Emodin Group Research Articles

In-vivo metabolic profiling of the Natural products Emodin and Emodin-8-O-β-D-glucoside in rats using liquid chromatography quadrupole Orbitrap mass spectrometry

Emodin (EM) and emodin-8-O-β-D-glucoside (EG) were found in various medicinal plants such as Rheum palmatum, Aloe vera, Polygonum multiflorum, and Polygonum cuspidatum. They have different pharmacological properties and are considered potentially toxic substances. It is necessary to identify the metabolites and their distribution in the body. In this study, a comprehensive analytical strategy was developed to characterize the metabolites of EM and EG in vivo using UHPLC-Q-Exactive Orbitrap MS. 190 metabolites were identified in the bio-samples, in addition to the commonly reported glycoside hydrolysis, hydrogenation, hydroxylation, glucuronide conjugation, and sulfation conjugation. We also discovered new pathways such as formylation, acetylation, glycol acylation, lactation, glycerolization, malonylation, glycerol acid acylation, hydroxyvalerylation, erythrosylation, glutaric acidfication, hydroxybenzoylation, glutamylation, hydroxyglutamylation, ascorbylation, aspartylglycylation, dihydroxyphenylglycylation, trihydroxyphenylglycylation, dihydroxymethoxyphenylglycylation, and ring-opening of EM. Cluster analysis revealed that each tissue in the EM and EG groups exhibited a high degree of similarity in their metabolic pathway preferences and bodily distributions, as they clustered together. Interestingly, the presence of glycol acylation, glycerolization, and glycerol acid acylation in the liver may be related to the lipid-lowering effects of EM and EG. These findings offer valuable insights for a more comprehensive understanding of the safety and efficacy of EM and EG, as well as valuable methods for metabolic characterization.

Emodin attenuates hypoxic-ischemic brain damage by inhibiting neuronal apoptosis in neonatal mice

Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to obtain and has good neuroprotective effects. This study aimed to investigate the neuroprotective effect of emodin on neonatal mouse HIBD. The modified Rice–Vannucci method was used to induce HIBD in mouse pups. Eighty postnatal 7-day (P7) C57BL/6 neonatal mice were randomly divided into the sham group (sham), vehicle group (vehicle), and emodin group (emodin). TTC staining and whole-brain morphology were used to evaluate the infarct volume and morphology of the brain tissue. The condition of the neurons was observed through Nissl staining, HE staining, FJC staining, immunofluorescence and Western blot for NeuN, IBA-1, and GFAP. The physiological status of the mice was evaluated using weight measurements. The neural function of the mice was assessed using the negative geotaxis test, righting reflex test, and grip test. TUNEL staining was used to detect apoptosis in brain cells. Finally, Western blot and immunofluorescence were used to detect the expression levels of apoptosis-related proteins, such as P53, cleaved caspase-3, Bax and Bcl-2, in the brain. Experiments have shown that emodin can reduce the cerebral infarct volume, brain oedema, neuronal apoptosis, and degeneration and improve the reconstruction of brain tissue morphology, neuronal morphology, physiological conditions, and neural function. Additionally, emodin inhibited the expression of proapoptotic proteins such as P53, Bax and cleaved caspase-3 and promoted the expression of the antiapoptotic protein Bcl-2. Emodin attenuates HIBD by inhibiting neuronal apoptosis in neonatal mice.

Emodin ameliorates acute radiation proctitis in mice by regulating AKT/MAPK/NF-κB/VEGF pathways

BackgroundEmodin, a natural anthraquinone derivative isolated from the roots of Rheum officinale Baill, has many pharmacological effects including anti-inflammatory, antioxidant, antiviral, antibacterial and anti-cancer. However, little is known about the effect of emodin on acute radiation proctitis (ARP). The present study was conducted to determine its effects and elucidate its mechanisms involving AKT/MAPK/NF-κB/VEGF pathways in ARP mice. MethodsTotal 60 C57BL/6 mice were divided randomly into control group, ARP group, AKT inhibitor MK-2206 group, and different doses of emodin groups. ARP mice were induced by 27 Gy of 6 MV X-ray pelvic local irradiation. MK-2206 was given orally for 2 weeks on alternate days. Emodin was administered daily by oral gavage for 2 weeks. Subsequently, all mice were sacrificed on day 15. The rectal tissues were obtained for further tests. The general signs score and the pathological grade were used to evaluate the severity of ARP. The expression of NF-κB, VEGF and AQP1 were determined by immunohistochemistry and western blot. The expression of p-AKT, p-ERK, p-JNK, p-p38, Bcl-2 and Bax were assessed using western blot. ResultsThe worse general signs and damaged tissue structure of ARP mice were profoundly ameliorated by emodin. The expression of p-AKT, p-ERK, NF-κB, VEGF and AQP1 were significantly increased, resulting in the inflammation-induced angiogenesis in ARP mice. However, the expression of p-JNK and p-p38 were decreased, leading to the reduction of apoptosis in ARP mice. Excitedly, emodin reversed these changes, not only inhibited inflammation-induced angiogenesis, but also promoted apoptosis. Notably, the effects of emodin were similar to that of AKT inhibitor MK-2206, suggesting the involvement of AKT signaling in the effect of emodin. ConclusionThese results suggest that emodin attenuates ARP in mice, and the underlying mechanism might involve inhibition of the AKT/ERK/NF-κB/VEGF pathways and the induction of apoptosis mediated by JNK and p38.

Integration of microbiota and metabolomics reveals the analgesic mechanisms of emodin against neuropathic pain

Background and objectiveNeuropathic pain (NeP) induced dysbiosis of intestinal microbiota in chronic constriction injury (CCI) rats. Emodin has analgesic effect but the detailed mechanism is not clear at the present time. This study aims to explore the underling mechanism of action of emodin against NeP with in CCI model. MethodsMale SD rats (180–220 g) were randomly divided into three groups: sham group, CCI group, and emodin group. Behavioral tests were performed to evaluate the therapeutic effects of emodin on CCI model. Feces and spinal cords of all rats were collected 15 days after surgery. 16S rDNA sequencing, untargeted metabolomics, qPCR and ELISA were performed. ResultsMechanical withdrawal thresholds (MWT), thermal withdrawal latency (TWL) and Sciatic functional index (SFI) in emodin group were significantly higher than CCI group (P < 0.05). Emodin not only inhibited the expression of pro-inflammatory cytokines in the spinal cords and colonic tissue, but also increased the expression of tight junction protein in colonic tissue. 16S rDNA sequencing showed that emodin treatment changed the community structure of intestinal microbiota in CCI rats. Untargeted metabolomics analysis showed that 33 differential metabolites were screened out between CCI group and emodin group. After verification, we found that emodin increased the level of S-adenosylmethionine (SAM) and Histamine in the spinal cord of CCI rats. ConclusionEmodin was effective in relieving neuropathic pain, which is linked to inhibition inflammatory response, increasing the proportion of beneficial bacteria and beneficial metabolites.

Histological Effect of Emodin on Acute Vocal Fold Injury in a Rat Model

Emodin has beneficial effects on wound healing and reduces excessive fibrosis during tissue regeneration. Its positive effects on the wound-healing process were demonstrated on human fibroblasts. The aim of the present study was to evaluate the effectiveness of emodin application on acute vocal fold injury. Twenty-four Wistar albino rats were divided into three groups: control, sham, and emodin group. The glottis was examined using a 30°-2.7mm diameter telescope, and vocal folds was unilaterally wounded by a microscissor through the entire layer of the lamina propria down to the vocalis muscle. While no procedure(no acute injury of the vocal fold or an injection of saline/emodin) was applied to the control group, 0.5 cc of saline was injected into the sham group and 0.5 cc of emodin in the emodin group, just lateral to the vocal folds, with 27 gauge injectors. Animals were sacrificed on the 21st day after the procedure. After excised larynx experiments, serial sections were prepared from the vocal fold. Hematoxylin eosin and immunohistochemical staining were performed and fibroblast density, lamina propria thickness, and vessel formation were graded from 0 (none) to 3 (severe reaction). Transforming growth factor-beta 1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) staining was used for immunohistochemical examinations. Four-point scoring scale for intensity being scored as 0 (no staining) to 3 (severeley stained) to quantify immonuhistochemical reaction. This scoring system was applied to vocal fold epithelium, lamina propria, vessel wall, and vocalis muscle tissues. The groups were compared with the Kruskal Wallis and Dunn tests. Histologically, there was no significant difference (P>0.05) between the sham group and the emodin group in terms of fibroblast density, vessel formation, and lamina propria thickness. These parameters were higher (P<0.05) in both groups compared to the control group. In the lamina propria and vessel wall, MMP-9 staining was more intense in the emodin group than in the sham group. TGF-β1 staining of lamina propria, epithelial tissue, and vocalis muscle was significantly more intense in the emodin group than in the other groups. Emodin induced MMP-9 and TGF-1 staining in the vocalis muscle and epithelium, as well as TGF-1 staining in the lamina propria. In terms of fibroblast density, new vascular creation, and LP thickness in acute vocal fold damage, there was no difference between saline administration and emodin injection. It may increase fibroblast activation in the acute phase of wound healing, but its long-term effects should be further investigated.

Effects of emodin and different protein levels on growth and immunity of the blunt snout bream (Megalobrama amblycephala) for in-pond raceway aquaculture systems

The present study aimed to evaluate the effects of emodin and different protein levels on growth-promoting antioxidant capacity and protein utilization of blunt snout bream to in-pond raceway aquaculture systems (IPRS). The experiment was divided into three groups: low protein group (LP) (29% low protein level), high protein group (HP) (32% high protein level), and emodin group (ED) (29% protein level + 0.05% emodin). At 210 days in the late stage of culture, the weight of the ED and HP groups was higher than the LP groups (P &lt; 0.05). Compared with the LP group, the number of hematological parameters (white blood cell, WBC; red blood cell, RBC; hemoglobin, HGB; and hematocrit, HCT), blood antioxidant enzymes (anti-superoxide anion free radical, ASAFA; glutathione peroxidase, GPx; superoxide dismutase, SOD; and nitric oxide, NO) activity in the ED group were significantly increased (P &lt; 0.05), and the serum malondialdehyde (MDA) content were significantly reduced (P &lt; 0.05). Besides, the content of serum triglyceride (TG) and blood antioxidant enzymes (ASAFA, GPx, and SOD) in the HP group were significantly increased compared with the LP group (P &lt; 0.05), and the content of serum Creatinine (CREA) significantly lower than that of the control (P &lt; 0.05). The results of this experiment indicate that emodin and appropriate protein levels can increase the content of antioxidant enzymes, enhance immunity, and promote the growth of M. amblycephala.

Emodin, a Natural Anthraquinone, Increases Uric Acid Excretion in Rats with Potassium Oxonate-Induced Hyperuricemia.

The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn to Chinese medicine as an alternative. Therefore, it is crucial to design a preclinical study to obtain more convincing data on the treatment of hyperuricemia and gout with Chinese medicine. This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. In this study, we used 36 Sprague-Dawley rats, which were randomly divided into six groups for experimentation. Hyperuricemia was induced in rats by intraperitoneal injections of potassium oxonate. The efficacy of emodin in reducing serum uric acid levels was demonstrated by comparing the positive control group with groups treated with three different concentrations of emodin. The inflammatory profiles, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels, were unaffected by emodin treatment. In the experimental results, it was observed that the serum uric acid concentration in the vehicle control group was 1.80 ± 1.14, while the concentrations in the moderate and high concentration emodin groups were 1.18 ± 0.23 and 1.12 ± 0.57, resulting in no significant difference in uric acid concentration between these treatment groups and the control group, indicating that emodin has a therapeutic effect on hyperuricemia. The increase in the fractional excretion of uric acid (FEUA) demonstrated that emodin promoted urinary uric acid excretion without significantly affecting the inflammatory profile. Thus, emodin reduced the serum uric acid concentration to achieve effective treatment of hyperuricemia and gout by increasing urinary excretion. These results were supported by the measured serum uric acid and FEUA levels. Our data have potential implications for the treatment of gout and other types of hyperuricemia in clinical practice.

Study on 3D-Printed Emodin/Nano-Hydroxyapatite Scaffolds Promoting Bone Regeneration by Supporting Osteoblast Proliferation and Macrophage M2 Polarization

The treatment of bone defects caused by diseases, trauma, or tumor has always been a great clinical challenge. Implantation of bone biomaterials into bone defect areas is an effective method for bone injury repair. In this study, we used three-dimensional (3D) printing technology to prepare nano-hydroxyapatite (nHA)/sodium alginate (SA)/gelatin (Gel) hydrogel scaffolds loaded with different ratios (0, 0.13, 0.26, 0.39, 0.53, and 0.79‰) of emodin (EM) (EM/nHA/SA/Gel). Scanning electron microscopy showed that the scaffolds had a smooth surface without fracture and nHA was evenly distributed on the surface. The cell proliferation and migration results showed that the 0.39‰ EM group, in particular, could significantly promote the proliferation and migration of mouse embryonic osteoblast precursor (MC3T3-E1) cells and significantly increase the mRNA expression of osteogenic differentiation-related genes (bone morphogenetic protein/BMP-2, BMP-9, osteocalcin). In addition, the 0.39‰ EM group exhibited the best effect on osteogenic differentiation-related proteins (alkaline phosphatase, Runx 2, OSX). The expression of M2 polarization-related genes (arginase-1, CD206) also significantly increased after the treatment with the 0.39‰ EM group. Micro-CT showed that in the rat skull defect model, the EM/nHA/SA/Gel scaffold group significantly promoted bone regeneration after being implanted into the skull for 30 days. Our results indicate that the EM/nHA/SA/Gel hydrogel scaffolds can not only directly promote the proliferation and differentiation of osteoblasts but also indirectly promote osteogenic differentiation by supporting M2 polarization of macrophages. EM/nHA/SA/Gel hydrogel scaffolds are potential bone tissue engineering materials for bone regeneration.

Protective effect of emodin on Streptococcus pneumoniae and matrix-assisted laser desorption time-of-flight mass spectrometry for serotype detection

This study assessed the impact of emodin on Streptococcus pneumoniae serotype using Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) technology. After establishment of animal models, rats were classified into sham operation group, model group, low-dose and high-dose emodin group (n = 10, each group). After treatment, the pathology of rat lung tissue was detected along with analysis of the levels of Interleukin-1β, IL-1β(IL-1β), Tumor Necrosis Factor alpha (TNF-α), and IL-6. MALDI-TOF MS was used to examine the serotype of Streptococcus pneumoniae as NF-κB level in the rat lung tissue and capsular polysaccharide protein levels were detected. Compared with healthy tissues, the lung tissues in the model group exhibited collapse of alveoli and infiltration of inflammatory cells, which were greatly alleviated in low-dose and high-dose emodin groups, with more significant effect in high-dose emodin group. Additionally, treatment with emodin dramatically decreased the contents of IL-1β, TNF-α and IL-6 (P &lt;0.05), which were lowest in the high-dose group. 60 representative strains of Streptococcus pneumoniae were divided into 18 mass spectrum types, whilst six serotypes (19F, 19A, 23F, 23A, 3 and 14) were identified. Moreover, 18 strains of serotype 19F accounted for 30% (18/60) and were distributed in 6 different MALDI-TOF MS types, and another 3 serotypes were distributed in the corresponding MALDI-TOF MS types. NF-κB and capsular polysaccharide protein expressions declined after emodin treatment (P &lt;0.05). Collectively, Emodin effectively alleviated infection caused by Streptococcus pneumoniae and inflammatory response and improved conditions of patients while decreasing their levels of NF-κB and capsular polysaccharide protein, affecting typing of Streptococcus pneumoniae.

Emodin alleviates lung ischemia-reperfusion injury by suppressing gasdermin D-mediated pyroptosis in rats.

Pyroptosis refers to programmed cell death associated with inflammation. Emodin has been reported to alleviate lung injuries caused by various pathological processes and attenuate ischemia-reperfusion (I/R) injuries in diverse tissues. Lewis rats were assigned into the sham, the I/R, and the I/R + emodin groups. Emodin and phosphate-buffered saline were intraperitoneally injected into rats of the emodin group and I/R group for 30 min, respectively. These rats were then subjected to left thoracotomy followed by 90-min clamping of the left hilum and 120-min reperfusion. Sham-operated rats underwent 210-min ventilation. Lung functions, histological changes, lung edema, and cytokine levels were assessed. Protein levels were measured by western blotting. Immunofluorescence staining was conducted to evaluate pyroptosis. Emodin alleviated the I/R-induced lung dysfunction, lung damages, and inflammation. Protective effects of emodin against I/R-mediated endothelial pyroptosis was observed in vivo and in vitro. Mechanistically, emodin inactivated the TLR4/MyD88/NF-κB/NLRP3 pathway. Emodin attenuates lung ischemia-reperfusion injury by inhibiting GSDMD-mediated pyroptosis in rats.

Proteomic and metabolomic approaches elucidate the molecular mechanism of emodin against neuropathic pain through modulating the gamma-aminobutyric acid (GABA)-ergic pathway and PI3K/AKT/NF-κB pathway.

Neuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-κB pathway.

Emodin Regulates lncRNA XIST/miR-217 Axis to Protect Myocardial Ischemia-Reperfusion Injury.

This study is aimed at investigating the effect of emodin on myocardial ischemia-reperfusion injury (MIRI) and mechanism. Eighty healthy adult male SD rats (weighing 230-250 g) were utilized to establish I/R model, which were randomly divided into five groups (16 rats in each group): sham operation group, myocardial ischemia-reperfusion injury group (I/R group), emodin group, emodin +NC group, and emodin +XIST group. The contents of CK, CK-MB, LDH, and HBDH in serum were determined by ELISA kit. LDH was detected by ELISA assay, SOD was detected by the xanthine oxidase method, and MDA was detected by the thiobarbituric acid method. The relative expression of XIST and miR-217 was evaluated by RT-qPCR. Western blot was applied to detect the protein expression. Flow cytometry was applied to detect cardiomyocyte apoptosis. Myocardial infarction area was obviously increased in I/R model rats, while emodin decreased the myocardial infarction in I/R model rats. In addition, cardiac enzymes (CK, CK-MB, LDH, and HBDH) and apoptosis were obviously increased in MIRI model rats, while emodin obviously decreased cardiac enzymes and apoptosis. The ROS and MDA levels were raised while the activities of SOD were declined in the I/R model group. The ROS and MDA levels were decreased while the activities of SOD were raised in the emodin group. The XIST expression was markedly raised in the I/R model group while decreased in the emodin group, and the overexpression of XIST reversed the protective effect of emodin on myocardial infarction, oxidative stress, and cardiomyocyte apoptosis. In addition, XIST directly regulated the expression of miR-217, and si-XIST inhibited H/R-induced oxidative damage of cardiomyocytes via inhibiting miR-217. Emodin protected MIRI both in vitro and in vivo via inhibiting lncRNA XIST to upregulate miR-217.

Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis.

Metastasis is one of the main obstacles for the treatment and prognosis of breast cancer. In this study, the effects and possible mechanisms of aloe emodin (AE) and emodin (EMD) for inhibiting breast cancer metastasis were investigated via cell metabolomics. First, a co-culture model of MCF-7 and HUVEC cells was established and compared with a traditional single culture of MCF-7 cells. The results showed that HUVEC cells could promote the development of cancer cells to a malignant phenotype. Moreover, AE and EMD could inhibit adhesion, invasion, and angiogenesis and induce anoikis of MCF-7 cells in co-culture model. Then, the potential mechanisms behind AE and EMD inhibition of MCF-7 cell metastasis were explored using a metabolomics method based on UPLC-Q-TOF/MS multivariate statistical analysis. Consequently, 27 and 13 biomarkers were identified in AE and EMD groups, respectively, including polyamine metabolism, methionine cycle, TCA cycle, glutathione metabolism, purine metabolism, and aspartate synthesis. The typical metabolites were quantitatively analyzed, and the results showed that the inhibitory effect of AE was significantly better than EMD. All results confirmed that AE and EMD could inhibit metastasis of breast cancer cells through different pathways. Our study provides an overall view of the underlying mechanisms of AE and EMD against breast cancer metastasis.

Mechanism of combined treatment of rhein and emodin in Rhubarb for ulcerative colitis

This study aimed to explore the efficacy and mechanism of combined rhein and emodin in the treatment of ulcerative colitis(UC) from the aspects of network pharmacology, animal inflammation improvement and molecular mechanism. Network pharmacology predicted that combined rhein and emodin acted on 52 potential targets, mainly participating in signaling pathways such as cancer, PI3 K/AKT, microRNAs in cancer and apoptosis. PI3 K/AKT signaling pathway has been reported to be closely related to UC, and the optimal candidate pathway for combined therapy. The UC mice model was established by dextran sodium sulfate, and then the modeled mice were randomly divided into control group, model group, rhein group, emodin group, rhein+emodin group and sulfasalazine group. After administration, compared with the conditions in model group, body weight, disease activity index(DAI) score, colon length, TNF-α, IL-6, IL-1β and myeloperoxidase(MPO) of mice in rhein+emodin group were improved(P&lt;0.01); colonic mucosal injury was significantly reduced; the expression of p-PI3 K/PI3 K and p-AKT/AKT proteins were down-regulated(P&lt;0.01). All the above indices were better than those in the rhein/emodin group alone. The Jin's Q-values of the effect of combined rhein and emodin on colon length, TNF-α, IL-6, IL-1β, MPO, p-PI3 K/PI3 K and p-AKT/AKT were all greater than 1.15, which indicated that there was obvious synergistic effect between rhein and emodin. In all, rhein and emodin have synergistic effect in the treatment of UC, and the mechanism may be related to the inhibition of PI3 K/AKT signaling pathway and the down-regulation of proinflammatory factors. They are the new components in the treatment of UC, which is worthy of attention.

Construction and Application of Hepatocyte Model Based on Microfluidic Chip Technique in Evaluating Emodin.

The current cytological evaluation technique of health food raw materials does not entirely meet the needs of evaluating health food. Our study adopted the microfluidic chip technique for the first time to construct a hepatocyte model of evaluating emodin, which was composed of a human hepatocellular carcinoma cell (HepG2) and microfluidic chip. The mixed glue of a model with rat tail collagen type I (1.3 mg/mL) + gelatin (7.5%) was used to simulate the microenvironment of a cell. The validity of this model was evaluated by cell proliferation activity and cell staining, and the toxicity of emodin was evaluated by a series of metabolic indicators on this model. The results indicated that the repeatability of the constructed hepatocyte model was favorable, with a coefficient of variation (CV) of 2.8%. After emodin continuously was exposed for 48 h, the cell inhibition was obvious at 100 and 200 μM, and the number of dead cells gradually increased with the increasing of emodin concentration, and the difference of BUN was significant between the emodin group and blank group (p < 0.05). The constructed model has a favorable applicability in evaluating emodin. This study provides an important platform and a potential in vitro alternative model for assessing and predicting the health effects of health food.

Network Pharmacology Experiments Show That Emodin Can Exert a Protective Effect on MCAO Rats by Regulating Hif-1α/VEGF-A Signaling.

Modern pharmacological studies have shown that emodin, the main effective component of rhubarb, has good anti-inflammatory and antioxidant effects, but its pharmacodynamic mechanism remains unclear yet. This study aims to elucidate the multitarget action mechanism of emodin in ischemic stroke through network pharmacology and in vivo experiments. Sprague–Dawley rats were randomly divided into control (normal saline), sham (normal saline), model (normal saline), and emodin groups (n = 9 per group). Emodin was administered at 40 mg/kg/d for 3 consecutive days. The rats were subjected to middle cerebral artery occlusion for 2 h, followed by reperfusion for 24 h to establish the cerebral ischemia–reperfusion injury. To search for relevant studies in databases, emodin, ischemic stroke, and stroke were used as keywords. Subsequently, protein–protein interaction networks and complex disease target networks were established, and an enrichment analysis and molecular docking of core targets were performed. Gene expression was detected through western blotting and reverse-transcription polymerase chain reaction. Localization and expression of proteins were detected through immunohistochemistry. Furthermore, the neurological function, 2,3,5-triphenyltetrazolium chloride staining, levels of brain tissue inflammatory factors, the role of the blood–brain barrier (BBB), and relevant signaling pathways were assessed in vivo. The molecular docking of core targets revealed that the docking between vascular endothelial growth factor A (VEGF-A) and emodin was the most efficient. Emodin pretreatment decreased the neurological score from 2.875 to 1.125. Moreover, emodin inhibited the degradation of occludin and claudin-5 caused by matrix metalloprotein kinase (MMP)-2/MMP-9, thereby protecting the BBB. Additionally, related proteins such as hypoxia-inducible factor-1α/VEGF-A and nuclear factor kappa B were down-regulated. Thus, emodin may play a protective role during cerebral ischemia reperfusion through mediation of the Hif-1α/VEGF-A signaling pathway to inhibit the expression of inflammatory factors.

Emodin Ameliorates Acute Pancreatitis-Associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis.

Objective: To investigate the protective effect of emodin in acute pancreatitis (AP)-associated lung injury and the underlying mechanisms. Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into four groups: sham, AP, Ac-YVAD-CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed with H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot. Results: Emodin, similar to the positive control AYC, significantly alleviated pancreas and lung damage in rats and mice. Additionally, emodin mitigated the pyroptotic process of AMs by decreasing the level of inflammatory cytokines and lactate dehydrogenase. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention. Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which may result from the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling pathways.

Mechanism of emodin in relieving neuropathic pain by regulating serum metabolism

The present study investigated the effect of emodin on the serum metabolite profiles in the chronic constriction injury(CCI) model by non-target metabolomics and explored its analgesic mechanism. Twenty-four Sprague Dawley(SD) rats were randomly divided into a sham group(S), a CCI group(C), and an emodin group(E). The rats in the emodin group were taken emodin via gavage once a day for fifteen days(50 mg·kg~(-1)) on the first day after the CCI surgery. Mechanical withdrawal threshold(MWT) and thermal withdrawal threshold(TWL) in each group were performed before the CCI surgery and 3,7, 11, and 15 days after surgery. After 15 days, blood samples were collected from the abdominal aorta. The differential metabolites were screened out by non-target metabolomics and analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG) and ingenuity pathway analysis(IPA). From the third day after CCI surgery, the MWT and TWL values were reduced significantly in both CCI group and emodin group, compared with the sham group(P&lt;0.01). At 15 days post-surgery, the MWT and TWL values in emodin group increased significantly compared with the CCI group(P&lt;0.05). As revealed by non-target metabolomics, 72 differential serum metabolites were screened out from the C-S comparison, including 41 up-regulated and 31 down-regulated ones, while 26 differential serum metabolites from E-C comparison, including 10 up-regulated and 16 down-regulated ones. KEGG analysis showed that the differential metabolites in E-C comparison were enriched in the signaling pathways, such as sphingolipid metabolism, arginine biosynthesis, glycerophospholipid metabolism, and tryptophan metabolism. IPA showed that the differential metabolites were mainly involved in the lipid metabolism-molecular transport-small molecule biochemistry network. In conclusion, emodin can exert an analgesic role via regulating sphingolipid metabolism and arginine biosynthesis.

Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway

ABSTRACT Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K–Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.

Emodin inhibits the proliferation of papillary thyroid carcinoma by activating AMPK.

Emodin has been demonstrated to serve antitumor roles in a variety of tumor types, but the effect of emodin on papillary thyroid carcinoma and its molecular mechanisms remain unclear. In the current study, the role of emodin on papillary thyroid carcinoma was analyzed in vitro and in vivo. TPC-1 cells were treated with emodin (0, 10, 25 or 50 µM), and cell viability and apoptosis were detected using Cell Counting Kit-8 and flow cytometry, respectively. The expression levels of AMPK-associated proteins were examined using western blot analysis. To study the effect of emodin on the AMPK pathway, AMPK activator, AICAR and an AMPK inhibitor, Dorsomorphin, were used in TPC-1 cells. In vivo, mice were used to confirm the mechanism of emodin on papillary thyroid carcinoma. The results of the current study indicated that emodin treatment induced cell apoptosis and cell cycle arrest in TPC-1 cells. Furthermore, the inhibitory effect increased in a dose dependent manner. Following emodin treatment, the cell viability of TPC-1 cells was significantly decreased, and apoptosis rate increased (P<0.05). Furthermore, the expression levels of AMPK were increased in the emodin group compared with the control group (P<0.05). Similar effects were observed following AMPK activator treatment in TPC-1 cells. Following AMPK activator treatment, cell proliferation and the cell cycle were inhibited. Also, the AMPK inhibitor was demonstrated to mediate the therapeutic effect of emodin. In addition, the results of the present study demonstrated that emodin inhibited the MEK/ERK pathway. Additionally, the in vivo results of the current study were consistent with those in vitro. In conclusion, the current study demonstrated that the administration of Emodin inhibited the proliferation of papillary thyroid cancer cells via activating AMPK pathway activity.