Liver organoids: a promising three-dimensional model for insights and innovations in tumor progression and precision medicine of liver cancer.

Primary liver cancer (PLC) is one type of cancer with high incidence rate and high mortality rate in the worldwide. Systemic therapy is the major treatment for PLC, including surgical resection, immunotherapy and targeted therapy. However, mainly due to the heterogeneity of tumors, responses to the above drug therapy differ from person to person, indicating the urgent needs for personalized treatment for PLC. Organoids are 3D models derived from adult liver tissues or pluripotent stem cells. Based on the ability to recapitulate the genetic and functional features of in vivo tissues, organoids have assisted biomedical research to make tremendous progress in understanding disease origin, progression and treatment strategies since their invention and application. In liver cancer research, liver organoids contribute greatly to reflecting the heterogeneity of liver cancer and restoring tumor microenvironment (TME) by co-organizing tumor vasculature and stromal components in vitro. Therefore, they provide a promising platform for further investigation into the biology of liver cancer, drug screening and precision medicine for PLC. In this review, we discuss the recent advances of liver organoids in liver cancer, in terms of generation methods, application in precision medicine and TME modeling.

Anti-aging effects of polysaccharides from ginseng extract residues in Caenorhabditis elegans.

Aging is a process of progressive deterioration of multiple physiological functions within an organism. This study investigated the anti-aging effects of polysaccharides extracted from ginsenoside residues (GRP) in Caenorhabditis elegans using physiological, microbiomic, and transcriptomic approaches. GRP treatment prolonged the mean lifespan of C. elegans by 58.60 % (19.64 days) and did not affect locomotive behaviors. It reduced levels of lipofuscin and reactive oxygen species (ROS), and increased superoxide dismutase activity, which prevented oxidative damage caused by aging. Microbiomic data indicated that GRP administration significantly altered the composition of gut flora and increased the abundance of beneficial bacteria. Transcriptomic analyses identified 201 differentially expressed genes (DEGs). GRP treatment may enhance fatty acid degradation and induce preferential synthesis of beneficial fatty acids. It may also activate the metabolism of certain amino acids. The transcriptomic data were reliably reproduced using seven vital DEGs, which were confirmed by qRT-PCR analysis. These findings show that GRP has positive effects that prolong lifespan and alleviate aging in C. elegans. GRP should be explored as an effective dietary supplement for the development of functional foods. We propose a potentially novel mechanism that more fully describes the anti-aging mechanisms induced by GRP.

Identification of key gene networks controlling polysaccharide accumulation in different tissues of Polygonatum cyrtonema Hua by integrating metabolic phenotypes and gene expression profiles.

Plant polysaccharides, a type of important bioactive compound, are involved in multiple plant defense mechanisms, and in particular polysaccharide-alleviated abiotic stress has been well studied. Polygonatum cyrtonema Hua (P. cyrtonema Hua) is a medicinal and edible perennial plant that is used in traditional Chinese medicine and is rich in polysaccharides. Previous studies suggested that sucrose might act as a precursor for polysaccharide biosynthesis. However, the role of sucrose metabolism and transport in mediating polysaccharide biosynthesis remains largely unknown in P. cyrtonema Hua. In this study, we investigated the contents of polysaccharides, sucrose, glucose, and fructose in the rhizome, stem, leaf, and flower tissues of P. cyrtonema Hua, and systemically identified the genes associated with the sucrose metabolism and transport and polysaccharide biosynthesis pathways. Our results showed that polysaccharides were mainly accumulated in rhizomes, leaves, and flowers. Besides, there was a positive correlation between sucrose and polysaccharide content, and a negative correlation between glucose and polysaccharide content in rhizome, stem, leaf, and flower tissues. Then, the transcriptomic analyses of different tissues were performed, and differentially expressed genes related to sucrose metabolism and transport, polysaccharide biosynthesis, and transcription factors were identified. The analyses of the gene expression patterns provided novel regulatory networks for the molecular basis of high accumulation of polysaccharides, especially in the rhizome tissue. Furthermore, our findings explored that polysaccharide accumulation was highly correlated with the expression levels of SUS, INV, SWEET, and PLST, which are mediated by bHLH, bZIP, ERF, ARF, C2H2, and other genes in different tissues of P. cyrtonema Hua. Herein, this study contributes to a comprehensive understanding of the transcriptional regulation of polysaccharide accumulation and provides information regarding valuable genes involved in the tolerance to abiotic stresses in P. cyrtonema Hua.

 Polygonatumpraecox (Asparagaceae), a new species from mid-eastern China revealed by morphological and molecular evidence.

A new species, Polygonatumpraecox Y.F.Hu & J.W.Shao (Asparagaceae), is described and illustrated. This species is similar to P.cyrtonema, P.odoratum and P.caulialatum, but can be distinguished from P.cyrtonema by its racemose inflorescence, cylindrical hairless filaments and apex without a retrorse spur; from P.odoratum by its stout moniliform rhizome, straight stem and longer (1.7-2.2 cm long) floral tube; and from P.caulialatum by its upper part straight stem, yellowish-green corolla, lobes excurved and earlier flowering. The complete chloroplast genome of this new species is 155,115-155,256 bp in length. Phylogenetic analysis revealed that P.praecox is not genetically related to the above three morphological similar species, but is closely related to the two European species (P.multiforum and P.latifolium). This species is relatively common in mid-eastern China and has previously been confused with P.cyrtonema. As its wild resources have decreased in recent years due to over-exploitation for medicinal or edible purposes, we classify it as Near Threatened (NT) according to the IUCN Red List Criteria.

Integration of transcriptomics and metabolomics confirmed hepatoprotective effects of steamed shoot extracts of ginseng (Panax ginseng C.A. Meyer) on toxicity caused by overdosed acetaminophen.

The study aimed, by integrating transcriptomics and metabolomics, to reveal novel biomarkers caused by overdosed acetaminophen (APAP) and liver protection substances procured by pre-administration of ginseng shoots extract (GSE). Totally 4918 genes and 127 metabolites were identified as differentially expressed genes and differential metabolites, respectively. According to KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, such pathways as primary bile acid biosynthesis, bile secretion, retinol metabolism, histidine and several other amino-related metabolism were significantly altered by GSE and disturbed by subsequent overdosed APAP at the transcriptomic as well as metabolomic levels. Fifteen key biomarker metabolites related to these pathways were up-regulated in APAP-treated vs GSE-pretreated liver tissues, and were reported exerting anti-oxidant, anti-inflammatory, anti-apoptotic and/or immunomodulate functions, three of which even possessed direct hepatoprotection effects. Twenty five vital unigenes modulating these metabolites were further verified by correlation analysis and expression levels of fifteen of them were examined by qRT-PCR. Our findings indicate that GSE may be an effective dietary supplement for preventing the liver damage caused by the overdosed APAP.

Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer.

Lung cancer is one of the most lethal diseases and therefore poses a significant threat to human health. The Warburg effect, which is the observation that cancer cells predominately produce energy through glycolysis, even under aerobic conditions, is a hallmark of cancer. 6­phosphofructo­2­kinase/fructose­2,6­biphosphatase 2 (PFKFB) is an important regulator of glycolysis. Shikonin is a Traditional Chinese herbal medicine, which has been reported to exert antitumor effects. The present study aimed to investigate the anticancer activity of shikonin in lung cancer. Cell Counting Kit­8 (CCK­8) and colony formation assays were used to analyze proliferation in A549 and H446 cells. Wound healing and Transwell assays were used to measure migration and invasion in A549 and H446 cells. Cell apoptosis was analyzed using flow cytometry. Lactate levels, glucose uptake and cellular ATP levels were measured using their corresponding commercial kits. Western blotting was performed to analyze the protein expression levels of key enzymes involved in aerobic glucose metabolism. Reverse transcription­quantitative PCR was used to analyze the mRNA expression levels of PFKFB2. The results of the present study revealed that PFKFB2 expression levels were significantly upregulated in NSCLC tissues. Shikonin treatment decreased the proliferation, migration, invasion, glucose uptake, lactate levels, ATP levels and PFKFB2 expression levels and increased apoptosis in lung cancer cells in a dose­dependent manner. The overexpression of PFKFB2 increased the proliferation, migration, glucose uptake, lactate levels and ATP levels in lung cancer cells, while the knockdown of PFKFB2 expression exerted the opposite effects. Moreover, there were no significant differences in lung cancer cell migration, apoptosis, glucose uptake, lactate levels and ATP levels between cells with knocked down PFKFB2 expression or treated with shikonin and the knockdown of PFKFB2 in cells treated with shikonin. In conclusion, the results of the present study revealed that shikonin inhibited the Warburg effect and exerted antitumor activity in lung cancer cells, which was associated with the downregulation of PFKFB2 expression.

Pollen micromorphology of eastern Chinese Polygonatum and its role in taxonomy by using scanning electron microscopy.

Although considerable progress has recently been made in the taxonomic study of Asparagaceae, but the Polygonatum remains one of the most poorly investigated genus. Therefore, the present study was designed with the aim, to document the pollen micromorphology of closely related Polygonatum taxa and its taxonomic significance. Pollen micro-morphological features were observed using scanning electron microscopy-SEM). The pollen grains are monad, navicular, monocolpate, and radially symmetrical. A significant variation was observed in the exine sculpturing. Moreover, most of the Polygonatum taxa have perforate pollen while some of them were mixed with psilate to perforate, perforate to microreticulate, sometimes scabrate, gemmate with baculate. Hence, this study documented the pollen morphology of Polygonatum taxa and strengthens the taxonomic identification of the genus Polygonatum based on pollen characters, which helps and can be used as an additional tool for the correct identification and discrimination of the species of Polygonatum at generic and species level.

OsPPR939, a nad5 splicing factor, is essential for plant growth and pollen development in rice.

KEY MESSAGE: P-subfamily PPR protein OsPPR939, which can be phosphorylated by OsS6K1, regulates plant growth and pollen development by involving in the splicing of mitochondrial nad5 introns 1, 2, and 3. In land plants, pentatricopeptide repeat (PPR) proteins play key roles in mitochondrial group II intron splicing, but how these nucleus-encoded proteins are imported into mitochondria is unknown. To date, a few PPR proteins have been characterized in rice (Oryza sativa). Here, we demonstrate that the mitochondrion-localized P-subfamily PPR protein OsPPR939 is required for the splicing of nad5 introns 1, 2, and 3 in rice. Complete knockout or partial disruption of OsPPR939 function resulted in different degrees of growth retardation and pollen sterility. The dramatically reduced splicing efficiency of these introns in osppr939-4 and osppr939-5 led to reduced mitochondrial complex I abundance and activity and enhanced expression of alternative respiratory pathway genes. Complementation with OsPPR939 rescued the defective plant morphology of osppr939-4 and restored its decreased splicing efficiency of nad5 introns 1, 2, and 3. Therefore, OsPPR939 plays crucial roles in plant growth and pollen development by splicing mitochondrial nad5 introns 1, 2, and 3. More importantly, the 12th amino acid Ser in the N-terminal targeting sequence of OsPPR939 is phosphorylated by OsS6K1, and truncated OsPPR939 with a non-phosphorylatable S12A mutation in its presequence could not be imported into mitochondria, suggesting that phosphorylation of this amino acid plays an important role in the mitochondrial import of OsPPR939. To our knowledge, the 12th residue Ser on OsPPR939 is the first experimentally proven phosphorylation site in PPR proteins. Our results provide a basis for investigating the regulatory mechanism of PPR proteins at the post-translational level.

Antioxidant evaluation-guided chemical profiling and structure-activity analysis of leaf extracts from five trees in Broussonetia and Morus (Moraceae).

Morus and Broussonetia trees are widely used as food and/or feed. Among 23 phenolics identified from leaves of five Moraceae species using UPLC-QTOF-MS/MS, 15 were screened using DPPH/ABTS-guided HPLCs, including seven weak (flavonoids with one hydroxyl on B-ring) and eight strong (four caffeoylquinic acids and four flavonoids, each with a double hydroxyl on B-ring) antioxidants. We then determined the activity and synergistic effects of individual antioxidants and a mixture of the eight strongest antioxidants using DPPH-guided HPLC. Our findings revealed that (1) flavonoid glucuronide may have a more negative effect on antioxidant activity than glucoside, and (2) other compounds in the mixture may exert a negative synergistic effect on antioxidant activity of the four flavonoids with B-ring double hydroxyls but not the four caffeoylquinic acids. In conclusion, the eight phenolics with the strongest antioxidant ability reliably represented the bioactivity of the five extracts examined in this study. Moreover, the Morus alba hybrid had more phenolic biosynthesis machinery than its cross-parent M. alba, whereas the Broussonetia papyrifera hybrid had significantly less phenolic machinery than B. papyrifera. This difference is probably the main reason for livestock preference for the hybrid of B. papyrifera over B. papyrifera in feed.

Screen for Potential Candidate Alternatives of Sargentodoxa cuneata from Its Six Adulterants Based on Their Phenolic Compositions and Antioxidant Activities.

Daxueteng, the liana stem of Sargentodoxa cuneata, is a widely used Traditional Chinese Medicine facing the overflow of its commercial adulterants. A method for discriminating adulterants and screening potential candidate alternatives of S. cuneata was thus established. Total phenols and flavonoids of S. cuneata and its six adulterants and their abilities to scavenge DPPH• and ABTS•+, to absorb peroxyl radicals (ORAC), and to inhibit AAPH-induced supercoiled plasmid DNA strand scission were comprehensively assessed. Polygonum cuspidatum and Bauhinia championii, two of the six adulterants of S. cuneate, shared considerably higher antioxidant activities as well as phenolic contents and, therefore, were considered as potential candidate alternatives. Phenolic compositions of the two potential candidate alternatives and S. cuneata itself were further determined by UPLC-QTOF-MS/MS. Totally 38 phenolics, including four hydroxybenzoic acids, two tyrosols, two caffeoylquinic acids, seven flavanol or its oligomers, two lignans, three hydroxycinnamic acids, six stilbenes, seven anthraquinones, and five flavanones were determined from three species. Furthermore, contents of different phenolic categories were semi-quantified and the major antioxidant contributors of S. cuneata and the two potential candidate alternatives were subsequently determined. It is concluded that tyrosols and caffeoylquinic acids were unique categories making great antioxidant contributions in S. cuneata and thus were considered as effective biomarkers in distinguishing its potential candidate alternatives.

Phenolic Compounds and Ginsenosides in Ginseng Shoots and Their Antioxidant and Anti-Inflammatory Capacities in LPS-Induced RAW264.7 Mouse Macrophages.

We conducted this study for the first time to evaluate changes in the composition and contents of phenolic compounds and ginsenosides in ginseng shoot extracts (GSEs) prepared with different steaming times (2, 4, and 6 h) at 120 °C, as well as their antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages (RAW264.7 cells). The results show that total phenol and flavonoid contents were both significantly higher in steamed versus raw GSEs, and the same trend was found for 2,2'-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) scavenging capacities. Among the 18 ginsenosides quantified using high-performance liquid chromatography (HPLC) with the aid of pure standards, polar ginsenosides were abundant in raw GSEs, whereas less-polar or rare ginsenosides appeared after steaming at 120 °C and increased with steaming time. Furthermore, steamed GSEs exhibited a greater ability to inhibit the production of inflammatory mediators and pro-inflammatory cytokines, such as nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in LPS-induced RAW264.7 cells at the same concentration. Relative expression levels of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, and cyclooxygenase-2 (COX-2) mRNAs were attenuated by the GSEs, probably due to the enrichment of less-polar ginsenosides and enhanced antioxidant activity in steamed GSEs. These findings, combined with correlation analysis, showed that less-polar ginsenosides were major contributors to the inhibition of the overproduction of various inflammatory factors, while the inhibitory effects of total phenols and total flavonoids, and their antioxidant abilities, are also important.

Changes in treatment status of patients with severe mental illness in rural China, 1994-2015.

BACKGROUND: Although it is crucial to improve the treatment status of people with severe mental illness (SMI), it is still unknown whether and how socioeconomic development influences their treatment status.AimsTo explore the change in treatment status in people with SMI from 1994 to 2015 in rural China and to examine the factors influencing treatment status in those with SMI. METHOD: Two mental health surveys using identical methods and ICD-10 were conducted in 1994 and 2015 (population ≥15 years old, n = 152 776) in the same six townships of Xinjin County, Chengdu, China. RESULTS: Compared with 1994, individuals with SMI in 2015 had significantly higher rates of poor family economic status, fewer family caregivers, longer duration of illness, later age at first onset and poor mental status. Participants in 2015 had significantly higher rates of never being treated, taking antipsychotic drugs and ever being admitted to hospital, and lower rates of using traditional Chinese medicine or being treated by traditional/spiritual healers. The factors strongly associated with never being treated included worse mental status (symptoms/social functioning), older age, having no family caregivers and poor family economic status. CONCLUSIONS: Socioeconomic development influences the treatment status of people with SMI in contemporary rural China. Relative poverty, having no family caregivers and older age are important factors associated with a worse treatment status. Culture-specific, community-based interventions and targeted poverty-alleviation programmes should be developed to improve the early identification, treatment and recovery of individuals with SMI in rural China.Declaration of interestNone.

Comparison of Free, Esterified, and Insoluble-Bound Phenolics and Their Bioactivities in Three Organs of Lonicera japonica and L. macranthoides.

Dried flower buds of Lonicera japonica and L. macranthoides have long been used as herbs in numerous Chinese traditional medicines. Comparisons of three phenolic fractions (i.e., free, esterified, and insoluble-bound phenolics) in three different organs (i.e., flower, leaf, and stem) of the two species revealed that the free phenolics were the highest in terms of total phenol and total flavonoid content, composed of the most numerous phenolics and flavonoids; thus, they exhibited the most excellent antioxidant activities (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) (ABTS), and oxygen radical absorbance capacity (ORAC)), as well as protective effects on DNA damage induced by free radicals. In identical free and esterified phenolics of a same organ, higher contents and bioactivities were observed in L. macranthoides than in L. japonica. Phenolics identified by ultra-performance liquid chromatography with a diode array detector, alongside tandem mass spectrometry coupled with a quadrupole time-of-flight mass spectrometer (UPLC-DAD⁻QTOF-MS/MS) mainly included chlorogenic acid and its five derivatives, three flavonoids that were only found in the free phenolic fraction and closely correlated with its bioactivity, and caffeic acid that was the major contributor to antioxidant activity of the esterified and insoluble-bound phenolic fractions. It was, thus, concluded that, like L. japonica, L. macranthoides, which was underestimated since being separately listed by the 2010 edition of the Chinese Pharmacopoeia, is also a good (and better) herbal medicine.

Comparative transcriptome analyses on terpenoids metabolism in field- and mountain-cultivated ginseng roots.

BACKGROUND: There exist differences in morphological traits and phytochemical compositions between field- and mountain-cultivated Panax ginseng (FCG and MCG), which might be attributed to variations of terpenoids metabolism adapting to different growth conditions. The present work aims to uncover these variations. RESULTS: Among 26,648 differentially expressed genes, 496 genes distributed in seven dominant terpenoids pathways were identified. Diterpenoids and triterpenoids biosynthesis genes were significantly higher-expressed in FCG root. Conversely, biosynthesis of carotenoids was significantly more active in MCG root. Additionally, terpenoids backbones, monoterpenoids, sesquiterpenoids, and terpenoid-quinones biosyntheses were neither obviously inclined. Our determination also revealed that there were more gibberellins and steroids accumulated in FCG root which might be responsible for its quick vegetative growth, and enriched abscisic acid and germacrenes as well as protopanaxatriol-type ginsenosides might be major causes of enhanced stress-resistance in MCG root. CONCLUSIONS: The study firstly provided an overview of terpenoids metabolism in roots of FCG and MCG in elucidating the underlying mechanisms for their different morphological appearances and phytochemical compositions.

Gene expression profile-based drug screen identifies SAHA as a novel treatment for NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Being part of the metabolic syndrome, NAFLD is characterized by the deposition of triglycerides (TGs) as lipid droplets in the cytoplasm of hepatic cells. Recently, the rapid development of high-throughput genome analysis technologies provided opportunities to screen for new drugs for NAFLD. In this study, we screened for potential drugs based on the gene expression profiles of 73 compounds and identified histone deacetylase (HDAC) inhibitors as a novel treatment for the accumulation of lipids in hepatocytes. In the subsequent analysis and experiments, we discovered that SAHA inhibited the fatty acid and lipid metabolism pathways in hepatic cells and induced a significant deficiency of lipid accumulation in HepG2 and SMMC-7721 cells. Furthermore, SAHA inhibited lipid synthesis in hepatic cells by directly suppressing the expression of DGAT2. Hence, our study provides a novel method to screen for effective drugs for liver diseases and identifies SAHA as a potent treatment for NAFLD.

Identification of bioactive phenolics from Porana sinensis Hemsl. stem by UPLC-QTOF-MS/MS and the confirmation of anti-inflammatory indicators using LPS-induced RAW264.7 cells.

To characterise bioactive phenolics and confirm anti-inflammatory indicators in Porana sinensis stem, 23 phenolics were identified by UPLC-QTOF-MS/MS from crude extract (CE) prepared optimally with 80% methanol. Further fractionalisation using D101 macroporous resin resulted in predominant enrichment of total phenols and flavonoids into Fr.II. Correspondingly, the bioactive components-enriched Fr.II exhibited the lowest IC50 for scavenging DPPH and ABTS and the highest oxygen radical absorbance capacity or ORAC followed by Fractions Fr.I + Fr.II, CE and Fr.I, implying that certain phenolics possessing lower antioxidant activity completely remained in CE. Anti-inflammatory tests with LPS-stimulated RAW264.7 cells showed that CE possessed the highest inhibition of NO-production followed by Fr.II and Fr.I, meaning that CE might contain compounds that expressed higher anti-inflammatory but lower antioxidant activities or possessed synergistic interactions but were not fractionated together. Quantitative determination of nine major phenolics revealed that caffeic acid and 3-, 4- and 5-caffeoylquinic acids were concentrated into Fr.I, whereas scopolin, scopoletin and 3,5-, 3,4- and 4,5-dicaffeoylquinic acids were enriched into Fr.II. Further experiments with three selected major phenolics reduced the proposed synergistic interactions. Anti-inflammatory tests of the nine major phenolics evidenced that caffeic acid and the six caffeoylquinic acids produced higher, and the three dicaffeoylquinic acids at 140 µΜ showed even more significant activities in suppressing NO-production and mRNA expression of iNOS, TNF-α, COX-2, and IL-6, suggesting that these three dicaffeoylquinic acids could be indicators of the anti-inflammatory potential of P. sinensis stem. These findings provided novel insights for potential use of P. sinensis or liana, as an important source of natural antioxidants, against inflammation.

Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane.

Antiviral drug development against respiratory syncytial virus (RSV) is urgently needed due to the public health significance of the viral infection. Here, we report the anti-RSV activity of a small molecule, (1S,3R,4R,5R)-3,4- bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-1,5-dihydroxycyclohexane-1-carboxylic methyl ester (3,4-DCQAME) or 3,4- O-Dicaffeoylquinic acid methyl ester, which can be isolated from several plants of traditional Chinese medicine. We showed for the first time that compound 3,4-DCQAME potently inhibits RSV entry and infection. In vitro, 3,4-DCQAME can interact with F(ecto), the ectodomain of RSV fusion (F) protein. In cultured cells, the compound can block the interaction of F(ecto) protein with the cellular membrane and inhibit viral fusion during RSV entry, leading to inhibition of viral gene expression and infection. In RSV-infected mice that were treated with 3,4-DCQAME, we observed a reduction of RSV-induced pathologic changes and substantial inhibition of viral infection and growth in the lung tissues. Our results provide the first direct evidence of the anti-RSV activity of 3,4-DCQAME. Furthermore, these results suggest that 3,4-DCQAME represents a promising lead compound for anti-RSV therapeutic development.-Tang, W., Li, M., Liu, Y., Liang, N., Yang, Z., Zhao, Y., Wu, S., Lu, S., Li, Y., Liu, F. Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane.

Effects of thermal treatments on 10 major phenolics and their antioxidant contributions in Acer truncatum leaves and flowers.

This study aimed to investigate effects of thermal treatments on major phenolics and their antioxidant contributions in Acer truncatum leaves and flowers (ATL and ATF, respectively). With ultra performance liquid chromatography-diode array detector-quadrupole time-of-flight-mass spectrometer/mass spectrometer, phenolic compositions of ATF were first characterized and compared with those of ATL. An optimized high performance liquid chromatography fingerprint was then established, and 10 major phenolics existing in both ATL and ATF were quantified. Gallic acid derivatives and flavonol-3-O-glycosides were found to be their dominant phenolic constituents, with the former being key constituents which was affected by thermal treatments and further influencing the variations of total phenols. Moreover, the mechanism underlining the changes of phenolics in ATL and ATF by the treatments was characterized as a thermolhydrolysis process. During thermal treatments, polymerized gallotannins were hydrolysed to 1,2,3,4,6-pentakis-O-galloyl-ß-d-glucose, ethyl gallate and gallic acid, resulting in more than fivefold and twofold increase of their contents in ATL and ATF, respectively. By contrast, contents and antioxidant contributions of flavonol-3-O-glycosides gradually decreased during the process.\absbreak Overall, this is, to our knowledge, the first report on the effects of thermal treatments on phenolics and their antioxidant contributions in ATL and ATF, and the three gallic acid derivatives with potentially higher bioactivity could be efficiently achieved by thermal treatments.

Simultaneous Preparation of Salidroside and p-Tyrosol from Rhodiola crenulata by DIAION HP-20 Macroporous Resin Chromatography Combined with Silica Gel Chromatography.

The Rhodiola species have a long history of utilization in traditional medicine and have been considered as a source of adaptation to environmental challenges; salidroside and p-tyrosol are the major responsible compounds. Here we propose a novel UPLC-guided two-step method consisting of a DIAION HP-20 adsorption and silica gel column chromatographies, which can simultaneously prepare high purities of salidroside and p-tyrosol with noticeable yields from the rhizome of Rhodiola crenulata. Results demonstrated that DIAION HP-20 could successfully remove all impurities except crenulatin during a gradient elution with 5⁻20% ethanol, which could achieve an optimal purification of salidroside and p-tyrosol with increasing rates of 29.19% and 33.44%, respectively. Furthermore, chloroform was selected as an ideal solvent for separating p-tyrosol with salidroside, and thus crenulatin was subsequently applied in the silica gel chromatography, and the separation of salidroside with crenulatin could be achieved using silica gel chromatography with a mixture of chloroform and methanol at a volume ratio of 4:1. High purity rates of 94.17% and 97.29% and overall yields of 39.09% and 43.73% for salidroside and p-tyrosol were simultaneously achieved. Our method provides a new way to simultaneously obtain salidroside and p-tyrosol from R. Crenulata, as well as other related plant species.

Hypoglycemic Effects in Alloxan-Induced Diabetic Rats of the Phenolic Extract from Mongolian Oak Cups Enriched in Ellagic Acid, Kaempferol and Their Derivatives.

Our previous reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent in vitro antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of cholesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of cholesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes.