Graptopetalum Paraguayense Research Articles

First report of Kalanchoe Latent Virus naturally infecting common bean (Phaseolus vulgaris L.) in South Korea.

The common bean (Phaseolus vulgaris; family: Fabaceae) is an economically and nutritionally important food crop worldwide (Ganesan et al. 2017). In 2021, several plants collected from different provinces in South Korea had symptoms of viral infections (e.g., mild yellow-greenish speckling, stunting, crinkling, and deformed leaves). To identify the causal pathogens, total RNA was isolated from pooled leaf tissues from all samples (n = 29) for paired-end high-throughput sequencing (HTS). The cDNA library was constructed after eliminating ribosomal RNA using the TruSeq RNA Sample Prep Kit and then sequenced using the Illumina NovaSeq 6000 platform (Macrogen, Korea). The 297,868,156 paired-end clean reads (150 nt) were de novo assembled using Trinity with default parameters. BLASTx was used for the contig analysis, which revealed the pooled samples were infected with several plant viruses (e.g., turnip mosaic virus, zucchini yellow mosaic virus, cucumber mosaic virus, lily mottle virus). Notably, the assembled contigs included a single viral contig (8,472 nt) comprising the nearly complete KLV genome (HTS mean coverage: 39.46%). Kalanchoe latent virus (KLV; genus: Carlavirus; family: Betaflexiviridae) has been detected in Kalanchoë blossfeldiana (Hearon 1982), Chenopodium quinoa (Dinesen et al. 2009), and Graptopetalum paraguayense (Sorrentino et al. 2017). The sequence was most similar (96.28% nucleotide identity; 99% query coverage) to KLV isolate DSMZ PV-0290 (GenBank: OP525283) from Denmark. The contig sequence was validated via reverse transcription-polymerase chain reaction (RT-PCR) using total RNA extracted from the 29 individually stored samples and nine primer sets specific for the KLV contig. All nine contig-specific overlapping fragments were amplified from only a P. vulgaris plant with mild yellowing mosaic symptoms collected on July 6, 2021, in Jeongseon County, South Korea. Additionally, 5' and 3' rapid amplification of cDNA ends (RACE)-specific primers were designed for the KLV contig sequence to determine the terminal ends of the genome of the South Korean KLV isolate using the 5'/3' RACE System (Invitrogen, Carlsbad, CA, USA). All of the amplified and overlapping fragments were cloned into the RBC T&A Cloning Vector (RBC Bioscience, Taipei, Taiwan) and sequenced using the Sanger method. The obtained full-length genomic sequence of the KLV isolate (KLV-SK22) was 8,517 nt long and was deposited in GenBank OQ718816. According to the BLASTn analysis, KLV-SK22 was highly similar (96.30% sequence identity; 100% query coverage) to the DSMZ PV-0290 isolate. Phylogenetic trees constructed on the basis of coat protein and RNA-dependent RNA polymerase amino acid sequences revealed that KLV-SK22 is closely related to the DSMZ PV-0290 and PV-0290B isolates from Denmark, respectively. At the genome and gene levels, the individual sequence identities between the carlaviruses and other KLV isolates were 96.29% to 100% (Adams et al. 2004). Additionally, an RT-PCR analysis using detection primers specific for KLV-SK22 did not detect KLV in 15 samples (P. vulgaris = 3, Glycine max = 8, Pueraria montana = 2, Trifolium repens = 1, and Vigna angularis = 1) randomly collected from different regions in South Korea. Based on these results, KLV infection may not be widespread at this time in South Korea. To the best of our knowledge, this is the first report of KLV in P. vulgaris in South Korea or elsewhere. Our findings will aid future research on the epidemiology and long-term management of KLV-related diseases.

Protective Effects of Graptopetalum paraguayense E. Walther against Methylglyoxal-Induced Liver Damage and Microflora Imbalances Caused by High-Fructose Induction

Methylglyoxal (MG) is a highly reactive dicarbonyl aldehyde and a major precursor of advanced glycation end products that result in oxidative stress. Graptopetalum paraguayense E. Walther (WGP) is a herbal medicine of Taiwan with the hepatoprotective property. The aim of this study was to investigate the protective effects of the water extract of WGP on MG-induced liver damage in a rat model. The results showed that WGP lowered the total cholesterol level and the low-density lipoprotein cholesterol level. WGP could help normalize the MG level. The amelioration of inflammatory factors such as transformation growth factor-β1 was observed in the WGP treatment group. In another animal model, a high-fructose diet (HFD) was used to induce intestinal dysfunction in C57BL/6 mice. The results indicated that the HFD induction resulted in intestinal dysbiosis, including inflammation, microflora imbalances, and reductions in tight-junction proteins. However, both WGP and its active compound gallic acid could improve intestine function. According to the above, WGP can improve hyperlipidemia in the liver, inhibit inflammatory cytokine production, and regulate intestinal flora in mice, as well as enhance the intestinal barrier. These findings provide a basis for the development of health products.

Alien flora in Calabria (Southern Italy): an updated checklist

An updated checklist of the Calabrian alien vascular flora is presented. By way of field, bibliographic, and herbarium research, we recorded 382 alien taxa (representing almost 14% of all regional flora), of which 371 are angiosperms, nine gymnosperms, and two ferns. In relation to the state of spread, the majority of alien species are casual (207 taxa; 54%), followed by naturalized (127; 33%) and invasive (48; 13%), these last include four on the list of Union Concern, sensu Regulation (EU) no. 1143/2014. The most represented families are Asteraceae (39 taxa) and Poaceae (39). Among genera, Amaranthus (nine taxa), Prunus, Euphorbia, and Oxalis (seven taxa) make up those with the greatest number of taxa. A total of 21 taxa were reported for the first time, three of them are new to the European flora (Camptosema rubicundum, Musa ×paradisiaca and, only for continental Europe, Ipomoea hederacea), two to the Italian peninsula (Pelargonium graveolens, Schinus terebinthifolia) and 16 to the Calabrian flora (Aeonium arboreum, Asparagus asparagoides, Aspidistra elatior, Bidens sulphurea, Catalpa bignonioides, Citrus ×aurantium, Crassula ovata, Cucurbita ficifolia, Dimorphotheca ecklonis, Graptopetalum paraguayense subsp. paraguayense, Kalanchoë laxiflora, Nicotiana tabacum, Phytolacca dioica, Portulaca umbraticola, Talinum paniculatum, Tecomaria capensis). In terms of residence status, there are 291 neophytes (76%), 73 archaeophytes (19%), and 18 regional aliens (5%); neophytes are the most represented group (45 out of 48) among invasive taxa. Concerning life forms, the two most abundant groups are therophytes (30.1%, 115 taxa) and phanerophytes (29.6%, 113 taxa). Regarding habitats, 72% of alien taxa occur in artificial (199 taxa, 52%) and agricultural habitats (75 taxa, 20%). The majority of alien taxa are native to the Americas (159; 41.6%), numerous aliens also originated in Asia (76; 19.9%) and Africa (56; 14.7%). The majority of taxa were introduced for ornamental purposes (55%). Over the past decade, alien taxa in the flora in Calabria have increased from 190 to the current 382 taxa. While this trend could be linked to some extent to increasing awareness of the problem of alien species and the increasing intensity of research over recent decades, it is also most probably due to new introductions resulting from the globalization that relentlessly affects the whole planet.

Potential of hydroxybenzoic acids from Graptopetalum paraguayense for inhibiting of herpes simplex virus DNA polymerase – metabolome profiling, molecular docking and quantum-chemical analysis

According to our previous investigation the total methanol extract from Graptopetalum paraguayense E. Walther demonstrates a significant inhibitory effect on herpes simplex virus type 1 (HSV-1). To clarify what causes this inhibitory activity on HSV-1, a metabolic profile of the plant was performed. Three main fractions: non-polar substances, polar metabolites and phenolic compounds were obtained and gas chromatography–mass spectrometry (GC-MS) analysis was carried out. Since it is well known that phenolic compounds show a significant anti-herpes effect and that viral DNA polymerase (DNApol) appears to play a key role in HSV virus replication, we present a docking and quantum-chemical analysis of the binding of these compounds to viral DNApol amino acids. Fourteen different phenolic acids found by GC-MS analyses, were used in molecular docking simulations. According to the interaction energies of all fourteen ligands in the DNApol pockets based on docking results, density functional theory (DFT) calculations were performed on the five optimally interacting with the receptor acids. It was found that hydroxybenzoic acids from phenolic fraction of Graptopetalum paraguayense E. Walther show a good binding affinity to the amino acids from the active site of the HSV DNApol, but significantly lower than that of acyclovir. The mode of action on virus replication of acyclovir (by DNApol) is different from that of the plant phenolic acids one, probably.

Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems.

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer’s disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses β-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

Effects of Gibberellin and Abscisic Acid on Asexual Reproduction from Graptopetalum paraguayense Leaves

Graptopetalum paraguayense E. Walther is an edible succulent plant that is native to Mexico. When leaves of G. paraguayense are detached from the mother plant, shoots and roots regenerate from the leaf base. To investigate the endogenous hormonal regulation of plant regeneration in G. paraguayense, we evaluated the effects of applying gibberellin (GA), abscisic acid (ABA), and phytohormone biosynthesis inhibitors to leaves detached from the mother plant. GA3 and paclobutrazol did not affect plant regeneration of G. paraguayense, whereas ABA treatment significantly suppressed plant regeneration. When leaves were treated with the ABA biosynthesis inhibitor fluridone at 10 μM, the frequency of shoot regeneration was more than twice that of the control on the 6th day after leaf detachment. In addition, when both fluridone and ABA were applied at the same time, the frequency of plant regeneration decreased to control levels or below. Endogenous ABA in leaves was approximately 1.3 ng gFW−1 just after leaf detachment, decreased to 0.3 ng gFW−1 by the 1st day after leaf detachment, and increased to 3.0 ng gFW−1 by the 9th day after leaf detachment. These findings indicate that ABA plays an important role in suppression of plant regeneration in G. paraguayense. Although plant regeneration during storage and transportation currently reduces the economic value of G. paraguayense, our findings may provide a method to delay unwanted plant formation at the leaf base.

Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer\u2019s disease using patient iPSC-derived neurons

Alzheimer’s disease (AD) is the most common type of dementia and also one of the leading causes of death worldwide. However, the underlying mechanisms remain unclear, and currently there is no drug treatment that can prevent or cure AD. Here, we have applied the advantages of using induced pluripotent stem cell (iPSC)-derived neurons (iNs) from AD patients, which are able to offer human-specific drug responsiveness, in order to evaluate therapeutic candidates for AD. Using approach involving an inducible neurogenin-2 transgene, we have established a robust and reproducible protocol for differentiating human iPSCs into glutamatergic neurons. The AD-iN cultures that result have mature phenotypic and physiological properties, together with AD-like biochemical features that include extracellular β-amyloid (Aβ) accumulation and Tau protein phosphorylation. By screening using a gene set enrichment analysis (GSEA) approach, Graptopetalum paraguayense (GP) has been identified as a potential therapeutic agent for AD from among a range of Chinese herbal medicines. We found that administration of a GP extract caused a significantly reduction in the AD-associated phenotypes of the iNs, including decreased levels of extracellular Aβ40 and Aβ42, as well as reduced Tau protein phosphorylation at positions Ser214 and Ser396. Additionally, the effect of GP was more prominent in AD-iNs compared to non-diseased controls. These findings provide valuable information that suggests moving extracts of GP toward drug development, either for treating AD or as a health supplement to prevent AD. Furthermore, our human iN-based platform promises to be a useful strategy when it is used for AD drug discovery.

Antioxidant Activity of Graptopetalum paraguayense E. Walther Leaf Extract Counteracts Oxidative Stress Induced by Ethanol and Carbon Tetrachloride Co-Induced Hepatotoxicity in Rats.

(1) Background: Graptopetalum paraguayense E. Walther is a traditional Chinese herbal medicine. In our previous study, 50% ethanolic G. paraguayense extracts (GE50) demonstrated good antioxidant activity. (2) Methods: To investigate the hepatoprotective effects of GE50 on ethanol and carbon tetrachloride (CCl4) co-induced hepatic damage in rats, Sprague–Dawley rats were randomly divided into five groups (Control group; GE50 group, 0.25 g/100 g BW; EC group: Ethanol + CCl4, 1.25 mL 50% ethanol and 0.1 mL 20% CCl4/100 g BW; EC + GE50 group: Ethanol + CCl4 + GE50; EC + silymarin group: ethanol + CCl4 + silymarin, 20 mg/100 g BW) for six consecutive weeks. (3) Results: Compared with the control group, EC group significantly elevated the serum aspartate aminotransferase (AST), alanine aminitransferase (ALT), and lactate dehydrogenase (LDH). However, GE50 or silymarin treatment effectively reversed these changes. GE50 had a significant protective effect against ethanol + CCl4 induced lipid peroxidation and increased the levels of glutathione (GSH), vitamin C, E, total antioxidant status (TAS), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferases (GST). Furthermore, in EC focal group, slight fat droplet infiltration was observed in the livers, while in the GE50 or silymarin treatment groups, decreased fat droplet infiltration. HPLC phytochemical profile of GE50 revealed the presence of gallic acid, flavone, genistin, daidzin, and quercetin. (4) Conclusions: The hepatoprotective activity of GE50 is proposed to occur through the synergic effects of its chemical component, namely, gallic acid, flavone, genistin, daidzin, and quercetin. Hence, G. paraguayense can be used as a complementary and alternative therapy in the prevention of alcohol + CCl4-induced liver injury.

Graptopetalum paraguayense Inhibits Liver Fibrosis by Blocking TGF-β Signaling In Vivo and In Vitro.

Background and Aims: Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, which occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension. Activated hepatic perivascular stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines, such as TGF-β1. The inhibition of TGF-β1 function or synthesis is a major target for the development of antifibrotic therapies. Our previous study showed that the water and ethanol extracts of Graptopetalum paraguayense (GP), a Chinese herbal medicine, can prevent dimethylnitrosamine (DMN)-induced hepatic inflammation and fibrosis in rats. Methods: We used rat hepatic stellate HSC-T6 cells and a diethylnitrosamine (DEN)-induced rat liver injury model to test the potential mechanism of GP extracts and its fraction, HH-F3. Results: We demonstrated that GP extracts and HH-F3 downregulated the expression levels of extracellular matrix (ECM) proteins and inhibited the proliferation and migration via suppression of the TGF-β1 pathway in rat hepatic stellate HSC-T6 cells. Moreover, the HH-F3 fraction decreased hepatic collagen content and reduced plasma AST, ALT, and γ-GT activities in a DEN-induced rat liver injury model, suggesting that GP/HH-F3 has hepatoprotective effects against DEN-induced liver fibrosis. Conclusion: These findings indicate that GP/HH-F3 may be a potential therapeutic agent for the treatment of liver fibrosis. The inhibition of TGF-β-mediated fibrogenesis may be a central mechanism by which GP/HH-F3 protects the liver from injury.

Anti-Herpes Simplex virus and antibacterial activities of Graptopetalum paraguayense E. Walther leaf extract: a pilot study

Graptopetalum paraguayense E. Walther (GP) belongs to the Crassulaceae family and has several health benefits. In the present study we evaluated the cytotoxic, anti-Herpes Simplex virus (HSV) and antibacterial activities of a total methanol/water GP extract. The results from the cytotoxicity investigation of the tested extract showed a high cell tolerable concentration range. The GP extract demonstrated a significant inhibitory effect on the wild-type HSV-1 strain Victoria in a concentration of 0.0001 mg/mL equal to the maximal nontoxic concentration (with 97.5% protection of the cells). Regarding the acyclovir-resistant mutant HSV-2 strain PU and wild-type HSV-2 strain Bja, the antiviral activity and selectivity of the extract were very low, with EC50 values from 0.1 to 0.01 mg/mL, and the selectivity index ranging from 25 to 250, respectively. The GP extract exhibited selective inhibitory activity also on the growth of Gram-positive bacterial pathogens, with Staphylococcus aureus being most sensitive. It also prevented the formation of MRSA biofilm up to 50% at a concentration of 1.6 mg/mL and up to 90% at a concentration of 2.5 mg/mL. The anti-herpetic and antibacterial activities demonstrated in our investigation are probably related to the presence of phenols, and in particular gallic acid. The antimicrobial activity of the GP extract holds a promise for the future development of nutrition supplements based on G. paraguayense and therefore warrants further studies aimed at isolating biologically active compounds or mixtures thereof with subsequent in-depth investigation of their anti-HSV and antibacterial mechanisms of action.

Etiology of hepatocellular carcinoma and treatment through medicinal plants: a comprehensive review

Liver is a power house of the body for many components such as vitamins, minerals, iron and glycogen and play role in biotransformation. Some ingredients of our diet (foodstuffs may contain with aflatoxin B1, vinyl chloride, tobacco, heavy alcohol intake, fried meat, coffee and oral contraceptives),when metabolized become tremendous for liver and leads toward hepatocellular carcinoma (HCC). HCC occurs through cyclical liver injury due to inflammation and DNA damaging as a result of oxidative stress. Phytochemicals of medicinal plants have curative potential against liver cancer due to presence of linalool, eucalyptol, borneol, thujone, camphor, 4-terpineol, monoterpenes and α-cadinol, sophytotherapies have several advantages over conventional chemotherapies. According to literature survey Acanthus ilicifolius, Allium sativum, Artemisiaprinceps, Artemisia vulgaris, Amorphophallus campanulatus, Brucea javanica, Broussonetia luzonica, Dracocephalum kotschyi, Graptopetalum paraguayense, Nigella sativa, Petasites japonicas, Silybum marianum, Bergenia ciliata, Cassia fistula and Picrorhiza scrophularilora have vital bioactive compounds used against hepatocellular carcinoma.

Morphological Changes of Mexican Native Succulent Plants in a Vertical Greenery System Compared with Pot Conditions

Adaptation parameters as leaf width, leaf length, mesophyll thickness, number of adaxial and abaxial stomata, and biomass were measured in eight stonecrop species (Crassulaceaae), spider plant (Chlorophytum comosum), and maria’s heart (Peperomia tepoztecoana) in vertical greenery system (VGS) and containers (POT). Statistical significance among parameters was probed by t test and principal component analysis was performed to detect global morphological changes. Mexican gem (Echeveria elegans), graptosedum (× Graptosedum ‘Vera Higgins’), lavender scallops (Kalanchoe fedtschenkoi), coppertone sedum (Sedum nussbaumerianum), ghost plant (Graptopetalum paraguayense), and jelly-beans (Sedum rubrotinctum) were the species that did not change significantly their morphological traits during growth in the VGS. This provides evidence of the potential for these species to be used in green walls or any VGS while maintaining their characteristic shape and beauty. Graptopetalum (Graptopetalum macdougalli), gray sedum (Sedum griseum), maria’s heart, and spider plant showed changes in its morphology during growth in the VGS when compared with growth in POT, indicating a lower potential for adaption to VGS.

First Report of Kalanchoe mosaic virus and Kalanchoe latent virus Infecting Ghost Plant (Graptopetalum paraguayense) in Italy

First report of [i]Kalanchoe mosaic virus[/i] and [i]Kalanchoe latent virus[/i] infecting Ghost plant ([i]Graptopetalum paraguayense W.[/i]) in Italy

Antioxidant hydrocolloids from herb Graptopetalum paraguayense leaves show anti-colon cancer cells and anti-neuroinflammatory potentials

Leaves of herb Graptopetalum paraguayense E. Walther are considered to be applied for functional drinks or isolated for nutraceutical ingredients. This study was to preliminarily elucidate the antioxidant activities and potentials for anti-colon cancer cells and anti-neuroinflammation of the hot-water extracts and its macromolecular hydrocolloids from freeze-dried G. paraguayense leaves, in relation to detectable polysaccharide compositions and associated phenolic and non-phenolic compounds. It is indicated that the 100oC-water extract (GW100) form G. paraguayense leaves contained glucans at a molar ratio of glucose (Glc): fucose (Fuc): xylose (Xyl): ribose (Rib) = 1:0.29:0.13:0.13 and a major macromolecular species with an averaged molecular weight (Mw) = 2172. The macromolecular GW100E, i.e. 72%-ethanol precipitate of GW100, contained pectin substance like arabino-rhamnogalactans at a molar ratio of galactose (Gal): arabinose (Ara): rhamnose (Rha): Glc = 1:0.81:0.34:0.32, and only one macromolecular species with an averaged Mw = 2405. Both GW100 and GW100E exhibited excellent antioxidant activities in scavenging α, α-diphenyl-β-picrylhydrazyl radicals (DPPH⋅), 2,2-azino-bis [3-ethylbenzthiazoline-6-sulfonic acid] radicals (ABTS+), and superoxide anions (O2−), great potential in anti-proliferation against human colon adenocarcinoma Caco-2 cells, and significant immunomodulatory activities on murine microglia BV-2 cells. Comparatively, GW100 was outstanding in scavenging ABTS+ and O2− and inhibiting significantly tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) production by lipopolysaccharide (LPS)-treated BV-2 cells. GW100E excelled in scavenging DPPH⋅ and anti-Caco-2 proliferation. Conclusively, GW100 and GW100E could be good candidates for anti-neuro-inflammation potentials and anti-Caco-2 proliferation, respectively.

Anti-Glycation of Active Compounds Purified from G raptopetalum Paraguayense

Graptopetalum paraguayense was shown to exhibit antioxidant, hepatoprotective and anti-hepatocellular carcinoma activities in a recent study. In this work, fractions of the G. paraguayense aqueous solution were extracted using n-hexane, ethyl acetate (EF) and n-butanol, and its antioxidative and anti-glycative activities were evaluated. The EF extract exhibited the highest antioxidative activity, potently inhibited the formation of advanced glycation end products (AGEs) and reduced glycation-induced protein oxidation. Additionally, the EF extract protected Hep G2 cells against AGE-induced DNA damage. Five major components were isolated and identified in the EF fraction by semi-preparative high-performance liquid chromatography, liquid chromatography-tandem mass spectroscopy and nuclear magnetic resonance: gallic acid, isoquercitrin-6-(3-hydroxy-3-methylglutarate), astragalin-6-(3-hydroxy-3-methylglutarate), isoquercitrin-2-acetyl-6-(3-hydroxy-3-methylglutarate) and astragalin-2-acetyl-6-(3-hydroxy-3-methylglutarate). G. paraguayense exhibited antioxidant and anti-glycation activities, likely because of the presence of gallic acid. The findings indicate the potential for using G. paraguayense for development of novel treatments for diabetes. Practical Applications Herbal treatments for hyperlipidemia are relatively cheap and locally available. The results indicated that the extracts of Graptopetalum paraguayense may be developed as functional foods for antidiabetic treatment mediated by attenuations of advanced glycation end product oxidation.

Abstract 1132: Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway

Abstract Peroxisome proliferator-activated receptor-γ coactivator 1 (PGC-1α), a major metabolic regulator of gluconeogenesis and lipogenesis, is known to be strongly induced to coactivate HBV gene expression in the liver of fasting mice. In this study, we found that the combination of 8-Br-cAMP and glucocorticoids showed the synergistic induction of PGC-1α and its downstream gene expression, including the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Moreover, HBV corepromoter activity was synergistically enhanced by the combination of 8-Br-cAMP and glucocorticoid treatment. Graptopetalum paraguayense (GP), a herbal medicine, is commonly used in Taiwan to treat liver disorders. Here, we found that a partially purified fraction of GP (named HH-F3) dose dependently suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCKand PGC-1α expression as well as suppressed HBV core promoter activity. Additionally, HH-F3 blocked HBV core promoter activity via the inhibition of PGC-1α expression. The ectopic expression of PGC-1α effectively reversed the HH-F3-mediated inhibition of HBV core promoter activity.HH-F3-reduced HBV surface antigen expression, HBV mRNA production, core protein level, and HBV replication were drastically rescued by ectopically expressed PGC-1α. In addition, HH-F3 could also inhibit fatty acid synthase (FASN) expression as well as decrease lipid accumulation by the down-regulation of PGC-1α in human hepatocarcinoma cell lines. In conclusion, HH-F3 could inhibit HBV replication, gluconeogenesis, and lipogenesis through the down-regulation of PGC-1α. Our study indicates that targeting PGC-1α may be a novel therapeutic strategy for HBV infection. Together, HH-F3mighthave potential use for the treatment of chronic hepatitis B patients with associated metabolic syndrome. Citation Format: Wei-Hsiang Hsu, Hong-Jhih Jhuang, Chi-Ying Huang. Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1132. doi:10.1158/1538-7445.AM2015-1132

Anti‐inflammatory effect of water extracts of Graptopetalum paraguayense supplementation in subjects with metabolic syndrome: a preliminary study

Many studies have demonstrated that Graptopetalum paraguayense has good antioxidant ability; however, few studies have examined its anti-inflammatory effect. The study aimed to investigate the anti-inflammatory effects of water extracts of G. paraguayense (WGP, 4 g day(-1)) in subjects with metabolic syndrome (MS). Intervention was administered for 12 weeks. Levels of inflammatory markers [high sensitivity C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6)] and antioxidant enzymes activities were measured. Forty-two subjects completed the 12 week intervention study (placebo, n = 19; WGP, n = 23). After 12 weeks supplementation, subjects in WGP group had significantly lower levels of inflammatory markers than the baseline (P < 0.05) and the placebo group (CRP, P = 0.07; TNF-α, P = 0.04; IL-6, P = 0.03). The changes in levels of the inflammatory markers were significantly decreased in WGP group (CRP, P = 0.04; TNF-α, P = 0.06; IL-6, P = 0.01) compared to the placebo group. Levels of inflammatory markers were significantly negatively correlated with the antioxidant enzymes activities after supplementation. This study demonstrated a significant reduction in inflammatory status in MS after WGP supplementation. WGP may exert an anti-inflammatory effect on MS in addition to its antioxidant ability.

Chemical characterization and antioxidative activity of four 3-hydroxyl-3-methylglutaroyl (HMG)-substituted flavonoid glycosides from Graptopetalum paraguayense E. Walther.

BackgroundGraptopetalum paraguayense E. Walther is a popular traditional Chinese herb and possesses several health benefits. In earlier studies, we demonstrated that G. paraguayense showed no genotoxicity and showed several biological activities. However, the constituents of G. paraguayense have not been studied yet. In this present study, we isolated and identified the constituents of the leaves of G. paraguayense E. Walther.ResultsA total of seven flavonoid compounds were isolated from the methanolic extract of G. paraguayense. The four major compounds isolated were flavonoid glucoside derivatives of quercetin (1, 3) and kampferol (2, 4), each presenting a 3-hydroxyl-3-methylglutaroyl (HMG) substituent; compounds 3 and 4—the 2´´-acetyl derivatives of 1 and 2, respectively—are novel compounds isolated from nature for the first time. High-performance liquid chromatography for the quantitative analyses of the four major HMG-substituted flavonoid glycosides in G. paraguayense E. Walther were accomplished to acquire the high yields of 1–4 in the methanolic extract (4.8, 5.7, 4.3, and 2.5 mg/g, respectively). Furthermore, the antioxidant activities, including radical-scavenging, reducing power and lipid peroxidation inhibitory effects of these isolated flavonoids were also evaluated. All seven of the isolated flavonoid compounds possessed antioxdative activity.ConclusionsIn this study of the constituents of the leaves of G. paraguayense E. Walther, we isolated four major components from its methanolic extract and determined their structures to be (acetylated) HMG-substituted flavonol glycosides, which are rare in nature. All seven of the isolated compounds possessed antioxdative activity, and those flavonoid compounds may be responsible for the functional ingredients in G. paraguayense. Further investigation of their bioactivities or pharmacological activities will be continued.Electronic supplementary materialThe online version of this article (doi:10.1186/s40529-015-0088-4) contains supplementary material, which is available to authorized users.

Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway

PGC-1α, a major metabolic regulator of gluconeogenesis and lipogenesis, is strongly induced to coactivate Hepatitis B virus (HBV) gene expression in the liver of fasting mice. We found that 8-Br-cAMP and glucocorticoids synergistically induce PGC-1α and its downstream targets, including PEPCK and G6Pase. Also, HBV core promoter activity was synergistically enhanced by 8-Br-cAMP and glucocorticoids. Graptopetalum paraguayense (GP), a herbal medicine, is commonly used in Taiwan to treat liver disorders. Partially purified fraction of GP (named HH-F3) suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCK and PGC-1α expression and suppressed HBV core promoter activity. HH-F3 blocked HBV core promoter activity via inhibition of PGC-1α expression. Ectopically expressed PGC-1α rescued HH-F3-inhibited HBV surface antigen expression, HBV mRNA production, core protein levels, and HBV replication. HH-F3 also inhibited fatty acid synthase (FASN) expression and decreased lipid accumulation by down-regulating PGC-1α. Thus, HH-F3 can inhibit HBV replication, gluconeogenesis and lipogenesis by down-regulating PGC-1α. Our study indicates that targeting PGC-1α may be a therapeutic strategy for treatment of HBV infections. HH-F3 may have potential use for the treatment of chronic hepatitis B patients with associated metabolic syndrome.

Anti-conjunctivitis effect of fresh juice of xGraptoveria (Crassulaceae): A phytochemical and ethnobotanical study.

Aim:The parent of xGraptoveria, Graptopetalum paraguayense, is used in Chinese folk medicine for alleviating hepatic disorders, detumescence and detoxication, lowering of blood pressure, inhibition of cancer cells, exerting diuretic effects, relieving pain and infections. No data are available regarding its anti-conjunctivitis effect. The aim of this preliminary study is to test the anti-conjunctivitis properties of xGraptoveria (Crassulaceae) and to identify its bioactive constituents.Materials and Methods:Fresh watery juice of leaves of xGraptoveria was extracted with n-butanol and the extract was analyzed using gas chromatography-mass spectrometry (GC/MS). The ethnobotanical appraisal of the anti-conjunctivitis properties of xGraptoveria was based on 11 interviews about the symptoms against which this plant demonstrated positive effect.Results:Fresh juice of xGraptoveria leaves applied directly to the irritated eye 2 times per day cured conjunctivitis in all reported cases. The main groups of organic compounds identified by GC/MS analysis in the fresh extracted leaf juice of xGraptoveria were: Alkylamines, hydroxycarboxylic acids, aliphatic and aromatic carboxylic acids, amino acids, alcohols, aromatic and aliphatic hydrocarbons.Conclusion:In this preliminary study, it is suggested that xGraptoveria exerts anti-conjunctivitis activity, through synergistic effect of different chemical compounds, most probably alkylamines and mainly hydroxycarboxylic, aliphatic, and aromatic carboxylic acids.