The chemical components and biological activity of Camellia mistletoe, Korthalsella japonica (Loranthaceae) are relatively unknown compared to other mistletoe species. Therefore, we investigated the phytochemical properties and biological activity of this parasitic plant to provide essential preliminary scientific evidence to support and encourage its further pharmaceutical research and development. The major plant components were chromatographically isolated using high-performance liquid chromatography and their structures were elucidated using tandem mass spectrometry and nuclear magnetic resonance anlysis. Furthermore, the anti-inflammatory activity of the 70% ethanol extract of K. japonica (KJ) and its isolated components was evaluated using a nitric oxide (NO) assay and western blot analysis for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Three flavone di-C-glycosides, lucenin-2, vicenin-2, and stellarin-2 were identified as major components of KJ, for the first time. KJ significantly inhibited NO production and reduced iNOS and COX-2 expression in lipopolysaccharide-stimulated RAW 264.7 cells at 100 μg/mL while similar activity were observed with isolated flavone C-glycosides. In conclusion, KJ has a simple secondary metabolite profiles including flavone di-C-glycosides as major components and has a strong potential for further research and development as a source of therapeutic anti-inflammatory agents.
Anti-Inflammatory Agents ; Blotting, Western ; Camellia* ; Chromatography, Liquid ; Ethanol ; Magnetic Resonance Spectroscopy ; Mistletoe* ; Nitric Oxide ; Nitric Oxide Synthase ; Plant Structures ; Plants ; Prostaglandin-Endoperoxide Synthases ; RAW 264.7 Cells ; Tandem Mass Spectrometry ; Viscaceae*

The present study aims to investigate the effect of methanol extract of Korean mistletoe (KM; Viscum album var. coloratum), on amyloid beta protein (Abeta) (25-35), a synthetic 25-35 amyloid peptide, -induced neurotoxicity in cultured rat cerebral cortical neurons and memory impairment in mice. Exposure of cultured neurons to 10 microM Abeta (25-35) for 24 h induced a neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. KM (10, 30 and 50 microg/ml) significantly inhibited the Abeta (25-35)-induced apoptotic neuronal death. KM (50 microg/ml) inhibited 10 microM Abeta (25-35)-induced elevation of intracellular calcium concentration ([Ca2+]i), which was measured by a fluorescent dye, Fluo-4 AM. Glutamate release into medium and generation of reactive oxygen species (ROS) induced by 10 microM Abeta (25-35) were also inhibited by KM (10, 30 and 50 microg/ml). These results suggest that KM may mitigate the Abeta (25-35)-induced neurotoxicity by interfering with the increase of [Ca2+]i and then inhibiting glutamate release and generation of ROS in cultured neurons. In addition, orally administered KM (25 and 50 mg/kg, 7 days) significantly prevented memory impairment induced by intracerebroventricular injection of Abeta (25-35) (8 nmol). Taken together, it is suggested that anti-dementia effect of KM is due to its neuroprotective effect against Abeta (25-35)-induced neurotoxicity and that KM may have therapeutic role in prevention of the progression of Alzheimer's disease.
Alzheimer Disease ; Amyloid beta-Peptides* ; Amyloid* ; Animals ; Calcium ; Cell Death ; Glutamic Acid ; Memory* ; Methanol ; Mice ; Mistletoe* ; Neurons* ; Neuroprotective Agents ; Rats ; Reactive Oxygen Species ; Viscum album

PURPOSE: To reduce the side effects and improve the effectiveness of standard chemoradiation therapy, many complementary or alternative medicines have been tried. However, little is known about its immunologic effects in breast cancer patients. The aim of this study was to assess the immunologic effects of mistletoe extract (Viscum album L., VAE) in patients with early breast cancer after surgery followed by standard adjuvant chemoradiation therapy. METHODS: A total 20 patients with early breast cancer treated with breast conserving surgery followed conventional chemoradiation therapy. Ten of these patients received subcutaneous injections of VAE for 7 weeks. IL-2, IL-4, IL-6, IL-10, TGF-beta, and IFN-gamma levels in serum samples were measured in all patients. RESULTS: The concentrations of IL-2, IL-4, IL-10, and TGF-beta were not significantly changed between before and after VAE treatment in both test and control group. The concentration of IL-6 in the test group was increased from 8.19+/-1.75 pg/mL to 9.86+/-1.46 pg/mL after treatment (p=0.013). The concentration of IFN-gamma in the test group was remarkably increased from 91.76+/-17.16 pg/mL to 167.42+/-66.61 pg/mL after treatment (p=0.009). CONCLUSION: Significant increases in the concentration of IL-6 and IFN-gamma were observed after VAE treatment. These results suggest that VAE treatment can stimulate immune responses, especially cell-mediated immunity in immune-compromised patients received the chemoradiation for breast cancer.
Breast ; Breast Neoplasms ; Humans ; Immunity, Cellular ; Injections, Subcutaneous ; Interleukin-10 ; Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Mastectomy, Segmental ; Mistletoe ; Transforming Growth Factor beta

Complementary Therapy for Improvement of Quality of Life in Cancer Patients. As a results of reviews of database for effects of complementary therapies for improvement of Quality of Life on cancer patients, there were 8 mind-body therapies, 2 manual based therapies, 17 biologic based therapies(3 vitamin or minerals, 6 health nutrient products, 8 herbs). There were relative much more proportional studies of mind-body therapies and manual based therapies for quality of life of cancer. It were reported much more positive results in cognitive behavioral therapy, meditation, art therapy, music therapy, yoga included to mind-body therapies also it were reported much more positive result in massage & acupressure included to manual based therapies. And then these findings can be considered to us clinical application of these therapies by additional studies. On the other hand, the amount of study for quality of life of cancer in biologic based therapies was relatively more smaller than mind-body therapies and the results were contrary to each other. The mistletoe, one of the biological therapeutic products, can be considered to relatively useful material as a results of this review and its seems like to have positive value for further study, materials such as honey, ginseng or heat-treated ginseng, AHCCR, selenium. The others of biologic based therapies were inconclusive due to relatively small amounts of studies or revealed negative conclusion or negative tendency by their studies. The high usual rate of complementary therapy in cancer patients in Korea is applying the screw to us study for complementary medicine and is producing needs of complementary closed co-works or cooperation between the citizens, the government, medical doctors for high quality study.
Acupressure ; Art Therapy ; Cognitive Therapy ; Complementary Therapies ; Hand ; Honey ; Humans ; Korea ; Massage ; Meditation ; Mind-Body Therapies ; Minerals ; Mistletoe ; Music Therapy ; Panax ; Quality of Life ; Selenium ; Vitamins ; Yoga

Many patients with cancer use complementary medicine that is used together with conventional medicine. The widespread use of complementary therapies in cancer patients has major implications for research and clinical practices. Some complementary therapies, such as polysaccharide K, Astragalus membranaceus and A. mistletoe, may offer therapeutic benefits for patients with cancer. However, others did not show significant clinical effects for cancer treatment. Therefore, it is important for physicians to communicate openly with cancer patients about the use of complementary therapy. In order to encourage open communications with their patients, physicians should be knowledgeable about the most commonly used remedies, or at least they should be able to direct patients to reliable sources of information.
Astragalus membranaceus ; Complementary Therapies ; Humans ; Mistletoe

BACKGROUND: The immunomodulatory effects of Korean mistletoe (Viscum album Coloratum) on the innate immune responses of eel (Anguilla japonica) were studied. METHODS: Mistletoe, Freund's complete adjuvant (FCA), or phosphate-buffered saline (PBS) as a control was injected into eel peritoneal cavities. RESULTS: Nitroblue tetrazolium (NBT)-positive cells in the head kidney of eel were significantly augmented by the second day post-injection of mistletoe. Reactive oxygen intermediates (ROI) were more produced in mistletoe-injected fish kidney leucocytes than in FCA-injected ones. The level of lysozyme activity in the serum of fish 2 days after injection with mistletoe was also significantly higher than that in the serum of the control fish. The optimal concentration of mistletoe in inducing the highest serum lysozyme activity was revealed to 500microgram/200 g of fish. In phagocytic activity assay, mistletoe-sensitized eel kidney phagocytes captured more zymosan than did the control fish. CONCLUSION: Korean mistletoe appeared to be a good activator of the non-specific immune responses of eel.
Eels ; Head Kidney ; Immunity, Innate ; Kidney ; Mistletoe ; Muramidase ; Nitroblue Tetrazolium ; Oxygen ; Phagocytes ; Zymosan

PURPOSE: Mistletoe extract was widely used for cancer treatment as complementary or alternative therapy in European area from early twenty century. It is currently used as alternative anti-cancer remedy by piecemeal in domestic medical group, however, the anti-cancer mechanism of mistletoe extract was not known precisely until now. In this study the effect of mistletoe extract on gastric cancer was studied vis cell line experiments. MATERIALS AND METHODS: The SNU719 gastric cancer cell line was used, and ABNOBAviscum-Q and ABNOBAviscum-F were treated to cells as mistletoe extract, or 5-FU and cisplatin were used with mistletoe extract. The cell viability and cell death rate were estimated by CCK-8 assay kit and lactate dehydrogenase (LDH) assay kit in each. Caspase 3 assay kit was used to measure caspase 3 activity. The protein expression amounts of Bcl2, p53, and PTEN were estimated through Western blot analysis. RESULTS: The co-treatments of mistletoe extract Q/F and 5-FU/cisplatin decreased lesser cell viability than only mistletoe treat. Caspase 3 activity was increased 4~6 times in co-treatment of mistletoe extracts and 5-FU than control. Bcl2 protein expression was reduced by mistletoe extracts or anti-cancer drugs, further more, the co-treatment of mistletoe extracts and 5-FU/cisplatin diminished more the expression than only mistletoe treatment. Mistletoe extracts did not affect the protein expressions of p53 and PTEN. CONCLUSION: It was concluded that the anti-cancer mechanism of mistletoe extracts was made by caspase 3 activation and lowered Bcl2 expression, and this apoptosis inducing mechanism was independent to p53.
Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Death ; Cell Line ; Cell Survival ; Cisplatin ; Fluorouracil ; L-Lactate Dehydrogenase ; Mistletoe ; Sincalide ; Stomach Neoplasms

PURPOSE: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. MATERIALS AND METHODS: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum Q(R) was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-1beta, IL-2, IL-6, IFN-gamma, TNF-alpha) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. RESULTS: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. CONCLUSION: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.
Cisplatin ; Cytokines ; Drug Therapy ; Eosinophils ; Europe ; Fluorouracil ; Gastrectomy ; Humans ; Interleukin-2 ; Interleukin-6 ; Lymphocyte Count ; Mistletoe* ; Mitomycin ; Neutrophils ; Prospective Studies ; Stomach Neoplasms*

OBJECTIVE: This study was designed to establish the treatment strategy on postoperative persistent pain of endometriosis. METHODS: During a 12-month period from March 2000 to February 2001, 62 patients had postoperative persistent pelvic pain. 62 patients of them were treated with GnRH analogue for 6 months. If they were not responsive to those treatment, It were recommended high dose progesterone treatment for 6 months after trigger point injection to differentiate from trigger point pain. and then for remained pain, Nonsteroidal antiinflammatory drugs (NSAIDs) and tricyclic antidepressants (TCAs) were supplied for 6 months. Finally, contineously remained pelvic pain was treated by mistletoe extract. RESULTS: 62 patients had a postoperative persistent pelvic pain. GnRH analogue were supplied to 62 patients, and then 23 patients had persistent pain. These 23 patients undertook lidocaine injection on trigger point to differentiate from trigger point pain. Two patients were responsive to injection. Remained 21 patients were treated with high dose progesterone for 6 months. Thereafter unresponded 14 patients were supplied with NSAIDs and TCAs. Finally, remained 5 patients that were uncontrolled with previous treatments were injected with mistletoe extract. Three patients were controlled with mistletoe extract. CONCLUSION: Most of persistent pain after laparoscopic operation of endometriosis were successfully controlled by sequential treatment of GnRH analogue, trigger point injection, high dose progesterone, NSAIDs and TCAs, and mistletoe extract injection.
Anti-Inflammatory Agents, Non-Steroidal ; Antidepressive Agents, Tricyclic ; Endometriosis* ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Lidocaine ; Mistletoe ; Pelvic Pain ; Progesterone ; Trigger Points

OBJECTIVE: Chronic pelvic pain is pelvic pain which is not completely controlled by classical treatments. In many reports, immune alternation is related to original diseases that induce the chronic pelvic pain. Mistletoe extract has been known that it has immune modulation effect. Therefore the purpose of this study is to determine the pain-reducing effects of mistletoe extract for chronic pelvic pain that is not controlled by classical treatments. METHODS: The fitty-eight patients who visited to outpatient department of Department of Obstetrics and Gynecology, Chonnam National University Hospital due to chronic pelvic pain. Mistletoe extract (Helixor-A(R)) 5-10 mg was injected subcutaneously 3 times per week for 5 weeks, and the change of pain and short-term side-effects after injections were observed. In patients after 6 month of follow-up, the change of pain and long-term side-effects were also observed. RESULTS: In 2 of 58 patients (0.03%), treatments were discontinued doe to severe general side effect. In 48 of 56 patients (85.7%), chronic pelvic pains were improved. In 40 of 56 patients (69%), mild side effects as like mild itching were appeared and they were easily controlled by anti-histamines and conservative treatments. In 6 months after injection, general itching sensation and easily catched common cold were complaint in 4 of 10 patients. CONCLUSION: The subcutaneous injection of mistletoe extract may effective treatment method for the chronic pelvic pain that is not controlled by classical treatment. However more studies about log-term effect of mistletoe therapy are needed.
Common Cold ; Follow-Up Studies ; Gynecology ; Humans ; Injections, Subcutaneous* ; Jeollanam-do ; Mistletoe* ; Obstetrics ; Outpatients ; Pelvic Pain* ; Pruritus ; Sensation