Rhein (molecule)

Last updated
Rhein
Cassic acid.svg
Cassic-acid-3D-balls.png
Names
Preferred IUPAC name
4,5-Dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid
Other names
Rhubarb Yellow
Monorhein
Cassic acid
Rheic acid
Chrysazin-3-carboxylic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.006.839 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 207-521-4
KEGG
MeSH Rhein
PubChem CID
UNII
  • 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) X mark.svgN
    Key: FCDLCPWAQCPTKC-UHFFFAOYSA-N X mark.svgN
  • InChI=1/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)
    Key: FCDLCPWAQCPTKC-UHFFFAOYAT
  • C1=CC2=C(C(=C1)O)C(=O)C3=C(C=C(C=C3C2=O)C(=O)O)O
Properties
C15H8O6
Molar mass 284.22 g/mol
AppearanceOrange crystals [1]
Density 1.687 g/cm3
Melting point 350 to 352 °C (662 to 666 °F; 623 to 625 K) [1]
Boiling point 597.8 °C (1,108.0 °F; 870.9 K) at 760 mmHg
Insoluble in water
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
Irritant
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319, H335
Flash point 329.4 °C (624.9 °F; 602.5 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Rhein, also known as cassic acid, is a substance in the anthraquinone group obtained from rhubarb. [2] Like all such substances, rhein is a cathartic, which is commonly found as a glycoside such as rhein-8-glucoside or glucorhein. [2] Rhein was first isolated in 1895. [3] It is found in rhubarb species like Rheum undulatum [4] and Rheum palmatum [5] as well as in Cassia reticulata . [6]

Originally the rhubarb plant which contains rhein was used as a laxative. It was believed that rhein along with other anthraquinone glycosides imparted this activity. [2]

Rhein has been reevaluated as an antibacterial agent against Staphylococcus aureus in 2008. [7] Synergy or partial synergy has been demonstrated between rhein and the antibiotics oxacillin and ampicillin. [8]

Rhein has been shown to inhibit the fat mass and obesity-associated protein, an enzyme responsible for removing the methylation from N6-methyladenosine in nucleic acids. [9] [10]

The pharmacokinetics of rhein have not been intensively studied in humans, but at least one study in healthy male volunteers found that rhein was better absorbed from oral administration of rhubarb than from a retention enema. [11] Rhein (at an oral dose of 50 mg twice per day) was shown to be safe when administered for five days to elderly patients with chronic congestive heart failure. [12]

See also

Related Research Articles

<span class="mw-page-title-main">Rhubarb</span> Species of herbaceous perennial plant with fleshy, sour edible stalks

Rhubarb is the fleshy, edible stalks (petioles) of species and hybrids of Rheum in the family Polygonaceae, which are cooked and used for food. The plant is a herbaceous perennial that grows from short, thick rhizomes. Historically, different plants have been called "rhubarb" in English. The large, triangular leaves contain high levels of oxalic acid and anthrone glycosides, making them inedible. The small flowers are grouped in large compound leafy greenish-white to rose-red inflorescences.

<i>Staphylococcus aureus</i> Species of Gram-positive bacterium

Staphylococcus aureus is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

<span class="mw-page-title-main">Sultamicillin</span> Chemical compound

Sultamicillin, sold under the brand name Unasyn among others, is an oral form of the penicillin antibiotic combination ampicillin/sulbactam. It is used for the treatment of bacterial infections of the upper and lower respiratory tract, the kidneys and urinary tract, skin and soft tissues, among other organs. It contains esterified ampicillin and sulbactam.

<span class="mw-page-title-main">Flucloxacillin</span> Penicillin

Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to treat pneumonia, and endocarditis. It may also be used prior to surgery to prevent Staphylococcus infections. It is not effective against methicillin-resistant Staphylococcus aureus (MRSA). It is taken by mouth or given by injection into a vein or muscle.

<span class="mw-page-title-main">Anthrone</span> Chemical compound

Anthrone is a tricyclic aromatic ketone. It is used for a common cellulose assay and in the colorimetric determination of carbohydrates.

<span class="mw-page-title-main">Dicloxacillin</span> Chemical compound

Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

<span class="mw-page-title-main">Oxacillin</span> Chemical compound

Oxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham.

<i>Rheum</i> (plant) Genus of flowering plants

Rheum is a genus of about 60 herbaceous perennial plants in the family Polygonaceae. Species are native to eastern Europe, southern and eastern temperate Asia, with a few reaching into northern tropical Asia. Rheum is cultivated in Europe and North America. The genus includes the vegetable rhubarb. The species have large somewhat triangular shaped leaves with long, fleshy petioles. The flowers are small, greenish-white to rose-red, and grouped in large compound leafy inflorescences. A number of cultivars of rhubarb have been domesticated both as medicinal plants and for human consumption. While the leaves are slightly toxic, the stalks are used in pies and other foods for their tart flavor.

<span class="mw-page-title-main">Anthraquinones</span>

For the parent molecule 9,10-anthraquinone, see anthraquinone

<i>Rheum officinale</i> Species of flowering plant

Rheum officinale, the Chinese rhubarb, or Indian rhubarb is a rhubarb from the family Polygonaceae native to China. In Chinese it is called yào yòng dà huáng, literally meaning medicinal rhubarb.

<span class="mw-page-title-main">Emodin</span> Chemical compound

Emodin (6-methyl-1,3,8-trihydroxyanthraquinone) is a chemical compound, of the anthraquinone family, that can be isolated from rhubarb, buckthorn, and Japanese knotweed. Emodin is particularly abundant in the roots of the Chinese rhubarb, knotweed and knotgrass as well as Hawaii ‘au‘auko‘i cassia seeds or coffee weed. It is specifically isolated from Rheum palmatum L. It is also produced by many species of fungi, including members of the genera Aspergillus, Pyrenochaeta, and Pestalotiopsis, inter alia. The common name is derived from Rheum emodi, a taxonomic synonym of Rheum australe, and synonyms include emodol, frangula emodin, rheum emodin, 3-methyl-1,6,8-trihydroxyanthraquinone, Schüttgelb (Schuttgelb), and Persian Berry Lake.

β-Lactamase inhibitor Family of enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

<span class="mw-page-title-main">Ceftobiprole</span> Chemical compound

Ceftobiprole (Zevtera/Mabelio) is a fifth-generation cephalosporin for the treatment of hospital-acquired pneumonia and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica in the United Kingdom, Germany, Switzerland and Austria under the trade name Zevtera, in France and Italy under the trade name Mabelio. Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues. Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae (penicillin-intermediate), to penicillin-binding protein 2x in Streptococcus pneumoniae (penicillin-resistant), and to penicillin-binding protein 5 in Enterococcus faecalis.

<span class="mw-page-title-main">Aloe emodin</span> Chemical compound

Aloe emodin is an anthraquinone and an isomer of emodin present in aloe latex, an exudate from the aloe plant. It has a strong stimulant-laxative action. Aloe emodin is not carcinogenic when applied to the skin, although it may increase the carcinogenicity of some kind of radiation.

mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.

<i>Senna reticulata</i> Species of legume

Senna reticulata, the mangerioba grande or maria mole in Portuguese, is a pioneer tree species found on highly fertile floodplains in South America. It has some medicinal uses, but is regarded by farmers as a noxious weed, named matapasto due to its ability to grow fast and outshade neighbouring plants.

<span class="mw-page-title-main">Verbascoside</span> Chemical compound

Verbascoside is a caffeoyl phenylethanoid glycoside in which the phenylpropanoid caffeic acid and the phenylethanoid hydroxytyrosol form an ester and an ether bond respectively, to the rhamnose part of a disaccharide, namely β-(3′,4′-dihydroxyphenyl)ethyl-O-α-L-rhamnopyranosyl(1→3)-β-D-(4-O-caffeoyl)-glucopyranoside.

<i>Rheum australe</i> Species of flowering plant

Rheum australe, synonym Rheum emodi, is a flowering plant in the family Polygonaceae. It is commonly known as Himalayan rhubarb, Indian rhubarb and Red-veined pie plant. It is a medicinal herb used in the Indian Unani system of medicine, and formerly in the European system of medicine where it was traded as Indian rhubarb. The plant is found in the sub-alpine and alpine Himalayas at an altitude of 4000 m.

<span class="mw-page-title-main">Chrysophanol</span> Chemical compound

Chrysophanol, also known as chrysophanic acid, is a fungal isolate and a natural anthraquinone. It is a C-3 methyl substituted chrysazin of the trihydroxyanthraquinone family.

References

  1. 1 2 Cassic acid on www.naturestandard.com Archived 2011-07-14 at the Wayback Machine
  2. 1 2 3 Pharmacognosy of Rhubarb | Chemical Constituents
  3. Hesse O (1895). "The Chemistry of rhubarb (EN)". Pharmaceutical Journal and Transactions. 1: 325.
  4. Lee JH, Kim JM, Kim CS (2003). "Pharmacokinetic analysis of rhein in Rheum undulatum L.". J Ethnopharmacol. 84 (1): 5–9. doi:10.1016/S0378-8741(02)00222-2. PMID   12499069.
  5. Hoerhammer L, Wagner H, Koehler I (1959). "Neue Untersuchungen über die Inhaltsstoffe von Rheum palmatum L. 1. Mitteilung: Zur Analytik des Rheins" [New investigations on the components of Rheum palmatum L. Part 1: On the analysis of rhein]. Archiv der Pharmazie (in German). 292 (64): 591–601. doi:10.1002/ardp.19592921105. PMID   14402302. S2CID   94169376.
  6. Anchel M (1949). "Identification of the antibiotic substance from Cassia reticulata as 4,5-Dihydroxyanthraquinone-2-carboxylic acid" (PDF). J Biol Chem. 177 (1): 169–177. doi: 10.1016/S0021-9258(18)57072-1 . PMID   18123056.
  7. Yu L, Xiang H, Fan J, et al. (2008). "Global transcriptional response of Staphylococcus aureus to rhein, a natural plant product". J Biotechnol. 135 (3): 304–308. doi:10.1016/j.jbiotec.2008.04.010. PMID   18514345.
  8. Joung DK, Joung H, Yang DW, et al. (2012). "Synergistic effect of rhein in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus". Exp Ther Med. 3 (4): 608–612. doi:10.3892/etm.2012.459. PMC   3438619 . PMID   22969937.
  9. Yu, Jun; Chen, Mengxian; Huang, Haijiao; Zhu, Junda; Song, Huixue; Zhu, Jian; Park, Jaewon; Ji, Sheng-Jian (2017-11-23). "Dynamic m6A modification regulates local translation of mRNA in axons". Nucleic Acids Research. 46 (3): 1412–1423. doi:10.1093/nar/gkx1182. ISSN   0305-1048. PMC   5815124 . PMID   29186567.
  10. Jia, Guifang; Fu, Ye; Zhao, Xu; Dai, Qing; Zheng, Guanqun; Yang, Ying; Yi, Chengqi; Lindahl, Tomas; Pan, Tao (2011-10-16). "N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO". Nature Chemical Biology. 7 (12): 885–887. doi:10.1038/nchembio.687. ISSN   1552-4450. PMC   3218240 . PMID   22002720.
  11. Zhu W, Wang XM, Zhang L, Li XY, Wang BX (2005). "Pharmacokinetic of rhein in healthy male volunteers following oral and retention enema administration of rhubarb extract: a single dose study". Am J Chin Med. 33 (6): 839–850. doi:10.1142/S0192415X05003508. PMID   16355440.
  12. La Villa G, Marra F, Laffi G, et al. (1989). "Effects of rhein on renal arachidonic acid metabolism and renal function in patients with congestive heart failure". Eur J Clin Pharmacol. 37 (1): 1–5. doi:10.1007/bf00609415. PMID   2512175. S2CID   6338421.