Biological activities of Viscum tuberculatum aqueous leaf extract.

CONTENT: Plant-based natural products have served as sources of remedies against pathogenic microorganisms. Although the biological activities of Viscum (Santalaceae) species are widely recognized, there is no scientific evidence for Viscum tuberculatum A. Rich. in Ethiopia. OBJECTIVE: To investigate the antimicrobial, acute toxicity, anti-inflammatory properties and phytochemical constituents of an aqueous extract of V. tuberculatum from Ethiopia. MATERIALS AND METHODS: The antibacterial activity of the aqueous leaf extract of V. tuberculatum was tested against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of this extract were determined using the broth macrodilution method. The acute toxicity and anti-inflammatory effects of the extract were investigated using standard procedures on female and male white albino mice, aged 8 and 10 weeks, respectively. The phytochemical constituents of V. tuberculatum were determined using LC-MS QTOF. RESULTS: The MIC and MBC values against S. aureus were found to be 6.25 and 100 mg/mL. The LD50 value was more than 2000 mg/kg body weight of the mouse. The 400 mg/kg dose exerts 87% inhibition after 5 h of carrageenan injection. Twenty-five different metabolites, mainly flavonoids, phenolic acids and alkaloids, were identified. CONCLUSIONS: These findings demonstrate the potential antimicrobial and anti-inflammatory potential of the aqueous extract of V. tuberculatum.

Chemical-activity-based quality marker screening strategy for Viscum articulatum.

Viscum articulatum Burm. f. is a parasitic plant rich in flavonoids, triterpenoids, and catechins and has a high nutritional value. It has been reported that consuming V. articulatum can prevent cardiac diseases. In this study, six bioactive compounds, including catechins, triterpenoids, and phenylpropanoid glycosides, were determined in alcohol extracts of the plant using HPLC. The anti-inflammatory and antioxidant activities of three catechins, two triterpenoids, and three combination drugs were measured in cardiomyocytes, and the results showed that the anti-inflammatory activity was significantly enhanced while retaining strong antioxidant activity when epicatechin and ursolic acid were used in combination. The main quality markers epicatechin and ursolic acid were screened based on the specificity of the genuine herb and a potent synergistic effect, and the lowest limitation contents of V. articulatum which could discriminate it from some other taxonomically similar materials were accordingly determined. This self-built lowest limitation content of the two screened quality markers could quickly and accurately reflect the efficacy in terms of chemical composition and reverse the disorderly market use of nongenuine herbs or confusing species for adulteration. This study is of some significance for market regulation, drug development, and clinical medication.

[Lectins in Viscum:a progress review].

Viscum plants,the evergreen perennial parasitic shrubs or subshrubs,are mainly distributed in tropical and subtropical regions. There are about 70 Viscum species around the world,including 11 species and one variety in China. Mistletoe lectins are typeⅡ ribosome-inactivating proteins( RIPs) extracted from Viscum plants with anticancer and immunoregulatory activities. Many studies have focused on the mistletoe lectins isolated from V. album in Europe and V. album var. coloratum distributed in South Korea,respectively,and several preparations,such as Iscucin Ⓡ,were developed and clinically applied for cancer treatment. Although Viscum plants are widely distributed in China,only a few studies of mistletoe lectins have been reported. The recent progress of mistletoe lectins was reviewed from extraction,purification,quantitative/qualitative detection,molecular structure,pharmacological activities,toxicities,and clinical application,aiming at providing a reference for in-depth research and utilization of mistletoe lectins produced in China.

Viscum pleurodesis is as effective as talc pleurodesis and tends to have less adverse effect.

PURPOSE: Many patients diagnosed with advanced cancer have malignant pleural effusion that does not respond to chemotherapy or radiation therapy. These patients often have respiratory symptoms, especially dyspnea. In order to relieve these symptoms, various procedures including chemical pleurodesis have been performed. Although talc is the most widely used and effective sclerosing agent, there it has various adverse effects. The objective of this study was to determine whether Viscum (ABNOVA Viscum® Fraxini Injection, manufactured by ABNOVA GmbH, Germany) could be used as an agent to replace talc in clinical practice. METHODS: Data of 56 patients with malignant pleural effusion who received chemical pleurodesis after tube thoracostomy from January 2003 to December 2017 were retrospectively reviewed to analyze clinical course and response after pleurodesis with each agent. RESULTS: After pleurodesis, changes in numeric rating scale (NRS) was 1.4 ± 1.6 in the talc group and 0.5 ± 1.5 in the Viscum group (p = 0.108). Changes in white blood cell counts after pleurodesis were 4154.8 ± 6710.7 in the talc group and 3487.3 ± 6067.7 in the Viscum group (p = 0.702). Changes in C-reactive protein (CRP) were 9.03 ± 6.86 in the talc group and 6.3 ± 7.5 in the Viscum group (p = 0.366). The success rate of pleurodesis was 93.3% in the talc group and 96% in the Viscum group (p = 0.225). CONCLUSION: Viscum pleurodesis showed comparable treatment results with talc pleurodesis while its adverse effects such as chest pain and fever tended to be relatively weak.

1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one induces lung cancer cell apoptosis via the PI3K/Akt and ERK1/2 pathways.

1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one (EB30) is a diarylheptanoid-like compound isolated from Viscum coloratum. This curcumin analog exhibits significant cytotoxic activity against HeLa, SGC-7901, and MCF-7 cells. However, little is known about the anticancer effects and mechanisms of EB30 in human lung cancer. The current study reports that EB30 significantly reduced the cell viability of A549 and NCI-H292 human lung cancer cells. Further examination revealed that EB30 not only induced cell cycle arrest and promoted the generation of reactive oxygen species (ROS) but also induced cell apoptosis through the intrinsic and extrinsic signaling pathways. Furthermore, EB30 upregulated the expression levels of p-ERK1/2 and p-P90RSK, whereas downregulating the phosphorylation of Akt and P70RSK. Cell viability was further inhibited by the combination of EB30 with LY294002 (a specific PI3K inhibitor) or U0126 (a MEK inhibitor). The current study indicates that EB30 is a potential anticancer agent that induces cell apoptosis via suppression of the PI3K/Akt pathway and activation of the ERK1/2 pathway.

Morphology, geographic distribution, and host preferences are poor predictors of phylogenetic relatedness in the mistletoe genus Viscum L.

Besides their alleged therapeutic effects, mistletoes of the genus Viscum L. (Viscaceae) are keystone species in many ecosystems across Europe, Africa, Asia and Australia because of their complex faunal interactions. We here reconstructed the evolutionary history of Viscum based on plastid and nuclear DNA sequence data. We obtained a highly resolved phylogenetic tree with ten well-supported clades, which we used to understand the spatio-temporal evolution of these aerial parasites and evaluate the contribution of reproductive switches and shifts in host ranges to their distribution and diversification. The genus Viscum originated in the early Eocene in Africa and appeared to have diversified mainly through geographic isolation, in several cases apparently coinciding with shifts in host preferences. During its evolution, switches in the reproductive mode from ancestral dioecy to monoecy imply an important role in the long-distance dispersal of the parasites from Africa to continental Asia and Australia. We also observed multiple cases of photosynthetic surface reduction (evolution of scale leaves) within the genus, probably indicative of increasing specialization associated with the parasitic lifestyle. Even compared with other parasitic angiosperms, where more host generalists than specialists exist, Viscum species are characterized by extraordinarily broad host ranges. Specialization on only a few hosts from a single family or order occurs rarely and is restricted mostly to very recently evolved lineages. The latter mostly derive from or are closely related to generalist parasites, implying that niche shifting to a new host represents an at least temporary evolutionary advantage in Viscum.

Miniaturized mitogenome of the parasitic plant Viscum scurruloideum is extremely divergent and dynamic and has lost all nad genes.

Despite the enormous diversity among parasitic angiosperms in form and structure, life-history strategies, and plastid genomes, little is known about the diversity of their mitogenomes. We report the sequence of the wonderfully bizarre mitogenome of the hemiparasitic aerial mistletoe Viscum scurruloideum. This genome is only 66 kb in size, making it the smallest known angiosperm mitogenome by a factor of more than three and the smallest land plant mitogenome. Accompanying this size reduction is exceptional reduction of gene content. Much of this reduction arises from the unexpected loss of respiratory complex I (NADH dehydrogenase), universally present in all 300+ other angiosperms examined, where it is encoded by nine mitochondrial and many nuclear nad genes. Loss of complex I in a multicellular organism is unprecedented. We explore the potential relationship between this loss in Viscum and its parasitic lifestyle. Despite its small size, the Viscum mitogenome is unusually rich in recombinationally active repeats, possessing unparalleled levels of predicted sublimons resulting from recombination across short repeats. Many mitochondrial gene products exhibit extraordinary levels of divergence in Viscum, indicative of highly relaxed if not positive selection. In addition, all Viscum mitochondrial protein genes have experienced a dramatic acceleration in synonymous substitution rates, consistent with the hypothesis of genomic streamlining in response to a high mutation rate but completely opposite to the pattern seen for the high-rate but enormous mitogenomes of Silene. In sum, the Viscum mitogenome possesses a unique constellation of extremely unusual features, a subset of which may be related to its parasitic lifestyle.

Comparative mitogenomics indicates respiratory competence in parasitic Viscum despite loss of complex I and extreme sequence divergence, and reveals horizontal gene transfer and remarkable variation in genome size.

BACKGROUND: Aerobically respiring eukaryotes usually contain four respiratory-chain complexes (complexes I-IV) and an ATP synthase (complex V). In several lineages of aerobic microbial eukaryotes, complex I has been lost, with an alternative, nuclear-encoded NADH dehydrogenase shown in certain cases to bypass complex I and oxidize NADH without proton translocation. The first loss of complex I in any multicellular eukaryote was recently reported in two studies; one sequenced the complete mitogenome of the hemiparasitic aerial mistletoe, Viscum scurruloideum, and the other sequenced the V. album mitogenome. The V. scurruloideum study reported no significant additional loss of mitochondrial genes or genetic function, but the V. album study postulated that mitochondrial genes encoding all ribosomal RNAs and proteins of all respiratory complexes are either absent or pseudogenes, thus raising questions as to whether the mitogenome and oxidative respiration are functional in this plant. RESULTS: To determine whether these opposing conclusions about the two Viscum mitogenomes reflect a greater degree of reductive/degenerative evolution in V. album or instead result from interpretative and analytical differences, we reannotated and reanalyzed the V. album mitogenome and compared it with the V. scurruloideum mitogenome. We find that the two genomes share a complete complement of mitochondrial rRNA genes and a typical complement of genes encoding respiratory complexes II-V. Most Viscum mitochondrial protein genes exhibit very high levels of divergence yet are evolving under purifying, albeit relaxed selection. We discover two cases of horizontal gene transfer in V. album and show that the two Viscum mitogenomes differ by 8.6-fold in size (66 kb in V. scurruloideum; 565 kb in V. album). CONCLUSIONS: Viscum mitogenomes are extraordinary compared to other plant mitogenomes in terms of their wide size range, high rates of synonymous substitutions, degree of relaxed selection, and unprecedented loss of respiratory complex I. However, contrary to the initial conclusions regarding V. album, both Viscum mitogenomes possess conventional sets of rRNA and, excepting complex I, respiratory genes. Both plants should therefore be able to carry out aerobic respiration. Moreover, with respect to size, the V. scurruloideum mitogenome has experienced a greater level of reductive evolution.

Articulatin-D induces apoptosis via activation of caspase-8 in acute T-cell leukemia cell line.

Leukemia is among the most aggressive and prevalent human malignant carcinoma. Chemotherapy is the preferred therapeutic strategy; however, recurrence of cancer and non-selective cytotoxicity are the major concerns. Unlike synthetic chemotherapeutic agents, mistletoe ribosome-inactivating protein (RIP) displays anti-tumor function in various types of cancers. However, its effect on leukemia cells is little explored. In this study, we assessed the impact of Viscum articulatum RIP (Articulatin-D) on the survival of acute T-cell leukemia cells and the involved molecular and cellular mechanisms. Cell proliferation assay showed that Articulatin-D suppressed the viability of leukemia cells selectively. We further confirmed that the elevation of mitochondrial membrane potential and exposure of phosphatidylserine are the early events of apoptosis induction in Articulatin-D-treated Jurkat cells. Subsequently, we found that Articulatin-D treatment induces apoptosis in Jurkat cells in a time- and concentration-dependent manner. In conclusion, we provided evidence that Articulatin-D efficiently activates caspase-8 involved in extrinsic pathway of apoptosis induction, which ultimately results in caspase-3-dependent DNA fragmentation of Jurkat cells. Further evaluation of Articulatin-D in cell culture and animal models may provide novel information on selective cytotoxicity to acute T-cell leukemia and its involvement in targeting tumor cell survival pathways.

Inhibitory Effects of Viscum coloratum Extract on IgE/Antigen-Activated Mast Cells and Mast Cell-Derived Inflammatory Mediator-Activated Chondrocytes.

The accumulation and infiltration of mast cells are found in osteoarthritic lesions in humans and rodents. Nonetheless, the roles of mast cells in osteoarthritis are almost unknown. Although Viscum coloratum has various beneficial actions, its effect on allergic and osteoarthritic responses is unknown. In this study, we established an in vitro model of mast cell-mediated osteoarthritis and investigated the effect of the ethanol extract of Viscum coloratum (VEE) on IgE/antigen (IgE/Ag)-activated mast cells and mast cell-derived inflammatory mediator (MDIM)-stimulated chondrocytes. The anti-allergic effect of VEE was evaluated by degranulation, inflammatory mediators, and the FcεRI signaling cascade in IgE/Ag-activated RBL-2H3 cells. The anti-osteoarthritic action of VEE was evaluated by cell migration, and the expression, secretion, and activity of MMPs in MDIM-stimulated SW1353 cells. VEE significantly inhibited degranulation (IC50: 93.04 µg/mL), the production of IL-4 (IC50: 73.28 µg/mL), TNF-α (IC50: 50.59 µg/mL), PGD2 and LTC4, and activation of the FcεRI signaling cascade in IgE/Ag-activated RBL-2H3 cells. Moreover, VEE not only reduced cell migration but also inhibited the expression, secretion, and/or activity of MMP-1, MMP-3, or MMP-13 in MDIM-stimulated SW1353 cells. In conclusion, VEE possesses both anti-allergic and anti-osteoarthritic properties. Therefore, VEE could possibly be considered a new herbal drug for anti-allergic and anti-osteoarthritic therapy. Moreover, the in vitro model may be useful for the development of anti-osteoarthritic drugs.

Effect of Viscum schimperi on advanced glycation endproducts formation.

Diabetes is a disease characterized by elevated uncontrolled glucose level. Hyperglycemia results in diabetic complication due to a reaction between sugar and amino acid of proteins to form advanced glycation endproducts (AGEs) in different tissues. Medicinal plants are considered as a great source of bioactive compounds that affect many ailments. In this regard; AGEs formation could be inhibited by many bioactive compounds isolated from medicinal plants. Viscum schimperi Engl. is a plant belongs to Loranthaceae and known for its antidiabetic activity. In this study; total methanol extract of V. schimperi (VT) was prepared, suspended in water and subjected to fractionation with chloroform followed by n-butanol to give (VC) and (VB) fractions respectively. The aqueous mother liquor was evaporated to form (VA) fraction. The inhibitory effect of all prepared fraction on the formation of advanced glycation endproducts (AGEs) was studied. The results revealed that V. schimperi extract and its different fractions inhibited protein glycation and oxidation of BSA induced by ribose together with decrease of protein aggregation. In conclusion; V. schimperi will be useful in management of diabetic complications based on its inhibition of advanced glycation endproduct formation.

Development of a sensitive ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nine active compounds in rat plasma and its application to a pharmacokinetic study after administration of Viscum coloratum extracts.

A simple, specific, and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous quantification of nine compounds including a new compound, rhamnazin-3-Ο-ß-D-(6″-ß-hydroxy-ß-methyglutaryl)-ß-D-glucoside-4'-Ο-ß-D-glucoside, in rat plasma using baicalin as an internal standard. The plasma samples were pretreated and extracted by protein precipitation with 0.2% formic acid in acetonitrile. The analytes were separated on a Thermo Syncronis C18 column by gradient elution with a mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at a flow rate of 0.25 mL/min. The detection of the analytes was performed on an electrospray ionization interface operating in positive-ion and multiple reaction monitoring acquisition modes. The calibration curves of these analytes showed good linearity (r > 0.99) within the test ranges. The lower limit of quantification ranged from 0.4 to 20.1 ng/mL for the analytes. The intra- and interday precision and accuracy were all within ±15%, and the recoveries were higher than 80.0%. The validated method was successfully applied to a pharmacokinetic study of the nine flavonoids after administration of the Viscum coloratum extracts by intravenous injection.

Mechanistic Evidence of Viscum schimperi (Viscaceae) Antihyperglycemic Activity: From a Bioactivity-guided Approach to Comprehensive Metabolite Profiling.

Diabetes mellitus is possibly the world's largest growing metabolic disorder. Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Viscum schimperi Engl. is a plant growing in Saudi Arabia and known for its antidiabetic activity. The potential antidiabetic activity of its methanol extract as well as its chloroform, n-butanol, and the remaining water fractions was evaluated in streptozotocin-induced diabetic rats at two dose levels. The antidiabetic activity was assessed through the determination of fasting blood glucose level, insulin levels, area under the curve (AUC) in oral glucose tolerance test, glucose absorption in isolated rat gut assay, and glucose uptake by psoas muscle. Moreover, large-scale untargeted metabolite profiling of methanol extract was performed via UPLC-PDA and qTOF-MS (ultra-performance liquid chromatography photodiode array detection and quadrupole time-of-flight mass spectrometry) respectively, to explore its chemical composition and standardization of its extract. Multivariate statistical analysis including principal component analysis and orthogonal projection to latent structures discriminant analysis was used to determine bioactives in its fractions. In conclusion, oleanane triterpenes and O-caffeoyl quinic acid conjugates were the major compounds that might account for antihyperglycemic effect of the plant.

Lasiodiplodia sp. ME4-2, an endophytic fungus from the floral parts of Viscum coloratum, produces indole-3-carboxylic acid and other aromatic metabolites.

BACKGROUND: Studies on endophytes, a relatively under-explored group of microorganisms, are currently popular amongst biologists and natural product researchers. A fungal strain (ME4-2) was isolated from flower samples of mistletoe (Viscum coloratum) during a screening program for endophytes. As limited information on floral endophytes is available, the aim of the present study is to characterise fungal endophytes using their secondary metabolites. RESULTS: ME4-2 grew well in both natural and basic synthetic media but produced no conidia. Sequence analysis of its internal transcribed spacer rDNA demonstrated that ME4-2 forms a distinct branch within the genus Lasiodiplodia and is closely related to L. pseudotheobromae. This floral endophyte was thus identified as Lasiodiplodia sp. based on its molecular biological characteristics. Five aromatic compounds, including cyclo-(Trp-Ala), indole-3-carboxylic acid (ICA), indole-3-carbaldehyde, mellein and 2-phenylethanol, were found in the culture. The structures of these compounds were determined using spectroscopic methods combined with gas chromatography. To the best of our knowledge, our work is the first to report isolation of these aromatic metabolites from a floral endophyte. Interestingly, ICA, a major secondary metabolite produced by ME4-2, seemed to be biosynthesized via an unusual pathway. Furthermore, our results indicate that the fungus ME4-2 is a potent producer of 2-phenylethanol, which is a common component of floral essential oils. CONCLUSIONS: This study introduces a fungal strain producing several important aromatic metabolites with pharmaceutical or food applications and suggests that endophytic fungi isolated from plant flowers are promising natural sources of aromatic compounds.

Photosynthesis, ionomics and metabolomics of the host-hemiparasite association Acacia gerrardii-Viscum schimperi.

Viscum schimperi is an evergreen hemiparasitic plant that can grow on stems and branches of several tree species. It penetrates the host tissues and forms a vascular bridge (haustorium) to withdraw the nutritive resources. Its relationships with hosts remain unknown. This study aimed to investigate the physiological and biochemical attributes of the host-hemiparasite association Acacia gerrardii -Viscum schimperi . The hemiparasite exhibited 2.4- and 3.0-fold lower photosynthetic activity and water use efficiency, and 1.2- and 4.1-fold higher transpiration rate and stomatal conductance. Equally, it displayed 4.9- and 2.6-fold greater water potential and osmotic potential, and in least 3.0times more accumulated 39 K, 85 Rb and 51 V, compared to the host. Nevertheless, it had no detrimental effect on photosynthetic activity, water status and multi-element accumulations in the host. Based on metabolome profiling, V. schimperi could use xanthurenic acid and propylparaben to acquire potassium from the host, and N -1-naphthylacetamide and N -Boc-hydroxylamine to weaken or kill the distal part of the infected branch and to receive the total xylem contents. In contrast, A. gerrardii could used N -acetylserotonin, arecoline, acetophenone and 6-methoxymellein to defend against V. schimperi infection.

Effects of Viscum coloratum (Kom.) Nakai on collagen-induced rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum coloratum (Kom.) Nakai has been traditionally used in China for nearly a thousand years to treat rheumatic diseases. However, its efficacy and mechanisms in treating rheumatoid arthritis (RA) have not been demonstrated. AIM OF THE STUDY: To investigate the anti-arthritic effects and molecular mechanisms of Viscum coloratum (Kom.) Nakai on collagen-induced arthritic mice through network pharmacology technology and experimental validation. MATERIALS AND METHODS: First, the main ingredients of the extract of Viscum coloratum (Kom.) Nakai (EVC) were identified through chemical composition characterization using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS). Then, the collagen-induced arthritis (CIA) model was established in DBA/1 J mice and the ameliorative effects of EVC on the progression of CIA mice were evaluated by oral treatment with different doses of the EVC for 28 days. After that, cytokine antibody microarray assay was used to detect the levels of multiple inflammation-related cytokines and chemokines in each group, and performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Subsequently, the potential target for the effective chemical components of EVC in treating RA was identified using various databases. Additionally, a drug-disease target protein-protein interaction network (PPI) was conducted using Cytoscape for visualization and clustering, while GO and KEGG enrichment analyses were performed with the Metascape database. Finally, identified phenotypes and targets by network pharmacology analysis were experimentally validated in vivo. RESULTS: Treatment with EVC significantly suppressed the severity of CIA with a dramatic reduction of paw swelling, arthritis index, levels of IgGs (IgG, IgG1, IgG2a, and IgG2b), multi-inflammation-related cytokines and chemokines on the progression of CIA. Histopathological examinations showed EVC could markedly inhibit inflammatory cell infiltration, tartrate-resistant acid phosphatase (TRAP) activity of osteoclast, and bone destruction. Furthermore, GO and KEGG enrichment analyses revealed that EVC could ameliorate RA by inhibiting osteoclast differentiation and regulating multiple signaling pathways including Osteoclast differentiation, IL-17, and TNF. PPI network analysis demonstrated that AKT1, MMP9, MAPK3, and other genes were highly related to EVC in treating RA. Finally, we proved that EVC could inhibit the expression of NFTAc1, MMP9, Cathepsin K, and AKT which were closely related to osteoclast activity. CONCLUSIONS: EVC could treat RA through multiple components, multiple targets, and multiple pathways. The present study demonstrated the therapeutic efficacy of EVC and its molecular mechanisms in treating RA, indicating that it would be a potent candidate as a novel botanical drug for further investigation.

The identification of in vitro production of lectin from callus cultures of Korean mistletoe (Viscum album L. var. coloratum).

Despite potential medical, economical, and agronomical importance, the bioprocessing of mistletoe cell cultures, from callus cultures to mass production of high-value products (e.g., lectins and viscotoxins), has been unsuccessful to date. In this study, we confirmed the potential of in vitro lectin production from callus cultures of Korean mistletoe (Viscum album L. var. coloratum).

[Study on the chemical constituents of Viscum ovalifolium].

OBJECTIVE: To study the chemical constituents of Viscum ovalifolium. METHODS: The chemical constituents from Viscum ovalifolium were isolated and purified by silica gel column chromatography, polyamide column chromatography and recrystallization methods. Their structures were elucidated by physicochemical properties and spectral analysis. RESULTS: Twelve compounds were isolated and their structures were identified as 1-octadecene (1), ethyl palmitate (2), 28-hydrxy-amyrone (3), betulinic acid (4), rutin (5), quercetin (6), beta-amyrinpalmitate (7), lupeol acetate (8), beta-amyrin (9), beta-sitosterol (10), lupeol (11) and oleanolic acid (12). CONCLUSION: Compounds 1 - 6 are obtained from this plant for the first time.

Study on the dynamic variation of the secondary metabolites in Viscum coloratum using targeted metabolomics.

Viscum coloratum (Kom.) Nakai is a well-known medicinal plant. However, the optimal harvest time for V. coloratum is unknown. Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control. Our study aimed to comprehensively evaluate the quality of V. coloratum in different growth stages, and determine the dynamic variation of metabolites. Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V. coloratum harvested in six growth periods, and the associated biosynthetic pathways were explored. The accumulation of different types of compounds were analyzed based on their synthesis pathways. Grey relational analysis was used to evaluate the quality of V. coloratum across different months. The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test. The results showed that the quality of V. coloratum was the hightest in March, followed by November, and became the lowest in July. During storage, compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids, leading to an increase followed by a decrease in the content of some compounds, and resulted in a large gap during the degradation time course among different compounds. Due to the rapid rate and large degree of degradation, five compounds were tentatively designated as "early warning components" for quality control. This report provides reference for better understanding the biosynthesis and degradation of metabolites in V. coloratum and lays a theoretical foundation for rational application of V. coloratum and better quality control of V. coloratum during storage.

Assessment of extracts from mistletoe (Viscum album) for herb-drug interaction by inhibition and induction of cytochrome P450 activities.

Three commercially available extracts from mistletoe (Viscum album L.) grown on ash tree (abnobaVISCUM(®) Fraxini 20 mg), on fir (abnobaVISCUM(®) Abietis 20 mg), and on pine (abnobaVISCUM(®) Pini 20 mg) were tested in vitro for their potential to interfere with the major drug metabolizing cytochromes P450 by hepatocyte viability, by inhibition of cytochromes P450 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4, and by the induction of cytochromes P450 1A2, 2B6, 2C9, 2E1 and 3A4. As the three extracts are produced from mistletoe plants belonging to three different subspecies of Viscum album L. they have explicit differences in the content and spectrum of various active ingredients, e.g. mistletoe specific lectins. Cytotoxic effects on liver cells were observed for abnobaVISCUM(®) Fraxini with a high lectin content with an EC(50) value of 2.56 µg/mL, for abnobaVISCUM(®) Abietis with a moderate lectin content with an EC(50) value of 5.79 µg/mL and for abnobaVISCUM(®) Pini with a low lectin content with an EC(50) value of 30.86 µg/mL. The induction of cytochromes P450 was tested on human liver cells from three donors. Inhibition of cytochromes P450 was carried out on human liver microsomes. No or minor induction and inhibition was observed for all three extracts. The data indicate no or minor potential for herb-drug interactions by interference with cytochromes P450 by any of the three mistletoe extracts.