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.

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.

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.

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.

[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.

Cytotoxic constituents of Viscum coloratum.

Phytochemical studies on Viscum coloratum have resulted in the isolation of nineteen compounds. The structures of the isolated compounds were identified on the basis of 1D, 2D NMR and HR-ESI-Q-TOF-MS. Pachypodol (4) and ombuine (6) were characterized in the family Loranthaceae for the first time. 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one (8) and 5-hydroxy-3,7,3'-trimethoxyflavone-4'-O-beta-D-glucoside (13) were two new natural compounds, which exhibited cytotoxic activities against four human tumour cell lines (HeLa, SGC-7901, MCF-7, and U251).

Chemical constituents of Viscum coloratum (Kom.) Nakai and their cytotoxic activities.

A new diarylheptanoid, (1 R,2S,3S,5S)-2,3-dihydroxy-3',3''-dimethoxy-4'-de-O-methylcentrolobine (1) and a new bisabolane-type sesquiterpenoid, (1 R,7S)-1,12,13-trihydroxybisabola-3,10-diene (2), together with nineteen known compounds (3-21) were isolated from the EtOH extract of the stems and branches of Viscum coloratum (Kom.) Nakai. Their structures were elucidated by extensive analysis of 1 D and 2 D NMR spectra and from the HRESIMS. All the compounds were evaluated for their cytotoxic activity against eight human tumor cell lines.

Oleanolic acid prevents glucocorticoid-induced hypertension in rats.

The present study was designed to evaluate the antihypertensive activity of oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a probable mechanism of action for this effect. Male Wistar rats (300-350 g) received dexamethasone (20 µg/kg/day s.c.) or saline (vehicle) for 10 days. In a prevention study, the rats received oleanolic acid (60 mg/kg i.p.) for 5 days, followed by dexamethasone or saline for 10 days. During this period the systolic blood pressure and body weight were evaluated on alternate days. At the end of the experiment, the weight of the thymus gland, plasma nitrate/nitrite (nitric oxide metabolites) concentration and cardiac lipid peroxidation value were determined. Oleanolic acid (60 mg/kg i.p.) significantly prevented a rise in the systolic blood pressure and cardiac lipid peroxidation level after administration of dexamethasone (p < 0.01 and p < 0.05, respectively) without showing any significant effect on the dexamethasone-induced change in body and thymus weights. The decrease in concentration of plasma nitrate/nitrite due to dexamethasone was prevented significantly in the group treated with oleanolic acid (p < 0.05). These findings suggest that oleanolic acid (60 mg/kg i.p.) prevents dexamethasone-induced hypertension in rats, which may be attributed to its antioxidant and nitric oxide releasing action.

Simultaneous determination of ten flavonoids from Viscum coloratum grown on different host species and different sources by LC-MS.

A high-performance liquid chromatographic-mass spectrometric method was developed for the simultaneous determination of 10 flavonoids in Viscum coloratum obtained from different host species and different sources. Viscum coloratum was extracted with 50% methanol. The extracts were separated on a C(18) column with a gradient of 0.1% (v/v) formic acid and methanol. The flavonoids in the extracts were detected by negative electrospray ionization mass spectrometry in selective ion monitoring mode. The calibration curves showed good linearity (r>0.998) within the test ranges (homoeriodictyol: 0.149-8.940 µg/ml, homoeriodictyol-7-O-ß-D-glycoside: 0.230-13.80 µg/ml, homoeriodictyol-7-O-ß-D-apiose (1→2)-ß-D-glycoside: 5.000-300.0 µg/ml, homoeriodictyol-7-O-ß-D-apiose (1→5)-ß-D-apiose (1→2)-ß-D-glycoside: 0.835-125.3 µg/ml, rhamnazin-3-O-ß-D-glucoside: 0.064-3.840 µg/ml, rhamnazin-3-O-ß-D-(6″-ß-hydroxy-ß-methyglutaryl)-glucoside: 1.435-86.10 µg/ml, isorhamnetin-3-O-ß-D-glucoside: 0.930-55.80 µg/ml, 5-hydroxy-3,7,3'-trimethoxyflavone-4'-O-ß-D-glucoside: 0.067-4.020 µg/ml, 5,7,4'-trihydroxy-3,3'-dimethoxyflavone: 0.270-16.20 µg/ml, pachypodol: 0.110-6.600 µg/ml). The limits of quantification were between 0.006-0.720 µg/ml. The assay was reproducible and the overall intra- and inter-day variations were less than 4.6%. The recoveries varied from 93.4 to 103.9% at three different concentration levels. The validation method was used to determine the contents of 10 flavonoids in Viscum coloratum. A one-way analysis of variance was applied to evaluate Viscum coloratum-host-source interactions. Compared with the host species, the sample source had a significant impact on the sample content.

Flavanone glycosides from viscum coloratum and their inhibitory effects on osteoclast formation.

Two novel flavanone glycosides, homoeriodictyol 7-O-ß-D-[6-(3-hydroxybutanoyl)glucopyranoside] (viscumneoside IX; 1) and homoeriodictyol 7-O-ß-D-[6-(3-hydroxybutanoyl)glucopyranosyl](1→2)-ß-D-glucopyranoside (viscumneoside X; 2), together with four known flavanoids, 2-homoeriodictyol 7-O-ß-D-glucopyranoside (3), viscumneoside I (4), viscumneoside III (5), and 4',5-dihydroxy-3'-methoxy-7-(2-O-α-L-rhamnopyranosyl-ß-D-glucopyranosyloxy)flavanone (6) were isolated from stems and leaves of Viscum coloratum. Their structures were elucidated on the basis of their NMR spectra, HR-FAB-MS data, and acid hydrolysis. Inhibitory effects of the four compounds 1-4 on the formation of osteoclast-like multinucleated cells were investigated. As a result, all the four flavanoids showed significant inhibitory effects on the formation of osteoclast-like multinuclear cells even at a low concentration of 2 µg/ml. The activities of 1-4 at such a concentration exceeded or approximated to that of elcitonin, the positive control drug at a concentration of 2 U/ml, suggesting that they may be of interest for the development of new anti-osteoporosis drugs.

[Triterpenoids and triterpenoid saponins of Viscum liquidambaricolum].

To study the triterpenoids and triterpenoid saponins of Viscum liquidambaricolum further, chemical constituents were isolated from the title plant by various chromatographic methods such as silica gel and ODS medium pressure column chromatography, Sephadex LH-20 column chromatography, et al. Their structures were elucidated by physiochemical properties and spectral analysis. Eight triterpenoids and triterpenoid saponins were isolated and identified as myricadiol(1), maslinic acid(2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic acid(3), oleanolic acid 3-O-beta-D-glucuronopyranoside-6'-O-methyl ester(4), oleanolic acid 3-O-beta-D-glucuropyranoside(5), oleanolic acid 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-L-arabinopyranoside (6), 3-O-beta-D-glucuronopyranosyl-oleanolic acid-28-O-beta-D-glucopyranoside (7), 3-O-beta-D-glucuronopyranosyl-oleanolic acid-28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (8). Compounds 1-8 were isolated from this plant and the genus for the first time.

Exploring the resources of the genus Viscum for potential therapeutic applications.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Viscum comprises approximately 100 species that are mainly distributed across Africa, Asia and Europe. The extracts and preparations of Viscum species are widely used as common complementary and alternative medicines in the treatment of rheumatism and cancer. AIM OF THE REVIEW: This review aims to explore the medicinal properties of twelve species belonging to the genus Viscum for potential therapeutic applications. MATERIALS AND METHODS: We collected online information (including PubMed, CNKI, Google Scholar, and Web of Science) from January 1915 to April 2021 and knowledge from classical books on Chinese herbal medicines available for 12 species of the genus Viscum, including Viscum coloratum (Kom.) Nakai, Viscum album L., Viscum articulatum Burm. f., Viscum liquidambaricola Hayata, Viscum ovalifolium DC., Viscum capitellatum Sm., Viscum cruciatum Sieber ex Boiss., Viscum nudum Danser, Viscum angulatum B.Heyne ex DC., Viscum tuberculatum A.Rich., Viscum multinerve Hayata, and Viscum diospyrosicola Hayata. RESULTS: At least 250 different compounds have been reported across twelve Viscum species, including amino acid and peptides, alkaloids, phenolic acids, flavonoids, terpenoids, carbohydrates, fatty acids, lipids, and other types of compounds. In particular, for Viscum coloratum (Kom.) Nakai and Viscum album L., the plants, preparations, and bioactive components have been thoroughly reviewed. This has allowed to elucidate the role of active components, including lectins, viscotoxins, flavonoids, terpenoids, phenolic acids, and polysaccharides, in multiple bioactivities, such as anti-cancer, anti-rheumatism arthralgia, anti-inflammation, anti-cardiovascular diseases, enhancing immunity, and anti-chemotherapy side effects. We also evaluated quality control methods based on active compounds, in vivo exposure compounds, and discriminated chemical markers. CONCLUSIONS: This is the first report to systematically review the pharmaceutical development history, chemical composition, clinical evidence, pharmacological activity, discriminated chemical markers, in vivo exposure, and quality control on twelve distinct species of Viscum plants with medicinal properties. The significant safety and efficacy, along with the minor side effects are constantly confirmed in clinics. The genus Viscum is thus an important medicinal resource that is worth exploring and developing in future pharmacological and chemical studies.

Flavanone and diphenylpropane glycosides and glycosidic acyl esters from Viscum articulatum.

Seven new compounds including three flavanone glycosides, visartisides A-C (1-3), three glycoside acyl esters, visartisides D-F (4-6), and one diphenylpropane glycoside, (4'-hydroxy-2',3',6',3''-tetramethoxy-1,3-diphenylpropane)-4''-O-beta-d-glucopyranoside (7), along with four known flavanone glycosides (8-11) were isolated from the leaves and stems of Viscum articulatum. The structure elucidation of 1-7 was based on spectroscopic data analysis. Biological evaluation showed that 1, 2, and 10 exhibited antioxidant activity using a DPPH method and that compounds 1, 3, and 11 were active in a lipopolysaccharide-induced nitric oxide assay.