Emodin inhibits the differentiation and maturation of dendritic cells and increases the production of regulatory T cells

Zhang, Wei; Li, Hong; Bu, He‐Qi; Chen, Hui; Tong, Hongfei; Liu, Dianlei; Guo, Hong-Chun; Lin, Sensen

doi:10.3892/ijmm.2011.820

Cited by 11 publications

(4 citation statements)

References 25 publications

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“…It remains to be determined why emodin differentially impacts CD11c + CD86 + and CD11c + CD80 + subsets of DCs in the LNs and spleens of the recipient mice. However, our results are actually consistent with a previous study showing that emodin inhibited DC maturation in vitro (53), implying that emodin indeed suppresses DC differentiation or maturation. It is also unclear how emodin reduces DC numbers.…”

Section: Figure 7 | Depleting Regulatory T Cells (Tregs) Largely Revesupporting

confidence: 93%

A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection

et al. 2017

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Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity. In this study, we investigated the capacity of emodin, an anthraquinone molecule originally extracted from certain natural plants, to prolong transplant survival in a mouse model and explored the cellular and molecular mechanisms underlying its action. We found that emodin significantly extended skin allograft survival and hindered CD3+ T cell infiltration in the allograft, accompanied by an increase in CD4+Foxp3+ and CD8+CD122+ Treg frequencies and numbers but a reduction in effector CD8+CD44highCD62Llow T cells in recipient mice. Emodin also inhibited effector CD8+ T cells proliferation in vivo. However, CD4+CD25+, but not CD8+CD122+, Tregs derived from emodin-treated recipients were more potent in suppression of allograft rejection than those isolated from control recipients, suggesting that emodin also enhances the suppressive function of CD4+CD25+ Tregs. Interestingly, depleting CD25+ Tregs largely reversed skin allograft survival prolonged by emodin while depleting CD122+ Tregs only partially abrogated the same allograft survival. Furthermore, we found that emodin hindered dendritic cell (DC) maturation and reduced alloantibody production posttransplantation. Finally, we demonstrated that emodin inhibited in vitro proliferation of T cells and blocked their mTOR signaling as well. Therefore, emodin may be a novel mTOR inhibitor that suppresses alloimmunity by inducing both CD4+FoxP3+ and CD8+CD122+ Tregs, suppressing alloantibody production, and hindering DC maturation. Thus, emodin is a newly emerging immunosuppressant and could be utilized in clinical transplantation in the future.

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Section: Figure 7 | Depleting Regulatory T Cells (Tregs) Largely Revesupporting

confidence: 93%

A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection

et al. 2017

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“…AE not only exerts antineoplastic and anti-inflammatory actions, but also inhibits the differentiation and maturation of dendritic cells (DCs), induces the proliferation of T lymphocytes in vitro [ 40 ], and affects Natural killer (NK) cell activity in a dose-dependent manner [ 41 ]. This suggests that AE has a significant effect on the immune system.…”

Section: Resultsmentioning

confidence: 99%

Peptide-Mediated Targeted Delivery of Aloe-Emodin as Anticancer Drug

Stringaro

Serra²,

Gori³

et al. 2022

Molecules

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Breast cancer is one of the most diffuse cancers in the world and despite the availability of the different drugs employed against it, the need for new and particularly more specific molecules is ever growing. In this framework, natural products are increasingly assuming an important role as new anticancer drugs. Aloe-emodin (AE) is one of the best characterized molecules in this field. The functionalization of bioactive natural products with selected peptide sequences to enhance their bioavailability and specificity of action is a powerful and promising strategy. In this study, we analyzed the cell specificity, cell viability effects, intracellular distribution, and immune cell response of a new peptide conjugate of Aloe-emodin in SKBR3 and A549 cell lines by means of viability tests, flow cytometry, and confocal microscopy. The conjugate proved to be more effective at reducing cell viability than AE in both cell lines. Furthermore, the results showed that it was mainly internalized within the SKBR3 cells, showing a nuclear localization, while A459 cells displayed mainly a cytoplasmic distribution. A preserving effect of the conjugate on NKs’ cell function was also observed. The designed conjugate showed a promising specific activity towards HER2-expressing cells coupled with an enhanced water solubility and a higher cytotoxicity; thus, the resulting proof-of-concept molecule can be further improved as an anticancer compound.

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“…[ 22 ] Emodin also acts as an anti-inflammatory agent by inhibiting the differentiation and maturation of dendritic cells and increasing the number of regulatory T-cells. [ 23 ] Astragaloside is a main active ingredient in traditional Chinese medicine and acts both as an anti-inflammatory and antifibrotic agent,[ 24 25 ] while salvianolic acid A has been shown to have cardiovascular protective effects. [ 26 27 ] Recent studies have shown that compound Danshen dripping pills, which contain salvianolic acid A, can prevent contrast-induced nephropathy in patients with acute coronary syndrome.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction

Zheng

Cai

et al. 2017

Chinese Medical Journal

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Background:Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods:The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min−1·1.73 m−2, aged 18–70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis.Results:A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (−13.0–24.1) and 11.7 (−2.6–42.9) μmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was −0.2 (−4.3–2.7) and −2.2 (−5.7–0.8) ml·min−1·1.73 m−2, respectively (Z = −2.408, P = 0.016). There were no significant differences in adverse events between the groups.Conclusions:Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.Trial Registration:Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

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Emodin inhibits the differentiation and maturation of dendritic cells and increases the production of regulatory T cells

Cited by 11 publications

References 25 publications

A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection

A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection

Peptide-Mediated Targeted Delivery of Aloe-Emodin as Anticancer Drug

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction

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