Geraniin Research Articles

Geraniin Alleviates Mouse Laser-Induced Choroidal Neovascularisation by Inhibiting Choroidal Endothelial Cell ACE2/Ang-(1-7)/MasR/IL-10 Pathway.

Anti-vascular endothelial growth factor (VEGF) drugs suppress choroidal neovascularisation (CNV), thus improving vision. However, some patients may have a poor response or develop resistance to anti-VEGF drugs. Geraniin (GE), a polyphenol isolated from an herb called Phyllanthus amarus, possesses anti-angiogenic properties. This study aimed to explore the mechanism of action of GE in CNV. GE was found to activate the angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang-[1-7])/MAS1 proto-oncogene, G protein-coupled receptor (MasR)/interleukin-10 (IL-10) pathway in hypoxic human choroidal endothelial cells (HCECs) invitro and mouse models of laser-induced CNV invivo. Activation of the ACE2/Ang-(1-7)/MasR/IL-10 pathway by GE attenuated the proliferative, migratory, and tube-forming abilities of hypoxic HCECs and prevented the development of CNV in mice. Notably, GE did not cause ocular or systemic toxicity in mice with CNV. These findings suggest that GE alleviates CNV by activating the ACE2/Ang-(1-7)/MasR/IL-10 pathway in choroidal endothelial cells (CECs).

Effects of Polyphenols and Lignans of Phyllanthus amarus Schumach. and Thonn. on IL-1β and TNF-α Secretions from LPS-induced THP-1-derived Macrophages

Background: Phyllanthus amarus exhibited immunosuppressive and anti-inflammatory effects in several in vitro and in vivo studies. However, there is no report on the inhibitory effects of its secondary metabolites on pro-inflammatory cytokines secretion from human THP-1-derived macrophages. background: Phyllanthus amarus exhibited immunosuppressive and anti-inflammatory effects in several in vitro and in vivo studies. However, there is no report on the inhibitory effects of its secondary metabolites on pro-inflammatory cytokines secretion from human THP-1-derived macrophages. Objective: The objective of this study was to correlate the polyphenols (ellagic acid (EA), gallic acid (GA), geraniin (GER), and corilagin (COR)) and lignans ((phyllanthin (PHY), hypophyllanthin (HYPO), niranthin (NIR), phyltetralin (PHYLT), and isolintetralin (ISO)) of 80% ethanol extract of P. amarus with their inhibitory effect against IL-1β and TNF-α secretions from LPS-induced THP-1- derived macrophages. Methods: Chemical profiling of P. amarus was carried out by LC-MS/MS analysis. Validated qualitative and quantitative reversed-phase HPLC analyses of the P. amarus extract were performed for the determination of lignan and polyphenol contents. Human THP-1-derived macrophages were prepared by treatment of THP-1 cells with phorbol 12-myristate 13-acetate (PMA). The inhibition of cytokines released by the extract, lignans and polyphenols in the cells was investigated using ELISA assay. method: Chemical profiling of P. amarus was carried out by LC-MS/MS analysis. Validated qualitative and quantitative reversed phase HPLC analyses of the P. amarus extract were performed for determination of lignan and polyphenol contents. Human THP-1 derived macrophages were prepared by treatment of THP-1 cells with phorbol 12-myristate 13-acetate (PMA). The inhibition of cytokines release by the extract, lignans and polyphenols in the cells were investigated using ELISA assay. Results: P. amarus extract and its chemical constituents significantly reduced the levels of IL-1β and TNF-α in a dose-dependent manner. At a dose of 50 μM, COR exhibited a maximum inhibition of 81.11% on TNF-α secretion, while GER showed 72.56% inhibition on IL-1β secretion. COR demonstrated the strongest inhibition of TNF-α secretion, exhibiting an IC50 value of 9.06 μM, which was comparable to that of dexamethasone (7.07 μM). Meanwhile, GER was the most potent against IL- 1β secretion, exhibiting an IC50 value of 20.09 μM. In the case of TNF-α secretion, the order of potency observed among the active compounds, with regard to IC50 value, was COR > GER > HYPO > PHY > NIR > GA > EA >ISO > PHYLT. For IL-1β secretion, the order of potency was GER > NIR > COR > GA > EA > PHY > HYPO > PHYLT > 1SO. Conclusion: The polyphenol contents of P. amarus, especially COR and GER, contributed significantly to the suppression of cytokines secretion, and they have the potential to be developed into agents for the treatment of pathologic inflammation.

Enhancing the Bioavailability of the Ellagitannin, Geraniin: Formulation, Characterization, and in vivo Evaluation

Geraniin (GE), an ellagitannin (ET) renowned for its promising health advantages, faces challenges in its practical applications due to its limited bioavailability. This innovative and novel formulation of GE and soy-phosphatidylcholine (GE-PL) complex has the potential to increase oral bioavailability, exhibiting high entrapment efficiency of 100.2 ± 0.8 %, and complexation efficiency of 94.6 ± 1.1 %. The small particle size (1.04 ± 0.11 μm), low polydispersity index (0.26 ± 0.02), and adequate zeta potential (−26.1 ± 0.12 mV), indicate its uniformity and stability. Moreover, the formulation also demonstrates improved lipophilicity, reduced aqueous and buffer solubilities, and better partition coefficient. It has been validated by various analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. Oral bioavailability and pharmacokinetics of free GE and GE-PL complex investigated in rabbits demonstrated enhanced plasma concentration of ellagic acid (EA) compared to free GE. Significantly, GE, whether in its free form or as part of the GE-PL complex, was not found in the circulatory system. However, EA levels were observed at 0.5 h after administration, displaying two distinct peaks at 2 ± 0.03 h (T1max) and 24 ± 0.06 h (T2max). These peaks corresponded to peak plasma concentrations (C1max and C2max) of 588.82 ng/mL and 711.13 ng/mL respectively, signifying substantial 11-fold and 5-fold enhancements when compared to free GE. Additionally, it showed an increased area under the curve (AUC), the elimination half-life (t1/2, el) and the elimination rate constant (Kel). The formulation of the GE-PL complex prolonged the presence of EA in the bloodstream and improved its absorption, ultimately leading to a higher oral bioavailability. In summary, the study highlights the significance of the GE-PL complex in overcoming the bioavailability limitations of GE, paving the way for enhanced therapeutic outcomes and potential applications in drug delivery and healthcare.

Geraniin-Based Self-Assemble Nanoplatform for Antioxidation Reduced Cardiotoxicity and Tumor Synergistic Therapy

Reducing the cardiotoxicity caused by DOX is a difficult problem in clinical cancer therapy. The small hydrophobic polyphenolic compound geraniin (GE) was designed as a DOX nanocarrier to coordinate with Fe3+, forming DOX-Fe3+@GE-PEG (GDFP) nanoparticles (NPs). DOX-induced cardiotoxicity mediated by the Nrf2/HO-1 pathway was studied in vitro and in vivo. The targeting ability of GDFP NPs toward tumor cells or tissues was assessed using NIR imaging and pharmacokinetics studies. The synergistic therapeutic efficacy of the DOX and GE-based GDFP NPs was evaluated in vitro and in vivo. GE-based GDFP NPs promoted SOD and GSH-Px activities, inhibited Nrf2 protein expression, and enhance HO-1 protein expression, which contributed to the reduction of DOX-induced cardiotoxicity. The blood-circulation half-life of GDFP NPs was longer than 20 h determined by the NIR imaging and DOX plasma level calculations. The results indicated that high tumor accumulation of GDFP NPs could be achieved by retention (EPR) effect. The GDFP NPs showed an improved synergistic antitumor effect. Our work has explored a novel approach for overcoming DOX-induced cardiotoxicity and achieving synergistic chemotherapy, which holds great potential for future clinical application.

Geraniin inhibits whole blood IFN-γ and IL-6 and promotes IL-1β and IL-8, and stimulates calcium-dependent and sucrose-sensitive erythrocyte death

Correlations between circulating cytokine levels and disease states are well established, and pharmacological modulation of the immune response is thus an important aspect of the assessment of investigational new drugs. Moreover, chemotherapy-related anemia is a major obstacle in cancer treatment. Geraniin (GRN), a tannin extracted from Geranium and other plants, possesses promising antitumor potential. However, the effect of GRN on whole blood (WB) cytokine response and RBC physiology remains unexplored. Heparinized blood from consented, healthy adults was challenged with 100 ng/mL of lipopolysaccharide (LPS) with and without pretreatment with 10 μM of GRN for 24 h at 37 °C, and tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-8, and IL-10 were assayed by ELISA. Moreover, single-cell RBC suspensions were treated with 5–100 μM of GRN for 24 or 48 h at 37 °C and cytotoxicity and canonical eryptotic markers were examined by flow cytometry. It was revealed that GRN significantly attenuated LPS-induced IFN-γ levels, increased IL-1β, decreased IL-6 only in absence of LPS, and aggravated LPS-induced IL-8 while together with LPS significantly diminished IL-10. Furthermore, GRN induced dose-responsive, Ca2+-dependent, and sucrose-sensitive hemolysis, along with phosphatidylserine exposure and Ca2+ accumulation with no appreciable cell shrinkage or oxidative damage. GRN was also selectively toxic to platelets, significantly delayed reticulocyte maturation, and significantly disrupted leukocyte proportions. In conclusion, GRN regulates the WB cytokine response and promotes premature hemolysis and eryptosis. This study provides insights into the therapeutic utility of GRN in a highly relevant cellular model system.

Potent antiviral activity of the extract of Elaeocarpus sylvestris against influenza A virus in vitro and in vivo

BackgroundElaeocarpus sylvestris (Lour.) Poir. (Elaeocarpaceae) belongs to a genus of tropical and semitropical evergreen trees, which has known biological activities such as antiviral and immunomodulatory activities. However, its antiviral potential against influenza virus infection remains unknown. PurposeIn this study, we investigated the antiviral activity of the 50% aqueous ethanolic extract of E. sylvestris (ESE) against influenza A virus (IAV) infection, which could lead to the development of novel phytomedicine to treat influenza virus infection. MethodsTo investigate the in vitro antiviral activity of ESE and its main ingredients, 1,​2,​3,​4,​6-​penta-​O-​galloyl-β-d-glucose (PGG) and geraniin (GE), the levels of viral RNAs, proteins, and infectious viral particles in IAV-infected MDCK cells were analyzed. Molecular docking analysis was performed to determine the binding energy of PGG and GE for IAV proteins. To investigate in vivo antiviral activity, IAV-infected mice were treated intranasally or intragastrically with ESE, PGG, or GE. ResultsESE and its gallate main ingredients (PGG and GE) strongly inhibited the production of viral RNAs, viral proteins, and infectious viral particles in vitro. Also through the viral attachment on cells, polymerase activity, signaling pathway, we revealed the ESE, PGG, and GE inhibit multiple steps of IAV replication. Molecular docking analysis revealed that PGG and GE could interact with 12 key viral proteins (M1, NP, NS1 effector domain (ED), NS1 RNA-binding domain (RBD), HA pocket A, HA receptor-binding domain (RBD), NA, PA, PB1, PB2 C-terminal domain, PB2 middle domain, and PB2 cap-binding domain) of IAV proteins with stable binding energy. Furthermore, intranasal administration of ESE, PGG, or GE protected mice from IAV-induced mortality and morbidity. Importantly, oral administration of ESE suppressed IAV replication and the expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 in the lungs to a large extent. ConclusionESE and its major components (PGG and PE) exhibited strong antiviral activity in multiple steps against IAV infection in silico, in vivo, and in vitro. Therefore, ESE could be used as a novel natural product derived therapeutic agent to treat influenza virus infection.

Research progress on anti-osteoporotic mechanism of geraniin

Geraniin is a kind of polyphenolic compound, which derived from Euphorbia Phyllanthus. Several studies reported that geraniin had a variety of pharmacological effects, such as anti-osteoporosis, anti-virus and anti-tumor. Thus, this paper summarized the researches and development of new anti-osteoporosis drugs, and the progress of anti-osteoporosis pharmacological mechanism of geraniin. Key words: Geraniin; Osteoporosis; Osteoclast; Mechanism; Review

The physicochemical properties of geraniin, a potential antihyperglycemic agent

Context: Natural products play a vital role in the discovery of leads for novel pharmacologically active drugs. Geraniin (GE) was identified as the major compound in the rind of Nephelium lappaceum L. (Sapindaceae), while ellagic and gallic acids have been shown to be its main metabolites. GE and its metabolites possess a range of bioactive properties including being an anti-infective, anticarcinogenic, antihyperglycemic, and antihypertensive.Objective: GE and its metabolites were investigated to establish its gastrointestinal absorption and physicochemical properties.Materials and methods: GE was purified from N. lappaceum rind extract using reverse-phase C18 column chromatography. Lipophilicity (log P) was determined using the 1-octanol/water shake-flask method. Equilibrium solubility of GE and its metabolites (20 mg) was determined in water and four biorelevant media: simulated gastric, simulated intestinal, fasted state-simulated intestinal, and fed state-simulated intestinal after 72 h.Results and discussion: The purification yield was 10.8%; where a 97–99% pure GE was obtained. Log P values for GE, ellagic, and gallic acids were established as −0.73 ± 0.17, 0.11 ± 0.06, and 0.71 ± 0.21, respectively, establishing them as polar compounds. All three compounds were found to exhibit poor solubility in gastric (0.61–8.10 mg/mL) but good solubility in intestinal fluids (3.59–14.32 mg/mL).Conclusion: The above results indicate that the compounds have limited gastrointestinal absorption due to its polarities. To consider these compounds as oral drug candidates, formulation strategies are being developed.

Effect of geraniin on dexamethasone-induced rat osteoporosis

Objective To observe the effect of geraniin on dexamethasone- induced experimental osteoporosis. Methods The female Wistar rats were randomly divided into control group, model group, geraniin(5,10 or 20 mg/kg)groups and alendronate group. The bone mineral density (BMD)and histomorphometry of both femur and lumbar vertebra were measured. Results The BMD of the femur and lumbar vertebra in the control group was(0.20±0.01)and(0.18±0.01)g/cm2, and that in model group was(0.15±0.01)and(0.10±0.01)g/cm2, with the difference being significant(P< 0.05). As compared with the model group, 10 and 20 mg/kg geraniin significantly increased the BMD of both femur and lumbar vertebra. For the model rats administrated with geraniin (5 mg/kg), some parameters including percentage of trabecular area(% Tb.Ar), the trabecular separation(Tb.Sp)and trabecular joint(JOINT)were increased. For both fermur and vertebra, geraniin(10 or 20 mg/kg)increased the trabecular number(Tb.N), trabecular width(Tb.Wi),% Tb.Ar and JOINT of the model rats. Conclusion Geraniin inhibits dexamethasone-induced rat osteoporosis with a dose-response relationship. Key words: Geraniin; Bone mineral density; Osteoporosis

Effects of geraniin on osteoblastic proliferation and osteoprotegerin expression

Objective To observe the effects of geraniin on osteoblastic proliferation and osteoprotegerin (OPG) expression.Methods The osteoblasts (MC3T3-E1) were cultured with different concentrations of geraniin.Cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) colorimetric assay.The protein and mRNA expression levels of OPG were measured by immunocytochemistry and in situ hybridization (ISH) respectively.Results The absorbance values of the control group and geraniin (10-12-10-8mol/L) groups were 0.777 ±0.088,0.958 ±0.054,0.943 ±0.029,0.918 ±0.070,0.899 ± 0.04 and 0.793 ± 0.074 respectively with the differences being statistically significant between control group and geraniin groups except 10-8 mol/L geraniin group.The average absorbance values of OPG protein in the control group and geraniin (10-12-10-8 mol/L) groups were 0.231 ± 0.022,0.249 ± 0.015,0.255 ±0.021,0.302 ± 0.025 and 0.328 ± 0.021 respectively; and those of OPG mRNA were 0.297 ±0.041,0.307 ±0.039,0.318 ±0.035,0.394 ±0.036 and 0.429 ±0.050 respectively,showing geraniin promoted the protein and mRNA expression of OPG in a concentration-dependent manner.Conclusion It suggests that geraniin promotes osteoblast proliferation and upregulates the protein and mRNA expression of OPG. Key words: Geraniin; Osteoblast; Osteoprotegerin

Optimisation of microwave-assisted enzymatic extraction of corilagin and geraniin from Geranium sibiricum Linne and evaluation of antioxidant activity

Plant polyphenols exhibit effective bio-activities, particularly antioxidant activities. Previous studies showed that Geranium sibiricum Linne contains high levels of polyphenolic compounds such as corilagin (CG) and geraniin (GE). In this study, a microwave-assisted enzymatic extraction (MAEE) method was evaluated for the simultaneous extraction of CG and GE only with deionised water. The optimal extraction conditions were as follows: irradiation power 500 W, ratio of solvent to material 40 ml/g, irradiation temperature 33 °C, pH 5.2, amount of cellulase 3600 U/g and irradiation time 9 min. Under these conditions, the extraction yields of CG and GE achieved were 6.79 and 19.82 mg/g, which increased by 64.01% and 72.95%, respectively, as compared with the control ones. Furthermore, the antioxidant activities of crude extracts were 2.61 mmol FeSO 4/g DW and 0.118 mg/ml (IC 50), according to the FRAP and DPPH assays, which indicated G. sibiricum Linne possesses good potential for natural antioxidants.

Anti-Oxidant Activity of Polyphenols from Phyllanthus debilis Klein ex Willd

Phyllanthus debilis Klein ex Willd. (Euphorbiaceae) usually used as substitute/adulterant to Phyllanthus amarus , a hepatoprotective drug. However, the phytochmeical investigation of P.debilis has not been performed much. In the present study, five compounds were isolated from the ethyl acetate extract of aerial parts of P.debilis and they were identified as Gallic acid, Rutin, Corilagin, Furosin and Geraniin. All the constituents have been reported for the first time from this plant. Their structures were elucidated by spectral techniques. Furthermore, the phenolic compounds were tested for antioxidant activity against DPPH (1,1-diphenyl picrylhydrazyl) and by the phosphomolybdenum method. Ascorbic acid is used as the reference standard. From the isolated compounds, the Geraniin had showed highest activity in DPPH assay and Gallic acid in phosphomolybdenum method.

Phenolic Constituents from the Flowers of Euphoria longana Lam.

Thirteen phenols were isolated from the flowers of Euphoria longana. These compounds included six hydrolyzable tannins: 1-O-galloyl-3, 6-(R)-HHDP-4-O-brevifolincarboxyl-β-D-glucopyranose (1), corilagin (2), repandusinic acid A (3), phyllanthusiin C (4), furosin (5) and geraniin (6); two phenolcarboxylic acids: brevifolincarhoxylic acid (7) and p-coumaric acid (8); and live flavonoids: luteolin (9), kaempferol (10), chrysoeriol (11), quercetin (12) and hyperin (13). Their structures were identified on the basis of spectroscopic and chemical evidence. Compound 1 was isolated for the first time from nature.

Isolation and Characterization of Geraniin and Galloyl-Geraniin fromSpondias mombin

Isolation and Characterization of Geraniin and Galloyl-Geraniin from<i>Spondias mombin</i>