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Inhibition of Rabies Virus by 1,2,3,4,6-Penta-O-galloyl-?-d-Glucose Involves mTOR-Dependent Autophagy.

ABSTRACT: The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug.

SUBMITTER: Tu Z

PROVIDER: S-EPMC5923495 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Inhibition of Rabies Virus by 1,2,3,4,6-Penta-O-galloyl-β-d-Glucose Involves mTOR-Dependent Autophagy.

Tu Zhongzhong Z Gong Wenjie W Zhang Yan Y Feng Ye Y Liu Yan Y Tu Changchun C

Viruses 20180417 4

The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only supp ...[more]

PMID: 29673174

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Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-β-D-glucose-induced senescence-like growth arrest in human cancer cells.

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Expression data from Huh7 cells after 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside (PGG) treatment

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2018-11-16 | GSE75024 | GEO

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1,2,3,4,6-Penta-O-galloyl-d-glucose Interrupts the Early Adipocyte Lifecycle and Attenuates Adiposity and Hepatic Steatosis in Mice with Diet-Induced Obesity.

Project description:Phytochemicals that interrupt adipocyte lifecycle can provide anti-obesity effects. 1,2,3,4,6-penta-O-galloyl-d-glucose (PGG) is a tannin with two isomers that occurs widely in plants and exhibits various pharmacological activities. The aim of the investigation is to comprehensively examine effects of PGG isomer(s) on adipocyte lifecycle and diet-induced obesity. Human mesenchymal stem cells (hMSC), 3T3-L1 fibroblasts, and H4IIE hepatoma cells were used to determine the effects of PGG isomers on cell viability and adipogenesis. Mice with diet-induced obesity were generated from male C57/BL6 mice fed with a 45% high fat diet. Oral administration of β-PGG (0.1 and 5 mg/kg) lasted for 14 weeks. Viability was reduced by repeated PGG treatment in hMSC, preadipocytes, and cells under differentiation. PGG mainly induces apoptosis, and this effect is independent of its insulin mimetic action. In vivo, administration of β-PGG attenuated shortening of the colon, hyperlipidaemia, fat cells and islet hypertrophy in DIO mice. Hepatic steatosis and related gene expression were improved along with glucose intolerance. Increased serum adiponectin, leptin, and glucagon-like peptide-1 levels were also observed. In conclusion, repeated PGG treatment interrupts the adipocyte lifecycle. PGG administration reduces adiposity and fatty liver development in DIO mice, and therefore, PGG could aid in clinical management of obesity.

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The genome-wide expression profile of 1,2,3,4,6-penta-O-galloyl-?-D-glucose-treated MDA-MB-231 breast cancer cells: molecular target on cancer metabolism.

Project description:1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), a polyphenolic compound isolated from Rhus chinensis Mill. PGG has been known to have anti-tumor, anti-angiogenic and anti-diabetic activities. The present study revealed another underlying molecular target of PGG in MDA-MB-231 breast cancer cells by using Illumina Human Ref-8 expression BeadChip assay. Through the Beadstudio v3 micro assay program to compare the identified genes expressed in PGG-treated MDA-MB-231 cells with untreated control, we found several unique genes that are closely associated with pyruvate metabolism, glycolysis/gluconeogenesis and tyrosine metabolism, including PC, ACSS2, ACACA, ACYP2, ALDH3B1, FBP1, PRMT2 and COMT. Consistent with microarray data, real-time RT-PCR confirmed the significant down-regulation of these genes at mRNA level in PGG-treated MDA-MB-231 cells. Our findings suggest the potential of PGG as anticancer agent for breast cancer cells by targeting cancer metabolism genes.

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Opposing Effects of Cucurbit[7]uril and 1,2,3,4,6-Penta-O-galloyl-?-d-glucopyranose on Amyloid ?25-35 Assembly.

Project description:Alzheimer's disease (AD) is a neurodegenerative disease characterized by extracellular deposits of amyloid ? protein (A?) in the brain. The conversion of soluble monomers to amyloid A? fibrils is a complicated process and involves several transient oligomeric species, which are widely believed to be highly toxic and play a crucial role in the etiology of AD. The development of inhibitors to prevent formation of small and midsized oligomers is a promising strategy for AD treatment. In this work, we employ ion mobility spectrometry (IMS), transmission electron microscopy (TEM), and molecular dynamics (MD) simulations to elucidate the structural modulation promoted by two potential inhibitors of A? oligomerization, cucurbit[7]uril (CB[7]) and 1,2,3,4,6-penta-O-galloyl-?-d-glucopyranose (PGG), on early oligomer and fibril formation of the A?25-35 fragment. One and two CB[7] molecules bind to A?25-35 monomers and dimers, respectively, and suppress aggregation by remodeling early oligomer structures and inhibiting the formation of higher-order oligomers. On the other hand, nonselective binding was observed between PGG and A?25-35. The interactions between PGG and A?25-35, surprisingly, enhanced the formation of A? aggregates by promoting extended A?25-35 conformations in both homo- and hetero-oligomers. When both ligands were present, the inhibitory effect of CB[7] overrode the stimulatory effect of PGG on A?25-35 aggregation, suppressing the formation of large amyloid oligomers and eliminating the structural conversion from isotropic to ?-rich topologies induced by PGG. Our results provide mechanistic insights into CB[7] and PGG action on A? oligomerization. They also demonstrate the power of the IMS technique to investigate mechanisms of multiple small-molecule agents on the amyloid formation process.

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