| Description: |
Emodin has neuroprotective and antidepressant activity, can up-regulate GR and BDNF levels in hippocampus; it also has significant anti-neoplastic activity against bladder cancer cells and myeloid leukemia, by suppressing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), iNOS and COX-2 expression.
Emodin has protective effects, may be related to the inhibition of CCL5 expression and subsequent cell stress/inflammatory events possibly mediated by activation of MAPK signaling pathways. |
| Targets: |
p38MAPK | ERK | PARP | Caspase | PI3K | Akt | Bcl-2/Bax | mTOR | NF-kB | IkB | JNK | PPAR | NOS | COX | IL Receptor | TNF-α | IKK |
| In vitro: |
| Biochem Pharmacol. 2015 Mar 1;94(1):39-45. | | Protection of vascular endothelial cells from high glucose-induced cytotoxicity by emodin.[Pubmed: 25619422] | Induction of endothelial cytotoxicity by hyperglycemia in diabetes has been widely accepted. Emodin is a natural anthraquinone in rhubarb used for treatment of diabetes, but its mechanism of action is not fully understood. This study aimed to examine the potential beneficial effects of emodin on endothelial cytotoxicity caused by high glucose milieu.
METHODS AND RESULTS:
Culture of human umbilical vein endothelial cells (HUVECs) with high concentrations of glucose resulted in damage to the cells, leading to decreased formazan products by 14-27%, reduced DNA contents by 12-19%, and increased hypodiploid apoptosis by 40-109%. These adverse effects of high glucose could be prevented to a large extent by co-culture with 3 μM of emodin which per se did not affect HUVECs viability. In addition, CCL5 expression of HUVECs cultured in high glucose medium was significantly elevated at both mRNA and protein levels, an effect abolished after treatment with emodin. Moreover, the enhanced adhesion of monocytes to HUVECs (2.1-2.2 fold over control) and elevated chemotaxis activities (2.3-2.4 fold over control) in HUVECs cultured in high glucose medium were completely reversed by emodin. Emodin also suppressed activation of p38 MAPK and ERK1/2 due to high glucose.
CONCLUSIONS:
Our data demonstrated that endothelial cytotoxicity occurred clearly when HUVECs were exposed to high glucose milieu and emodin was able to alleviate the impairments. The protective effects of emodin might be related to the inhibition of CCL5 expression and subsequent cell stress/inflammatory events possibly mediated by activation of MAPK signaling pathways. | | Int J Oncol. 2014 Nov;45(5):2076-84. | | Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells.[Pubmed: 25174432] | Emodin, an extracted natural compound from the root and rhizome of Rheum palmatum L, has been shown to have multiple biological activities including anticancer functions in previous studies.
METHODS AND RESULTS:
In this study, we investigated the anti-leukemic activity of Emodin alone or Emodin in the presence all-trans retinoic acid (ATRA) in acute myeloid leukemia (AML) cells and the potential signaling pathway involved. We demonstrated that Emodin could significantly enhance the sensitivity to ATRA and present additive differentiation-inducing effects in AML cell line NB4 cells and, especially, in NB4-derived ATRA-resistant MR2 cells. Further study showed that increasing dose of Emodin could effectively induce growth inhibition and apoptotic effects in both cell lines as well as in primary leukemic cells from AML patients. Moreover, the apoptotic induction in AML cells was associated with the activation of caspase cascades involving caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage. In addition, leukemic cell response to Emodin stimuli in vitro was observed through the decreased expression levels of Bcl-2 and retinoic acid receptor α (RARα). Importantly, Emodin was demonstrated as a new inhibitor of PI3K/Akt in AML cells, even in primary AML cells. It inhibited Akt phosphoration (p-Akt) at Ser473 as efficiently as mTOR at Ser2448.
CONCLUSIONS:
Consistently, it exerted suppression effects on the phosphoration of mTOR downstream targets, 4E-BP1 and p70S6K. Taken together, these findings indicate that Emodin might be developed as a promising anti-leukemic agent to improve the patient outcome in AML. |
|
| In vivo: |
| Fitoterapia. 2014 Oct;98:1-10. | | Emodin opposes chronic unpredictable mild stress induced depressive-like behavior in mice by upregulating the levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor.[Pubmed: 24932776] | Emodin, the major active component of Rhubarb, has shown neuroprotective activity. This study is attempted to investigate whether Emodin possesses beneficial effects on chronic unpredictable mild stress (CUMS)-induced behavioral deficits (depression-like behaviors) and explore the possible mechanisms.
METHODS AND RESULTS:
ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, Emodin and fluoxetine (positive control drug) were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests: open field test (OFT), sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST) were applied to evaluate the antidepressant effects of Emodin. Then plasma corticosterone concentration, hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) levels were tested to probe the mechanisms. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with high, plasma corticosterone concentration and low hippocampal GR and BDNF expression levels. Whereas, chronic Emodin (20, 40 and 80 mg/kg) treatments reversed the behavioral deficiency induced by CUMS exposure. Treatment with Emodin normalized the change of plasma corticosterone level, which demonstrated that Emodin could partially restore CUMS-induced HPA axis impairments. Besides, hippocampal GR (mRNA and protein) and BDNF (mRNA) expressions were also up-regulated after Emodin treatments.
CONCLUSIONS:
In conclusion, Emodin remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the up-regulating GR and BDNF levels in hippocampus. |
|
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
