Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells

Jiang, Dongxiao; Ding, Shufei; Mao, Zhu-Jun; You, Lijun; Ruan, Yuanyuan

doi:10.1186/s12935-021-01942-8

Cited by 12 publications

(4 citation statements)

References 44 publications

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“…Emodin, a natural anthraquinone derivative found in various Chinese herbs such as rhubarb and aloe, exhibits diverse pharmacological effects (Stompor-Goracy, 2021). Its anticancer properties are notable, as emodin induces apoptosis and cell cycle arrest in cancer cells (Jiang et al, 2021). In colon cancer cells, emodin inhibits proliferation, upregulates the pro-apoptotic protein Bax, and downregulates the anti-apoptotic protein Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Drug-likeness evaluation and inhibitory mechanism of emodin derivative on cardiac fibrosis based on MTA3 pathway

Liu,

Wang,

et al. 2024

Preprint

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Background In our previous research, we demonstrated that emodin inhibits cardiac fibrosis through MTA3. However, the limited bioavailability of emodin has hindered its clinical translation. Aim To safely and effectively apply the pharmacology of emodin to disease treatment, a new emodin derivative (emodin succinyl ethyl ester) was synthesized through structural modification at the 3'-OH position. This study primarily focused on the favorable properties of the emodin derivative, including drug-likeness assessment, evaluation of anti-fibrotic abilities, and the molecular mechanism involving the MTA3 pathway. Methods Computational-aided drug design (CADD) was applied for drug-likeness evaluations, including the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the emodin derivative, as well as molecular docking and molecular dynamics simulations. An experimental animal model of transverse aortic constriction (TAC)-induced cardiac fibrosis was established to compare the pharmacological effects of the emodin derivative versus emodin in the progression of cardiac fibrosis. Cardiac collagen deposition, morphological, and functional indices were collected via immunohistochemical staining and animal echocardiography, revealing that the emodin derivative possesses superior capability in inhibiting cardiac fibrosis and restoring MTA3 expression. Primary isolated cardiac fibroblasts were used as in vitro study subjects. The relationships between MTA3 and its upstream transcription factors were predicted through bioinformatics analysis of PROMO database and validated using CADD, chromatin Immunoprecipitation (ChIP), Luciferase reporter assays, and loss-of- and gain-of-function experiments. Results The emodin derivative demonstrates superior properties compared to emodin in terms of drug-likeness, anti-cardiac fibrosis effects, inhibition of cardiac fibroblast transdifferentiation, and restoration of MTA3 expression levels. Consistent with emodin, MTA3 mediates the inhibitory effects against cardiac fibroblast transdifferentiation of the emodin derivative. E2F1 was predicted and then verified as the transcriptional regulator and observed that E2F1 positively promoted the expression of α-SMA and COL1A2, negatively regulating its expression. Emodin and its derivatives were found to directly bind to the transcription site of E2F1, with the emodin derivative showing a more robust and stable binding property compared to emodin. The emodin derivative also reduced the expression of E2F1, and conversely, interfering with E2F1 similarly affected the inhibitory action of the emodin derivative on the transdifferentiation of cardiac fibroblasts. Conclusion This study demonstrated that emodin derivative exhibits superior drug-likeness properties and more potent inhibition of cardiac fibrosis compared to emodin, by directly targeting the transcriptional regulatory site of E2F1, disrupting its pro-fibrotic function, thereby restoring MTA3 expression and halting cardiac fibrosis progression. These findings advance emodin potential as a clinical therapy for cardiac fibrosis and provide insights into its molecular mechanisms of anti-fibrotic action.

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Section: Discussionmentioning

confidence: 99%

Drug-likeness evaluation and inhibitory mechanism of emodin derivative on cardiac fibrosis based on MTA3 pathway

Liu,

Wang,

et al. 2024

Preprint

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“…Additionally, AE decreased the release of HMGB1 by restoring the expression of the endothelial association protein, ZO-1/2, ultimately inhibiting the formation and activation of the NLRP3 inflammasome regulated by NLRP1 ubiquitination and consequently reducing the inflammatory response [12]. AE can impede apoptosis by reducing the cysteine aspartate protease (Caspase-3) expression levels [25] and can treat subarachnoid hemorrhage (SAH) by modulating the NF-κB and cyclic adenosine phosphate/protein kinase A/responsive element binding protein pathways, thereby inhibiting hemorrhage-induced inflammatory cytokines and nerve cell apoptosis [26]. These findings indicate that AE merits further investigation as a means of preventing and managing sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Healthy organisms maintain homeostasis by balancing the host inflammatory response and gut-mediated immunity in a dynamic equilibrium [26]. Sepsis-induced alterations in the composition of the gut microbiome lead to organ dysfunction through an intricate interplay between the microbiota and the immune system.…”

Section: Discussionmentioning

confidence: 99%

Aloe-Emodin Ameliorates Cecal Ligation and Puncture-Induced Sepsis

Chen

Xiao

et al. 2023

IJMS

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Sepsis remains a major challenge owing to its severe adverse effects and high mortality, against which specific pharmacological interventions with high efficacy are limited. Mitigation of hyperactive inflammatory responses is a key factor in enhancing the likelihood of survival in patients with sepsis. The Aloe genus has several health benefits, including anti-inflammatory properties. The toxicological implications of aloe-emodin (AE), extracted from various Aloe species, remain uncertain in clinical contexts. However, AE has been shown to inhibit inflammatory responses in lipopolysaccharide-induced mice, indicating its potential as a therapeutic approach for sepsis treatment. Nonetheless, there is a paucity of data regarding the therapeutic benefits of AE in the widely recognized cecal ligation and puncture (CLP)-induced sepsis model, which is commonly used as the gold standard model for sepsis research. This study demonstrates the potential benefits of AE in the treatment of CLP-induced sepsis and investigates its underlying mechanism, along with the efficacy of postoperative AE treatment in mice with CLP-induced sepsis. The results of this study suggest that AE can mitigate sepsis in mice by diminishing systemic inflammation and regulating the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.

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“…In addition, the results show that cytochrome C protein expression was upregulated in the cytosol but decreased in mitochondria. In the mitochondrial pathway of apoptosis, the release of cytochrome C plays a key role in the beginning of the pathway and activation of caspases [45].…”

Section: Rumex Confertus Anticancer Propertiesmentioning

confidence: 99%

Overview of the Biological Activity of Anthraquinons and Flavanoids of the Plant Rumex Species

2022

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Rumex confertus belongs to the genus Rumex and is classified as an invasive parasitic plant in agriculture. Despite other Rumex species being widely used in herbal medicine due to their antimicrobial, antioxidant, antitumor, and anti-inflammatory effects, there are almost no information about the potential of Rumex confertus for the treatment of various diseases. In this review we analyzed scientific articles revealing properties of Rumex plant’s substances against cancer, diabetes, pathogenic bacterial invasions, viruses, inflammation, and oxidative stress for the past 20 years. Compounds dominating in each composition of solvents for extraction were discussed, and common thin layer chromatography(TLC) and high performance liquid chromatography(HPLC) methods for efficient separation of the plant’s extract are included. Physico-chemical properties such as solubility, hydrophobicity (Log P), pKa of flavonoids, anthraquinones, and other derivatives are very important for modeling of pharmacokinetic and pharmacodynamics. An overview of clinical studies for abounded selected substances of Rumex species is presented.

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Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells

Cited by 12 publications

References 44 publications

Drug-likeness evaluation and inhibitory mechanism of emodin derivative on cardiac fibrosis based on MTA3 pathway

Drug-likeness evaluation and inhibitory mechanism of emodin derivative on cardiac fibrosis based on MTA3 pathway

Aloe-Emodin Ameliorates Cecal Ligation and Puncture-Induced Sepsis

Overview of the Biological Activity of Anthraquinons and Flavanoids of the Plant Rumex Species

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