corilagin and Geraniin

Ellagitannins are literally a class of tannins. Triggered by the oxidation of the phenolic parts on β-pentagalloyl-d-glucose, ellagitannins are generated through various structural conversions, such as the coupling of the phenolic parts, oxidation to highly complex structures, and the formation of dimer and lager analogs, which expand the structural diversity. To date, more than 1000 natural ellagitannins have been identified. Since these phenolic compounds exhibit a variety of biological activities, ellagitannins have potential applications in medicine and health enhancement. Within the context of identifying suitable applications, considerations need to be based on correct structural features. This review describes the structural revisions of 32 natural ellagitannins, namely alnusiin; alnusnin A and B; castalagin; castalin; casuarinin; cercidinin A and B; chebulagic acid; chebulinic acid; corilagin; geraniin; isoterchebin; nobotanin B, C, E, G, H, I, J, and K; punicalagin; punicalin; punigluconin; roxbin B; sanguiin H-2, H-3, and H-6; stachyurin; terchebin; vescalagin; and vescalin. The major focus is on the outline of the initial structural determination, on the processes to find the errors in the structure, and on the methods for the revision of the structure.

Topics: Benzopyrans; Glucosides; Hydrolyzable Tannins; Molecular Structure; Oxidation-Reduction; Phenols; Terminology as Topic

Topics: Acetylcholinesterase; Binding Sites; Fruit; Hydrolyzable Tannins; Kinetics; Molecular Docking Simulation; Protein Binding; Spectroscopy, Fourier Transform Infrared; Terminalia

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Biological Transport; Cell Differentiation; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucose; Glucosides; Hydrolyzable Tannins; Hyperglycemia; Insulin; Lipolysis; Mice; Obesity; Plant Extracts; Sapindaceae

Ellagitannins, found abundantly in berries, pomegranates, walnuts and almonds, have been increasingly investigated for their health benefits. Geraniin (GE), an ellagitannin, found predominantly in herbal plants, as well has been shown to exhibit a number of biological activities. Like many hydrolysable tannins, geraniin is water-soluble and readily undergoes hydrolysis in the presence of hot water, weak acids and weak bases to yield several metabolites including corilagin (CO), ellagic acid (EA) and gallic acid (GA). There are numerous studies on the pharmacological effectiveness of GE, CO and GA. However, the intestinal permeability of GE and CO has never been investigated before. Caco-2 cell transport assay was utilized to evaluate the in vitro permeability of GE and its metabolites. GE, CO and EA were found to have no apparent permeability (Papp) while GA displayed a Papp value of 31.3 ± 1.1 × 10-6 cm s-1. Mass balance studies showed a loss of geraniin and its metabolites during transport. Chemical stability studies in the transport buffers revealed that GE and CO were hydrolyzed in the HBSS buffers. Experiments using lysed cells revealed that GE and its metabolites were metabolized during transport. Absorption and desorption studies confirmed the accumulation of EA inside the cells. The above results indicate that the compounds have poor oral absorption. To consider these compounds or their natural extracts as oral nutraceutical candidates, formulation strategies are mandatory.

Topics: Adenocarcinoma; Biological Transport; Caco-2 Cells; Cell Survival; Colonic Neoplasms; Ellagic Acid; Gallic Acid; Glucosides; Humans; Hydrolyzable Tannins; Molecular Structure; Permeability

This study was aimed at characterising the secondary metabolites responsible for antibacterial and antioxidant activities of Acalypha wilkesiana. Purification of the defatted methanol leaves extract was guided by the DPPH free radical scavenging assay as well as by evaluation of the antibacterial activity against four bacterial strains. As a result, geraniin, corilagin, quadrangularic acid M and shikimic acid were purified and isolated. Shikimic acid, reported for the first time from this plant, proved to be the major metabolite of the extract. All the four isolated compounds showed bactericidal activity against extended spectrum beta-lactamase-producing Klebsiella pneumoniae (700603), while corilagin was the single compound to exhibit antioxidant activity (IC50 53 μg/mL).

Topics: Acalypha; Anti-Bacterial Agents; Free Radical Scavengers; Glucosides; Hydrolyzable Tannins; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Structure; Phytosterols; Plant Extracts; Plant Leaves; Shikimic Acid

Generation of amyloid β peptide through the proteolytic process of amyloid precursor protein by β-secretase and γ-secretase is a main casual factor of Alzheimer's disease, since amyloid β peptide is a major and crucial component of senile plaques in Alzheimer's disease brains. In the process of searching for β-secretase inhibitors from natural resources, the EtOAc soluble fraction of Geranium thunbergii exhibited significant β-secretase inhibitory activity. Two compounds, geraniin and corilagin, isolated from the most active EtOAc fraction of G. thunbergii, exhibited predominant inhibition against β-secretase with IC₅₀ values of 4.0 × 10⁻⁶ M and 3.4 × 10⁻⁵ M, respectively. Dixon plot of geraniin and corilagin demonstrated that the β-secretase inhibition was noncompetitive with the substrate, thus clearly suggesting that these compounds might bind either to the β-secretase subsites or to another regulatory domain with Ki values of 2.8 × 10⁻⁶ M and 7.9 × 10⁻⁵ M, respectively. Both compounds exhibited no significant inhibition against α-secretase and other serine proteases including trypsin and chymotrypsin, showing that they were relatively specific and selective inhibitors of β-secretase. These novel findings suggest that geraniin and corilagin from G. thunbergii may be effective therapeutic agents for further drug development in Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Dose-Response Relationship, Drug; Geranium; Glucosides; Humans; Hydrolyzable Tannins; Plants, Medicinal

Leaves from Phyllanthus muellerianus (Kuntze) Exell. are traditionally used for wound healing in Western Africa. Aqueous extracts of dried leaves recently have been shown to stimulate proliferation of human keratinocytes and dermal fibroblasts. Within bioassay-guided fractionation the ellagitannins geraniin (1), corilagin (2), furosin (3), the flavonoids quercetin-3-O-β-D-glucoside (isoquercitrin), kaempferol-3-O-β-D-glucoside (astragalin), quercetin-3-O-D-rutinoside (rutin), gallic acid, methyl gallate, caffeic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid and caffeoylmalic acid (phaselic acid) have been identified in P. muellerianus for the first time. Geraniin was shown to be the dominant component of an aqueous extract. Suitable analytical methods for quality control of geraniin in P. muellerianus extract (methanol/water, 70/30) have been developed and validated based on ICH guidelines (ICH-compliant protocol). Geraniin and furosin increased the cellular energy status of human skin cells (dermal fibroblasts NHDF, HaCaT keratinocytes), triggering the cells towards higher proliferation rates, with fibroblasts being more sensitive than keratinocytes. Highest stimulation of NHDF by geraniin was found at 5 μM, and of keratinocytes at 50-100 μM. Furosin stimulated NHDF at about 50 μM, keratinocytes at about 150-200 μM. Necrotic cytotoxicity of geraniin, as measured by LDH release, was observed at 20 μM for NHDF and 150 μM for keratinocytes. Toxicity of furosin--less than that of geraniin--was observed at > 400 μM. Furosin and geraniin stimulated the biosynthesis of collagen from NHDF at 50 μM and 5-10 μM respectively. Geraniin at 105 μM significantly stimulated the differentiation in NHEK while furosin had a minor influence on the expression of involucrin and cytokeratins K1 and K10. The study proves clearly that hydrophilic extracts from P. muellerianus and especially the lead compound geraniin exhibit stimulating activity on dermal fibroblasts and keratinocytes, leading to increased cell proliferation, barrier formation and formation of extracellular matrix proteins. From these findings the traditional clinical use of such extracts for wound healing seems to be justified.

Topics: Cell Differentiation; Chromatography, High Pressure Liquid; Collagen; Fibroblasts; Flavonoids; Glucosides; Humans; Hydrolyzable Tannins; Keratinocytes; Medicine, African Traditional; Phyllanthus; Plant Extracts; Plant Leaves; Plants, Medicinal; Skin; Wound Healing

Substantial progress has been made in research on natural products which effectively inhibit HIV-1 replication. Many active compounds were isolated from traditionally used medicinal plants including Phyllanthus species. This study shows that aqueous as well as alcohol-based Phyllanthus amarus extracts potently inhibit HIV-1 replication in HeLa CD4(+) cells with 50% effective concentration (EC(50)) values ranging from 0.9 to 7.6 microg/ml. A gallotannin enriched fraction showed enhanced activity (0.4 microg/ml), and the purified gallotannins geraniin and corilagin were most active (0.24 microg/ml). HIV-1 replication was also blocked in CD4(+) lymphoid cells with comparable EC(50) values. Applying a cell-based internalization assay, we could demonstrate 70-75% inhibition of virus uptake at concentrations of 2.5 microg/ml for the water/alcohol extract and geraniin. In addition, a concentration-dependent inhibition of HIV-1 reverse transcriptase (RT) could be demonstrated in vitro. The 50% inhibitory concentration (IC(50)) values varied from 1.8 to 14.6 microg/ml. The ability to inhibit replication of a variety of RT inhibitor-resistant HIV-1 strains points to the potential of P. amarus extracts, as natural products, in the chemotherapy of HIV infections.

Topics: CD4 Antigens; Drug Resistance, Viral; Euphorbiaceae; Glucosides; HeLa Cells; HIV-1; HIV-2; Humans; Hydrolyzable Tannins; Plant Extracts; Plants, Medicinal; Reverse Transcriptase Inhibitors; Tannins; Tumor Cells, Cultured; Virus Replication

The success of green tea as a cancer preventive is based on evidence that green tea contains tannins and antioxidants, does not show toxicity in humans and has long traditional use in Asia. In the light of this, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using the inhibition of TNF-alpha release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-alpha release was found in the leaf extract rather than the bark extract, and the main active constituents were identified as geraniin and corilagin, which are present in another Japanese traditional herb, Geranium thunbergii (Genno-shoko). The IC50 values of TNF-alpha release inhibition were 43 microM for geraniin and 76 microM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG) was 26 microM. Treatment with geraniin prior to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-bearing mice from 80.0 to 40.0% and the average numbers of tumor per mouse from 3.8 to 1.1 in week 20. Thus, geraniin has slightly weaker inhibitory activity than EGCG. Since geraniin and corilagin have been well investigated as representative tannins, we discuss here the new possibility of classical herbal medicine in the development of preventive agents for cancer and other life-style related diseases.

Topics: 3T3 Cells; 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Carcinogens; Chromatography, High Pressure Liquid; Glucosides; Hydrolyzable Tannins; Mice; Mice, Inbred BALB C; Plant Extracts; Plant Leaves; Plants, Medicinal; Skin Neoplasms; Tannins; Tumor Necrosis Factor-alpha

An activity directed fractionation of a 50% aqueous ethanol extract of A. wilkesiana and A. hispida leaves resulted in the isolation of gallic acid, corilagin and geraniin as the compounds responsible for the observed antimicrobial activity. Quercetin 3-O-rutinoside and kaempferol 3-O-rutinoside were also isolated from the inactive fraction of A. hispida. The structures were established by permethylation, 2D - NMR ((1)H and (13)C) and MS data.

Topics: Anti-Bacterial Agents; Euphorbiaceae; Glucosides; Humans; Hydrolyzable Tannins; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Plant Extracts; Plant Leaves; Plants, Medicinal; Tannins

Topics: Arachidonic Acid; Arachidonic Acids; Benzopyrans; Ellagic Acid; Glucosides; Glycosides; Humans; Hydrolyzable Tannins; In Vitro Techniques; Leukocytes; Tannins