Advances in the pharmacological effects and molecular mechanisms of emodin in the treatment of metabolic diseases

Yu, Linyuan; Zhao, Yongliang; Zhao, Yongli

doi:10.3389/fphar.2023.1240820

Cited by 9 publications

(5 citation statements)

References 200 publications

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“…Once the AMPK, p-ACC, and CPT-1 pathways are activated, fatty acid oxidation occurs [50]. The overexpression of SREBP-1c causes lipogenesis, which is correlated with the FAS genes that synthesize fatty acids [51]. In this study, the ACC in the HF group showed the highest protein expression levels among all groups, but the lowest activating expression levels were found for p-ACC.…”

Section: Discussionmentioning

confidence: 48%

Effects of Cinnamon (Cinnamomum zeylanicum) Extract on Adipocyte Differentiation in 3T3-L1 Cells and Lipid Accumulation in Mice Fed a High-Fat Diet

Oh,

Ahn,

Zhou

et al. 2023

Nutrients

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Flavonoids and phenolic acid are two of the rich polyphenols found in cinnamon (Cinnamomum zeylanicum). The effects of cinnamon extract on the inhibition of adipocyte differentiation in 3T3-L1 fibroblast cells and prohibitory lipid accumulation in male mice fed a high-fat diet were examined. Upon treating 3T3-L1 cells with cinnamon for 3 days, the cinnamon inhibited lipid accumulation and increased gene expression levels, such as those of adiponectin and leptin. In in vivo experiments, mice were randomized into four groups after a one-week acclimation period, as follows: normal diet, normal diet + 1% cinnamon extract, high-fat diet, and high-fat diet + 1% cinnamon extract. After 14 weeks of supplementation, we found that cinnamon extract increased the expression of lipolysis-related proteins, such as AMPK, p-ACC, and CPT-1, and reduced the expression of lipid-synthesis-related proteins, such as SREBP-1c and FAS, in liver tissue. Our results show that cinnamon extract may exhibit anti-obesity effects via the inhibition of lipid synthesis and adipogenesis and the induction of lipolysis in both 3T3-L1 fibroblast cells and mice fed a high-fat diet. Accordingly, cinnamon extract may have potential anti-obesity effects.

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Section: Discussionmentioning

confidence: 48%

Effects of Cinnamon (Cinnamomum zeylanicum) Extract on Adipocyte Differentiation in 3T3-L1 Cells and Lipid Accumulation in Mice Fed a High-Fat Diet

Oh,

Ahn,

Zhou

et al. 2023

Nutrients

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“…Additionally, emodin has been shown potential as candidate drugs for treating hyperlipidemia by activating the AMPK/SREBP-2/PCSK9/LDLR signaling pathway (He et al, 2022). In diabetes, emodin accelerate wound healing by promoting angiogenesis through the FGFR1/ERK signaling pathway (Yu et al, 2023a). They enhance granulation tissue formation, neovascularization, collagen deposition, and reduce in ammatory cell in ltration, suggesting their potential as topical treatments for diabetic wounds (Chen et al, 2022).…”

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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“…Emodin regulates lipid metabolism and adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptors, and nuclear factor kappa B signaling pathways, preventing the development of obesity, hyperlipidemia, nonalcoholic fatty liver disease, diabetes, atherosclerosis, and osteoporosis. 103 Emodin also has anticancer, antiinflammatory, and anti-oxidant potential. 102…”

Section: Emodinmentioning

confidence: 99%

(Epi)genetic Aspects of Metabolic Syndrome Pathogenesis in Relation to Brain-derived Neurotrophic Factor Expression: A Review

Todosenko,

Yurova,

Khaziakhmatova

et al. 2024

Gene Expr

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A key element in the pathogenesis of metabolic syndrome (MetS) is the reprogramming of hypothalamic cells at the genetic level (in the prenatal phase), which leads to neuroinflammation. We hypothesize that alterations in the structure of hypothalamic neurons mediated by (epi)genetic alterations are directly related to impaired expression/production of neurotrophins and neurotransmitters that control the metabolism of substances in the brain and periphery, including brain-derived neurotrophic factor (BDNF). The aim of this review is to describe the molecular genetic and epigenetic role of BDNF in the development of MetS. Articles entered into the National Library of Medicine Medline database via the PubMed interface were used to create this review. We attempted to include as much literature as possible, including reviews, animal studies, cell culture studies, and clinical trials. Studies on BDNF point to its role in metabolic processes, including glucose, insulin, and cholesterol homeostasis. Evidence-based studies show that multiple genes in close proximity to BDNF are involved in the development of MetS. Studies aimed at analyzing BDNF in metabolic diseases using different biological samples will reveal clear pathophysiological links

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Advances in the pharmacological effects and molecular mechanisms of emodin in the treatment of metabolic diseases

Cited by 9 publications

References 200 publications

Effects of Cinnamon (Cinnamomum zeylanicum) Extract on Adipocyte Differentiation in 3T3-L1 Cells and Lipid Accumulation in Mice Fed a High-Fat Diet

Effects of Cinnamon (Cinnamomum zeylanicum) Extract on Adipocyte Differentiation in 3T3-L1 Cells and Lipid Accumulation in Mice Fed a High-Fat Diet

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

(Epi)genetic Aspects of Metabolic Syndrome Pathogenesis in Relation to Brain-derived Neurotrophic Factor Expression: A Review

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