Pentagalloyl Glucose Treatment Research Articles

Pharmacoinformatic screening of phytoconstituent and evaluation of its anti-PDAC effect using in vitro studies

With no prominent treatment for pancreatic ductal adenocarcinoma (PDAC) in conventional chemotherapy, recent studies have focused on uniting conventional and traditional medicines including plant phytoconstituents. Herein, we used pharmacoinformatic studies to identify potent phytoconstituent as ligand having inhibition activities against canonical anticancer targets, and evaluated its effect on PDAC cell lines. SwissTargetPrediction and SuperPred tools were utilized to segregate protein targets of ligand in humans, following which FunRich was applied to garner its targets in PDAC. STRING analysis predicted protein–protein interactions and dynamic simulation studies confirmed stability of ligand–protein complex. For in vitro cytotoxic potential, ligand treatment at different concentrations was given to PDAC cell lines both alone and combined with gemcitabine, followed by evaluation of effects on migration. Differential gene expression was checked using PCR for evaluating mechanism of cytotoxicity. Results showed pentagalloylglucose (PGG) with highest docking and MMGBSA scores for Cyclooxygenase 2 (Cox2) inhibition site. SwissTargetPrediction and SuperPred analysis detected 40 targets of PGG in PDAC. Simulation data showed stability of protein–ligand complex. In in vitro experiments Mia-PaCa-2 was more sensitive to PGG than Panc-1. PGG successfully inhibited migration both alone and in combination with gemcitabine. Additionally, PGG treatment induced apoptosis in both the cell lines; but showed antagonism when combined with gemcitabine. In conclusion, our report demonstrates PGG has good binding with Cox2 and showed anti-PDAC activity by inhibiting migration and inducing apoptosis, thus it can be used as a therapy option. But further studies are required to confirm its behaviour as a combination therapy drug. Communicated by Ramaswamy H. Sarma

Pentagalloyl Glucose (PGG) Prevents and Restores Mechanical Changes Caused by Elastic Fiber Fragmentation in the Mouse Ascending Aorta.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aorta that can lead to dissection or rupture. Degradation of elastic fibers is a consistent histopathological feature of TAA that likely contributes to disease progression. Pentagalloyl glucose (PGG) shows promise for stabilizing elastic fibers in abdominal aortic aneurysms, but its efficacy and mechanical effects in the thoracic aorta are unknown. We simulated TAAs using elastase (ELA) to degrade elastic fibers in the mouse ascending aorta and determined the preventative and restorative potential of PGG. Biaxial mechanical tests, constitutive model fitting, and multiphoton imaging were performed on untreated (UNT), PGG, ELA, PGG + ELA, and ELA + PGG treated aortas. PGG treatment alone does not significantly alter mechanical properties or wall structure compared to UNT. ELA treatment alone causes an increase in the unloaded diameter and length, decreased compliance, significant changes in the material constants, and separation of the outer layers of the aortic wall compared to UNT. PGG treatment before or after ELA ameliorates the mechanical and structural changes associated with elastic fiber degradation, with preventative PGG treatment being most effective. These results suggest that PGG is a potential pharmaceutical option to stabilize elastic fibers in TAA.

Pentagalloylglucose suppresses the growth and migration of human nasopharyngeal cancer cells via the GSK3β/β-catenin pathway in vitro and in vivo

BackgroundNasopharyngeal carcinoma (NPC) is a type of malignant squamous cell tumour originating from the nasopharynx epithelium. Pentagalloylglucose (PGG) is a natural polyphenolic compound that exerts anticancer effects in many types of tumours. However, the role and underlying mechanism of PGG in NPC cells have not been fully defined. PurposeThis study aimed to investigate the anticancer activity of PGG as well as the potential mechanism in NPC cells. MethodsThe effects of PGG on the proliferation, apoptosis and cell cycle distribution of CNE1 and CNE2 cells were assessed by MTT and flow cytometry assays. Cell migration was evaluated using wound healing and transwell assays. The expression of microtubule-associated protein 1 light chain 3 beta (LC3B) was observed by immunofluorescence staining. Western blotting was used to explore the levels of related proteins and signalling pathway components. Furthermore, the effects of PGG on NPC cell growth were analysed in a xenograft mouse model in vivo using cisplatin as a positive control. ResultsPGG dose-dependently inhibited the proliferation of CNE1 and CNE2 cells. PGG regulated the cell cycle by altering p53, cyclin D1, CDK2, and cyclin E1 protein levels. PGG induced apoptosis and autophagy in NPC cells and elevated the Bax/Bcl-2 ratio and the protein levels of LC3B. Moreover, PGG decreased NPC cell migration by increasing E-cadherin and decreasing N-cadherin, vimentin and CD44 protein levels. Mechanistically, PGG treatment downregulated p-mTOR and β-catenin expression but upregulated p-p38 MAPK and p-GSK3β expression. In addition, PGG significantly inhibited NPC cell tumour growth and lung metastasis in vivo. ConclusionPGG may suppress cell proliferation, induce apoptosis and autophagy, and decrease the metastatic capacity of NPC cells through the p38 MAPK/mTOR and Wnt/β-catenin pathways. The present study provides evidence for PGG as a potential therapy for NPC.

Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury.

Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3–4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl2 model had significantly higher Green–Lagrange circumferential cyclic strain in PGG-treated animals (p < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl2 model. These findings highlight the continued need for improved understanding of PGG’s effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation.

Intraluminal infusion of Penta-Galloyl Glucose reduces abdominal aortic aneurysm development in the elastase rat model.

An abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta with terminally rupture when the aortic wall is so weakened that aortic wall stress exceeds wall strength. No effective medical treatment exists so far. We aimed to test whether intraluminal admission of Penta-Galloyl Glucose (PGG) treatment in a rodent AAA model could hold the potential to inhibit aneurysmal progression. Male Sprague Dawley rats had either intraluminal elastase infused for AAA induction or saline to serve as controls. In two independent experimental series, elastase was used to induce AAA followed by an intraluminal PGG (directly or by a drug eluting balloon) treatment. All rats were followed for 28 days and euthanized. In both series, maximal infrarenal aortic diameter was measured at baseline and at termination as a measure of AAA size. In series 2, maximal internally AAA diameter was followed by ultrasound weekly. AAA tissues were analyzed for elastin integrity by millers stain, collagen deposition by masson trichrome staining. In other AAA tissue samples the mRNA level of CD45, lysyloxidase (LOX), lysyloxidase like protein 1 (LOXL1) were determined by qPCR. Direct administration of PGG significantly reduced AAA expansion when compared to controls. PGG treatment resulted in a higher number and more preserved elastic fibers in the aneurysmal wall, while no significant difference was seen in the levels of CD45 and LOX mRNA levels. The drug eluting balloon (DEB) experiment showed no significant difference in AAA size observed neither macroscopically nor ultrasonically. Also the aneurysmal mRNA levels of CD45, LOX and LOXL1 were unchanged between groups. A significant reduced expansion of AAAs was observed in the PGG group, suggesting PGG as a drug to inhibit aneurysmal progression, while administration through a DEB did not show a promising new way of administration.

Pentagalloyl glucose (PGG) Inhibits IL‐1β‐induced pro‐inflammatory cytokine production and matrix metalloproteinase activation in human osteoarthritis synovial fibroblasts

Osteoarthritis (OA) is a chronic degenerative joint disease in which the pro‐inflammatory cytokine, interleukin‐1β (IL‐1β), plays a central role in propagating inflammation and cartilage degradation by activating inflammatory mediators and cartilage degrading matrix metalloproteinases (MMPs). In the present study, we evaluated the efficacy of pentagalloyl glucose (PGG), a natural antioxidant, in suppressing IL‐1β‐induced mediators of inflammation and cartilage degradation in human osteoarthritis synovial fibroblasts (OASFs). PGG treatment (0.5–50 μM) for 24 hours had no significant effect on human OASF cell viability (n=3; p&lt;0.01). Analysis of the conditioned media using ELISA showed that PGG (0.5–5 uM/ml) pretreatment significantly inhibited IL‐1β‐induced production of IL‐6 (45–90%), IL‐8 (40–95%), MCP‐1/CCL2 up to 80%, and RANTES/CCL5 by (45–90%) (n=3; p&lt;0.05). In addition, we observed a significant dose‐dependent inhibition in MMP‐1 and MMP‐3 production by PGG in human OASFs (n=3; p&lt;0.05). Furthermore, in‐gel zymography results using conditioned media showed that the enzymatic activity of IL‐1β‐induced gelatinases MMP‐2 and MMP‐9 were markedly reduced upon PGG treatment (n=3; p&lt;0.05). PGG (5 μg/mL) significantly inhibited the degradation of type‐I collagen compared to IL‐1β stimulation alone in human OASFs (n=3; p&lt;0.05). Examination of the mitogen‐activated protein kinase (MAPK) signaling pathway showed that PGG interfered with IL‐1β‐induced ERK1/2 and JNK/SAPK, but not p38 MAPK, to inhibit downstream phosphorylation and nuclear translocation of transcription factor c‐Jun. Immunofluorescence study confirmed that PGG pretreatment inhibits phospho‐c‐Jun and NF‐κB p65 nuclear translocation. Overall, our findings suggest that PGG inhibits IL‐1β‐induced mediators of inflammation and tissue destruction in human OASFs by reducing the activation of MAPK signaling pathway.Support or Funding InformationThis study was supported by the NIH/NIAMS grant R01AR072615 (S.A.), and the Washington State University College of Pharmacy (S.A.), the Summer Undergraduate Research Fellowship from ASPET (M.T.), and Special thanks to Erwin &amp; Jennie Foisy Scholarship Fund (M.H.).

The role of NFκB in pentagalloyl glucose inhibition of TNF‐α‐induced CXCL1 expression and induction of apoptosis‐related genes in racially different triple negative breast cancer cells.

Drug resistance is the leading cause of breast cancer‐related mortality in women, and triple negative breast cancer (TNBC) is the most aggressive subtype. CXCL1/GRO‐α has been identified as a pro‐inflammatory chemokine overexpressed in breast cancer, promoting angiogenesis and having an increased potential to metastasize. The current study investigated the effect of the naturally occurring polyphenolic compound pentagalloyl glucose (PGG) in TNF‐α‐induced CXCL1 expression in MDA‐MB‐231 (Caucasian) and MDA‐MB‐468 (African American) TNBC cells. In addition, PGG apoptotic effect was evaluated through the study of apoptosis‐related genes in both cell lines. Results showed that PGG inhibited TNF‐α‐stimulated CXCL1 expression in the transcription and protein level in Caucasian and African American TNBC cell lines. Through mRNA quantification analysis, data showed that PGG downregulated IKBKE (expressed in 60.4% of the breast cancer tumors) and MAPK1/ERK2 (expressed in tumor tissues with 5 to 10‐fold increase) expression in both cell lines. Moreover, PGG was more effective in inhibiting IKBKE expression in MDA‐MB‐231 compared to MDA‐MB‐468 (9 and 2‐fold inhibition, respectively). Also, PGG reduced MAPK1 gene expression in 3‐fold in Caucasian and 6‐fold in the African American cells. Gene transcription studies showed that PGG induced expression of the pro‐apoptotic genes BNIP3, BNIP3L, GADD45A, TP53BP2, and RIPK2, which are critical initiators of the intrinsic and extrinsic apoptotic pathways. Although PGG increased the expression of apoptosis‐related genes in both cell lines, there was a significantly higher expression in MDA‐MB‐231 cells (5 to 14.7‐fold) compared to MDA‐MB‐468 cells (2 to 5.8‐fold). Furthermore, BAK1 gene expression was only induced in African American cells showing a 35.7‐fold increase after PGG treatment. The obtained data show that PGG inhibited the expression of CXCL1 pro‐inflammatory chemokine and upregulated the expression of specific pro‐apoptotic genes. It was concluded that PGG might have great potential in target therapy for TNBC.Support or Funding InformationThis work was supported by a grant from the NIH/NIMHD grant U54 007582

Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice.

AimAbdominal aortic aneurysms (AAA) is a life-threatening weakening and expansion of the abdominal aorta due to inflammatory cell infiltration and gradual degeneration of extracellular matrix (ECM). There are no pharmacological therapies to treat AAA. We tested the hypothesis that nanoparticle (NP) therapy that targets degraded elastin and delivers anti-inflammatory, anti-oxidative, and ECM stabilizing agent, pentagalloyl glucose (PGG) will reverse advance stage aneurysm in an elastase-induced mouse model of AAA.Method and resultsPorcine pancreatic elastase (PPE) was applied periadventitially to the infrarenal aorta in mice and AAA was allowed to develop for 14 days. Nanoparticles loaded with PGG (EL-PGG-NPs) were then delivered via IV route at 14-day and 21-day (10 mg/kg of body weight). A control group of mice received no therapy. The targeting of NPs to the AAA site was confirmed with fluorescent dye marked NPs and gold NPs. Animals were sacrificed at 28-d. We found that targeted PGG therapy reversed the AAA by decreasing matrix metalloproteinases MMP-9 and MMP-2, and the infiltration of macrophages in the medial layer. The increase in diameter of the aorta was reversed to healthy controls. Moreover, PGG treatment restored degraded elastic lamina and increased the circumferential strain of aneurysmal aorta to the healthy levels.ConclusionOur results support that site-specific delivery of PGG with targeted nanoparticles can be used to treat already developed AAA. Such therapy can reverse inflammatory markers and restore arterial homeostasis.

Pentagalloyl glucose increases elastin deposition, decreases reactive oxygen species and matrix metalloproteinase activity in pulmonary fibroblasts under inflammatory conditions

Emphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i.e., tumor necrosis factor-α (TNF-α) and cigarette smoke extract (CSE) to mimic the disease. Parameters like lysyl oxidase (LOX) and elastin gene expression, MMP-9 activity in the medium, lysyl oxidase (LOX) activity and ROS levels were studied to assess the effect of PGG on pulmonary fibroblasts. CSE inhibited lysyl oxidase (LOX) enzyme activity that resulted in a decreased elastin formation. Similarly, TNF-α treated cells showed less elastin in the cell layers. Both these agents caused increase in MMP activity and ROS levels in cells. However, when supplemented with PGG treatment along with these two inflammatory agents, we saw a significant increase in elastin deposition, reduction in both MMP activity and ROS levels. Thus PGG, which has anti-inflammatory, anti-oxidant properties coupled with its ability to aid in elastic fiber formation, can be a multifunctional drug to potentially arrest the progression of emphysema.

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection.

Herpes simplex virus type 1 (HSV-1), a widespread virus, causes a variety of human viral diseases worldwide. The serious threat of drug-resistance highlights the extreme urgency to develop novel antiviral drugs with different mechanisms of action. Pentagalloylglucose (PGG) is a natural polyphenolic compound with significant anti-HSV activity; however, the mechanisms underlying its antiviral activity need to be defined by further studies. In this study, we found that PGG treatment delays the nuclear transport process of HSV-1 particles by inhibiting the upregulation of dynein (a cellular major motor protein) induced by HSV-1 infection. Furthermore, PGG treatment affects the nucleocapsid egress of HSV-1 by inhibiting the expression and disrupting the cellular localization of pEGFP-UL31 and pEGFP-UL34, which are indispensable for HSV-1 nucleocapsid egress from the nucleus. However, the over-expression of pEGFP-UL31 and pEGFP-UL34 could decrease the antiviral effect of PGG. In this study, for the first time, the antiviral activity of PGG against acyclovir-resistant virus was demonstrated in vitro, and the possible mechanisms of its anti-HSV activities were identified based on the inhibition of nuclear transport and nucleocapsid egress in HSV-1. It was further confirmed that PGG could be a promising candidate for HSV therapy, especially for drug-resistant strains.

Evaluation of elastin-derived vascular grafts in a circulatory model

Purpose: To evaluate pentagalloyl-glucose (PGG) stabilized elastinderived vascular grafts (EDVGs) in terms of their suitability as vascular substitutes. Methods: EDVGs were prepared by alkaline decellularization (0.1 M NaOH at 37°C for 3 h), rinsing and sterilization in 0.1% peracetic acid. Batches of EDVG scaffolds were treated with sterile 0.1% PGG (pH 5.5) containing 20% isopropanol for 24 h, rinsed and stored in sterile PBS. A subset of PGG and non-PGG samples were additionally covalently heparinized via diamine coupling and reductive amination using nitrous acid degraded heparin. Grafts were implanted in a rat infrarenal aortic model for 4 and 8 weeks. Remodeling, patency, endothelialization and healing of the explants were determined by gross and histological evaluation. Results: While PGG treatment did not significantly affect the denaturation temperature (DT) of the tissue, heparinization resulted in significant increases in DT (from 52°C to 81–82°C) and heparin content (from baseline noise levels of b10 mg/g to N100 mg/g). Overall the nonheparinized groups showed strong evidence of remodeling and recellularization, with a high patency rate of 82%. At 8 weeks, only small fragments of the original grafts were preserved with good neovessel formation and moderate intimal hyperplasia (IH). The heparinized groups showed 100% patency, but with little remodeling, presumably due to the increased crosslink density resulting from the amination of the tissue prior to heparin attachment. Some surface endothelialization was observed in all treatment groups. Conclusions: EDVGs are promising candidates as vascular grafts, either as substrates for remodeling, or in more highly cross-linked and heparinized forms.

Tissue engineering of aortic valve leaflets using biomimetic composite poly(ethylene glycol) diacrylate hydrogels

Purpose: To evaluate pentagalloyl-glucose (PGG) stabilized elastinderived vascular grafts (EDVGs) in terms of their suitability as vascular substitutes. Methods: EDVGs were prepared by alkaline decellularization (0.1 M NaOH at 37°C for 3 h), rinsing and sterilization in 0.1% peracetic acid. Batches of EDVG scaffolds were treated with sterile 0.1% PGG (pH 5.5) containing 20% isopropanol for 24 h, rinsed and stored in sterile PBS. A subset of PGG and non-PGG samples were additionally covalently heparinized via diamine coupling and reductive amination using nitrous acid degraded heparin. Grafts were implanted in a rat infrarenal aortic model for 4 and 8 weeks. Remodeling, patency, endothelialization and healing of the explants were determined by gross and histological evaluation. Results: While PGG treatment did not significantly affect the denaturation temperature (DT) of the tissue, heparinization resulted in significant increases in DT (from 52°C to 81–82°C) and heparin content (from baseline noise levels of b10 mg/g to N100 mg/g). Overall the nonheparinized groups showed strong evidence of remodeling and recellularization, with a high patency rate of 82%. At 8 weeks, only small fragments of the original grafts were preserved with good neovessel formation and moderate intimal hyperplasia (IH). The heparinized groups showed 100% patency, but with little remodeling, presumably due to the increased crosslink density resulting from the amination of the tissue prior to heparin attachment. Some surface endothelialization was observed in all treatment groups. Conclusions: EDVGs are promising candidates as vascular grafts, either as substrates for remodeling, or in more highly cross-linked and heparinized forms.

Antiviral activity and possible mechanisms of action of pentagalloylglucose (PGG) against influenza A virus

Influenza A virus (IAV) infection is a major public health threat leading to significant morbidity and mortality. The emergence of drug-resistant virus strains highlights the urgent need to develop novel antiviral drugs with alternative modes of action. Pentagalloylglucose (PGG), a naturally occurring polyphenolic compound, possesses a broad spectrum of biological activities. In this study, we found that PGG has anti-influenza-virus activity, and investigated its possible mechanism(s) of action in vitro. Both pre-incubation of virus prior to infection and post-exposure of infected cells with PGG significantly inhibited virus yields. Influenza-virus-induced hemagglutination of chicken red blood cells was inhibited by PGG treatment, suggesting that PGG can inhibit IAV infection by interacting with the viral hemagglutinin. PGG did not affect viral protein synthesis or nuclear transport of viral nucleoprotein (NP) but greatly reduced plasma membrane accumulation of NP protein at the late stage of the replication cycle. Furthermore, PGG significantly reduced virus budding and progeny virus release from infected cells. This study revealed for the first time that PGG can inhibit IAV replication with a dual mode of action and offers new insights into its underlying mechanisms of antiviral action.

Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF- atg7 –/– cells (autophagy-defective cells) derived from an atg7 –/– knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

Polyphenol-Stabilized Tubular Elastin Scaffolds for Tissue Engineered Vascular Grafts

Tissue-engineered vascular grafts require elastic, acellular porous scaffolds with controlled biodegradability and properties matching those of natural arteries. Elastin would be a desirable component for such applications, but elastin does not easily regenerate experimentally. Our approach is to develop tubular elastin scaffolds using decellularization and removal of collagen from porcine carotid arteries ( approximately 5 mm diameter) using alkaline extraction. Because elastin is susceptible to rapid degeneration after implantation, scaffolds were further treated with penta-galloyl glucose (PGG), an established polyphenolic elastin-stabilizing agent. Scaffolds were compared in vitro with detergent-decellularized arteries for structure, composition, resistance to degradation, mechanical properties, and cytotoxicity and in vivo for cell infiltration and remodeling potential. Results showed effective decellularization and almost complete collagen removal by alkaline extraction. PGG-treated elastin scaffolds proved to be resistant to elastase digestion in vitro, maintained their cylindrical shapes, showed high resistance to burst pressures, and supported growth of endothelial cells and fibroblasts. In vivo results showed that PGG treatment reduced the rate of elastin biodegradation and controlled cell infiltration but did not hamper new collagen and proteoglycan deposition and secretion of matrix-degrading proteases. Alkali-purified, PGG-treated tubular arterial elastin scaffolds exhibit many desirable properties to be recommended for clinical applications as vascular grafts.

Elastin Stabilization for Treatment of Abdominal Aortic Aneurysms

Maintaining the integrity of arterial elastin is vital for the prevention of abdominal aortic aneurysm (AAA) development. We hypothesized that in vivo stabilization of aortic elastin with pentagalloyl glucose (PGG), an elastin-binding polyphenol, would interfere with AAA development. Safety and efficacy of PGG treatment were first tested in vitro using cytotoxicity, elastin stability, and PGG-elastin interaction assays. For in vivo studies, the efficacy of PGG was evaluated within a well-established AAA model in rats on the basis of CaCl2-mediated aortic injury. With this model, PGG was delivered periadventitially at 2 separate time points during the course of AAA development; aortic diameter, elastin integrity, and other pathological aspects were monitored and evaluated in PGG-treated aortas compared with saline-treated control aortas. Our results show that a one-time periadventitial delivery of noncytotoxic levels of PGG inhibits elastin degeneration, attenuates aneurysmal expansion, and hinders AAA development in rats without interfering with the pathogenic mechanisms typical of this model, namely inflammation, calcification, and high metalloproteinase activities. PGG binds specifically to arterial elastin and, in doing so, preserves the integrity of elastic lamellae despite the presence of high levels of proteinases derived from inflammatory cells. Periadventitial administration of PGG hinders the development of AAA in a clinically relevant animal model. Stabilization of aortic elastin in aneurysm-prone arterial segments offers great potential toward the development of safe and effective therapies for AAAs.