Spicatoside A derived from Liriope platyphylla root ethanol extract inhibits hepatitis E virus genotype 3 replication in vitro.
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ABSTRACT:
SUBMITTER: Park G
PROVIDER: S-EPMC6416393 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Project description:Liriope platyphylla (Liliaceae), a medical plant distributed mainly in China, Taiwan, and Korea, has been used traditionally for the treatment of cough, sputum, asthma, and neurodegenerative diseases. The present study involved the metabolic profiling of this plant and reports spicatoside A accumulation in four different varieties of L. platyphylla (Cheongyangjaerae, Seongsoo, Cheongsim, and Liriope Tuber No. 1) using HPLC and gas chromatography time-of-flight mass spectrometry (GC?TOFMS). A total of 47 metabolites were detected in the different cultivars using GC?TOFMS-based metabolic profiling. The resulting data were subjected to principal component analysis (PCA) for determining the whole experimental variation, and the different cultivars were separated by score plots. Furthermore, hierarchical clustering, Pearson's correlation, and partial least-squares discriminant analyses (PLS-DA) were subsequently performed to determine significant differences in the various metabolites of the cultivars. The HPLC data revealed that the presence of spicatoside A was detected in all four cultivars, with the amount of spicatoside A varying among them. Among the cultivars, Liriope Tuber No. 1 contained the highest amount of spicatoside A (1.83 ± 0.13 mg/g dry weight), followed by Cheongyangjaerae (1.25 ± 0.01 mg/g dry weight), Cheongsim (1.09 ± 0.04 mg/g dry weight), and Seongsoo (1.01 ± 0.02 mg/g dry weight). The identification of spicatoside A was confirmed by comparing the retention time of the sample with the retention time of the standard. Moreover, the Cheongsim cultivar contained higher levels of phenolic compounds-including vanillic acid, quinic acid, gallic acid, chlorogenic acid, caffeic acid, and benzoic acid-than those of the other two cultivars. On the other hand, the levels of amino acids were higher in the Seongsoo cultivar. Therefore, this study may help breeders produce new varieties with improved nutraceutical and nutritional qualities.
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Project description:Ampelopsis sinica root is widely used in Chinese folk medicine for treating liver disorders caused by the hepatitis B virus (HBV). The present study was performed in order to investigate the anti-HBV activity and mechanisms of the ethanol extract from A. sinica root (EASR) in vitro. The antiviral activity of EASR was examined by detecting the levels of HBsAg, HBeAg and extracellular HBV DNAs in stable HBV-producing human hepatoblastoma HepG2 2.2.15 cells. We found that EASR effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose-dependent manner, and it also suppressed the amount of extracellular HBV DNA. After EASR treatment, the percentage of apoptotic cells was found to be significantly higher than that of control by flow cytometric analysis. A luciferase reporter gene assay was used to determine the effects of EASR on the activities of HBV promoters and intracellular signaling pathways. The results showed that EASR selectively inhibited the activities of HBV promoters (Cp, S1p and Fp) and the p53 signaling pathway in HepG2 cells significantly. These data indicate that EASR exerts anti-HBV effects via inhibition of HBV promoters and the p53-associated signaling pathway, which helps to elucidate the mechanism underlying the potential therapeutic value of EASR.
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Project description:One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures of the isolates were established by spectroscopic analysis and comparison with the literature data. The results indicated that structures 1-3 are uncommon in Nature. Benzofuroisocoumarin 4, flavonoids 9, 10, and 13-15, and homoisoflavonoids 19 and 20 exhibited significant binding activity to estrogen-receptor ? and/or ? as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line.
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Project description:Liriope platyphylla is herbaceous perennial plant belonging to the Asparagaceae family and widely used both as ornamental plant and herbal medicine. The complete chloroplast genome of L. platyphylla was 156,754 bp in length, which was composed of four distinct parts; a large single copy (LSC) of 85,118 bp, a small single copy (SSC) of 18,680 bp, and a pair of inverted repeat regions (IRa and IRb) of 26,478 bp. A total of 130 genes including 83 protein-coding genes, 39 tRNA genes and 8 rRNA genes were identified. The phylogenetic tree showed that L. platyphylla has a close relationship with other Nolinoideae plants, especially with Maianthemum dilatatum and Nolina atopocarpa.
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Project description:Hepatitis B virus (HBV) infection is a major worldwide health problem which can cause acute and chronic hepatitis and can significantly increase the risk of liver cirrhosis and primary hepatocellular carcinoma (HCC). Nowadays, clinical therapies of HBV infection still mainly rely on nucleotide analogs and interferons, the usage of which is limited by drug-resistant mutation or side effects. Defensins had been reported to effectively inhibit the proliferation of bacteria, fungi, parasites and viruses. Here, we screened the anti-HBV activity of 25 scorpion-derived peptides most recently characterized by our group. Through evaluating anti-HBV activity and cytotoxicity, we found that BmKDfsin4, a scorpion defensin with antibacterial and Kv1.3-blocking activities, has a comparable high inhibitory rate of both HBeAg and HBsAg in HepG2.2.15 culture medium and low cytotoxicity to HepG2.2.15. Then, our experimental results further showed that BmKDfsin4 can dose-dependently decrease the production of HBV DNA and HBV viral proteins in both culture medium and cell lysate. Interestingly, BmKDfsin4 exerted high serum stability. Together, this study indicates that the scorpion defensin BmKDfsin4 also has inhibitory activity against HBV replication along with its antibacterial and potassium ion channel Kv1.3-blocking activities, which shows that BmKDfsin4 is a uniquely multifunctional defensin molecule. Our work also provides a good molecule material which will be used to investigate the link or relationship of its antiviral, antibacterial and ion channel-modulating activities in the future.
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Project description:Background and aimThe hepatitis C virus (HCV) is a single-strand RNA virus that infects millions of people worldwide. Recent advances in therapy have led to viral cure using two- and three- drug combinations of direct acting inhibitors of viral replication. CCR5 is a chemokine receptor that is expressed on hepatocytes and represents a key co-receptor for HIV. We evaluated the effect of CCR5 blockade or knockdown on HCV replication in Huh7.5JFH1 cells.MethodsCells were exposed to varying concentrations of maraviroc (CCR5 inhibitor), cenicriviroc (CCR2/CCR5 inhibitor), sofosbuvir (nucleotide polymerase inhibitor), or raltegravir (HIV integrase inhibitor).ResultsHCV RNA was detected utilizing two qualitative strand-specific RT-PCR assays. HCV core antigen and NS3 protein was quantified in the supernatant and cell lysate, respectively. siRNA was utilized to knockdown CCR5 gene expression in hepatocytes. Alternatively, anti-CCR5 antibodies were employed to block the receptor. Supernatant levels of HCV RNA (expressed as fold change) were not reduced in the presence of raltegravir but were reduced 8.55-fold and 12.42-fold with cenicriviroc and maraviroc, respectively. Sofosbuvir resulted in a 16.20-fold change in HCV RNA levels. HCV core and NS3 protein production was also reduced in a dose-dependent manner. Two distinct anti-CCR5 antibodies also resulted in a significant reduction in HCV protein expression, as did siRNA knockdown of CCR5 gene expression.ConclusionsThese data provide evidence that CCR5 modulation could have a significant effect on HCV replication in an in vitro system. Further evaluation of the role of CCR5 inhibition in clinical settings may be warranted.
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Project description:BackgroundSenna occidentalis (L.) Link has been used worldwide in traditional treatment of many diseases and conditions including snakebite. In Kenya, a decoction from the plant roots taken orally, is used as a cure for malaria. Several studies have demonstrated that extracts from the plant possess antiplasmodial activity, in vitro. However, the safety and curative potency of the plant root against established malaria infection is yet to be scientifically validated, in vivo. On the other hand, there are reports on variation in bioactivity of extracts obtained from this plant species, depending on the plant part used and place of origin among other factors. In this study, we demonstrated the antiplasmodial activity of Senna occidentalis roots extract in vitro, and in mice.MethodsMethanol, ethyl acetate, chloroform, hexane and water extracts of S. occidentalis root were tested for in vitro antiplasmodial activity against Plasmodium falciparum, strain 3D7. Cytotoxicity of the most active solvent extracts was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the curative potency in Plasmodium berghei infected mice evaluated by Rane's test.ResultsAll of the solvent extracts tested in this study inhibited the propagation of P. falciparum, strain 3D7, in vitro, with polar extracts being more active than non-polar ones. Methanolic extracts had the highest activity (IC50 = 1.76) while hexane extract displayed the lowest activity (IC50 = 18.47). At the tested concentrations, methanolic and aqueous extracts exhibited high selectivity index against P. falciparum strain 3D7 (SI > 10) in the cytotoxicity assay. Further, the extracts significantly suppressed the propagation of P. berghei parasites (P < 0.05) in vivo and increased the survival time of the infected mice (P < 0.0001).ConclusionsSenna occidentalis (L.) Link root extract inhibits the propagation of malaria parasites in vitro and in BALB/c mice.
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Project description:Influenza virus infections can lead to viral pneumonia and acute respiratory distress syndrome in severe cases, causing significant morbidity and mortality and posing a great threat to human health. Because of the diversity of influenza virus strains and drug resistance to the current direct antiviral agents, there have been no effective drugs as yet to cure all patients infected by influenza viruses. Natural products from plants contain compounds with diverse structures that have the potential to interact with multiple host and virus factors. In this study, we identified the ethanol extract of Caesalpinia decapetala (Roth) Alston (EEC) as an inhibitor against the replication of a panel of influenza A and B viruses both on human pulmonary epithelial A549 and human monocytic U937 cells. The animal study revealed that EEC administration reduces the weight loss and improves the survival rate of mice infected with lethal influenza virus. Also, EEC treatment attenuated lung injury and reduced virus titer significantly. In conclusion, we showed that EEC has antiviral activity both in vitro and in vivo, suggesting that the plant C. decapetala has the potential to be further developed as a resource of new anti-influenza drugs.
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Project description:Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC, we assessed whether Peretinoin and other retinoids have any effect on HCV infection. For this purpose, we measured the effects of several retinoids on the replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. Furthermore, it reduced infectious virus release by 80-90% without affecting virus assembly. These effects could be due to reduced signalling from lipid droplets, triglyceride abundance, and the expression of mature sterol regulatory element-binding protein 1c and fatty acid synthase. These negative effects of Peretinoin on HCV infection may be beneficial in addition to its potential for HCC chemoprevention in HCV-infected patients.
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