Rhein: A Review of Pharmacological Activities

Evidence-Based Complementary and Alternative Medicine, Jun 2015

Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) is a lipophilic anthraquinone extensively found in medicinal herbs, such as Rheum palmatum L., Cassia tora L., Polygonum multiflorum Thunb., and Aloe barbadensis Miller, which have been used medicinally in China for more than 1,000 years. Its biological activities related to human health are being explored actively. Emerging evidence suggests that rhein has many pharmacological effects, including hepatoprotective, nephroprotective, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The present review provides a comprehensive summary and analysis of the pharmacological properties of rhein, supporting the potential uses of rhein as a medicinal agent.

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Rhein: A Review of Pharmacological Activities

Rhein: A Review of Pharmacological Activities Yan-Xi Zhou,1,2 Wei Xia,3 Wei Yue,1 Cheng Peng,2 Khalid Rahman,4 and Hong Zhang1,5 1Central Laboratory, Shanghai Seventh People’s Hospital, Shanghai 200137, China 2Key Laboratory of Standardization of Chinese Herbal Medicines of Ministry of Education, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China 3Department of Nuclear Medicine, Shanghai Seventh People’s Hospital, Shanghai 200137, China 4School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, Liverpool L3 3AF, UK 5Department of Pharmaceutical Botany, School of Pharmacy, Second Military Medical University, Shanghai 200433, China Received 7 March 2015; Revised 13 May 2015; Accepted 25 May 2015 Academic Editor: Antonella Fioravanti Copyright © 2015 Yan-Xi Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) is a lipophilic anthraquinone extensively found in medicinal herbs, such as Rheum palmatum L., Cassia tora L., Polygonum multiflorum Thunb., and Aloe barbadensis Miller, which have been used medicinally in China for more than 1,000 years. Its biological activities related to human health are being explored actively. Emerging evidence suggests that rhein has many pharmacological effects, including hepatoprotective, nephroprotective, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The present review provides a comprehensive summary and analysis of the pharmacological properties of rhein, supporting the potential uses of rhein as a medicinal agent. 1. Introduction Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid, Figure 1) is a lipophilic anthraquinone extensively found in medicinal herbs Rheum palmatum L., Cassia tora L., Polygonum multiflorum Thunb. and Aloe barbadensis Miller, and so on, which have been used medicinally in China for more than 1,000 years. Diarrhea, the most common side effect, is well tolerated in humans. Rhein exhibits linear pharmacokinetics between 50 and 200 mg [1] and has many pharmacological effects, including hepatoprotective, nephroprotective, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities (summarized in Table 1). These pharmacological effects lay the foundation for the treatment of hepatic disease [2], osteoarthritis [3], diabetes [4], atherosclerosis [5], and various cancers, such as nasopharyngeal carcinoma [6], tongue cancer [7], hepatocellular carcinoma [8], and lung cancer [9]. The aim of the present review was to give a comprehensive summary and analysis of the pharmacological properties of rhein, supporting the potential uses of rhein as a medicinal agent. Table 1: Summary of the in vitro and in vivo evidence for the biological activities of rhein. Figure 1: Chemical structure of rhein. 2. Pharmacology2.1. Hepatoprotective Activity Rhein has been shown to modulate cytochrome P450 (CYP) enzymes in rat liver microsomes. For example, rhein significantly inhibited CYP2E1; inhibition constant (Ki) = 10 μm (mixed); CYP2C9 and CYP3A were also inhibited evidently; Ki = 38 μm (mixed) and Ki = 30 μm (mixed), respectively; but rhein revealed only mild inhibitory effects on CYP1A2 (Ki = 62 μm, uncompetitive) and CYP2D6 (Ki = 74 μm, mixed) [10]. In hepatitis B virus-transgenic mice with nonalcoholic steatohepatitis induced by a high-fat (HF) diet, rhein was found to attenuate the serum levels of total cholesterol, triglyceride, and fasting plasma glucose, ameliorating glucose and lipid metabolism [11]. Oral administration of rhein significantly accelerated energy expenditure and decreased the levels of cholesterol and liver triglyceride. It lowered body weight, the expression of the lipogenic enzyme sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes in liver, and the transcriptional activity of SREBP-1c through its upstream regulator, liver X receptor (LXR). Rhein also improved insulin resistance and hepatic steatosis and normalized alanine aminotransferase (ALT) levels in HF diet-induced obese mice. Moreover, rhein regulated the T helpers Th1/Th2 responses by inhibition of T-box expressed in T-cells (T-bet) expression and enhancement of GATA-binding protein-3 expression through increased signal transducer and activator of transcription 6 phosphorylation [12]. Fibrosis, characterized by extracellular matrix accumulation and disruption of normal tissue structure, is a common cause of chronic failure of many organs [13]. The recent evidence supports rhein as an antifibrotic agent in hepatic disorders. In carbon tetrachloride/ethanol-induced liver fibrosis rats, rhein downregulated the levels of serum ALT, hyalauronic acid, procollagen type III, and liver malondialdehyde (MDA (...truncated)


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Yan-Xi Zhou, Wei Xia, Wei Yue, Cheng Peng, Khalid Rahman, Hong Zhang. Rhein: A Review of Pharmacological Activities, Evidence-Based Complementary and Alternative Medicine, 2015, 2015, DOI: 10.1155/2015/578107