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Introduction: The aim of this study is to examine the physiological effects of emodin on intestinal microorganisms and the liver in the BALb/c mice. Method and Results: Following an 8-week administration of emodin at doses of 25, 50, and 100 mg/kg/day,pathological analyses revealed that emodin significantly reduced the colon length, induced colonic crypt inflammation,diminished the colonic mucus layer,and decreased the fluorescence intensity of colonic tight junction proteins ZO-1 and Occludin. Concurrently, 16S rDNA gene sequencing corroborated that emodin altered the diversity and composition of the intestinal microbiota by increasing the Firmicutes to Bacteroides ratio. Simultaneously, the non-targeted metabolomics analyses exhibited significant alternations in both short chain fatty acids and free fatty acids between the emodin-treated and the normal groups, indicating emodin-induced disturbance in intestinal metabolic disorder. Furthermore, emodin exhibited a significant elevation in LPS levels in colon, serum and liver as well an marked increase in the levels of TC, TG, AST, and ALT in serum. Additionally, histological examination employing by HE and oil-red O staining furtherly verified that the administration of varying doses emodin induced hepatic inflammation and lipid accumulation. Whereas qRT-PCR and Western blot analyses demonstrated that the administering of varying doses of emodin upregulated the mRNA levels of TNF-α, IL-1β, IL-6, and IL-18 as well as the expression of TLR4, Myd88, and P-65. Following the combined administration of probiotics, the high-dose emodin did not significantly influence ALT and AST levels in mice. However, the faeces of the high-dose emodin transplanted in mice and induced a significant increase in AST levels and in the relative abundance of Firmicutes and Proteobacteria. Discussion: These findings further corroborate that emodin induces liver injury via the intestinal dysfunction. These findings suggested that emodin may disrupt intestinal microbiota and resulted in significant alternations in endogenous metabolites in mice, thereby facilitating the entry of LPS and FFAs into the liver, potentially leading to hepatic injury. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common malignant tumors in the world, with high incidence rate and mortality. Monocarboxylate transporter (MCT) 1 has been found to be widely expressed in various tumors and plays a crucial role in regulating energy metabolism. Emodin, as an important traditional Chinese medicine in China, has been reported to inhibit the progression of lung cancer. However, its potential mechanism has not been fully elucidated. The effects of emodin and MCT1 inhibitor AZD3965 on the proliferation, migration, and invasion of lung cancer cells were detected using cell counting kit-8 (CCK-8) assay, wound-healing assay, and transwell small chamber assay. The content of glucose, lactate, and pyruvate in the cell culture medium was detected using a glucose, lactate, and pyruvate detection kit, and also detected protein expression using western blotting. In addition, to investigate the effects of emodin and AZD3965 on lung cancer in vivo, we constructed nude mice subcutaneous transplant tumor model by subcutaneous injection of lung cancer cells. The results showed that emodin and AZD3965 could inhibit the proliferation, migration, and invasion of lung cancer cells. At the same time, they could inhibit the expression of MCT1 in lung cancer cells and promote the release of lactate, but did not affect the content of glucose and pyruvate. In vivo experiments had shown that emodin and AZD3965 could effectively inhibit the growth of lung cancer and inhibit the expression of MCT1. All in all, our data suggested that emodin inhibited the proliferation, migration, and invasion of lung cancer cells, possibly by inhibiting MCT1, providing important theoretical basis for elucidating the mechanism of emodin in treating lung cancer.Highlights: Emodin could inhibit proliferation, migration, and invasion of lung cancer cells. Emodin could inhibit the expression of monocarboxylate transporter 1, a key mediator of lactate shuttle. Emodin could inhibit the expression of oncogenes in lung cancer cells. Emodin and AZD3965 could inhibit the growth of subcutaneous transplanted tumors in nude mice. [ABSTRACT FROM AUTHOR]

Aloe emodin is an anthraquinone of traditional Chinese medicine monomer, which plays a protective action in cardiovascular diseases. However, the regulatory mechanisms of aloe emodin in the protection of radiation‐induced heart damage (RIHD) are unclear. As a novel post‐translational modification, lactylation is considered as a critical mediator in inflammatory cascade and cardiac injury. Here, using a cross of differential omics and 4D label‐free lactylation omics, protein disulfide‐isomerase (P4HB) is identified as a novel target for lactylation, and aloe emodin inhibits the binding of lactate to the K311 site of P4HB. Aloe emodin stabilizes kynurenine metabolism through inhibition of aspartate aminotransferase (GOT2) accumulation on damaged mitochondria. Mechanistically, aloe emodin inhibits phosphorylated glycogen synthase kinase 3B (p‐GSK3B) transcription in the nucleus to repress the interaction of prostaglandin G/H synthase 2 (PTGS2) with SH3 domain of SH3 domain‐containing GRB2‐like protein B1 (SH3GLB1), thereby disrupting the functions of mitochondrial complexes and reducing SH3GLB1‐mediated mitoROS accumulation, eventually suppressing calcium‐binding and coiled‐coil domain‐containing protein 2 (NDP52)‐induced mitophagy. This study unveils the regulatory role of aloe emodin in RIHD alleviation through PTGS2/SH3GLB1/NDP52 axis, indicates aloe emodin stabilizes GOT2‐mediated kynurenine metabolism through P4HB lactylation. Collectively, this study provides novel insights into the regulatory mechanisms underlying the protective role of aloe emodin in cardiac injury, and opens new avenues for therapeutic strategies of aloe emodin in preventing RIHD by regulating lactylation. [ABSTRACT FROM AUTHOR]

Primary and metastatic tumors of the nervous system represent a diverse group of neoplasms, each characterized by distinct biological features, prognostic outcomes, and therapeutic approaches. Due to their molecular complexity and heterogeneity, nervous system cancers (NSCs) pose significant clinical challenges. For decades, plants and their natural products with established anticancer properties have played a pivotal role in the treatment of various medical conditions, including cancers. Anthraquinone derivatives, a class of tricyclic secondary metabolites, are found in several botanical families, such as Fabaceae, Polygonaceae, Rhamnaceae, and Rubiaceae. In a comprehensive review, recent advancements in the anticancer properties of 1,8-dihydroanthraquinone derivatives—such as emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion—were analyzed. These compounds have been studied extensively, both used individually and in combination with other chemotherapeutic agents, using in vitro and in vivo models of nervous system tumors. It was demonstrated that 1,8-dihydroanthraquinone derivatives induce apoptosis and necrosis in cancerous cells, intercalate into DNA, disrupting transcription and replication in rapidly dividing cells, and alter ROS levels, leading to oxidative stress that damages tumor cells. Additionally, they can influence signaling pathways involved in oncogenesis, such as MAPK, PI3K/Akt, or others crucial for the survival and the proliferation of NSC cells. The exploration of 1,8-dihydroanthraquinone derivatives aims to develop novel therapies that could overcome resistance and improve cancer patients' outcomes. [ABSTRACT FROM AUTHOR]

Background: Emodin has protective effects on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). This meta-analysis intended to illustrate the efficacy of emodin on ALI/ARDS animal models. Methods: Relevant preclinical studies were searched on PubMed, EMBASE, and Web of Science. Standardized mean differences (SMDs) with corresponding confidence intervals (CIs) were used to compare lung injury scores, lung wet-to-dry weight ratios (W/D), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-18, PaO2, and PaCO2 between the treatment and control groups. The article quality was appraised using the SYRCLE tool. Results: Twenty one studies published between 2014 and 2023 were enrolled. Compared with the control group, emodin significantly reduced lung injury scores (SMD: -3.63; 95% CI: -4.36, -2.90; p < 0.00001), W/D ratios (SMD: -3.23; 95% CI: -4.29, -2.16; p < 0.00001), and MPO levels (SMD: -2.96; 95% CI: -3.92, -1.99; p < 0.00001). Furthermore, emodin downregulated TNF-α (SMD: -3.04; 95% CI: -3.62, -2.47; p < 0.00001), IL-1β (SMD: -3.76; 95% CI: -4.65, -2.87; p < 0.00001), IL-6 (SMD: -3.19; 95% CI: -3.95, -2.43; p < 0.00001), and IL-18 levels (SMD: -4.83; 95% CI: -6.10, -3.57; p < 0.00001). Emodin improved gas exchange dysfunction, increased PaO2 (SMD: 3.76; 95% CI: 2.41, 5.11; p < 0.00001), and decreased PaCO2 (SMD: -3.83; 95% CI: -4.90, -2.76; p < 0.00001). Sensitivity analyses and stratified analyses were conducted for outcome measures with heterogeneity. Conclusions: Emodin treatment can effectively reduce the severity of ALI in animal models. Additional animal investigations and clinical trials involving human subjects are imperative. [ABSTRACT FROM AUTHOR]

Hydroxyanthracene derivatives (HADs) are plant substances produced by a variety of plant species, including different Aloe, Rheum, and Rhamnus species and Cassia senna. These plants are often used in food supplements to improve bowel function. However, recently, the European Commission prohibited a number of HADs due to toxicological concerns. These HADs included aloin (aloin A and aloin B), aloe-emodin, emodin, and danthron. Most of the currently available analytical methods are restricted to the analysis of only these compounds and do not include other HADs. In this view, a multi-analyte method could be useful for both regulatory analysis and dietary intake studies. To this end, such a method, employing liquid chromatography–tandem mass spectrometry and targeting 16 different HADs, was developed and validated in this study. Limits of quantification were in the range from 0.025 mg kg−1 to 1 mg kg−1. The recovery of the method was within the acceptable range of 80% to 120%, with the exception of physcion. Repeatability varied from 0.5% to 11.6%, and the range for within-laboratory reproducibility was from 3.4% to 16.3%. The expanded measurement uncertainty was below 50% for all HADs. Subsequently, 24 commercial samples of food supplements and herbal infusions sourced in Belgium were analyzed. The results indicated that although the industry put a great effort into minimizing the amount of aloin and danthron present in food supplements, more than half of the products still exceeded the maximum tolerated levels suggested for aloe-emodin and emodin. [ABSTRACT FROM AUTHOR]

Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis. [ABSTRACT FROM AUTHOR]

The Russian Far East is a region of unique biodiversity, with numerous plant species, including Reynoutria japonica and Reynoutria sachalinensis. These plants are considered a serious threat to biodiversity and are classified as threatened species. However, Reynoutria plants synthesize and accumulate a variety of metabolites that are valued for their positive effects on human health. The main objective of this study is to quantitatively and qualitatively evaluate the content of secondary metabolites in different parts of R. japonica and R. sachalinensis plants. In this study, the results of phylogenetic analysis of the ITS2, matK, and rps16 genes showed that samples collected in the Sakhalin region were closest to R. sachalinensis, while samples collected in Primorsky krai were closer to R. japonica. The high-performance chromatography and mass spectrometry (HPLC-MS/MS) method was used to identify the compounds. As a result of the identification of metabolites in the leaves, stem, and roots of R. japonica and R. sachalinensis, we showed the presence of a total of 31 compounds, including stilbenes, phenolic acids, flavan-3-ols, flavones and flavonols, naphthalene derivatives, anthraquinones and derivatives, and phenylpropanoid disaccharide esters. The root of R. japonica was shown to be a rich source of stilbenes (up to 229.17 mg/g DW), which was 8.5 times higher than that of R. sachalinensis root (up to 27.04 mg/g DW). The root also contained high amounts of emodin derivatives and vanicoside B. Quercetin and its derivatives were the major metabolites in the leaves and stems of both Reynoutria species. In R. japonica leaves, quercetin-3-O-pentoside was the major compound, reaching a total of 7 mg/g DW, accounting for 34% of all compounds analyzed. In contrast, in R. sachalinensis leaves, quercitrin was the major compound (up to 13.96 mg/g DW), accounting for 62% of all compounds and 12.7 times higher than in R. japonica leaves. In turn, R. japonica leaves also contained high amounts of phenolic acids (up to 10 mg/g DW). Thus, the obtained results showed significant differences in the qualitative and quantitative composition of metabolites between R. japonica and R. sachalinensis plants. Additionally, in this work, a cell culture of R. japonica was obtained and tested for its ability to synthesize and accumulate stilbenes. [ABSTRACT FROM AUTHOR]

Objective: In Tibetan dietary and folk medicine practices, Rheum austral is commonly used as an alternative to Rheum tanguticum , and there is a prevailing belief that wild rhubarb should not be substituted by its cultivated counterpart. However, these traditions are not supported by scientific evidence, particularly concerning the differences in endogenous metabolites between cultivated and wild rhubarbs, as well as between officially recognized and non-official rhubarbs. These uncertainties have also been hindering the vertical integration development of the local rhubarb industry. Methods: In this study, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) and biostatistical analysis were employed to systematically and comprehensively investigate the chemical constituents of rhubarbs from various sources, focusing on the differences in metabolic components between cultivated and wild rhubarbs. Results: The metabolic differences in rhubarb from various varieties and environments are pronounced. Among them, 39 differential metabolites were identified between cultivated R. tanguticum and wild R. tanguticum. cultivated R. tanguticum is rich in emodin, physcion, and rhapontigenin, whereas wild R. tanguticum exhibits a higher concentration of rhaponticin and is particularly abundant in anthraquinone compounds. Additionally, 33 differential metabolites distinguished wild R. tanguticum from wild R. austral , with R. austral being rich in stilbene derivatives and wild R. tanguticum predominantly containing coumarins. The correlations among these differential metabolites have also been further explored and presented. Conclusion: The metabolic disparities between cultivated and wild rhubarb varieties are substantial, with wild rhuabarb containing higher levels of effective components than its cultivated counterparts. However, wild varieties face issues with component instability and resource depletion, while cultivated varieties exhibit more stable effective components. Given these significant differences in metabolic components, it is essential to differentiate rhubarbs from various species and growing conditions to suit specific medicinal and dietary purposes effectively. This paper can lay a theoretical foundation for the vertical integration development of the rhubarb industry in Tibetan areas. [ABSTRACT FROM AUTHOR]

Sanhua Decoction (SHD) is a classic prescription for the treatment of stroke in the clinic. Based on the combination strategy in vitro and in vivo, the chemical constituents of SHD were characterized by ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry, and the metabolites of five effective anthraquinone aglycones (emodin, chrysophanol, rhein, aloe‐emodin, and physcion) of rhubarb in SHD were studied. A total of 222 compounds were isolated and identified in vitro, including 50 flavonoids and their glycosides, 41 coumarins, 22 anthraquinones, 22 tannins, 14 phenylpropanoids, 16 alkaloids, 18 organic acids and their esters, 14 lignans, six anthrones, and 19 other compounds. A total of 111 prototype components were isolated and identified in vivo. Among them, 26, 82, 101, and 46 prototype components and 87 metabolites were detected in plasma, urine, feces, and bile for the first time. This study provides a basis for the identification of chemical components in vivo and in vitro and the analysis of potential pharmacodynamic components of SHD, and provides a basis for further study of pharmacodynamic mechanism. [ABSTRACT FROM AUTHOR]

Emodin (EMO) is an anthraquinone compound derived from Rheum palmatum L., which has rich pharmacological activity. However, studies have shown that EMO may cause hepatotoxicity. In this study, EMO was combined with tetrandrine and prepared as lipid nanoparticles (E-T/LNPs). The anti-liver fibrosis activity of EMO before and after formulation was evaluated by zebrafish and mice. In addition, the toxicity of EMO and E-T/LNPs was compared and the toxicity–efficacy concentrations of E-T/LNPs in zebrafish were verified. E-T/LNPs are morphologically stable (particle size within 100 nm), have high encapsulation efficiency and good stability, and are capable of long-lasting slow release in vitro. The combination and preparation can reduce the toxicity and enhance the effect of EMO, and increase the toxicity and effect concentration of E-T/LNPs in vivo. In a short period, low doses of E-T/LNPs can be used for the treatment of liver fibrosis; high doses of E-T/LNPs cause toxicity in vivo. Immunohistochemistry showed that E-T/LNPs inhibited hepatic fibrosis by downregulating the levels of IL-1β and TGF-β. Based on the advantages of combination therapy and nanotechnology, it can play a role in reducing the toxicity and increasing the efficacy of EMO in the treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC50 value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to determine the preventive effects of emodin on cyclophosphamide (CYP)‐induced cystitis and to explore the molecular mechanism. Methods: In vivo, mice were modeled by CYP. Before a half hour of CYP treatment, Jumonji domain‐containing protein‐3 (JMJD3) inhibitors (GSK‐J4) and emodin were used to treat CYP model mice. Bladder samples were stained for hematoxylin‐eosin and toluidine blue. Next, JMJD3 was quantified by immunofluorescence staining, RT‐PCR, and Western blot. CXCR3 was quantified by Western blot and ELISA. In vitro, before stimulated by lipopolysaccharide (LPS), human bladder smooth muscle cells (hBSMCs) were transfected with pcDNA3.1‐JMJD3 plasmids, shRNA‐JMJD3 plasmids or pretreated with emodin. Collected cells to detect JMJD3 and CXCR3 ligands again; collected supernatant of culture for Transwell assay. Finally, as the JAK2 inhibitor, AG490 was used to pretreat LPS‐induced hBSMCs. Western blot was performed to quantify proteins. Results: Emodin inhibited mast cell migration and suppressed the expression of JMJD3, CXCR3, and CXCR3 ligands, not only in vivo but also in vitro. The pharmacological effects of emodin were similar to GSK‐J4 or JMJD3 inhibition. In addition, emodin significantly downregulated the phosphorylation of JAK2 and STAT3, and inhibited JMJD3/CXCR3 axis transduction like AG490. Conclusion: Emodin has a preventive effect on cystitis by inhibiting mast cell migration through inhibition of the JAK2/STAT3/JMJD3/CXCR3 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Emodin has protective effects on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). This meta-analysis intended to illustrate the efficacy of emodin on ALI/ARDS animal models. Methods Relevant preclinical studies were searched on PubMed, EMBASE, and Web of Science. Standardized mean differences (SMDs) with corresponding confidence intervals (CIs) were used to compare lung injury scores, lung wet-to-dry weight ratios (W/D), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-18, PaO2, and PaCO2 between the treatment and control groups. The article quality was appraised using the SYRCLE tool. Results Twenty one studies published between 2014 and 2023 were enrolled. Compared with the control group, emodin significantly reduced lung injury scores (SMD: -3.63; 95% CI: -4.36, -2.90; p

Objective To investigate the effect and mechanism of emodin on cell proliferation in OSCC. Methods CAL-27 cells and SCC-15 cells were intervened with different concentrations of emodin, and the proliferative activity of the cells was detected by CCK-8 method, and the appropriate concentration was screened for follow-up experiments. The colony formation experiment helped detect the colony formation ability. The expressions of PCNA, Beclin1 and LC3 were detected using Western blot. After treating the cells with rapamycin and emodin, the cell proliferation activity and the colony formation ability were examined. PCNA, Beclin1 and LC3 expressions were detected. The tumor formation experiment helped detect the effect of emodin on tumor weight and volume in nude mice. The liver and kidney structure in nude mice was observed using HE staining. Moreover, the PCNA and Beclin1 protein expression was detected by IHC. Results Emodin could significantly decrease the proliferative activity and aggregation ability of CAL-27 cells in a concentration-dependent manner. Emodin could down-regulate the PCNA, Beclin1, and LC3Ⅱ/LC3Ⅰ expression levels. RAPA could reverse the inhibitory effect of emodin on cell proliferation. Emodin had no significant hepatorenal toxicity and could reduce the volume and mass of the tumor and down-regulate the expression of PCNA and Beclin1 protein inside the tumor. Moreover, the expression of PCNA and Beclin1 in tumor showed a certain positive correlation. Conclusion Emodin can inhibit oral squamous cell proliferation, and its effect may be associated with autophagy inhibition.

Due to inadequate treatment, diabetes mellitus, which is characterized by hyperglycemia, is a global health challenge that requires creative management techniques. This study explores the therapeutic potential of Abelmoschus esculentus L. Moench fruit extracts in diabetes, offering an ample approach includes phytochemical analysis, qualitative and quantitative assessments, antidiabetic efficacy, antioxidant potential, and in vivo and in vitro investigations. Thin‐layer chromatography (TLC), high‐performance liquid chromatography (HPLC), and gas chromatography–mass spectrometry (GC–MS) were utilized to disclose the phytochemical profile of the fruit extracts, which indicated a diverse range of bioactive compounds. Four polyphenolic compounds including chlorogenic acid, quercetin, rutin, and morin were confirmed by HPLC fingerprinting, with rutin being the most prevalent. Qualitative analysis reveals the presence of carbohydrates, emodin, terpenoids, lignin, glycosides, and anthraquinones, while indicating the absence of amino acids, anthocyanins, phlobatannins, lactones, and leucoanthocyanins. Quantitative analysis reveals total phenolic, tannin, and flavonoid. In vitro assessments demonstrate the ability of the extracts to inhibit alpha amylase. Radical scavenging activities were evaluated through DPPH assay, underscoring their antioxidant capacity with high effect in methanol extracts. Additionally, the methanol extract decreased the blood glucose level of Type 2 diabetic mice. Notably, test samples stabilized blood glucose levels, reversed deviations in blood profile parameters, blood biochemistry, and regulated organ weight. Based on its antioxidant and antidiabetic effects, as well as positive effects on the physiology of Type 2 diabetic mice, A. esculentus emerges as an important nutraceutical vegetable. As an important nutraceutical vegetable, it holds promise for diabetes management. A. esculentus can be incorporated into dietary interventions for individuals with diabetes, harnessing its natural antioxidant and antidiabetic properties. Our findings validate the traditional use of A. esculentus in green therapeutics. In conclusion, A. esculentus emerges as a valuable ally in the fight against diabetes, bridging the gap between ancient wisdom and modern science. Further research and practical implementation are warranted to fully realize its potential. [ABSTRACT FROM AUTHOR]

Objective: In Tibetan dietary and folk medicine practices, Rheum austral is commonly used as an alternative to Rheum tanguticum, and there is a prevailing belief that wild rhubarb should not be substituted by its cultivated counterpart. However, these traditions are not supported by scientific evidence, particularly concerning the differences in endogenous metabolites between cultivated and wild rhubarbs, as well as between officially recognized and non-official rhubarbs. These uncertainties have also been hindering the vertical integration development of the local rhubarb industry. Methods: In this study, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) and biostatistical analysis were employed to systematically and comprehensively investigate the chemical constituents of rhubarbs from various sources, focusing on the differences in metabolic components between cultivated and wild rhubarbs. Results: The metabolic differences in rhubarb from various varieties and environments are pronounced. Among them, 39 differential metabolites were identified between cultivated R. tanguticum and wild R. tanguticum. cultivated R. tanguticum is rich in emodin, physcion, and rhapontigenin, whereas wild R. tanguticum exhibits a higher concentration of rhaponticin and is particularly abundant in anthraquinone compounds. Additionally, 33 differential metabolites distinguished wild R. tanguticum from wild R. austral, with R. austral being rich in stilbene derivatives and wild R. tanguticum predominantly containing coumarins. The correlations among these differential metabolites have also been further explored and presented. Conclusion: The metabolic disparities between cultivated and wild rhubarb varieties are substantial, with wild rhuabarb containing higher levels of effective components than its cultivated counterparts. However, wild varieties face issues with component instability and resource depletion, while cultivated varieties exhibit more stable effective components. Given these significant differences in metabolic components, it is essential to differentiate rhubarbs from various species and growing conditions to suit specific medicinal and dietary purposes effectively. This paper can lay a theoretical foundation for the vertical integration development of the rhubarb industry in Tibetan areas. [ABSTRACT FROM AUTHOR]

Jasmonates, including jasmonic acid (JA) and its derivatives such as methyl jasmonate (MeJA) or jasmonly isoleucine (JA-Ile), regulate plant responses to various biotic and abiotic stresses. In this study, we applied exogenous MeJA onto Senna tora leaves subjected to wounding and conducted a transcriptome deep sequencing analysis at 1 (T1), 3 (T3), 6 (T6), and 24 (T24) h after MeJA induction, along with the pretreatment control at 0 h (T0). Out of 18,883 mapped genes, we identified 10,048 differentially expressed genes (DEGs) between the T0 time point and at least one of the four treatment times. We detected the most DEGs at T3, followed by T6, T1, and T24. We observed the upregulation of genes related to JA biosynthesis upon exogenous MeJA application. Similarly, transcript levels of genes related to flavonoid biosynthesis increased after MeJA application and tended to reach their maximum at T6. In agreement, the flavonols kaempferol and quercetin reached their highest accumulation at T24, whereas the levels of the anthraquinones aloe-emodin, emodin, and citreorosein remained constant until T24. This study highlights an increase in flavonoid biosynthesis following both MeJA application and mechanical wounding, whereas no significant influence is observed on anthraquinone biosynthesis. These results provide insights into the distinct regulatory pathways of flavonoid and anthraquinone biosynthesis in response to MeJA and mechanical wounding. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have shown that silent mating-type information regulator 2 homolog 1 (SIRT1)-mechanistic target of rapamycin (mTOR) signaling plays an important role in the progression of osteoarthritis. Emodin has a protective effect on osteoarthritic chondrocytes.OBJECTIVE: To investigate the effects of emodin on the proliferation, apoptosis and oxidative stress of osteoarthritic chondrocytes based on the SIRT1-mTOR signaling. METHODS: Rat chondrocytes were isolated and cultured in vitro. Osteoarthritic chondrocyte model in vitro was induced by 10 ng/mL interleukin-1β. Cell counting kit-8 method was used to determine the viability of rat chondrocytes treated with 0, 20, 40, 80, 120, 160 µmol/L emodin, and the appropriate concentration of emodin was selected. Rat chondrocytes isolated and cultured in vitro were randomly divided into control group, model group, low-dose emodin group, high-dose emodin group, EX527 group, and high-dose emodin+EX527 group. In vitro osteoarthritis model was constructed by induction of 10 ng/mL interleukin 1β in all groups except the control group. The cells in the latter four groups were correspondingly treated with emodin or/and EX527. The proliferation and apoptosis of chondrocytes in each group were detected by cell counting kit-8, Edu staining and flow cytometry respectively. The relative content of reactive oxygen species and the levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase in chondrocytes of rats in each group were measured with the kit. The expression of proteins related to cell matrix degradation, apoptosis and the SIRT1-mTOR pathway-related proteins in each group were detected by western blot. RESULTS AND CONCLUSION: Compared with the control group, the survival rate of chondrocytes, the positive rate of Edu, the levels of superoxide dismutase, catalase, and glutathione peroxidase, and the expression of Bcl-2 and SIRT1 proteins in the model group were decreased, while the apoptosis rate, the relative content of reactive oxygen species, the level of malondialdehyde, the expression of Bax, matrix metalloproteinase 3, matrix metalloproteinase 9 proteins, and p-mTOR/mTOR were increased (P < 0.05). Compared with the model group, the survival rate of chondrocytes, the positive rate of Edu, the levels of superoxide dismutase, catalase, and glutathione peroxidase, and the expression of Bcl-2 and SIRT1 proteins in the low- and high-dose emodin groups were increased, while the apoptosis rate, the relative content of reactive oxygen species, the level of malondialdehyde, the expression of Bax, matrix metalloproteinase 3, matrix metalloproteinase 9 proteins, and p-mTOR/mTOR were decreased (P < 0.05). Compared with the low- and high-dose emodin groups, the indexes of EX527 group showed the opposite trend (P < 0.05). Compared with the high-dose emodin group, the survival rate of chondrocytes, the positive rate of Edu, the levels of superoxide dismutase, catalase, and glutathione peroxidase, and the expression of Bcl-2 and SIRT1 proteins in the high-dose emodin+EX527 group were decreased, while the apoptosis rate, the relative content of reactive oxygen species, the level of malondialdehyde, the expression of Bax, matrix metalloproteinase 3, matrix metalloproteinase 9 proteins, and p-mTOR/mTOR were increased (P < 0.05). To conclude, emodin can inhibit oxidative stress of osteoarthritic chondrocytes by activating the SIRT1-mTOR signaling, thereby promoting chondrocyte proliferation and reducing apoptosis. [ABSTRACT FROM AUTHOR]

AbstractMedium/long-chain fatty acids/alcohols as hydrogen bond donors coupled with methyltrioctylammonium chloride were used to prepare hydrophobic deep eutectic solvents (DESs) that were employed for the extraction of the anthraquinones (rhein, emodin, and chrysophanol) from fetal bovine serum. Hydrophobic DES-based liquid-phase microextraction and high-performance liquid chromatography were developed. The most suitable combination was optimized for liquid-phase microextraction. Spiked fetal bovine serum was analyzed with satisfactory extraction recoveries. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia induces cholelithiasis and dysfunction of gallbladder motility. Interstitial cells of Cajal (ICCs) contribute to gallbladder motility. Emodin modulates the contractility of the gallbladder muscle; however, the underlying mechanism is unknown. Aim: This study aimed to explore the effects of emodin on gallbladder ICCs with cholelithiasis in a guinea pig model. Methods: Animals were randomly divided into a healthy control group and three study groups. All study groups received a high-cholesterol diet (HCD) for 8 weeks. Subsequently, they were randomly assigned to either the HCD group or one of the emodin treatment groups lasting 4 or 8 weeks. Total cholesterol (TC) and triglycerides (TG) were measured to determine changes in serum lipid levels. Immunohistochemistry was performed to detect the morphology and number of ICCs. TUNEL assays were performed to detect ICC apoptosis. Transmission electron microscopy was employed to observe ICC structure. Western blotting and real-time polymerase chain reaction were used to detect changes in stem cell factor (SCF)/c-kit pathway expression. Results: Serum TC and TG were higher in all study groups. In cases of cholelithiasis, the SCF/c-kit pathway was downregulated, the number of gallbladder ICCs decreased, apoptosis increased, and the ICC network structure was damaged. After emodin treatment, the SCF/c-kit pathway was upregulated, the number of gallbladder ICCs increased, apoptosis decreased, and the ICC network structure recovered. Conclusion: Cholelithiasis downregulates the SCF/c-kit pathway and damages gallbladder ICCs. Emodin upregulates the SCF/c-kit pathway and increases gallbladder ICCs, contributing to recovery from gallbladder motility disorders. [ABSTRACT FROM AUTHOR]

Emodin, derived from Rheum officinale and aloe, is known for its diverse benefits such as antiinflammatory, antioxidant, and antibacterial properties. Currently, the impact of emodin on urosepsis is unclear. This study aims to investigate the mechanism of action of emodin in urosepsis. Peripheral blood mononuclear cells (PBMCs) were purchased from Cloud-Clone Animal Inc. and treated with emodin. Cell viability and the lactate dehydrogenase (LDH) level were then assessed. In a separate experiment, a urosepsis model was established in Sprague Dawley rats which were subsequently treated with emodin. The levels of oxidative stress-related factors, serum complements and inflammatory factors were measured using commercial kits. Blood urea nitrogen and serum creatinine levels were determined using a fully automatic biochemical analyzer. The levels of pro-inflammatory proteins and AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) pathway-related proteins were evaluated via Western blot. PBMCs were unaffected by emodin concentrations below 60 μg/mL, and minimal LDH levels were detected in the cells. Emodin attenuated the effects of Escherichia coli and diminished the production of serum complements, oxidative stress-related proteins, and inflammatory factors in PBMCs. Notably, the effects of emodin were lessened by an AMPK pathway inhibitor. Additionally, emodin alleviated oxidative stress, complement system activation, inflammation, and kidney injury in urosepsis rats through the AMPK/SIRT1 signaling pathway. Emodin improved kidney damage in urosepsis rats by activating the AMPK/SIRT1 signaling pathway, which reduced oxidative stress, inflammation, and complement system activation. [ABSTRACT FROM AUTHOR]

Anthraquinones exhibit a significant group of natural and synthetic quinone derivatives because of their biological activities and industrial applications. Rhamnaceae is one of the families known to contain different kinds of anthraquinones. In this study, it was aimed to quantify rhein, emodin, chrysophanol and physcion in fruits of Rhamnus petiolaris Boiss. & Balansa belonging to Rhamnaceae by solid phase extraction and high performance liquid chromatography with ultraviolet detection. The anthraquinones were separated using a C18 analytical column. Gradient elution was performed using a mobile phase consisted of 0.1% o -phosphoric acid solution and methanol. Analytes were detected at 254 nm. Calibration curves were prepared in the range of 0.25–5.00 μg/mL for rhein, chrysophanol, physcion, 1.00–50.00 μg/mL for emodin. Limits of detection and quantification were between 0.07–0.11 and 0.20–0.34 μg/mL, respectively. Relative standard deviations were ≤ 5.78% in repeatability and intermediate precision studies. Accuracy was determined as relative mean error (8.17–12.06%). Extraction was achieved by maceration with acetone and ethanol, followed by hydrophilic–lipophilic balance solid phase extraction. Recoveries were between 96.2 and 109.6%. The developed and validated method was successfully performed to quantify rhein, emodin, chrysophanol and physcion in R. petiolaris fruit extracts. Only physcion was not detected above limit of detection. [ABSTRACT FROM AUTHOR]

This experiment aimed to investigate the effects of emodin on the physiological responses and antioxidant gene expression of Wuchang bream infected with Aeromonas hydrophila. The experimental diets were prepared with supplementing 0, 30, 100 and 150 mg kg-1 emodin to basal (control) diet respectively, and fed to fish with initial weight of 50.4 ± 2.35 g. All fish were divided into five experimental groups: uninfected fish fed with basal control diet (negative control, NC), infected fish fed with the diet supplemented with 0 (positive control group, PC), 30, 100, and 150 mg kg-1 emodin. The fish were reared for 14 days, sampled at different time points and then analyzed. The results showed that the physiological responses and related antioxidant gene expression of infected Wuchang bream were significantly influenced by the dosage of added emodin and the feeding duration (P < 0.05). Comparing to the positive control group, emodin could inhibit the levels of cortisol (COR), triiodothyronine (T3), and thyroxine (T4) in infected Wuchang bream, with hormone levels reaching equilibrium in the shortest time at 30 and 100 mg kg-1 emodin supplementation. Meanwhile, emodin significantly affected alkaline phosphatase (AKP) activity, glucose (Glu) and triglyceride (TG) contents, and related antioxidant gene expression in infected Wuchang bream (P < 0.05), with the best effect observed at 100 mg kg-1 emodin supplementation in the diet. In conclusion, the supplementation of 100 mg/kg emodin to diet can enhance the resistance of Wuchang bream to A. hydrophila infection via promoting physiological metabolism and antioxidant capacity. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 continues to mutate and circulate at alarming levels around the world and is exemplified by the emergence of the new variant JN.1. The emergence of novel SARS-CoV variants underscores the urgency for the development of new drugs. Phytochemicals, known for their safety and efficacy, have been widely used to address various ailments. This study aims at identifying the anti-SARS-CoV potential of emodin, a bioactive anthraquinone, and its derivatives. Key proteins, including hemagglutinin-esterase (HE), papain-like protease (PLpro), major protease (3CLpro), non-structural protein (nsp3) and spike protein(S) of SARS-CoV, were used as protein targets for the virtual screening of 110 emodin derivatives (ED) and remdesivir a proven antiviral drug. Among the 110 derivatives, ED21, ED25, ED5 inhibited HE, 3CLpro and S protein, respectively. ED29 inhibited both PLpro and nsp3 with high binding affinity. Similar receptor binding sites were occupied by remdesivir and emodin derivatives. These emodin derivatives are bound to similar amino acids in receptors as compared to remdesivir. Further dynamic simulations studies with ED21-HE, ED25-3CLpro, ED5-S, ED29-PLpro and ED29-nsp3 complexes showed all of them are stable with minimum root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA) and radius of gyration (Rg) and are comparable to APO protein. All the ligands accepted Lipinski’s rule of five. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed only ED21 and ED5 as promising druglike candidates that can have high therapeutic value and no side effects. These in-silico findings contribute to the development of potent SARS-CoV-2 inhibitors, potentially advancing the quest for effective antiviral drugs. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection can cause condyloma acuminatum (CA), which is characterized by a high incidence and a propensity for recurrence after treatment. Angiogenesis plays an important role in the occurrence and development of CA. Seryl‐tRNA synthetase (SerRS) is a newly identified, potent anti‐angiogenic factor that directly binds to the vascular endothelial growth factor (VEGFA) promoter, thereby suppressing its transcription. Emodin is a natural anthraquinone derivative that can promote SerRS expression. This study aimed to investigate the effects of emodin on CA and explore combined treatment strategies. The HPV‐infected cell line SiHa was treated with either DMSO, emodin, ALA‐PDT or a combination of emodin and ALA‐PDT. We observed the effects on cell proliferation, apoptosis and the SerRS‐VEGFA pathway. Our findings demonstrated that emodin targets angiogenesis through the SerRS‐VEGFA pathway, resulting in the inhibition of SiHa cell proliferation and promotion of apoptosis (p < 0.001). To verify the therapeutic effect of emodin combined with ALA‐PDT on HPV‐associated tumours in vivo, we established an animal xenograft model by subcutaneously inoculating mice with SiHa cells (n = 4). The results showed that the combination of emodin and ALA‐PDT significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.001), thus showing an inhibitory effect on tumour (p < 0.001). Furthermore, we determined that the mechanism underlying the decrease in VEGFA expression after emodin combined with ALA‐PDT in CA may be attributed to the promotion of SerRS expression (p < 0.001). The combination of emodin and ALA‐PDT holds promise as a novel therapeutic target for CA by targeting neovascularization in condyloma tissues. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new programmed cell death characterized by iron-dependent lipid peroxidation. Targeting ferroptosis is considered a promising strategy for anti-cancer therapy. Recently, natural compound has gained increased attention for their advantage in cancer treatment, and the exploration of natural compounds as ferroptosis inducers offers a hopeful avenue for advancing cancer treatment modalities. Emodin is a natural anthraquinone derivative in many widely used Chinese medicinal herbs. In our previous study, we predicted that the anti-cancer effect of Emodin might related to ferroptosis by using RNA-seq in colorectal cancer (CRC). Thus, in this study, we aim to investigate the molecular mechanism underlying Emodin-mediated ferroptosis in CRC. Cell-based assays including CCK-8, colony formation, EdU, and Annexin V/PI staining were employed to assess Emodin's impact on cell proliferation and apoptosis. Furthermore, various techniques such as FerroOrange staining, C11-BODIPY 581/591 staining, iron, MDA, GSH detection assay and transmission electron microscopy were performed to examine the role of Emodin in ferroptosis. Additionally, specific NCOA4 knockdown cell lines were generated to elucidate the involvement of NCOA4 in Emodin-induced ferroptosis. Moreover, the effects of Emodin on ferroptosis were further confirmed through the application of inhibitors, including Ferrostatin-1, 3-MA, DFO, and PMA. As a results, Emodin inhibited proliferation and induced apoptosis in CRC cells. Emodin could decrease GSH content, xCT and GPX4 expression, meanwhile increasing ROS generation, MDA, and lipid peroxidation, and these effects could reverse by ferroptosis inhibitor, Ferostatin-1, iron chelator DFO, autophagy inhibitor 3-MA and NCOA4 silencing. Moreover, Emodin could inactivate NF-κb pathway, and PMA, an activator of NF-κb pathway could alleviate Emodin-induced ferroptosis in CRC cells. Xenograft mouse model also showed that Emodin suppressed tumor growth and induced ferroptosis in vivo. In conclusion, these results suggested that Emodin induced ferroptosis through NCOA4-mediated ferritinophagy by inactivating NF-κb pathway in CRC cells. These findings not only identified a novel role for Emodin in ferroptosis but also indicated that Emodin may be a valuable candidate for the development of an anti-cancer agent. [ABSTRACT FROM AUTHOR]

Background: The continuous emergence and spread of polymyxin-resistant Acinetobacter baumannii pose a significant global health challenge, necessitating the development of novel therapeutic strategies. Aloe, with its long-standing history of medicinal use, has recently been the subject of substantial research for its efficacy against pathogenic infections. Methods: This study investigates the potential application of anthraquinone components in aloe against polymyxin-resistant A. baumannii by liquid chromatography-mass spectrometry, in vitro activity assessment, and construction of animal infection models. Results: The findings demonstrate that aloe emodin, emodin, rhein, and their mixtures in equal mass ratios (EAR) exhibit strain-specific antibacterial activities against polymyxin-resistant A. baumannii. Co-administration of EAR with EDTA synergistically and universally enhanced the antibacterial activity and bactericidal efficacy of polymyxins against polymyxin-resistant A. baumannii, while also reducing the frequency of polymyxin-resistant mutations in polymyxinssensitive A. baumannii. Following toxicity assessment on human hepatic and renal cell lines, the combination therapy was applied to skin wounds in mice infected with polymyxin-resistant A. baumannii. Compared to monotherapy, the combination therapy significantly accelerated wound healing and reduced bacterial burden. Conclusions: The combination of EAR and EDTA with polymyxins offers a novel therapeutic approach for managing skin infections caused by polymyxinresistant A. baumannii. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) is a pressing global issue, with Hepatitis B virus (HBV) infection remaining the primary. Emodin, an anthraquinone compound extracted from the natural plant's. This study investigates the molecular targets and possible mechanisms of emodin in treating HBV-related HCC based on network pharmacology and molecular docking and validates the screened molecular targets through in vitro experiments. Methods: Potential targets related to emodin were obtained through PubChem, CTD, PharmMapper, SuperPred, and TargetNet databases. Potential disease targets for HBV and HCC were identified using the DisGeNET, GeneCards, OMIM, and TTD databases. A Venn diagram was used to determine overlapping genes between the drug and the diseases. Enrichment analysis of these genes was performed using GO and KEGG via bioinformatics websites. The overlapping genes were imported into STRING to construct a protein-protein interaction network. Cytoscape 3.9.1 software was used for visualizing and analyzing the core targets. Molecular docking analysis of the drug and core targets was performed using Schrodinger. The regulatory effects of emodin on these core targets were validate through in vitro experiments. Results: A total of 43 overlapping genes were identified. GO analysis recognized 926 entries, and KEGG analysis identified 135 entries. The main pathways involved in the KEGG analysis included cancer, human cytomegalovirus infection and prostate cancer. The binding energies of emodin with HSP90AA1, PTGS2, GSTP1, SOD2, MAPK3, and PCNA were all less than -5 kcal/mol. Compared to normal liver tissue, themRNA levels of XRCC1,MAPK3, and PCNAwere significantly elevated in liver cancer tissue. The expression levels of XRCC1, HIF1A, MAPK3, and PCNA genes were closely related to HCC progression. High expressions of HSP90AA1, TGFB1, HIF1A, MAPK3, and PCNA were all closely associated with poor prognosis in HCC. In vitro experiments demonstrated that emodin significantly downregulated the expression of HSP90AA1, MAPK3, XRCC1, PCNA, and SOD2, while significantly upregulating the expression of PTGS2 and GSTP1. Conclusion: This study, based on network pharmacology and molecular docking validation, suggests that emodin may exert therapeutic effects on HBV-related HCC by downregulating the expression of XRCC1, MAPK3, PCNA, HSP90AA1, and SOD2, and upregulating the expression of PTGS2 and GSTP1. [ABSTRACT FROM AUTHOR]

Skin cancer is threatening more and more people's health; its postoperative recurrence and wound infection are still critical challenges. Therefore, specialty wound dressings with multifunctional bioactivity are urgently desired. Emodin is a natural anthraquinone compound that has anti-cancer and anti-bacterial properties. Herein, we fabricated coaxial electrospinning nanofibers loaded with emodin to exploit a multifunctional wound dressing for skin cancer postoperative management, which encapsulated emodin in a polyvinylpyrrolidone core layer, combined with chitosan-polycaprolactone as a shell layer. The nanofibers were characterized via morphology, physicochemical nature, drug load efficiency, pH-dependent drug release profiles, and biocompatibility. Meanwhile, the anti-cancer and anti-bacterial effects were evaluated in vitro. The emodin-loaded nanofibers exhibited smooth surfaces with a relatively uniform diameter distribution and a clear shell-core structure; remarkably, emodin was evenly dispersed in the nanofibers with significantly enhanced dissolution of emodin. Furthermore, they not only display good wettability, high emodin entrapment efficiency, and biphasic release profile but also present superior biocompatibility and anti-cancer properties by increasing the levels of MDA and ROS in A-375 and HSC-1 cells via apoptosis-related pathway, and long-term anti-bacterial effects in a dose-independent manner. The findings indicate that the emodin-loaded nanofiber wound dressing can provide a potential treatment strategy for skin cancer postoperative management. [ABSTRACT FROM AUTHOR]

To combine the activity characteristics of 18β‐glycyrrhetinic acid (18β‐GA) and anthraquinone compounds (rhein and emodin), reduce toxicity, and explore the structure–activity relationship (SAR) of anthraquinones, 18β‐GA‐anthraquinone ester compounds were synthesized by one‐step organic synthesis. The products were separated and purified by HPLC and characterized by NMR and EI‐MS. It was finally determined as di‐18β‐GA‐3‐rhein ester (1, New), GA dimer (2, known), 18β‐GA‐3‐emodin ester (3, known), and di‐18β‐GA‐1‐emodin ester (4, new). The MIC of three reactants and four products against Escherichia coli and Staphylococcus aureus were detected in vitro. Its developmental toxicity and cardiotoxicity were assessed using zebrafish embryos. The experimental results showed that rhein had the best antibacterial activity against Staphylococcus aureus with MIC50 of 2.4 mM, and it was speculated that –COOH, –OH, and intramolecular hydrogen bonds in anthraquinone compounds would enhance the antibacterial effect, while the presence of‐CH3 might weaken the antibacterial activity. Product 1 increased the hatching rate and survival rate of zebrafish embryos and reduced the malformation rate and cardiomyocyte apoptosis. This experiment lays the foundation for further studying the SAR of anthraquinones and providing new drug candidates. [ABSTRACT FROM AUTHOR]

This review aims to gain insight into the major causes of hair graying (canities) and how plant-derived extracts and phytochemicals could alleviate this symptom. Research articles on human hair graying were searched and selected using the PubMed, Web of Science, and Google Scholar databases. We first examined the intrinsic and extrinsic factors associated with hair graying, such as the reduced capacity of melanin synthesis and transfer, exhaustion of melanocyte stem cells (MSCs) and melanocytes, genetics and epigenetics, race, gender, family history, aging, oxidative stress, stress hormones, systematic disorders, nutrition, smoking, alcohol consumption, lifestyle, medications, and environmental factors. We also examined various plants and phytochemicals that have shown a potential to interfere with the onset or progression of human hair graying at different levels from in vitro studies to clinical studies: the extract of Polygonum multiflorum and its major components, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside and emodin; the extract of Eriodictyon angustifolium and its major flavonoid compounds, hydroxygenkwanin, sterubin, and luteolin; the extracts of Adzuki beans (Vigna angularis), Fuzhuan brick tea (Camellia sinensis), and Gynostemma pentaphyllum; bixin, a carotenoid compound found in Bixa orellana; and rhynchophylline, an alkaloid compound found in certain Uncaria species. Experimental evidence supports the notion that certain plant extracts and phytochemicals could alleviate hair graying by enhancing MSC maintenance or melanocyte function, reducing oxidative stress due to physiological and environmental influences, and managing the secretion and action of stress hormones to an appropriate level. It is suggested that hair graying may be reversible through the following tactical approaches: selective targeting of the p38 mitogen-activated protein kinase (MAPK)–microphthalmia-associated transcription factor (MITF) axis, nuclear factor erythroid 2-related factor 2 (NRF2), or the norepinephrine–β2 adrenergic receptor (β2AR)–protein kinase A (PKA) signaling pathway. [ABSTRACT FROM AUTHOR]

• Emodin reduces HIBD in neonatal mice. • Emodin improves neurologic recovery of neonatal mice after HIBD. • Emodin can exert neuroprotective effects on HIBD by inhibiting neuronal apoptosis. 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. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A type of unique azole‐hybridized acylhydrazonyl aloe emodins (AAEs) were developed as new antibacterial agents for combating bacterial infections. Some target AAEs showed strong antibacterial activities, especially, tetrazolylthioether AAE 27a exhibited broad antibacterial spectrum with 16—256 folds and 8—64 folds more active antibacterial efficacy than the reference drugs aloe emodin and norfloxacin, respectively. Tetrazolylthioether AAE 27a also gave low hemolysis and cytotoxicity, as well as favorable bioavailability. Preliminary mechanism explorations revealed that tetrazolylthioether AAE 27a could cause bacterial membrane depolarization and damage the cell membrane, resulting in nucleic acid leakage. Moreover, compound 27a could intercalate into DNA to impede its replication and form supramolecular 27a‐DNA gyrase complex to disturb the function of DNA gyrase. These findings would provide valuable insights for the further exploration of azolyl acylhydrazonyl aloe emodins as new potential antibacterial candidates. [ABSTRACT FROM AUTHOR]

Objective: Resveratrol, a natural product found in plants, is a polyphenolic compound with strong antioxidant activity. In order to enhance the antioxidant activity of resveratrol, we have used a natural product emodin, which has multiple hydroxyl group structure similar to resveratrol. Methods: In this study, we investigated the antioxidant activities of resveratrol and emodin in vitro respectively, including their abilities to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, hydroxyl radicals, and superoxide radicals. Results and Discussion: our results demonstrated that the combination of resveratrol and emodin significantly enhances antioxidant activity. And the process of their DPPH radical scavenging follows a first-order reaction kinetics equation. Finally, a possible mechanism for the scavenging of DPPH free radicals by resveratrol and emodin was proposed. Conclusions: We found that emodin combined with resveratrol can increase antioxidant activity. This study provides a new sight to enhance antioxidant activity. [ABSTRACT FROM AUTHOR]

Background: Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages. Methods: Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1β, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD. Results: There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1β and TNF-α (p < 0.05) and the ratio of M1 macrophage surface markers F4/80 + CD86+ (p < 0.01) in the supernatant of RAW264.7 cells in a dose-dependent manner. Furthermore, the inhibitory effect of emodin on RAW264.7 cells was achieved by interfering with the EGFR/MAPK pathway. Moreover, emodin also affected the mRNA and protein expression of EGFR and Ras, leading to a decrease in the rate of M1 macrophages, thus inhibiting the pro-inflammatory effect of M1 macrophages. The addition of emodin reduced the rate of M1 macrophages in CKD and inhibited the further polarization of M1 macrophages, thus maintaining the pro-inflammatory and anti-inflammatory homeostasis in CKD, and these effects were achieved by emodin through the control of the EGRF/ERK pathway. Conclusion: Emodin attenuates M1 macrophage polarization and pro-inflammatory responses via the EGFR/MAPK signalling pathway. And the addition of emodin maintains pro- and anti-inflammatory homeostasis, which is important for maintaining organ function and tissue repair. [ABSTRACT FROM AUTHOR]

Traditional textile dyeing processes usually require large quantities of water and energy and generate wastewater that can be harmful to the environment. Dyeing in supercritical carbon dioxide (sc‐CO2) media is promising in textile coloration due especially to it providing a waterless process and eliminating the need for an energy intensive drying step. The natural anthraquinone emodin showed promising results for dyeing different fibres through sc‐CO2 process. However, emodin is mutagenic. The aim of this study was to develop non‐mutagenic derivatives of emodin that can be applied to textiles using sc‐CO2. Emodin structure was modified incorporating acryloyl groups, which are considered suitable for decreasing potential for DNA intercalation, and thus mutagenicity. The presence of acryloyl groups would also enable atmospheric plasma induced bonding with fibres. Molecular modelling studies showed that emodin derivatives became less planar with increasing number of attached acryloyl groups, making intercalation unlikely. The derivatives produced were tested to assess mutagenicity in vitro (Salmonella/microsome assay, TA1537, 10% S9) and in vivo (micronucleus test in hemocytes of aquatic crustacean). We found that emodin can be derivatised using acryloyl chlorides to give mono‐ and di‐acrylate esters suitable for dyeing polyester fibres in sc‐CO2. However, the new dyes presented mutagenicity for both in vitro and in vivo. Although the derivatives provided greenish‐yellow alternatives to emodin for dyeing synthetic fibres, they do not appear to be viable alternatives from the point of view of preserving human and environmental health. Plasma bonding studies are underway. [ABSTRACT FROM AUTHOR]

Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.

Background Emodin is a traditional medicine that has been shown to exert anti-inflammatory and anti-oxidative effects. Previous research has indicated that emodin can alleviate myocardial remodeling and inhibit myocardial hypertrophy and fibrosis. However, the mechanism by which emodin affects myocardial fibrosis (MF) has not yet been elucidated.Methods Fibroblasts were treated with ANGII, and a mouse model of MF was established by ligation of the left anterior descending coronary artery. Cell proliferation was examined by a Cell Counting Kit-8 (CCK8) assay. Dihydroethidium (DHE) was used to measure reactive oxygen species (ROS) levels, and Masson and Sirius red staining were used to examine changes in collagen fiber levels. PI3K was over-expressed by lentiviral transfection to verify the effect of emodin on the PI3K/AKT/mTOR signaling axis. Changes in cardiac function in each group were examined by echocardiography.Results Emodin significantly inhibited fibroblast proliferation, decreased intracellular ROS levels, significantly upregulated collagen II expression, downregulated α-SMA expression, and inhibited PI3K/AKT/mTOR pathway activation in vitro. Moreover, the in vivo results were consistent with the in vitro. Emodin significantly decreased ROS levels in heart tissue and reduced collagen fibrillogenesis. Emodin could regulate the activity of PI3K to increase the expression of collagen II and downregulate α-SMA expression in part through the PI3K/AKT/mTOR pathway, and emodin significantly improved cardiac structure and function in mice.Conclusions This study revealed that emodin targeted the PI3K/AKT/mTOR pathway to inhibit the development of myocardial fibrosis and may be an antifibrotic agent for the treatment of cardiac fibrosis.

At present, the role of active ingredients of traditional Chinese medicine in tumor therapy has gradually attracted people's attention, and anthraquinones, which are structurally similar to adriamycin and epirubicin, are one of the hotspots of research. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural anthraquinone compound isolated from rhubarb, Polygonum cuspidatum, and aloe vera. In recent years, emodin has received widespread attention for its remarkable anti-tumor effects, and its anti-breast cancer effects are manifested as induction of apoptosis, inhibition of tumor cell proliferation, inhibition of invasion and metastasis of tumor cells, and anti-tumor drug resistance. Moreover, emodin can act against multiple types of breast cancer cells by acting on different targets. In this paper, we reviewed the latest research progress on the anti-breast cancer effects of emodin and its anti-tumor mechanism, to provide reference and information for the treatment of breast cancer and the development of anti-tumor drugs.