietary Chinese medicines contain rhubarb. These medical plants are broadly used all over the world.
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Recent studies have indicated that rhein has lipid-lowering, anti-inflammatory, antitumor, and antihepatic fibrosis effects as wells as reduces blood glucose and improves renal interstitial fibrosis. The amount of rhein in these plants are approximately 4.7 mg/g (rhubarb), 0.29 mg/g ( Polygonum multiflorum), 0.24 mg/g ( Semen cassiae), and 0.4 mg/g ( Sennae folium), suggesting that the amount of rhein in rhubarb is relatively high. Rhein (PubChem CID: 10168) is widely found in medicinal plants such as rhubarb, Sennae folium, Semen cassiae, and Polygonum multiflorum.
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Thus, bile acids can be used as potential biomarkers for liver injury and dysfunction. Despite the limitations of clinical chemistry in sensitivity and specificity at the early stage of liver diseases, there are significant alterations of bile acids in plasma and urine. The homeostasis of bile acid levels is closely related to the occurrence and development of liver diseases. However, excessive amounts of bile acid results in hepatocyte injury, even liver cirrhosis and necrosis. Some liver diseases and drug-induced liver injury are often accompanied by obstacles in the synthesis, metabolism, and excretion of bile acids, potentially leading to the accumulation of bile acids.
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They are converted from cholesterol in liver by a series of enzymes, and they maintain a dynamic balance through the uptake and efflux of hepatocellular transporter as well as the enterohepatic circulation. Introductionīile acids play an important role in regulating the metabolism balance of lipids in vivo. 30 mg/kg rhein may promote bile acid transport and reduce bile acid accumulation by upregulating the expression of FXR mRNA and Mrp3 mRNA, potentially resulting in the decrease in serum UBCAs. These results denote that rhein is relatively safe to use at a reasonable dose and timing.
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Rhein close to the clinical dose (10 mg/kg and 30 mg/kg) reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of farnesoid X receptor (FXR), small heterodimer partner (SHP), and bile salt export pump (BSEP) mRNA, and upregulated the expression of (cholesterol 7 α-hydroxylase) CYP7A1 mRNA. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered with rhein for 5 weeks. However, the effects of repeated intake of rhein on liver function and bile acid metabolism are rarely reported. Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice.