20-Hydroxyecdysone from Dacrycarpus imbricatus bark inhibits the proliferation of acute myeloid leukemia cells

Abstract Objective To investigate the anti-proliferative effects of 20-hydroxyecdysone isolated from the bark of Dacrycarpus imbricatus (Blume) de Laub. Methods Column chromatography was used for isolation of compounds from plant material. The structure of the isolated compound was identified by mass spectrometry and nuclear magnetic resonance techniques, including HSQC, HMBC, NOE-difference experiments. The isolated compound was tested for its anti-proliferative activity in acute myeloid leukemia (AML) and OCI-AML cells. Results Compound 1 was isolated from the ethyl acetate fraction of Dacrycarpus imbricatus barks by column chromatography. Its chemical structure was identified as 20-hydroxyecdysone (20HE), a cholestane-type ecdysteroid, by a combination of mass spectrometry and nuclear magnetic resonance spectrometric analyses. Our goal was to test the anti-proliferative activity of 20HE using the OCI-AML cell line. 20HE significantly decreased OCI cell number at a concentration of 1 mg/mL, whereas lower concentrations were ineffective. Moreover, this decrease was due to partial blockage of the G 1 /S phase of the cell cycle, with a reduction of cells in the G 2 M phase, not due to increased apoptosis. Conclusions This indicates that 20HE significantly decreases the number of cells in the G 1 /S phase of the cell cycle in human AML cells. This is the first time that the anti-proliferative activity of 20HE against a human tumor cell line has been reported

Kaempferol, quercetin và dẫn xuất diglycosid của chúng tách từ lá chay bắc bộ (Artocarpus tonkinensis)

The present study reported the isolation and identification of five flavonols named kaempferol, kaempferol 3-rutinoside, kaempferol 3-neohesperidoside, quercetin-3-O-b-D-glucopyranoside and quercetin 3-rutinoside from the leaves of Artocarpus tonkinensis A. Chev. ex  Gagnep. Their structures were identified by combination of spectroscopic methods (NMR, HR-ESI-MS) and comparison with reported data. Three flavonol glycosides kaempferol 3-rutinoside, kaempferol 3-neohesperidoside and quercetin 3-rutinoside were found for the first time in the genus Artocarpus J.R. Forst. G. Forst. Keywords. Artocarpus tonkinensis; astragalin; kaempferol 3-rutinoside; kaempferol 3-neohesperidoside; quercetin 3-rutinoside

INVESTIGATING THE ANTI-INFLAMMATORY ACTIVITY OF AN ETHANOLIC EXTRACT FROM ARTOCARPUS TONKINENSIS LEAVES USING A COLLAGEN ANTIBODY-INDUCED ARTHRITIC MOUSE MODEL

The obtained results here demonstrate that the 70% ethanolic leaf extract of A. tonkinensis (AT2), traditionally used in Vietnamese folk medicine for treating arthritic symtoms, has beneficial effects on pro-inflammatory cytokine inhibition and in an experimental arthritic mouse model. LPS-stimulated RAW 264.7 macrophages treated with AT2 showed a significant decrease in the production of IL-6 and TNFa at concentrations of 12.5, 25 and 50 µg/mL (P0.05), indicating its potential anti-inflammatory properties. Treatment of CAIA mice with AT2 also led to diminish the incidence of arthritis at doses of 200 and 300 mg/kg body weight

Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

Programmed cell death protein 1 (PD-1) and its ligands, PD-L1/2, control T cell activation and tolerance. While PD-1 expression is induced upon T cell receptor (TCR) activation or cytokine signaling, PD-L1 is expressed on B cells, antigen presenting cells, and on non-immune tissues, including cancer cells. Importantly, PD-L1 binding inhibits T cell activation. Therefore, the modulation of PD-1/PD-L1 expression on immune cells, both circulating or in a tumor microenvironment and/or on the tumor cell surface, is one mechanism of cancer immune evasion. Therapies that target PD-1/PD-L1, blocking the T cell-cancer cell interaction, have been successful in patients with various types of cancer. Glucocorticoids (GCs) are often administered to manage the side effects of chemo- or immuno-therapy, exerting a wide range of immunosuppressive and anti-inflammatory effects. However, GCs may also have tumor-promoting effects, interfering with therapy. In this review, we examine GC signaling and how it intersects with PD-1/PD-L1 pathways, including a discussion on the potential for GC- and PD-1/PD-L1-targeted therapies to “confuse” the immune system, leading to a cancer cell advantage that counteracts anti-cancer immunotherapy. Therefore, combination therapies should be utilized with an awareness of the potential for opposing effects on the immune system

Role of Endogenous Glucocorticoids in Cancer in the Elderly

Although not a disease itself, aging represents a risk factor for many aging-related illnesses, including cancer. Numerous causes underlie the increased incidence of malignancies in the elderly, for example, genomic instability and epigenetic alterations that occur at cellular level, which also involve the immune cells. The progressive decline of the immune system functions that occurs in aging defines immunosenescence, and includes both innate and adaptive immunity; the latter undergoes major alterations. Aging and chronic stress share the abnormal hypothalamic⁻pituitary⁻adrenal axis activation, where altered peripheral glucocorticoids (GC) levels and chronic stress have been associated with accelerated cellular aging, premature immunosenescence, and aging-related diseases. Consequently, changes in GC levels and sensitivity contribute to the signs of immunosenescence, namely fewer naïve T cells, poor immune response to new antigens, decreased cell-mediated immunity, and thymic involution. GC signaling alterations also involve epigenetic alterations in DNA methylation, with transcription modifications that may contribute to immunosenescence. Immune cell aging leads to decreased levels of immunosurveillance, thereby providing tumor cells one more route for immune system escape. Here, the contribution of GC secretion and signaling dysregulation to the increased incidence of tumorigenesis in the elderly is reviewed

Herbal Dietary Supplements for Erectile Dysfunction: A Systematic Review and Meta-Analysis

Purpose: Erectile dysfunction (ED) is a common condition that significantly affects quality of life and interpersonal relationships. Objective: Our objective was to perform a systematic review and meta-analysis to evaluate the efficacy of herbal dietary supplements in the treatment of ED. Materials and Methods: We searched five databases to identify randomized controlled trials (RCTs) that evaluated the clinical efficacy of herbal medicines in ED. Quality was assessed and risk of bias was estimated using the Jadad score and the Cochrane risk-of-bias tool. Results: In total, 24 RCTs, including 2080 patients with ED, were identified. Among these, 12 evaluated monopreparations (five ginseng [n = 399], three saffron [n = 397], two Tribulus terrestris [n = 202], and one each Pinus pinaster [n = 21] and Lepidium meyenii [n = 50]), seven evaluated formulations (n = 544), and five investigated dietary supplements in combination with pure compounds (n = 410). Ginseng significantly improved erectile function (International Index of Erectile Function [IIEF]-5 score: 140 ginseng, 96 placebo; standardized mean difference [SMD] 0.43; 95% confidence interval [CI] 0.15\u20130.70; P < 0.01; I 2 = 0), P. pinaster and L. meyenii showed very preliminary positive results, and saffron and T. terrestris treatment produced mixed results. Several herbal formulations were associated with a decrease of IIEF-5 or IIEF-15, although the results were preliminary. The quality of the included studies varied, with only seven having a prevalent low risk of bias. The median methodological quality Jadad score was three out of a maximum of five. Adverse events were recorded in 19 of 24 trials, with no significant differences between placebo and verum in placebo-controlled studies. Conclusions: Encouraging evidence suggests that ginseng may be an effective herbal treatment for ED. However, further, larger, and high-quality studies are required before firm conclusions can be drawn. Promising (although very preliminary) results have also been generated for some herbal formulations. Overall, more research in the field, adhering to the CONSORT statement extension for reporting trials, is justified before the use of herbal products in ED can be recommended

Effect of p53 activation through targeting MDM2/MDM4 heterodimer on T regulatory and effector cells in the peripheral blood of Type 1 diabetes patients.

Various immunotherapies for the treatment of type 1 diabetes are currently under investigation. Some of these aim to rescue the remaining beta cells from autoimmune attack caused by the disease. Among the strategies employed, p53 has been envisaged as a possible target for immunomodulation. We studied the possible effect of p53 activation on Treg subsets and Treg/Teff balance in type 1 diabetes patients' PBMC. Upon p53 activation, we observed an increase in CD8+ Treg and activated CD8+ Teff whilst CD8+ Teff cells significantly decreased in healthy PBMC when stimulated with anti-CD3/CD28. No effect was detected on percentages of CD4+ Treg, while a reduction was seen in CD4+ Teff cells and an increase in activated CD4+ Teff cells. In patients' PBMC, upon p53 activation followed by 6 days of anti-CD3/CD28 stimulation, CD8+ Treg and activated CD8+ Teff were increased while CD8+ Teff were decreased. No differences were detected in the CD4+ counterparts. CD8+ Teff PD1+, CD8+ Teff PD1low were increased upon p53 activation in type 1 diabetics compared to controls while CD8+ Teff PD1high were increased in both groups. The same increased percentages were detected for CD4+ counterparts. CD4+ Treg PD1high cells were decreased in diabetics upon p53 activation at day 6 of anti-CD3/CD28 stimulation. In conclusion, a Teff dysregulation is observed upon p53 activation suggesting that molecules promoting p53 cannot be used for therapy in type 1 diabetics