Identification

Name
Rhein
Accession Number
DB13174
Type
Small Molecule
Groups
Experimental
Description

Rhein is an anthraquinone metabolite of rheinanthrone and senna glycoside is present in many medicinal plants including Rheum palmatum, Cassia tora, Polygonum multiflorum, and Aloe barbadensis [1]. It is known to have hepatoprotective, nephroprotective, anti-cancer, anti-inflammatory, and several other protective effects.

Structure
Thumb
Synonyms
Not Available
External IDs
NSC-38629
Categories
UNII
YM64C2P6UX
CAS number
478-43-3
Weight
Average: 284.2204
Monoisotopic: 284.032087988
Chemical Formula
C15H8O6
InChI Key
FCDLCPWAQCPTKC-UHFFFAOYSA-N
InChI
InChI=1S/C15H8O6/c16-9-3-1-2-7-11(9)14(19)12-8(13(7)18)4-6(15(20)21)5-10(12)17/h1-5,16-17H,(H,20,21)
IUPAC Name
4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid
SMILES
OC(=O)C1=CC2=C(C(O)=C1)C(=O)C1=C(C=CC=C1O)C2=O

Pharmacology

Indication

No approved indication.

Pharmacodynamics

*Liver: *Reverses animal models of non-alcoholic fatty liver disease by lowering liver lipids and reducing inflammation [5]. Also reverses and prevents fibrosis in liver injury [6].

*Kidney: *Protects against fibrosis in nephropathy models and improves epithelial tight junction function [7] [9].

Bone and joint: Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity [19][20] [21].

Lipid lowering and anti-obesity: Reduces body weight and fat content, and lowers high density lipoprotein and low density lipoprotein [14]. May prevent adipocyte differentiation [13].

Anti-oxidant/Pro-oxidant: Reduces levels of reactive oxygen species (ROS) at concentrations of about 2-16 microM but induces the generation of ROS at concentrations of 50 microM and above [15] [16].

Anti-cancer: Rhein has been observed to produce DNA damage and suppress DNA repair in cancer cells [22]. It induces apoptosis via ER stress, calcium, and mitochondria mediated pathways [23]. Rhein also prevents cancer cell invasion into systemic circulation by preventing angiogenesis and breakdown of the extracellular matrix [24]. Finally, rhein suppresses the activation of several tumor promoting signalling pathways [24] [25] [26].

*Anti-inflammatory: * Suppresses the production of pro-inflammatory cytokines such as interleukin-1beta and interleukin-6 [19] [20].

*Anti-diabetic: *Lowers plasma glucose and increases survival of islet beta cells in type 2 diabetes mellitus models [2].

Anti-microbial: Inhibits arylamine N-acteyltransferase and cell growth in Helicobacter pylori [11]. Rhien also appears to be effective against many genotypes of Staphylococcus aureus [12].

Anti-allergenic: Inhibits production of leukotrienes and the release of histamine from mast cells [17].

Mechanism of action

*Liver: *The reversal of non-alcoholic fatty liver disease stems from rhien's lipid lowering and anti-obesity actions which result in an overall decrease in body weight, high density lipoprotein, and low density lipoprotein as well as its anti-inflammatory action [5]. The reversal of hepatic fibrosis is thought to be due to rhien's anti-inflammatory and anti-oxidant action which suppresses the pro-fibrotic signalling from macrophages and further damage from reactive oxygen species respectively [6]. Ultimately this results in reduced expression of alpha-smooth muscle actin (Alpha-SMA) which is indicative of decreased hepatic stellate cell and myofibroblast activation. Rhein also appears to suppress the expression of transforming growth factor-Beta (TGF-Beta)

*Kidney: *The protection from fibrosis in the kidney also appears to stem from rhien's anti-inflammatory action resulting in less inflammatory cell infiltration along with suppression of alpha-SMA and fibronectin expression [7]. These indicate a reduction in the activation of interstitial fibroblasts which are responsible for excess production of extracellular matrix components. Rhien may also suppress TGF-beta expression in the kidney. The anti-fibrotic mechanism of rhien may involve the upregulation of bone morphogenetic protein 7 and hepatic growth factor [8]. In diabetic nephropathy rhein appears to suppress the expression of integrin-linked kinase leading to a reduction in the matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 ratio [10]. The improvement of epithelial tight junction function seems to involve upregulation of zona occludins protein-1 and occludin expression [9].

Bone and joint:Rhein reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)-1 and -3 as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs [21]. The anti-inflammatory action of rhein reduces the level of interleukin-1beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation [20]. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism [19].

*Lipid lowering and anti-obesity: *Rhein is known to bind and inhibit liver X receptor alpha and beta with Kd values of 46.7 microM and 31.97 microM respectively [14]. This decreases the expression of genes such as that of sterol regulatory element binding transcription factor 1 (SREBP1c) and its downstream genes for fatty acid synthase (FAS), steroyl-coenzyme A desaturase 1 (SCD1), and acetyl CoA carboxylase 1 (ACC1). SREBP1c, FAS, SCD1, and ACC1 are all involved in adipogenesis and their suppression results in less fat content. The genes for ABCA1 and ABCG1 are also suppressed. These correspond to cholesterol efflux trasporters and likely explain the reductiion in HDL and LDL seen with rhein. The inhibition of LXR by rhien relieves the inhibition on uncoupling protein 1 expression in brown adipose tissue. The result of this is increased thermogenesis which likely plays a role in the reduction of body weight produced by rhien. Additionally, rhein may downregulate peroxisome proliferator-receptor gamma and its downstream genes to inhibit adipocyte differentiation [13].

Anti-oxidant/Pro-oxidant: The antoxidant mechanism is unknown. The pro-oxidant action of rhien may involve the inhibition of mitochondrial respiratory complex 1 and subsequent facilitation of NADH and NADPH dependent lipid peroxidation [16].

Anti-cancer: The exact mechanism of rhein's ability to damage DNA and supress the expression of DNA repair enzymes ADR and MGMT is unknown [22]. The mechanism through which rhien induces ER stress is unknown but likely involves its pro-oxidant properties [23]. Rhein has been observed to produce increases in cytosolic calcium, reductions in mitochondrial membrane potential, and upregulation of pro-apoptotic proteins as well as leakage of cytochrome C which would induce apoptosis via the intrinsic pathway. The reduction of matrix metalloproteinase-9 serves to prevent extra cellular matrix breakdown by cancer cells and hinders their invasion into surrounding tissue [24]. Rhein also decreases vascular endothelial growth factor expression through an unknown mechanism to prevent cancer cells from stimulating agiogenesis. Rhein reduces the activity of the nuclear factor kappa (NFkappaB) pathway by preventing the destruction of IKBalpha [24] [27]. The activity of the phosphoinositol 3-kinase/Akt pathway is also reduced by rhien [25]. Rhein's inhibition of the mitogen-activated protein kinase pathways (particularly those involving extracellular signal regulated kinase) appears to follow a U-shaped dose response curve. ERK phosphorylation is inhibited at low concentrations of around 3microM but activated at higher concentrations of around 30microM [26]. Furthermore, ERK phosporylation is again inhibited at extremely high concentrations in excess of 100 microM [24]. The suppression of these three pathways is likely involved in the anti-proliferative effects of rhein.

Anti-inflammatory: The mechanism of rhein's anti-inflammatory effect likely involves its inhibition of the NFkappa B pathway which plays a role in the production of many pro-inflammatory cytokines [24] [27]. Rhein's anti-oxidant activity may also play a role in preventing damage during inflammation.

Anti-diabetic: Rhein is thought to increase islet beta cell survival by suppressing the expression of dynamin-related protein 1 and thereby preventing mitochondrial fission [2]. Rhein's anti-oxidant properties are also thought to play a role in protecting islet beta cells. The reduction in plasma glucose is likely due to increased survival of islet beta cells and subsequent increases in insulin secretion. Rhein's anti-inflammatory action may also serve to reduce insulin resistance.

Anti-microbial: Rhien inhibits H. pylori arylamine N-acetyltransferase in a dose dependent manner [11]. The mechanism of rhein's anti-microbial effect on H. pylori and S. aureus are unknown.

Anti-allergenic: Rhien inhibits 5-lipoxygenase with an IC50 of 13.7microM [17]. Rhien also inhibits mast cell degranulation although the specific mechanism is unknown.

TargetActionsOrganism
UOxysterols receptor LXR-alpha
inhibitor
Humans
UOxysterols receptor LXR-beta
inhibitor
Humans
UArylamine N-acetyltransferase (Helicobacter pylori)
inhibitor
Helicobacter pylori
UArachidonate 5-lipoxygenase
inhibitor
Humans
Absorption

Tmax of 1.6-2.6 hours [3].

Volume of distribution

15-60L [3].

Protein binding

99% bound to plasma proteins [3].

Metabolism

Metabolized primarily to rhein glucuronide and rhien sulfate [3].

Route of elimination

37% is excreted in urine and 53% in feces as estimated in rats [4].

Half life

4-10h [3].

Clearance

Total CL is 1.5 L/h and renal CL is 0.1 L/h [3].

Toxicity

Oral LD50 of >5000mg/kg in mice [MSDS].

Affected organisms
  • Helicobacter pylori
  • Staphylococcus aureus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Rhein.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Rhein.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Rhein.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Rhein.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Rhein.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Rhein.
9-DeazaguanineThe metabolism of 9-Deazaguanine can be decreased when combined with Rhein.
9-MethylguanineThe metabolism of 9-Methylguanine can be decreased when combined with Rhein.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Rhein.
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Rhein.
Food Interactions
Not Available

References

General References
  1. Zhou YX, Xia W, Yue W, Peng C, Rahman K, Zhang H: Rhein: A Review of Pharmacological Activities. Evid Based Complement Alternat Med. 2015;2015:578107. doi: 10.1155/2015/578107. Epub 2015 Jun 22. [PubMed:26185519]
  2. Liu J, Chen Z, Zhang Y, Zhang M, Zhu X, Fan Y, Shi S, Zen K, Liu Z: Rhein protects pancreatic beta-cells from dynamin-related protein-1-mediated mitochondrial fission and cell apoptosis under hyperglycemia. Diabetes. 2013 Nov;62(11):3927-35. doi: 10.2337/db13-0251. Epub 2013 Aug 6. [PubMed:23919963]
  3. Nicolas P, Tod M, Padoin C, Petitjean O: Clinical pharmacokinetics of diacerein. Clin Pharmacokinet. 1998 Nov;35(5):347-59. [PubMed:9839088]
  4. De Witte P, Lemli J: Excretion and distribution of [14C]rhein and [14C]rhein anthrone in rat. J Pharm Pharmacol. 1988 Sep;40(9):652-5. [PubMed:2907037]
  5. Sheng X, Wang M, Lu M, Xi B, Sheng H, Zang YQ: Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice. Am J Physiol Endocrinol Metab. 2011 May;300(5):E886-93. doi: 10.1152/ajpendo.00332.2010. Epub 2011 Mar 1. [PubMed:21364120]
  6. Guo MZ, Li XS, Xu HR, Mei ZC, Shen W, Ye XF: Rhein inhibits liver fibrosis induced by carbon tetrachloride in rats. Acta Pharmacol Sin. 2002 Aug;23(8):739-44. [PubMed:12147197]
  7. He D, Lee L, Yang J, Wang X: Preventive effects and mechanisms of rhein on renal interstitial fibrosis in obstructive nephropathy. Biol Pharm Bull. 2011;34(8):1219-26. [PubMed:21804209]
  8. Su J, Yin LP, Zhang X, Li BB, Liu L, Li H: Chronic allograft nephropathy in rats is improved by the intervention of rhein. Transplant Proc. 2013 Jul-Aug;45(6):2546-52. doi: 10.1016/j.transproceed.2013.03.030. [PubMed:23953579]
  9. Peng SN, Zeng HH, Fu AX, Chen XW, Zhu QX: Effects of rhein on intestinal epithelial tight junction in IgA nephropathy. World J Gastroenterol. 2013 Jul 14;19(26):4137-45. doi: 10.3748/wjg.v19.i26.4137. [PubMed:23864776]
  10. Peng L, Yang J, Ning C, Zhang J, Xiao X, He D, Wang X, Li Z, Fu S, Ning J: Rhein inhibits integrin-linked kinase expression and regulates matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio in high glucose-induced epithelial-mesenchymal transition of renal tubular cell. Biol Pharm Bull. 2012;35(10):1676-85. [PubMed:23037158]
  11. Chung JG, Tsou MF, Wang HH, Lo HH, Hsieh SE, Yen YS, Wu LT, Chang SH, Ho CC, Hung CF: Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients. J Appl Toxicol. 1998 Mar-Apr;18(2):117-23. [PubMed:9570694]
  12. Yu L, Xiang H, Fan J, Wang D, Yang F, Guo N, Jin Q, Deng X: Global transcriptional response of Staphylococcus aureus to rhein, a natural plant product. J Biotechnol. 2008 Jun 30;135(3):304-8. doi: 10.1016/j.jbiotec.2008.04.010. Epub 2008 Apr 29. [PubMed:18514345]
  13. Liu Q, Zhang XL, Tao RY, Niu YJ, Chen XG, Tian JY, Ye F: Rhein, an inhibitor of adipocyte differentiation and adipogenesis. J Asian Nat Prod Res. 2011 Aug;13(8):714-23. doi: 10.1080/10286020.2011.586341. [PubMed:21751839]
  14. Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [PubMed:23139635]
  15. Zhong XF, Huang GD, Luo T, Deng ZY, Hu JN: Protective effect of rhein against oxidative stress-related endothelial cell injury. Mol Med Rep. 2012 May;5(5):1261-6. doi: 10.3892/mmr.2012.793. Epub 2012 Feb 16. [PubMed:22344690]
  16. Glinn MA, Lee CP, Ernster L: Pro- and anti-oxidant activities of the mitochondrial respiratory chain: factors influencing NAD(P)H-induced lipid peroxidation. Biochim Biophys Acta. 1997 Jan 16;1318(1-2):246-54. [PubMed:9030267]
  17. Singh B, Nadkarni JR, Vishwakarma RA, Bharate SB, Nivsarkar M, Anandjiwala S: The hydroalcoholic extract of Cassia alata (Linn.) leaves and its major compound rhein exhibits antiallergic activity via mast cell stabilization and lipoxygenase inhibition. J Ethnopharmacol. 2012 May 7;141(1):469-73. doi: 10.1016/j.jep.2012.03.012. Epub 2012 Mar 17. [PubMed:22449441]
  18. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [PubMed:18814214]
  19. Pelletier JP, Lajeunesse D, Reboul P, Mineau F, Fernandes JC, Sabouret P, Martel-Pelletier J: Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone. J Rheumatol. 2001 Apr;28(4):814-24. [PubMed:11327257]
  20. Moldovan F, Pelletier JP, Jolicoeur FC, Cloutier JM, Martel-Pelletier J: Diacerhein and rhein reduce the ICE-induced IL-1beta and IL-18 activation in human osteoarthritic cartilage. Osteoarthritis Cartilage. 2000 May;8(3):186-96. [PubMed:10806046]
  21. Tamura T, Kosaka N, Ishiwa J, Sato T, Nagase H, Ito A: Rhein, an active metabolite of diacerein, down-regulates the production of pro-matrix metalloproteinases-1, -3, -9 and -13 and up-regulates the production of tissue inhibitor of metalloproteinase-1 in cultured rabbit articular chondrocytes. Osteoarthritis Cartilage. 2001 Apr;9(3):257-63. [PubMed:11300749]
  22. Chen YY, Chiang SY, Lin JG, Yang JS, Ma YS, Liao CL, Lai TY, Tang NY, Chung JG: Emodin, aloe-emodin and rhein induced DNA damage and inhibited DNA repair gene expression in SCC-4 human tongue cancer cells. Anticancer Res. 2010 Mar;30(3):945-51. [PubMed:20393018]
  23. Hsia TC, Yang JS, Chen GW, Chiu TH, Lu HF, Yang MD, Yu FS, Liu KC, Lai KC, Lin CC, Chung JG: The roles of endoplasmic reticulum stress and Ca2+ on rhein-induced apoptosis in A-549 human lung cancer cells. Anticancer Res. 2009 Jan;29(1):309-18. [PubMed:19331167]
  24. Lin ML, Chung JG, Lu YC, Yang CY, Chen SS: Rhein inhibits invasion and migration of human nasopharyngeal carcinoma cells in vitro by down-regulation of matrix metalloproteinases-9 and vascular endothelial growth factor. Oral Oncol. 2009 Jun;45(6):531-7. doi: 10.1016/j.oraloncology.2008.07.012. Epub 2008 Sep 18. [PubMed:18804415]
  25. Fernand VE, Losso JN, Truax RE, Villar EE, Bwambok DK, Fakayode SO, Lowry M, Warner IM: Rhein inhibits angiogenesis and the viability of hormone-dependent and -independent cancer cells under normoxic or hypoxic conditions in vitro. Chem Biol Interact. 2011 Jul 15;192(3):220-32. doi: 10.1016/j.cbi.2011.03.013. Epub 2011 Mar 30. [PubMed:21457705]
  26. Aviello G, Rowland I, Gill CI, Acquaviva AM, Capasso F, McCann M, Capasso R, Izzo AA, Borrelli F: Anti-proliferative effect of rhein, an anthraquinone isolated from Cassia species, on Caco-2 human adenocarcinoma cells. J Cell Mol Med. 2010 Jul;14(7):2006-14. doi: 10.1111/j.1582-4934.2009.00815.x. Epub 2009 Jun 16. [PubMed:19538468]
  27. Mendes AF, Caramona MM, de Carvalho AP, Lopes MC: Diacerhein and rhein prevent interleukin-1beta-induced nuclear factor-kappaB activation by inhibiting the degradation of inhibitor kappaB-alpha. Pharmacol Toxicol. 2002 Jul;91(1):22-8. [PubMed:12193257]
External Links
Human Metabolome Database
HMDB0032876
KEGG Compound
C10401
PubChem Compound
10168
PubChem Substance
347829278
ChemSpider
9762
BindingDB
32021
ChEBI
8825
ChEMBL
CHEMBL418068
HET
RHN
Wikipedia
Rhein_(molecule)
PDB Entries
3r2a / 4ie7 / 4rfr
MSDS
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Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>300MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.214 mg/mLALOGPS
logP2.18ALOGPS
logP3.27ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)3.4ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area111.9 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity72.37 m3·mol-1ChemAxon
Polarizability26.62 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kr-0090000000-6163d091b67836bcff63
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014r-0190000000-bd5d0494f66cd7d5828c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00rl-2290000000-33f58cc10ba47d1b818a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0090000000-05c98e64e03e092b3975
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0019-0090000000-ec4cf61d964a40527521
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00ku-4390000000-5d5e000d8c2e171dd309
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0090000000-9ac3e7791e49a21d3f7e
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-0090000000-8a0c3c4f77482fc05626
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-0190000000-a217257577bda56ddeb9
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0950000000-f5cac5a3a6c78fc4ed85
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0910000000-4671892dc0bcf7214bc0
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-000i-0090000000-5f27d9cb7d81c2b3da8d
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-000i-0190000000-87c468c6073faf9e5fae
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-001i-0920000000-0b0038f124d8c1494117
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0090000000-a2294fd7666d75dbcbd0
MS/MS Spectrum - , positiveLC-MS/MSsplash10-052u-0890000000-5f1951e9414e26b22db9

Taxonomy

Description
This compound belongs to the class of organic compounds known as anthracenecarboxylic acids. These are organic compounds containing a carboxylic acid group attached to an anthracene ring system.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Anthracenes
Sub Class
Anthracenecarboxylic acids and derivatives
Direct Parent
Anthracenecarboxylic acids
Alternative Parents
Anthraquinones / Naphthalenecarboxylic acids / Hydroxybenzoic acid derivatives / Aryl ketones / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides
show 1 more
Substituents
Anthracene carboxylic acid / 9,10-anthraquinone / Anthraquinone / 2-naphthalenecarboxylic acid / 2-naphthalenecarboxylic acid or derivatives / Hydroxybenzoic acid / Aryl ketone / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Vinylogous acid
show 9 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
anthracenes (CHEBI:8825) / Anthracenes and phenanthrenes, Anthraquinone type (C10401) / Anthracenes and phenanthrenes (LMPK13040015)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Nuclear receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by L...
Gene Name
NR1H3
Uniprot ID
Q13133
Uniprot Name
Oxysterols receptor LXR-alpha
Molecular Weight
50395.34 Da
References
  1. Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [PubMed:23139635]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Nuclear receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake t...
Gene Name
NR1H2
Uniprot ID
P55055
Uniprot Name
Oxysterols receptor LXR-beta
Molecular Weight
50973.375 Da
References
  1. Sheng X, Zhu X, Zhang Y, Cui G, Peng L, Lu X, Zang YQ: Rhein protects against obesity and related metabolic disorders through liver X receptor-mediated uncoupling protein 1 upregulation in brown adipose tissue. Int J Biol Sci. 2012;8(10):1375-84. doi: 10.7150/ijbs.4575. Epub 2012 Oct 29. [PubMed:23139635]
3. Arylamine N-acetyltransferase (Helicobacter pylori)
Kind
Protein
Organism
Helicobacter pylori
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. Chung JG, Tsou MF, Wang HH, Lo HH, Hsieh SE, Yen YS, Wu LT, Chang SH, Ho CC, Hung CF: Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients. J Appl Toxicol. 1998 Mar-Apr;18(2):117-23. [PubMed:9570694]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Iron ion binding
Specific Function
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name
ALOX5
Uniprot ID
P09917
Uniprot Name
Arachidonate 5-lipoxygenase
Molecular Weight
77982.595 Da
References
  1. Singh B, Nadkarni JR, Vishwakarma RA, Bharate SB, Nivsarkar M, Anandjiwala S: The hydroalcoholic extract of Cassia alata (Linn.) leaves and its major compound rhein exhibits antiallergic activity via mast cell stabilization and lipoxygenase inhibition. J Ethnopharmacol. 2012 May 7;141(1):469-73. doi: 10.1016/j.jep.2012.03.012. Epub 2012 Mar 17. [PubMed:22449441]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [PubMed:18814214]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [PubMed:18814214]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [PubMed:18814214]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Enzyme action is based on in vitro data.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [PubMed:18814214]
  2. Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Yiap BC, Ong CE: Cytochrome P450 2C9-natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from in vitro data. Biopharm Drug Dispos. 2018 Apr;39(4):205-217. doi: 10.1002/bdd.2127. Epub 2018 Mar 23. [PubMed:29488228]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Tang JC, Yang H, Song XY, Song XH, Yan SL, Shao JQ, Zhang TL, Zhang JN: Inhibition of cytochrome P450 enzymes by rhein in rat liver microsomes. Phytother Res. 2009 Feb;23(2):159-64. doi: 10.1002/ptr.2572. [PubMed:18814214]

Drug created on May 19, 2017 08:56 / Updated on November 02, 2018 07:35