Geraniin

Last updated
Geraniin
Geraniin.png
Names
IUPAC name
(1R,7R,8S,26R,28S,29R,38R)-1,13,14,15,18,19,20,34,35,39,39-Undecahydroxy-2,5,10,23,31-pentaoxo-6,9,24,27,30,40-hexaoxaoctacyclo[34.3.1.04,38.07,26.08,29.011,16.017,22.032,37]tetraconta-3,1 1,13,15,17,19,21,32,34,36-decaen-28-yl 3,4,5-trihydroxybenzoate
Identifiers
  • 60976-49-0
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
  • Oc1cc(cc(O)c1O)C(=O)O[C@@H]9O[C@@H]7COC(=O)c2cc(O)c(O)c(O)c2c3c(O)c(O)c(O)cc3C(=O)O[C@@H]8[C@H]9OC(=O)c4cc(O)c(O)c5O[C@@]6(O)C(=O)/C=C(\[C@@H](c45)C6(O)O)C(=O)O[C@H]78
Properties
C41H28O27
Molar mass 952.64 g/mol
Density 2.26 g/mL
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Geraniin is a dehydroellagitannin found in geraniums. [1] It is found for instance in Geranium thunbergii , which is one of the most popular folk medicines and also an official antidiarrheic drug in Japan. [2] It can also be found in the rind of Nephelium lappaceum (rambutan). [3]

It mediates apoptosis by cleavage of focal adhesion kinase through up-regulation of Fas ligand expression in human melanoma cells. [1]

Geraniin has also been shown to possess immunomodularity properties, as it inhibits tumor necrosis factor-alpha, and NF-κB in ovarian cancer cells. [4]

Geraniin was studied for its anticancer activity and shown to target apoptosis via inactivation of PI3K/Akt/mTOR signaling pathway involving NF-κB when treated against HT-29 human colorectal adenocarcinoma cells. [5]

It is formed with one hexahydroxydiphenic acid unit, one modified hexahydroxydiphenic acid unit (dehydrohexahydroxydiphenic acid or DHHDP) and one gallic acid unit linked to a glucose molecule. It is forming an equilibrium mixture of six-membered hemi-ketal and five-membered hemi-ketal forms.[ citation needed ]

Chebulagic acid is formed from geraniin through a glutathione-mediated conversion. [6]

Related Research Articles

Apoptosis Programmed cell death in multicellular organisms

Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between the ages of 8 and 14, approximately 20–30 billion cells die per day.

Clusterin

Clusterin is a 75 - 80 kDa disulfide-linked heterodimeric protein associated with the clearance of cellular debris and apoptosis. In humans, clusterin is encoded by the CLU gene on chromosome 8. CLU is a molecular chaperone responsible for aiding protein folding of secreted proteins, and its three isoforms have been differentially implicated in pro- or antiapoptotic processes. Through this function, CLU is involved in many diseases related to oxidative stress, including neurodegenerative diseases, cancers, inflammatory diseases, and aging.

Fas ligand

Fas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.

Catenin

Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two catenins that were identified became known as α-catenin and β-catenin. α-Catenin can bind to β-catenin and can also bind filamentous actin (F-actin). β-Catenin binds directly to the cytoplasmic tail of classical cadherins. Additional catenins such as γ-catenin and δ-catenin have been identified. The name "catenin" was originally selected because it was suspected that catenins might link cadherins to the cytoskeleton.

Betulinic acid Chemical compound

Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It is found in the bark of several species of plants, principally the white birch from which it gets its name, but also the ber tree, selfheal, the tropical carnivorous plants Triphyophyllum peltatum and Ancistrocladus heyneanus, Diospyros leucomelas, a member of the persimmon family, Tetracera boiviniana, the jambul, flowering quince, rosemary, and Pulsatilla chinensis.

Fas receptor

The Fas receptor, also known as Fas, FasR, apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the FAS gene. Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas is derived from FS-7-associated surface antigen.

EMR2

EGF-like module-containing mucin-like hormone receptor-like 2 also known as CD312 is a protein encoded by the ADGRE2 gene. EMR2 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

Peptidylprolyl isomerase A

Peptidylprolyl isomerase A (PPIA), also known as cyclophilin A (CypA) or rotamase A is an enzyme that in humans is encoded by the PPIA gene on chromosome 7. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to regulate many biological processes, including intracellular signaling, transcription, inflammation, and apoptosis. Due to its various functions, PPIA has been implicated in a broad range of inflammatory diseases, including atherosclerosis and arthritis, and viral infections.

CYR61

Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene.

GPX1

Glutathione peroxidase 1, also known as GPx1, is an enzyme that in humans is encoded by the GPX1 gene on chromosome 3. This gene encodes a member of the glutathione peroxidase family. Glutathione peroxidase functions in the detoxification of hydrogen peroxide, and is one of the most important antioxidant enzymes in humans.

PRKCQ

Protein kinase C theta (PKC-θ) is an enzyme that in humans is encoded by the PRKCQ gene. PKC-θ, a member of serine/threonine kinases, is mainly expressed in hematopoietic cells with high levels in platelets and T lymphocytes, where plays a role in signal transduction. Different subpopulations of T cells vary in their requirements of PKC-θ, therefore PKC-θ is considered as a potential target for inhibitors in the context of immunotherapy.

Leukotriene B<sub>4</sub> receptor 2

Leukotriene B4 receptor 2, also known as BLT2, BLT2 receptor, and BLTR2, is an Integral membrane protein that is encoded by the LTB4R2 gene in humans and the Ltbr2 gene in mice.

Decoy receptor 3

Decoy receptor 3 (Dcr3), also known as tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), TR6 and M68, is a soluble protein of the tumor necrosis factor receptor superfamily which inhibits Fas ligand-induced apoptosis.

DLC1

Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.

Death receptor 6

Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. It is mostly expressed in the thymus, spleen and white blood cells. The Gene for DR6 is 78,450 bases long and is found on the 6th chromosome. This is transcribed into a 655 amino acid chain weighing 71.8 kDa. Post transcriptional modifications of this protein include glycosylation on the asparagines at the 82, 141, 252, 257, 278, and 289 amino acid locations.

Ceruletide

Ceruletide (INN), also known as cerulein or caerulein, is a ten amino acid oligopeptide that stimulates smooth muscle and increases digestive secretions. Ceruletide is similar in action and composition to cholecystokinin. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle. It is used in paralytic ileus and as diagnostic aid in pancreatic malfunction. It is used to induce pancreatitis in experimental animal models.

GM3

GM3 (monosialodihexosylganglioside) is a type of ganglioside. The letter G refers to ganglioside, and M is for monosialic acid as it has one sialic acid only. The numbering is based on its relative mobility in electrophoresis among other monosialic gangliosides. Its structure can be condensed to NANA-Gal-Glc-ceramide. GM3 is the most common membrane-bound glycosphingolipid in tissues, composed of three monosaccharide groups attached to a ceramide backbone. GM3 serves as a precursor for other, more complex gangliosides. Like other gangliosides, GM3 is synthesized in the Golgi apparatus. It is then transported to the plasma membrane, where it functions in cellular signaling. GM3 also functions as an inhibitor; it inhibits cell growth, the function of growth factor receptors, and generation of cytokines by T cells.

Antineoplastic resistance, often used interchangeably with chemotherapy resistance, is the resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies. In some cases, cancers can evolve resistance to multiple drugs, called multiple drug resistance.

Paraptosis

Paraptosis is a type of programmed cell death, morphologically distinct from apoptosis and necrosis. The defining features of paraptosis are cytoplasmic vacuolation, independent of caspase activation and inhibition, and lack of apoptotic morphology. Paraptosis lacks several of the hallmark characteristics of apoptosis, such as membrane blebbing, chromatin condensation, and nuclear fragmentation. Like apoptosis and other types of programmed cell death, the cell is involved in causing its own death, and gene expression is required. This is in contrast to necrosis, which is non-programmed cell death that results from injury to the cell.

hPG80 refers to the extracellular and oncogenic version of progastrin. This name first appeared in a scientific publication in January 2020. Until that date, scientific publications only mention 'progastrin', without necessarily explicitly specifying whether it is intracellular or extracellular in the tumor pathological setting.

References

  1. 1 2 Lee, Jang-Chang; Tsai, Chih-Yen; Kao, Jung-Yie; Kao, Ming-Ching; Tsai, Shih-Chang; Chang, Chih-Shiang; Huang, Li-Jiau; Kuo, Sheng-Chu; et al. (2008). "Geraniin-mediated apoptosis by cleavage of focal adhesion kinase through up-regulation of Fas ligand expression in human melanoma cells". Molecular Nutrition & Food Research. 52 (6): 655–63. doi:10.1002/mnfr.200700381. PMID   18435487.
  2. Luger, P.; Weber, M.; Kashino, S.; Amakura, Y.; Yoshida, T.; Okuda, T.; Beurskens, G.; Dauter, Z. (1998). "Structure of the Tannin Geraniin Based on Conventional X-ray Data at 295 K and on Synchrotron Data at 293 and 120 K". Acta Crystallographica Section B. 54 (5): 687. doi:10.1107/S0108768198000081.
  3. Rapid isolation of geraniin from Nephelium lappaceum rind waste and its anti-hyperglycemic activity. Uma D. Palanisamy, Lai Teng Ling, Thamilvaani Manaharan, and David Appleton, Food Chemistry, 1 July 2011, Volume 127, Issue 1, Pages 21–27, doi : 10.1016/j.foodchem.2010.12.070
  4. Wang X, et al. Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression. J Biochem Mol Toxicol. 2017 Sep;31(9)
  5. Chan, Chim Kei; Tang, Liu Ying; Goh, Bey Hing; Abdul Kadir, Habsah (2019). "Targeting apoptosis via inactivation of PI3K/Akt/MTOR signaling pathway involving NF-κB by geraniin in HT-29 human colorectal adenocarcinoma cells". Progress in Drug Discovery & Biomedical Science. 2. doi:10.36877/pddbs.a0000030.
  6. Glutathione-mediated conversion of the ellagitannin geraniin into chebulagic acid. Tanaka T, Kouno I and Nonaka G.I, Chemical and pharmaceutical bulletin, 1996, volume 44, no 1, pages 34-40, INIST : 3003361