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1.
Ann Med ; 55(2): 2269969, 2023.
Article in English | MEDLINE | ID: mdl-37851870

ABSTRACT

BACKGROUND/OBJECTIVE: Plant-based diets reduce the risk of cardiovascular disease but also increase the risk of certain micronutrient deficiencies, particularly, of vitamin B12 (B12). The extent to which the unsupervised use of oral nutrient supplements is sufficient to prevent these deficiencies is not well established. We analyzed nutrient intake, laboratory biomarkers, supplementation behavior, and B12 status adequacy amongst young, healthy, physically active omnivores, lacto-ovo-vegetarians and vegans from Germany. METHODS: We recruited 115 participants (n = 40 omnivores; n = 37 lacto-ovo-vegetarians, and n = 38 vegans) with comparable age, sex, marital status, physical activity and educational levels through online advertisements and local newspapers in Freiburg, Germany. RESULTS: Energy intake and macronutrient distribution were comparable across diets. Major differences included intake of fiber, cholesterol, and several vitamins. Vegans had the lowest intake of B12 from foods (0.43 (0.58) µg/d), compared to omnivores (2.14 (2.29) µg/d) and lacto-ovo-vegetarians (0.98 (1.34) µg/day). Multivariate analysis of 36 blood biomarkers revealed that three major classes of biomarkers contributed the most to the clustering of individuals by dietary group, namely, biomarkers of B12 status (B12, holoTC, Hcy), iron (iron, ferritin, transferrin) and lipid metabolism (vitamin A, HDL, LDL, total cholesterol, TAG). This suggests that nutrients that modify the metabolic pathways represented by these biomarkers have the most penetrating effect on health status across diets. Analysis of B12 status (including 4cB12) revealed adequacy in omnivores and vegans, and a poorer B12 status amongst lacto-ovo-vegetarians. Fewer lacto-ovo-vegetarians used B12 supplements compared to vegans (51% versus 90%). CONCLUSIONS: Even amongst homogeneously healthy Germans, each diet manifested with measurable differences in dietary intakes and biomarkers of health. Plant-based diets, in particular the vegan diet, exhibited the most favorable patterns of lipid metabolism and glycemic control, but the lowest food intake of B12. Supplementation of healthy vegans with B12 (median 250 µg B12/day, over 2 years) secured an adequate B12 status that was comparable to that of healthy omnivores.Clinical Trial Registry: German Clinical Trial register number: DRKS00027425.


Plant-based diets, in particular the vegan diet, exhibited the most favorable patterns of lipid metabolism and glycemic control, but the lowest food intake of B12.Analysis of B12 status (including 4cB12) revealed adequacy in omnivores and vegans, and a poorer B12 status amongst lacto-ovo-vegetarians.Supplementation with B12 (median 250 µg B12/day, over 1 year) in healthy physically-active vegans secured an adequate B12 status that was comparable to that of healthy omnivores.


Subject(s)
Diet, Vegan , Vegans , Humans , Nutritional Status , Vitamin B 12 , Cross-Sectional Studies , Diet, Vegetarian , Vegetarians , Diet , Dietary Supplements , Vitamins , Cholesterol , Iron , Biomarkers
2.
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
3.
Int Immunopharmacol ; 103: 108448, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34998274

ABSTRACT

BACKGROUND: Cannabis sativa L. extracts (CSE) are used for treating inflammatory conditions, but little is known about their immunomodulatory effects. We investigated a novel CSE with high (14%) CBD and low (0.2%) THC concentration in comparison with pure CBD on primary human lymphocytes. METHODS: Proliferation, cell cycle distribution, apoptosis/necrosis and viability were analysed with standard methods. Genotoxicity was evaluated with the comet-assay. The effect on T lymphocyte activation was evaluated via CD25/CD69 marker expression, degranulation assays and the production of cytokines. The influence on the transcription factors was analysed using Jurkat reporter cell lines. Specific CB2 receptor antagonist SR144528 and TRPV1 receptor antagonist A78416B were used to study the involvement of CB2 or TRPV1 receptors. RESULTS: CSE inhibited the proliferation of activated T lymphocytes in a dose-dependent manner without inducing apoptosis, necrosis, or affecting cell viability and DNA integrity. The inhibitory effect was mediated via the suppression of T lymphocytes activation, particularly by the suppression of CD25 surface marker expression. Furthermore, CSE interferes with the functionality of the T lymphocytes, as indicated by inhibition of degranulation, IL-2, and IFN-γ production. AP-1-and-NFAT-reporter activation was reduced implicating an AP-1-and-NFAT-mediated mode of action. The effects were in part reversed by SR144528 and A78416B, showing that the effects were mainly mediated by CB2 and TRPV1 receptors. CONCLUSION: CSE and CBD have immunomodulatory effects and interfere with the activation and functionality of T lymphocytes. A comparison between CSE and CBD suggests that the immunosuppressive effect of CSE is mostly due to the effect of CBD.


Subject(s)
Immunosuppressive Agents/metabolism , Plant Extracts/metabolism , T-Lymphocytes/immunology , Apoptosis , Cannabis/immunology , Cell Degranulation , Cell Proliferation , Cells, Cultured , Gene Expression Regulation , Humans , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/metabolism , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Plant Extracts/immunology , Psychotropic Drugs , Receptor, Cannabinoid, CB2/metabolism , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism
4.
Biomed Pharmacother ; 144: 112326, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34653757

ABSTRACT

Some plants used in Traditional Chinese Medicine serve as treatment for disease states where a suppression of the cellular immune response is desired. However, the compounds responsible for the immunosuppressant effects of these plants are not necessarily known. The immunosuppressant compounds in the roots of Scutellaria baicalensis, one of the most promising plants identified in a previous screening, were tracked by HPLC activity profiling and concomitant on-line spectroscopic analysis. Compounds were then isolated by preparative chromatography, and structures elucidated by spectroscopic methods. Twelve flavonoids (5-16) were identified from the active time windows, and structurally related flavones 2, 4, and 17, and flavanones 1 and 3 were isolated from adjacent fractions. All flavonoids possessed an unusual substitution pattern on the B-ring, with an absence of substituents at C-3 and C-4. Compounds 11, 13, 14, and 16 inhibited T-cell proliferation (IC50 values at 12.1-39 µM) at non-cytotoxic concentrations. The findings may support the use of S. baicalensis in disorders where a modulation of the cellular immune response is desirable.


Subject(s)
Cell Proliferation/drug effects , Flavonoids/pharmacology , Immunosuppressive Agents/pharmacology , Lymphocyte Activation/drug effects , Plant Extracts/pharmacology , Scutellaria baicalensis , T-Lymphocytes/drug effects , Cells, Cultured , Flavonoids/isolation & purification , Humans , Immunosuppressive Agents/isolation & purification , Molecular Structure , Plant Extracts/isolation & purification , Plant Roots , Scutellaria baicalensis/chemistry , Structure-Activity Relationship , T-Lymphocytes/immunology
5.
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
6.
Fitoterapia ; 146: 104694, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32712132

ABSTRACT

Resins from various Boswellia species have a long track record in different cultures as a treatment for inflammatory diseases. This study was designed to provide evidence for the anti-inflammatory capacity and medicinal use of Boswellia carteri (Burseraceae). A dichloromethane (DCM) extract of B. carteri gum resin and isolated compounds thereof were immunologically characterized. Flow cytometric-based analysis was performed to investigate the impact of B. carteri extract on proliferation, viability, and function of anti-CD3 and anti-CD28 activated human primary T cells. The secretion level of IL-2 and IFN-γ was determined by a bead array-based flow cytometric technique. HPLC-based activity profiling of the B. carteri extract identified active compounds. The impact of B. carteri extract and isolated compounds on the IL-2 transcription factor activity was addressed using specially designed Jurkat reporter cells. The extract of B. carteri suppressed the proliferation of human primary T lymphocytes in vitro in a concentration-dependent manner, without inducing cytotoxicity. Thereby, the B. carteri extract further reduced the degranulation capacity and cytokine secretion of stimulated human T cells. Transcription factor analysis showed that the immunosuppressive effects of the extract are based on specific NFAT-conditioned suppression within T cell signaling. Through HPLC-based activity profiling of the extract, 3-O-acetyl-alpha-boswellic acid was identified as the compound responsible for the NFAT-based mechanism. The recent study presents a scientific base for the immunosuppressive effects of B. carteri gum resin extract including a mode-of-action via the NFAT-conditioned suppression of T lymphocyte proliferation. The immunosuppressive effects of 3-O-acetyl-alpha-boswellic acid are depicted for the first time.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Boswellia/chemistry , Immunosuppressive Agents/pharmacology , Plant Extracts/pharmacology , T-Lymphocytes/drug effects , Triterpenes/pharmacology , Anti-Inflammatory Agents/isolation & purification , Apoptosis , Cell Degranulation/drug effects , Cell Proliferation/drug effects , Cytokines/analysis , Humans , Immunosuppressive Agents/isolation & purification , Jurkat Cells , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Resins, Plant/pharmacology , Triterpenes/isolation & purification
7.
Front Pharmacol ; 11: 402, 2020.
Article in English | MEDLINE | ID: mdl-32322200

ABSTRACT

The need for novel drugs for the treatment of autoimmune diseases is high, since available pharmaceuticals often have substantial side effects and limited efficacy. Natural products are a good starting point in the development of immunosuppressive leads. Since enhanced T cell proliferation is a common feature of autoimmune diseases, we investigated the T cell proliferation inhibitory potential of an extract library of plants used in traditional Chinese medicine. Using a newly established cell-based screening platform, an ethyl acetate extract of Artemisia argyi H.Lév. & Vaniot (Asteraceae, A. argyi) was found to suppress the proliferation of human primary T lymphocytes in vitro in an IL-2-dependent manner. Flow cytometry- and ELISA-based techniques further demonstrated that the A. argyi extract reduced the activation and function of T cells. Transcription factor analysis and flow cytometric calcium influx investigations indicated that the immunomodulatory effect was based on specific modification of T cell signaling in a non-cytotoxic manner which is mediated via the NFAT pathway and a non-sequestrant inhibition of the calcium influx. A series of guaianolide and seco-guaianolide sesquiterpene lactones, as well as a flavonoid, were identified in a previous study as the bioactive compounds in the A. argyi extract. The effects of these bioactive compounds were compared to those of the crude extract. The tested sesquiterpene lactones act via the transcription factor NFAT and NF-κB, thereby exhibiting their immunosuppressive potential, but have an overall effect on T cell biology on a more-downstream level than the crude A. argyi extract.

8.
J Ethnopharmacol ; 235: 415-423, 2019 May 10.
Article in English | MEDLINE | ID: mdl-30794862

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The improvement of wound healing has always been an important issue for both ethnopharmacological and modern medical research. In this study, we used state-of-the-art methods to investigate extracts of plants used traditionally in Nepal for more than 1000 years to treat inflammatory injuries. AIM OF THE STUDY: We focused on the potential of the plant extracts to ameliorate wound healing and to influence immune modulatory properties. MATERIALS AND METHODS: Nine Nepalese plant extracts in three different solvents (methanol, ethyl acetate, petroleum ether) were immunologically characterised. Water-soluble tetrazolium (WST-1) assays and scratch assays were performed to determine their impact on viability and wound healing capacity of human keratinocytes and fibroblasts. Effects on proliferation, viability and function of physiologically relevant anti-CD3 and anti-CD28 stimulated primary human T lymphocytes were assessed using carboxyfluorescein succinimidyl ester (CFSE), annexin V/propidium iodide staining assays and flow cytometry-based surface receptor characterisation. The secretion level of interleukin-2 (IL-2) was analysed with the ELISA technique. Dendritic cells were generated out of peripheral blood mononuclear cells (PBMC) by CD14+ magnetic bead selection. Flow cytometry-based surface receptor characterisation and ELISA-based technique were used to evaluate the DC activation state and the interleukin-8 (IL-8) secretion level. RESULTS: We demonstrate that an ethyl acetate extract of Bassia longifolia and of Gmelina arborea have anti-inflammatory capacities, indicated by reduced proliferation, inhibition of IL-2 secretion and degranulation capacity of activated human T cells, when compared with adequate concentrations of synthetic positive drug controls. Furthermore, Gmelina arborea improved the wound healing of keratinocytes and fibroblasts and has tendency to increase the secretion of IL-8 by human primary dendritic cells. CONCLUSION: With this preliminary screening, we offer a scientific basis for the immunomodulatory properties of the two Nepalese medicinal plants Bassia longifolia and Gmelina arborea. However, further detailed studies regarding the responsible compounds are necessary.


Subject(s)
Immunologic Factors/pharmacology , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Wound Healing/drug effects , Adult , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Dendritic Cells/drug effects , Enzyme-Linked Immunosorbent Assay , Fibroblasts/drug effects , Fibroblasts/metabolism , Flow Cytometry , Humans , Immunologic Factors/isolation & purification , Keratinocytes/drug effects , Keratinocytes/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Medicine, Traditional , Nepal , Solvents/chemistry
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