Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B12. Little is known about the short-term effects of dietary change to plant-based nutrition on vitamin B12 metabolism. Systemic biomarkers of vitamin B12 status, namely, serum vitamin B12 and holotranscobalamin, may respond quickly to a reduced intake of vitamin B12. To test this hypothesis, 53 healthy omnivore subjects were randomized to a controlled unsupplemented vegan diet (VD, n = 26) or meat-rich diet (MD, n = 27) for 4 weeks. Vitamin B12 status was examined by measurement of serum vitamin B12, holotranscobalamin (holo-TC), methylmalonic acid (MMA) and total plasma homocysteine (tHcy). Holo-TC decreased significantly in the VD compared to the MD group after four weeks of intervention, whereas metabolites MMA and tHcy were unaffected. Body weight remained stable in both groups. VD intervention led to a significant reduction of cholesterol intake, and adequate profiles of nutrient and micronutrient status. Lower intake of vitamin B12 was observed in VD, which was mirrored by a lower concentration of serum vitamin B12 and reduced holo-TC after 4 weeks. Plasma holo-TC may be a fast-responding biomarker to monitor adequate supply of vitamin B12 in plant-based individuals.
The composition of diet strongly affects acid–base homeostasis. Western diets abundant in acidogenic foods (meat and cheese) and deficient in alkalizing foods (fruits and vegetables) increase dietary acid load (DAL). A high DAL has been associated with numerous health repercussions, including cardiovascular disease and type-2-diabetes. Plant-based diets have been associated with a lower DAL; however, the number of trials exploring this association is limited. This randomized-controlled trial sought to examine whether an isocaloric vegan diet lowers DAL as compared to a meat-rich diet. Forty-five omnivorous individuals were randomly assigned to a vegan diet (n = 23) or a meat-rich diet (n = 22) for 4 weeks. DAL was determined using potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores at baseline and after 3 and 4 weeks, respectively. After 3 weeks, median PRAL (−23.57 (23.87)) and mean NEAPR (12.85 ± 19.71) scores were significantly lower in the vegan group than in the meat-rich group (PRAL: 18.78 (21.04) and NEAPR: 60.93 ± 15.51, respectively). Effects were mediated by a lower phosphorus and protein intake in the vegan group. Our study suggests that a vegan diet is a potential means to reduce DAL, whereas a meat-rich diet substantially increases the DAL burden.
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.
Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays. Furthermore, we examined whether VAEI was able to counteract tumor-induced immunosuppression within this cellular system using a renal cancer cell model. The role of mistletoe lectin (ML) was analyzed using ML-specific antibodies and ML-depleted VAEI. VAEI and VAEA augmented the maturation of dendritic cells. VAEI abrogated tumor-induced immunosuppression of dendritic cells and both processes were partially mediated by ML since ML-depleted VAEI and ML-specific antibodies almost neutralized the rehabilitative effects of VAEI on DC maturation. Using these settings, co-culture experiments with purified CD4+ T cells had no influence on T cell proliferation and activation but did have an impact on IFN-γ secretion. The study provides a potential mode-of-action of VAE as an additive cancer therapy based on immunomodulatory effects. However, the impact on the in vivo situation has to be evaluated in further studies.
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-kB, 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.
is used as a traditional medicine in China. Previous investigations revealed promising immunomodulatory activity of fruit body extracts of . Bioactivity-guided fractionation showed that hispolon and hispidin were active substances.In this study, we analysed the effects of extract and selected constituents on different types of human immune cells and investigated the potential of extract as a medicinal mushroom. The influence of 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 extract. 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 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 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.
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--gallate only, we studied epicatechin-3--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--gallate, we synthesized a difluoro analogue, called (-)-5,7-difluoro-epicatechin-3--gallate. Both compounds reduced cell proliferation of human primary inflammatory lymphocytes in an apoptosis-specific fashion, while (-)-5,7-difluoro-epicatechin-3--gallate had a significantly higher activity compared to the natural product (-)-epicatechin-3--gallate. Treatment of low-metastatic LNCaP and high-metastatic PC-3 prostate cancer cells with (-)-epicatechin-3--gallate and (-)-5,7-difluoro-epicatechin-3--gallate demonstrated a dose-dependent inhibition of cell viability in the low micromolar range. These effects suggest that (-)-epicatechin-3--gallate and the more effective (-)-5,7-difluoro-epicatechin-3--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 experiments.
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