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1.
Chem Biodivers ; 21(6): e202400159, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38563619

ABSTRACT

While the flowers of Matricaria recutita L., German chamomile, are widely used for medicinal and cosmetic purposes, little is known about its roots, which are used in complementary medicine for the preparation of aqueous fermented extracts for the treatment of cramps and anxiety. To broaden the understanding of the active principles involved, a model fermentation approach was developed and fermentates were compared to commercially manufactured tinctures. Coumarins and hydroxycinnamates were among the major secondary metabolites characterized using HPLC-MSn. After six months of fermentation and storage, low-molecular organic acids were detected by GC-MS. Fermentation contributed to the stabilization of antioxidant and radical scavenging activities, which were in a range of about 8-10 mg gallic acid equivalents/g dry weight and 20-24 mg trolox equivalents/g dry weight, determined by Folin-Ciocalteu and DPPH assays, respectively. In addition, antibacterial activities of the extracts against Gram-positive and -negative bacteria increased during the first week of fermentation. Fermentates were neither cytotoxic nor pro- or anti-inflammatory. Thus, fermentation of chamomile roots is a suitable method for the safe production of biofunctional aqueous chamomile root extracts that remain stable without the addition of synthetic preservatives.


Subject(s)
Antioxidants , Fermentation , Matricaria , Phytochemicals , Plant Extracts , Plant Roots , Plant Roots/chemistry , Plant Roots/metabolism , Matricaria/chemistry , Matricaria/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/metabolism , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Phytochemicals/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Microbial Sensitivity Tests , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Water/chemistry , Animals , Picrates/antagonists & inhibitors , Biphenyl Compounds/antagonists & inhibitors , Cell Survival/drug effects
2.
Planta Med ; 89(15): 1493-1504, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37748505

ABSTRACT

Viola tricolor is a medicinal plant with documented application as an anti-inflammatory herb. The standard of care for the treatment of inflammatory bowel disease is immunosuppressive therapeutics or biologics, which often have undesired effects. We explored V. tricolor herbal preparations that are rich in an emerging class of phytochemicals with drug-like properties, so-called cyclotides. As an alternative to existing inflammatory bowel disease medications, cyclotides have immunomodulatory properties, and their intrinsic stability allows for application in the gastrointestinal tract, for instance, via oral administration. We optimized the isolation procedure to improve the yield of cyclotides and compared the cellular effects of violet-derived organic solvent-extracts, aqueous preparations, and an isolated cyclotide from this plant on primary human T lymphocytes and macrophages, i.e., cells that are crucial for the initiation and progression of inflammatory bowel disease. The hot water herbal decoctions have a stronger immunosuppressive activity towards proliferation, interferon-γ, and interleukin-21 secretion of primary human T cells than a DCM/MeOH cyclotide-enriched extract, and the isolated cyclotide kalata S appears as one of the active components responsible for the observed effects. This effect was increased by a longer boiling duration. In contrast, the DCM/MeOH cyclotide-enriched extract was more effective in reducing the levels of cytokines interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-α, and C - X-C motif chemokine ligand 10, secreted by human monocyte-derived macrophages. Defined cyclotide preparations of V. tricolor have promising pharmacological effects in modulating immune cell responses at the cytokine levels. This is important towards understanding the role of cyclotide-containing herbal drug preparations for future applications in immune disorders, such as inflammatory bowel disease.


Subject(s)
Cyclotides , Inflammatory Bowel Diseases , Plants, Medicinal , Viola , Humans , Cyclotides/chemistry , Viola/chemistry , T-Lymphocytes , Plant Extracts/pharmacology , Plant Extracts/chemistry
3.
Molecules ; 28(24)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38138432

ABSTRACT

Peyote (Lophophora williamsii) is a cactus that contains various biologically active alkaloids-such as pellotine, anhalonidine, hordenine and mescaline. Here, mescaline induces the psychoactive effects of peyote through the activation of the serotonin 5-HT2A receptor and the subsequent release of calcium (Ca2+) from the endoplasmic reticulum (ER). Moreover, an evaluation of the therapeutic benefits of mescaline is also currently the subject of research. It is important to consider that the outcome of taking a psychedelic drug strongly depends on the mindset of the recipient and the context (set and setting principle), including ceremonies and culture. This overview serves to summarise the current state of the knowledge of the metabolism, mechanism of action and clinical application studies of peyote and mescaline. Furthermore, the benefits of the potential of peyote and mescaline are presented in a new light, setting an example for combining a form of treatment embedded in nature and ritually enriched with our current highly innovative Western medicine.


Subject(s)
Alkaloids , Antineoplastic Agents , Cactaceae , Hallucinogens , Mescaline/pharmacology , Hallucinogens/pharmacology
4.
Planta Med ; 88(14): 1360-1368, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34706374

ABSTRACT

Equisetum arvense tea (TEA) contains high concentrations of silicon and has been used in folk medicine for the treatment of inflammatory ailments. We examined the resorption of silicon after TEA consumption. Safety and immunological effects were secondary outcomes. A monocentric, randomized, three-armed pilot study was conducted with 12 voluntary, healthy, male subjects. The study is registered in the German register for clinical trials (DRKS-ID: DRKS00016628). After a low silicon diet for 36 hours, 1000 mL TEA1 with approximately 200 000 µg silicon/L, TEA2 with approximately 750 000 µg silicon/L, or Si-low-Water (approximately 10 - 10 000 µg silicon/L as a control) were ingested on three consecutive days. Blood and urine samples were collected at baseline, day 1 examining silicon kinetics, day 3 examining silicon accumulation, and day 8 (safety, immunological parameters). Si-low-Water intake did not change silicon serum (Cmax 294 µg/L) or urine (19 000 µg/24 h) concentrations compared to baseline. Cmax was 2855 µg/L for TEA1 and 2498 µg/L for TEA2; tmax was 60 and 120 min, respectively. Silicon accumulation did not occur. Urine silica within 24 h (E24 h) was higher after TEA2 compared to TEA1 ingestion (142 000 vs. 109 000 µg/24 h). Serum silicon levels at t = 120 min differed significantly after intake of TEA2 or intake of Si-low-Water (p = 0.029). The immunological parameters did not show any significant changes indicating immunosuppressive effects in volunteers. TEA1 was well tolerated, while TEA2 caused diarrhoea in 4 subjects. Our investigations show that intake of TEA1 leads to significant rise in serum silicon concentration.


Subject(s)
Equisetum , Silicon , Pilot Projects , Water , Tea
5.
Planta Med ; 88(12): 1036-1046, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34624906

ABSTRACT

Pregnancy is a critical period for medical care, during which the well-being of woman and fetus must be considered. This is particularly relevant in managing non-psychotic mental disorders since treatment with central nervous system-active drugs and untreated NMDs may have negative effects. Some well-known herbal preparations (phytopharmaceuticals), including St. John's wort, California poppy, valerian, lavender, and hops, possess antidepressant, sedative, anxiolytic, or antidepressant properties and could be used to treat mental diseases such as depression, restlessness, and anxiety in pregnancy. Our goal was to assess their safety in vitro, focusing on cytotoxicity, induction of apoptosis, genotoxicity, and effects on metabolic properties and differentiation in cells widely used as a placental cell model (BeWo b30 placenta choriocarcinoma cells). The lavender essential oil was inconspicuous in all experiments and showed no detrimental effects. At low-to-high concentrations, no extract markedly affected the chosen safety parameters. At an artificially high concentration of 100 µg/mL, extracts from St. John's wort, California poppy, valerian, and hops had minimal cytotoxic effects. None of the extracts resulted in genotoxic effects or altered glucose consumption or lactate production, nor did they induce or inhibit BeWo b30 cell differentiation. This study suggests that all tested preparations from St. John's wort, California poppy, valerian, lavender, and hops, in concentrations up to 30 µg/mL, do not possess any cytotoxic or genotoxic potential and do not compromise placental cell viability, metabolic activity, and differentiation. Empirical and clinical studies during pregnancy are needed to support these in vitro data.


Subject(s)
Anti-Anxiety Agents , Hypericum , Mental Disorders , Oils, Volatile , Plants, Medicinal , Valerian , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Female , Glucose , Humans , Hypnotics and Sedatives/therapeutic use , Lactates , Mental Disorders/drug therapy , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Phytotherapy , Placenta , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Pregnancy
6.
Molecules ; 27(10)2022 May 17.
Article in English | MEDLINE | ID: mdl-35630688

ABSTRACT

Modern phytotherapy is part of today's conventional evidence-based medicine and the use of phytopharmaceuticals in integrative oncology is becoming increasingly popular. Approximately 40% of users of such phytopharmaceuticals are tumour patients. The present review provides an overview of the most important plants and nature-based compounds used in integrative oncology and illustrates their pharmacological potential in preclinical and clinical settings. A selection of promising anti-tumour plants and ingredients was made on the basis of scientific evidence and therapeutic practical relevance and included Boswellia, gingko, ginseng, ginger, and curcumin. In addition to these nominees, there is a large number of other interesting plants and plant ingredients that can be considered for the treatment of cancer diseases or for the treatment of tumour or tumour therapy-associated symptoms. Side effects and interactions are included in the discussion. However, with the regular and intended use of phytopharmaceuticals, the occurrence of adverse side effects is rather rare. Overall, the use of defined phytopharmaceuticals is recommended in the context of a rational integrative oncology approach.


Subject(s)
Integrative Oncology , Neoplasms , Zingiber officinale , Ginkgo biloba , Humans , Neoplasms/drug therapy , Phytotherapy
7.
J Nat Prod ; 84(1): 81-90, 2021 01 22.
Article in English | MEDLINE | ID: mdl-33397096

ABSTRACT

Cyclotides are plant-derived peptides found within five families of flowering plants (Violaceae, Rubiaceae, Fabaceae, Solanaceae, and Poaceae) that have a cyclic backbone and six conserved cysteine residues linked by disulfide bonds. Their presence within the Violaceae species seems ubiquitous, yet not all members of other families produce these macrocyclic peptides. The genus Palicourea Aubl. (Rubiaceae) contains hundreds of neotropical species of shrubs and small trees; however, only a few cyclotides have been discovered hitherto. Herein, five previously uncharacterized Möbius cyclotides within Palicourea sessilis and their pharmacological activities are described. Cyclotides were isolated from leaves and stems of this plant and identified as pase A-E, as well as the known peptide kalata S. Cyclotides were de novo sequenced by MALDI-TOF/TOF mass spectrometry, and their structures were solved by NMR spectroscopy. Because some cyclotides have been reported to modulate immune cells, pase A-D were assayed for cell proliferation of human primary activated T lymphocytes, and the results showed a dose-dependent antiproliferative function. The toxicity on other nonimmune cells was also assessed. This study reveals that pase cyclotides have potential for applications as immunosuppressants and in immune-related disorders.


Subject(s)
Cyclotides/drug effects , Cyclotides/metabolism , Fabaceae/chemistry , Lymphocytes/metabolism , Solanaceae/chemistry , Violaceae/chemistry , Brazil , Cyclotides/chemistry , Humans , Lymphocytes/chemistry , Lymphocytes/drug effects , Magnoliopsida , Mass Spectrometry , Plant Leaves/chemistry , Plant Leaves/metabolism
8.
J Nat Prod ; 83(10): 3012-3020, 2020 10 23.
Article in English | MEDLINE | ID: mdl-33001647

ABSTRACT

In a screening of an extract library from plants used in Traditional Chinese Medicine the MeOH extract of Toddalia asiatica inhibited proliferation of human primary T cells with an IC50 of 25.8 µg/mL. Activity in the extract was tracked by HPLC activity profiling, and a total of 15 compounds were characterized. Three compounds, toddalic acid (6) and both enantiomers (7a and 7b) of toddanolic acid (7), were new natural products, and two recently published compounds, (2'R)-toddalolactone 3'-O-ß-d-glucopyranoside (10) and (2'S)-toddalolactone 2'-O-ß-d-glucopyranoside (11), were described in detail for the first time. The absolute configurations of compounds 8, 9, 10, 12, 13, and 15 were determined by comparison of experimental and calculated ECD spectra. For glucosides 9 and 10, ECD data and chiral-phase HPLC of the aglycones after enzymatic hydrolysis confirmed the results. Nitidine chloride (4) inhibited proliferation of primary human T cells with an IC50 of 0.4 µM.


Subject(s)
Immunosuppressive Agents/pharmacology , Plant Extracts/pharmacology , Rutaceae , Coumarins , Glucosides , Molecular Structure , Plant Roots , Stereoisomerism
9.
Planta Med ; 86(2): 96-103, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31777053

ABSTRACT

Novel immunomodulating agents are currently sought after for the treatment of autoimmune diseases and cancers. In this context, a screening campaign of a collection of 575 cyanobacteria extracts for immunomodulatory effects has been conducted. The screening resulted in several active extracts. Here we report the results of subsequent studies on an extract from the cyanobacterium Hapalosiphon sp. CBT1235. We identified 5 hapalindoles as the compounds responsible for the observed immunomodulatory effect. These indole alkaloids are produced by several strains of the cyanobacterial family Hapalosiphonaceae. They are known for their anti-infective, cytotoxic, and other bioactivities. Modulation of the activity of human immune cells has not yet been described. The immunomodulatory activity of the hapalindoles was characterized in vitro using flow cytometry-based measurements of T cell proliferation after carboxyfluorescein diacetate succinimidyl ester staining, and apoptosis and necrosis induction after annexin V/propidium iodide staining. The most potent compound, hapalindole A, reduced T cell proliferation with an IC50 of 1.56 µM, while relevant levels of apoptosis were measurable only at 10-fold higher concentrations. Hapalindole A-formamide and hapalindole J-formamide, isolated for the first time from a natural source, had much lower activity than the nonformylated derivatives while, at the same time, being less selective for antiproliferative over apoptotic effects.


Subject(s)
Cell Proliferation/drug effects , Cyanobacteria/chemistry , Immunologic Factors/pharmacology , Indole Alkaloids/pharmacology , T-Lymphocytes/drug effects , Adult , Humans , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Indole Alkaloids/chemistry , Indole Alkaloids/isolation & purification , Molecular Structure , T-Lymphocytes/cytology
10.
J Nat Prod ; 82(6): 1424-1433, 2019 06 28.
Article in English | MEDLINE | ID: mdl-31181920

ABSTRACT

A library of extracts from plants used in Chinese Traditional Medicine was screened for inhibition of T lymphocyte proliferation. An ethyl acetate extract from aerial parts of Artemisia argyi showed promising activity and was submitted to HPLC-based activity profiling to track the active compounds. From the most active time window, three guaianolides (1, 2, and 5) and two seco-tanapartholides (3 and 4) were identified and, in a less active time window, five new sesquiterpene lactones (8-11, 17), along with six known sesquiterpene lactones and two known flavonoids. The absolute configurations of compounds 1, 2, 5-10, 13-15, 17, and 18 were established by comparison of experimental with calculated electronic circular dichroism (ECD) spectra. For seco-tanapartholides B (3) and A (4), ECD yielded ambiguous results, and their absolute configurations were determined by comparing experimental and calculated vibrational circular dichroism (VCD) spectra. Compounds 1-5 showed significant, noncytotoxic inhibition of T lymphocyte proliferation, with IC50 values between 1.0 and 3.7 µM.


Subject(s)
Artemisia/chemistry , Immunosuppressive Agents/chemistry , Lactones/chemistry , Plant Leaves/chemistry , Chromatography, High Pressure Liquid , Circular Dichroism , Immunosuppressive Agents/pharmacology , Lactones/pharmacology , Phytochemicals , Sesquiterpenes/pharmacology
11.
Proc Natl Acad Sci U S A ; 113(15): 3960-5, 2016 Apr 12.
Article in English | MEDLINE | ID: mdl-27035952

ABSTRACT

Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by auto-reactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2-dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders.


Subject(s)
Cell Proliferation/drug effects , Cyclotides/pharmacology , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Interleukin-2/metabolism , Multiple Sclerosis/drug therapy , T-Lymphocytes/drug effects , Animals , Cytokines/immunology , Disease Models, Animal , Disease Progression , Drug Evaluation, Preclinical , Inflammation/drug therapy , Mice , Mice, Inbred C57BL , Mice, Transgenic
12.
Planta Med ; 84(8): 519-526, 2018 May.
Article in English | MEDLINE | ID: mdl-29202511

ABSTRACT

Equisetum arvense, known as common horsetail, is used for the treatment of inflammatory diseases and is the plant with the highest concentration of silica. Yet it is unknown if the medicinal properties are mediated by its silica content. In the current study, optimal conditions for silica-rich horsetail preparations were identified. Bioactivity of the preparations was analyzed in vitro using flow cytometry-based activity and functionality profiling of primary human lymphocytes as well as cytokine measurement using a classical ELISA technique. Experiments revealed that horsetail preparations suppress activation and proliferation of lymphocytes by an interleukin-2-dependent mechanism. The effect increased with the silica concentration in the decoctions. Lymphocytes' polyfunctionality was also influenced, shown by a downregulation of IFN-γ. Analytical profiling by HPLC-UV-MS and bioactivity testing revealed relevant immunosuppressive concentrations of a component that has been identified as isoquercitrin. Our results show that both silica and isoquercitrin are active compounds of horsetail preparations.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Equisetum/chemistry , Plant Preparations/pharmacology , Quercetin/analogs & derivatives , Silicon Dioxide/pharmacology , Anti-Inflammatory Agents/chemistry , Chromatography, High Pressure Liquid , Humans , Lymphocytes/drug effects , Plant Preparations/chemistry , Quercetin/chemistry , Quercetin/isolation & purification , Quercetin/pharmacology , Silicon Dioxide/chemistry
13.
Planta Med ; 84(11): 813-819, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29466808

ABSTRACT

Among the known or suspected risk factors, inflammation plays an important role in infectious and non-infectious pathways leading to cancer. Green tea polyphenols have been associated with reducing inflammation and protection against carcinogenesis, especially in prostate cancer. While most of the research in this field, so far, has focussed on epigallocatechin-3-O-gallate only, we studied epicatechin-3-O-gallate, the second most abundant green tea polyphenol with essential therapeutic potential, to obtain a more detailed understanding of its anti-tumor and anti-inflammatory action. Furthermore, to improve the bioactivity of (-)-epicatechin-3-O-gallate, we synthesized a difluoro analogue, called (-)-5,7-difluoro-epicatechin-3-O-gallate. Both compounds reduced cell proliferation of human primary inflammatory lymphocytes in an apoptosis-specific fashion, while (-)-5,7-difluoro-epicatechin-3-O-gallate had a significantly higher activity compared to the natural product (-)-epicatechin-3-O-gallate. Treatment of low-metastatic LNCaP and high-metastatic PC-3 prostate cancer cells with (-)-epicatechin-3-O-gallate and (-)-5,7-difluoro-epicatechin-3-O-gallate demonstrated a dose-dependent inhibition of cell viability in the low micromolar range. These effects suggest that (-)-epicatechin-3-O-gallate and the more effective (-)-5,7-difluoro-epicatechin-3-O-gallate could be therapeutically used to inhibit tumorigenesis during initiation, promotion, and progression by diminishing the amount of inflammation due to a reduction of inflammatory lymphocytes. Further studies are needed to prove this in in vivo experiments.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Camellia sinensis/chemistry , Catechin/analogs & derivatives , Catechin/pharmacology , Prostatic Neoplasms/drug therapy , Tea/chemistry , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Apoptosis/drug effects , Catechin/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Fluorine , Humans , Inflammation/drug therapy , Inflammation/pathology , Lymphocytes/drug effects , Male , Polyphenols/chemistry , Polyphenols/pharmacology , Prostatic Neoplasms/pathology
14.
J Appl Toxicol ; 37(5): 563-572, 2017 05.
Article in English | MEDLINE | ID: mdl-27714827

ABSTRACT

Because different metals are used in complementary medicine for the treatment of diseases related to a dysfunction of the immune system, this study aimed at determining the immunomodulatory potential of Pb(NO3 )2 , AuCl3 , Cu(NO3 )2 , HgCl2 , AgNO3 , SnCl2 , AsCl3 and SbCl3 at sub-toxic concentrations and at assessing possible toxic side effects of low-concentrated metal preparations. The influence of the metal salts on primary human mononuclear cells was analyzed by measuring cell viability using the water-soluble tetrazolium salt assay, apoptosis and necrosis induction by annexin V/propidium iodide staining and proliferation by carboxyfluorescein diacetate succinimidyl ester staining and flow cytometry. Effects on T-cell activation were assessed with CD69 and CD25 expression using flow cytometry whereas CD83, CD86 and CD14 expression was measured to evaluate the influence on dendritic cell maturation. Alterations of interleukin-2 and interferon-γ secretion were detected by enzyme-linked immunosorbent assay and genotoxic effects were analyzed using the comet assay. At sub-toxic concentrations retardation of T-cell proliferation was caused by Pb(NO3 )2 , AuCl3 and Cu(NO3 )2 and inhibitory effects on interleukin-2 secretion were measured after incubation with Pb(NO3 )2 , AuCl3 , Cu(NO3 )2 , HgCl2 and AsCl3. Cu(NO3 )2 had immunosuppressive activity at dosages within the serum reference range for copper. All other metal salts showed effects at dosages above upper serum limits of normal. Therefore, only low-concentrated copper preparations are promising to have immunomodulatory potential. Toxic side effects of metal preparations used in complementary medicine are improbable because upper limits of metals set in the drinking water ordinance are either not exceeded or the duration of their application is limited. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Immunomodulation/drug effects , Metals/toxicity , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival , Comet Assay , Complementary Therapies , Cytokines/metabolism , Dendritic Cells/drug effects , Humans , Interferon-gamma/biosynthesis , Lymphocyte Activation/drug effects , Monocytes/drug effects , Necrosis/chemically induced , Necrosis/pathology , Neutrophils/drug effects , Salts , T-Lymphocytes/drug effects
15.
Z Naturforsch C J Biosci ; 72(7-8): 277-283, 2017 Jul 14.
Article in English | MEDLINE | ID: mdl-28315853

ABSTRACT

Tricholoma populinum Lange is an edible basidiomycete from the family Tricholomataceae. Extracts, fractions, and different metabolites isolated from the fruiting bodies of this mushroom were tested for degranulation-inhibiting activities on RBL-2H3 cells (rat basophils). Dichloromethane extracts decreased degranulation significantly, as did a fraction after column chromatography. In addition, the extract decreased the IL-2 release from Jurkat T cells and the release of IL-8 from HMC-1 human mast cells. The results show the significant effects of extracts of T. populinum on cells of the innate (basophils and mast cells) and adaptive (T cells) immune system and indicate the influence of the mushroom on different immunological processes. As one fraction showed activity, it seems to be possible that it includes an active principle. The compounds responsible for this effect, however, could not be identified as the contents oleic acid (1), ergosterol peroxide (2), and 9,11-dehydroergosterol peroxide (3) showed no effects. Nevertheless, the mushroom could be used for supporting allergy treatment in future studies.


Subject(s)
Basophils/drug effects , Biological Products/pharmacology , Cell Degranulation/drug effects , Mast Cells/drug effects , Tricholoma/chemistry , Animals , Basophils/physiology , Biological Products/chemistry , Cell Line , Cell Survival/drug effects , Chromatography, Gel/methods , Fruiting Bodies, Fungal/chemistry , Humans , Interleukin-2/metabolism , Interleukin-8/metabolism , Jurkat Cells , Magnetic Resonance Spectroscopy , Mast Cells/metabolism , Methylene Chloride/chemistry , Rats , Silica Gel/chemistry
16.
Planta Med ; 82(15): 1359-1367, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27428885

ABSTRACT

Inonotus hispidus is used as a traditional medicine in China. Previous investigations revealed promising immunomodulatory activity of fruit body extracts of I. hispidus. Bioactivity-guided fractionation showed that hispolon and hispidin were active substances.In this study, we analysed the effects of I. hispidus extract and selected constituents on different types of human immune cells and investigated the potential of I. hispidus extract as a medicinal mushroom. The influence of I. hispidus extract on activity and maturation of human T cells, purified natural killer cells, and dendritic cells was analysed using cytometric-based surface marker expression. The cell division characteristics of the activated T cells were assessed by membrane permeable dye, and the function of natural killer cells was investigated by a degranulation CD107a assay. Apoptosis induction was assessed by surface staining of phosphatidylserine, and camptothecin and cyclosporine A were used individually as controls. Phytochemical analysis, using TLC chromatograms and HPLC analysis, was conducted to characterise the I. hispidus extract. I. hispidus extract increased the activation and diminished the proliferation of activated human T cells in the presence of apoptosis. Natural killer cell activity and function were dose-dependently increased. Surface marker expression of dendritic cells demonstrated that I. hispidus extract has the potential to induce maturation. TLC and HPLC analyses showed that the extract contained hispidin and hispolon. Investigations using hispidin and hispolon demonstrated similar, albeit noncongruent, results with extracts on measured parameters.The results indicate that extracts from I. hispidus and their constituents, hispidin and hispolon, interfere with the function of multiple immune cells, thus providing a rationale for their potential as a medicinal mushroom.


Subject(s)
Basidiomycota/chemistry , Dendritic Cells/drug effects , Killer Cells, Natural/drug effects , Plant Extracts/pharmacology , T-Lymphocytes/drug effects , Antigens, CD/metabolism , Apoptosis/drug effects , Catechols/pharmacology , Cells, Cultured , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Dendritic Cells/immunology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Humans , Plant Extracts/chemistry , Pyrones/pharmacology , T-Lymphocytes/immunology
17.
BMC Complement Altern Med ; 16(1): 372, 2016 Sep 22.
Article in English | MEDLINE | ID: mdl-27660088

ABSTRACT

BACKGROUND: Medications from Anthroposophical Medicine (AM) are clinically used for the treatment of infections within a whole medical system but have not yet been evaluated regarding antibacterial effects. The aims of this study was to investigate antibacterial activity of AM medications in cell culture. METHODS: Screening of AM drug registers for preparations used to treat any kind of infection and being available in dilutions ≤ D2 and without alcoholic content. Selected medications were screened for antimicrobial activity against Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa using the agar diffusion method. For antimicrobial active preparations growth kinetics (drop plate method) and minimal inhibitory concentrations (MIC, macrodilution method) were determined. RESULTS: Thirty-three preparations matched the selection criteria and were chosen for own experiments. One of them (Berberis Decoctum D2) exhibited bactericidal activities against Bacillus subtilis and Staphylococcus aureus, including methicillin resistant strains. The MIC could be determined as 5 mg/ml. The effects could be related to the content of berberine in the extract. No activity towards gram-negative bacteria was found. The other tested extracts had no antibacterial effects. CONCLUSION: Berberis Decoctum D2 which is used in AM to treat infections exhibits bactericidal effects on Staphylococcus aureus, including methicillin resistant strains.

18.
BMC Complement Altern Med ; 15: 219, 2015 Jul 09.
Article in English | MEDLINE | ID: mdl-26156760

ABSTRACT

BACKGROUND: Preparations from anthroposophical medicine (AM) are clinically used to treat inflammatory disorders. We wanted to investigate effects of a selection of AM medications for parenteral use in cell-based systems in vitro. METHODS: Colchicum officinale tuber D3, Mandragora D3, Rosmarinus officinale 5% and Bryophyllum 5% were selected for the experiments. Induction of apoptosis and necrosis (human lymphocytes and dendritic cells [DCs]) and proliferation of lymphocytes as well as maturation (expression of CD14, CD83 and CD86) and cytokine secretion (IL-10, IL12p70) of DCs were analyzed. Furthermore, proliferation of allogeneic human T lymphocytes was investigated in vitro in coculture experiments using mature DCs in comparison to controls. RESULTS: The respective preparations did not induce apoptosis or necrosis in lymphocytes or DCs. Lymphocyte proliferation was dose-dependently reduced by Colchicum officinale tuber D3 while the viability was unchanged. Rosmarinus officinale 5%, but not the other preparations, dose-dependently inhibited the maturation of immature DCs, reduced secretion of IL-10 and IL-12p70 and slightly inhibited proliferation of allogeneic CD4(+) T-lymphocytes in coculture experiments with DCs. CONCLUSION: The selected preparations from AM for parenteral use are nontoxic to lymphocytes and DCs. Rosmarinus officinale 5% has immunosuppressive properties on key functions of the immune system which propose further investigation.


Subject(s)
Anthroposophy , Immunologic Factors/pharmacology , Plant Extracts/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Cytokines/metabolism , Dendritic Cells/drug effects , Humans , T-Lymphocytes/drug effects
19.
BMC Complement Altern Med ; 14: 283, 2014 Aug 04.
Article in English | MEDLINE | ID: mdl-25088216

ABSTRACT

BACKGROUND: In Europe, extracts of Equisetum arvense (common horsetail) have a long tradition in the treatment of inflammatory disorders. To understand the molecular basis for its use, we investigated the immunomodulatory capacity of a standardized commercially available common horsetail extract on human primary lymphocyte function in vitro. METHODS: The standardized extract of Equisetum arvense was phytochemically characterized. Effects on proliferation, viability and activity of mitogen-activated human lymphocytes were assessed in comparison to cyclosporine A using annexin V/propidium iodide staining assays and flow cytometry-based surface receptor characterization, respectively. Intracellular levels of effector molecules (IL-2, IFN-γ and TNF-α) were analyzed with cytokine assays. RESULTS: T cell proliferation was inhibited dose dependently by the Equisetum extract without induction of apoptosis or necrosis. This effect was mediated through inhibition of lymphocyte activation, specifically by diminishing CD69 and IL-2 surface receptor expression and intracellular IL-2 production. Furthermore, treatment with Equisetum arvense inhibited effector functions, as indicated by reduced production of IFN-γ and TNF-α. CONCLUSIONS: The data indicate that the used extract of Equisetum arvense interferes with the polyfunctionality of immunocompetent cells thereby providing an anti-inflammatory mode-of-action.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cytokines/immunology , Equisetum/chemistry , Lymphocytes/drug effects , Plant Extracts/pharmacology , T-Lymphocytes/drug effects , Adult , Anti-Inflammatory Agents/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Humans , Lymphocyte Activation/drug effects , Lymphocytes/immunology , Plant Extracts/chemistry , T-Lymphocytes/immunology
20.
Front Psychiatry ; 14: 1042440, 2023.
Article in English | MEDLINE | ID: mdl-36741125

ABSTRACT

Introduction: Classic psychedelics have been shown to exert therapeutic potential for the treatment of various psychiatric disorders, neuropsychiatric diseases, and neuronal damage. Besides their psychopharmacological activity, psychedelics have been reported to modulate immune functions. There has thus far been a sparse exploration of the direct immune-modulating effect of psychedelics on human immune cells in vitro. Since T cells are key mediators of several immune functions, inhibition of their function would increase the risk of infections. Methods: We investigated the effect of the classic psychedelics lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline on the proliferation and stimulated cytokine release of primary human T lymphocytes and on the stimulated NF-κB induction of monocytes. Results: We did not observe any relevant direct immune-modulatory effects of the tested classic psychedelics in either cell line. Discussion: We concluded that LSD, psilocin, DMT, or mescaline did not directly stimulate the proliferation or cytokine secretion of primary human T lymphocytes or stimulate NF-κB induction of monocytes. Our findings support the future safe use of classic psychedelics in assisted psychotherapy in patients with life-threatening diseases where immune suppression and diminished immune function would be detrimental.

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