Rhein: A Review of Pharmacological Activities

Zhou, Yan-Xi; Xia, Weiya; Yue, Wei; Peng, Cheng; Rahman, Khalid; Zhang, Hong

doi:10.1155/2015/578107

Cited by 150 publications

(125 citation statements)

References 58 publications

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“…As previously reported, DFD contains at least three bioactive compounds, which include rhein, aloe-emodin, and emodin [7]. Previous studies have shown that rhein can attenuate the expression of α -smooth muscle actin ( α -SMA) and the deposition of fibronectin (FN) in rat kidney, which in turn may improve kidney fibrosis [13, 14]. Additionally, emodin was found to be effective in suppressing NF- κ B-mediated TGF- β 1 and FN overexpression, thereby protecting against diabetic nephropathy [15].…”

Section: Discussionmentioning

confidence: 99%

Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

Shui

Sang

Yin

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD) on chronic aristolochic acid nephropathy (AAN) in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN), the saline-treated group (AAN + vehicle), the normal dose DFD-treated group (AAN + NDFD), the high dose DFD-treated group (AAN + HDFD), and the rosiglitazone treated group (AAN + Rosi). After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD) markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA), mitochondrial membrane potential (MMP), ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

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Section: Discussionmentioning

confidence: 99%

Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

Shui

Sang

Yin

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…Rhein is inactive for the inhibition of prolyl-4-hydroxylase in the in vitro screens, indicating that rhein is not a broad spectrum inhibitor of the 2OG-dependent hydroxylases (58). Rhein could moderately inhibit JMJD2A and JMJD2E in vitro, two iron(II) and 2OG-dependent histone demethylases.…”

Section: Panel)mentioning

confidence: 93%

Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage

Huang

Liu

et al. 2016

Journal of Biological Chemistry

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The AlkB repair enzymes, including Escherichia coli AlkB and two human homologues, ALKBH2 and ALKBH3, are iron(II)-and 2-oxoglutarate-dependent dioxygenases that efficiently repair N 1 -methyladenine and N 3 -methylcytosine methylated DNA damages. The development of small molecule inhibitors of these enzymes has seen less success. Here we have characterized a previously discovered natural product rhein and tested its ability to inhibit AlkB repair enzymes in vitro and to sensitize cells to methyl methane sulfonate that mainly produces N 1 -methyladenine and N 3 -methylcytosine lesions. Our investigation of the mechanism of rhein inhibition reveals that rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo. In addition, we have determined a new structural complex of rhein bound to AlkB, which shows that rhein binds to a different part of the active site in AlkB than it binds to in fat mass and obesity-associated protein (FTO). With the support of these observations, we put forth the hypothesis that AlkB repair enzymes would be effective pharmacological targets for cancer treatment.The nucleic acids in living cells are subject to modification by both endogenous and environmental agents (1). Direct-acting chemicals constantly damage nucleic acids and generate various methyl lesions with mutagenic and/or cytotoxic consequences (2, 3). O 6 -Methylguanine (O 6 mG) 2 and N 3 -methyladenine lesions have the highest potential for methylating damage by an SN1 agent such as N-methyl-NЈ-nitro-N-nitrosoguanidine (MNNG), which block replication and are thought to be toxic (4, 5). For the most part, the SN2 agent such as methyl methane sulfonate (MMS) produces N 1 -methyladenine (m 1 A) and N 3 -methylcytosine (m 3 C) lesions in single-stranded DNA (ssDNA). Accumulation of these adducts can lead to cell death (6, 7). Organisms have evolved several mechanisms to efficiently remove various methyl lesions, including suicidal methyltransferases, DNA glycosylases, and the AlkB family dioxygenases (see Fig. 1A) (8, 9). To date, AlkB repair appears to be the major natural defense mechanism with the power to restore the canonical base structure in vivo. Escherichia coli AlkB and its human homologues, ALKBH2 and ALKBH3, utilize iron(II) and 2-oxoglutarate (2OG) to achieve oxidative demethylation of m 1 A and m 3 C (see Fig. 1B) (10 -12). The lack of AlkB repair results in increased sensitivity to MMS, elevated level of mutations, and reduced cell proliferation (13-16). Furthermore, the accumulation of m 1 A and m 3 C lesions could also occur on RNA. Research suggests that the oxidative demethylation in mRNA and tRNA acts as a part of AlkB or ALKBH3 repair to protect cells against MMS (17, 18). The scope of substrates for AlkB repair has been largely extended to all simple N-alkyl lesions at the WatsonCrick base-pairing interface on the four bases (19), thus indicating the importance of oxidative demethylation for cell survival. In addition, human enzymes have been broadly linked to cancer. The housekeeping ...

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“…Thus, UC imposes a significant socioeconomic burden on society. Pathologically, inflammation, as evidenced by infiltration of neutrophils, macrophages, lymphocytes, and mast cells, occurs in the inner lining of the colon and rectum 1–6. Intestinal inflammation further disrupts mucosa and submucosa, eventually leading to intestinal ulcers.…”

Section: Introductionmentioning

confidence: 99%

Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro

Tang

Liang

et al. 2017

DDDT

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Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein. In addition, the production of proinflammatory cytokines, including IL-6, IL-1β, and tumor necrosis factor-α, were significantly reduced in lipopolysaccharide (LPS)-induced RAW264.7 macrophages treated with rhein. Parallel to the inhibition of proinflammatory cytokines, rhein significantly reduced phosphorylation levels of NF-κB p65 and inducible nitric oxide synthase, as well as COX-2 protein expression levels. Furthermore, rhein significantly reduced NALP3 and cleaved IL-1β expression in LPS + ATP-induced RAW264.7 macrophages. Thus, the present study demonstrates that rhein may exhibit its anti-inflammatory action via inhibition of NF-κB and NALP3 inflammasome pathways.

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Rhein: A Review of Pharmacological Activities

Cited by 150 publications

References 58 publications

Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage

Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro

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Rhein: A Review of Pharmacological Activities

Cited by 150 publications

References 58 publications

Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage

Rhein attenuates inflammation through inhibition of NF-&kappa;B and NALP3 inflammasome in vivo and in vitro

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Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro