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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-attributed mortality and the primary liver malignancy in the world. Echinacoside is a phenylethanoid glycoside derived from traditional Chinese medicinal herbs which possessed multiple health benefits on humans, including anti-tumor effects. This study aimed to demonstrate the function of echinacoside in HCC progression and the involvement of miR-30c-5p/FOXD1/KLF12 axis. The HepG2 cells were treated by different dose of echinacoside, miR-30c-5p mimic, miR-30c-5p inhibitor, and FOXD1 overexpression lentiviruses or siRNA individually or simultaneously. The cell invasion and migration were measured by transwell assay. RNA and protein levels were tested by RT-PCR and western blot, respectively. The regulatory function of miR-30c-5p on Forkhead box D1 (FOXD1), FOXD1 on Krüppel-like factor 12 (KLF12) was tested by luciferase reporter assay or/and ChIP assay. Meanwhile, a liver cancer lung metastasis mice model was used to examine the functions of echinacoside and miR-30c-5p on HCC metastasis in vivo. Moreover, the correlations among miR-30c-5p, FOXD1, KLF12, and HCC prognosis was analyzed using clinical sample and TCGA database. Based on both in vitro and in vivo investigations, we found that echinacoside could inhibit HCC cell migration, invasiveness, and tumor metastasis, and associated with the enhanced miR-30c-5p/FOXD1/KLF12 axis. Furthermore, through analyzing the interactions among intermediate molecules, we revealed that miR-30c-5p, FOXD1, and KLF12üere clinically relevant with each other in HCC patients, correlated with HCC prognosis, and regulated by echinacoside to contribute in the inhibition of HCC progression. These findings suggest that echinacoside could inhibit HCC progression, and the mechanism related to the enhanced miR-30c-5p/FOXD1/KLF12 axis. Moreover, the abovementioned intermediate molecules might serve as prospective biomarkers for HCC prognosis. [ABSTRACT FROM AUTHOR]

Background and aim: Pathological changes in the central nervous system (CNS) begin before the clinical symptoms of Alzheimer's Disease (AD) manifest, with the hippocampus being one of the first affected structures. Current treatments fail to alter AD progression. Traditional Chinese medicine (TCM) has shown potential in improving AD pathology through multi-target mechanisms. This study investigates pathological changes in AD hippocampal tissue and explores TCM active components that may alleviate these changes. Methods: GSE5281 and GSE173955 datasets were downloaded from GEO and normalized to identify differentially expressed genes (DEGs). Key functional modules and hub genes were analyzed using Cytoscape and R. Active TCM components were identified from literature and the Pharmacopoeia of the People's Republic of China. Enrichment analyses were performed on target genes overlapping with DEGs. Result: From the datasets, 76 upregulated and 363 downregulated genes were identified. Hub genes included SLAMF, CD34, ELN (upregulated) and ATP5F1B, VDAC1, VDAC2, HSPA8, ATP5F1C, PDHA1, UBB, SNCA, YWHAZ, PGK1 (downregulated). Literature review identified 33 active components from 23 herbal medicines. Target gene enrichment and analysis were performed for six components: dihydroartemisinin, berberine, naringenin, calycosin, echinacoside, and icariside II. Conclusion: Mitochondrial to synaptic vesicle dysfunction pathways were enriched in downregulated genes. Despite downregulation, UBB and SNCA proteins accumulate in AD brains. TCM studies suggest curcumin and echinacoside may improve hippocampal pathology and cognitive impairment in AD. Further investigation into their mechanisms is needed. [ABSTRACT FROM AUTHOR]

Introduction Cognitive dysfunction is an important comorbidity of diabetes. Insulin resistance may play a critical role in diabetes-related cognitive impairment. Echinacoside (ECH), a natural phenylethanoid glycoside, is the active component of anti-diabetes prescriptions in traditional Chinese medicine. Its effect on modulating insulin resistance has been confirmed but modulating neurodegenerative disease remains unclear. Methods Db/db mice, a spontaneous type 2 diabetes mode, were intragastrically administered ECH by 300 mg/kg or an equivalent volume of saline. Weight, blood glucose, and insulin resistance index were measured. Morris water maze test was performed to observe the compound effects on cognition. Hippocampal lesions were observed by histochemical analysis. Results In db/db mice, ECH alleviated diabetes symptoms, memory loss, and hippocampal neuronal damage. Next, the expression of CD44 and phosphorylated tau was upregulated in diabetic mice. In addition, the insulin receptor substrate-1/phosphatidylinositol 3-kinase /protein kinase B signaling pathway was dysregulated in diabetic mice. All these dysregulations could be reversed by ECH. Discussion This study provides theoretical support and experimental evidence for the future application of ECH in diabetic cognition dysfunction treatment, promoting the development of traditional medicines. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research is to demonstrate echinacoside promotes osteogenesis and angiogenesis and inhibits osteoclast formation. Methods: We conducted a cell experiment in vitro to study how echinacoside affects angiogenesis, osteogenesis and osteoclast formation. We used polymerase chain reaction and Western blotting to detect the expression levels of proteins and genes related to angiogenesis, osteogenesis and osteoclast formation. We established a bone fracture model with rats to test angiogenesis, osteogenesis and osteoclast formation of echinacoside. We labelled osteogenic markers, blood vessels and osteoclastic markers in fracture sections of rats. Results: The in vitro cell experiments showed echinacoside improved the osteogenic activity of mouse embryo osteoblast precursor cells and promoted the migration and tube formation of human umbilical vein endothelial cells. In addition, it inhibited differentiation of mouse leukaemia cells of monocyte macrophage. Echinacoside increased the expression of related proteins and genes and improved angiogenesis and osteogenesis while inhibiting osteoclast formation by repressing the expression of related proteins and genes. From in vivo experiments, the results of IHC and HE experiments demonstrated echinacoside significantly decreased the content of MMP‐9 and improved the content of VEGF and OCN. The fluorescence immunoassay showed echinacoside promoted the activities of RUNX2 and VEGF and inhibited CTSK. Echinacoside reduced the content of TNF‐α, IL‐1β and IL‐6, thus demonstrating its anti‐inflammatory activity. Conclusion: Echinacoside improved angiogenesis and osteogenesis and inhibited osteoclast formation to promote fracture healing. [ABSTRACT FROM AUTHOR]

Zemin Ou, Yun You, Hong Yi, Xiaoqian Liu, Yan Tong, Dewen Liu, Jinyu Wang Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Dewen Liu; Jinyu Wang, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 10700, People’s Republic of China, Email dwliu@icmm.ac.cn; wangjinyu@icmm.ac.cnIntroduction: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.Keywords: nanomedicine, brain delivery, angiopep-2, echinacoside, Parkinson’s disease, liposomes

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Objective　To investigate the effect and mechanism of echinacoside （ECH） in improving liver injury in rats with acute pancreatitis by establishing a rat model of acute pancreatitis and liver injury. Methods　A total of 24 Sprague-Dawley rats were randomly divided into blank group （Con group), control group （Con+ECH group), acute pancreatitis group （AP group), and acute pancreatitis+ ECH intervention （AP+ECH group). The rats were given intraperitoneal injection of 10 mg/kg ECH on day 7 before the establishment of the model of acute pancreatitis； at 24 hours after the last administration of cerulein, blood samples were collected via the abdominal aorta, and serum was separated for biochemical analysis including alanine aminotransferase （ALT), aspartate aminotransferase （AST), lactate dehydrogenase （LDH), gamma-glutamyl transpeptidase （GGT), alkaline phosphatase （ALP), albumin （Alb), total bilirubin （TBil), cholinesterase, blood amylase （Amy), and lipase （LPS). HE staining was used to observe the histopathological changes of the pancreas and the liver； transmission electron microscopy （TEM） was used to observe the microstructural changes of pancreas and liver tissue； ELISA was used to measure the levels of interleukin-1β （IL-1β), interleukin-16 （IL-6), tumor necrosis factor- α （TNF- α), and interleukin-10 （IL-10） in liver tissue homogenate； immunohistochemistry was used to measure the levels of TNF-α and p-p65 NF-κB in pancreas and liver tissue； Western blot was used to measure the expression levels of NF-κB pathway proteins in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK test or the Dunnett’s T3 method was used for further comparison between two groups. Results　Compared with the Con group, the AP group had significant increases in ALT, AST, GGT, LDH, ALP, TBil, Amy, and LPS（ all P<0.01), as well as significant increases in the levels of IL-1β, IL-6, IL-10, and TNF-α in liver tissue homogenate （all P<0.01). ECH intervention reduced the levels of ALT, AST, GGT, LDH, ALP, TBil, AMY, and LPS and inhibited the secretion of IL-1β, IL-6, and TNF-α in rats with acute pancreatitis. HE staining showed that ECH intervention alleviated the vacuolar degeneration of acinar cells, inflammatory cell infiltration in pancreatic tissue, and the necrosis of hepatocytes compared with the AP group. TEM showed that compared with the AP group, there was a reduction in the degree of mitochondrial swelling in liver and pancreatic cells after ECH intervention. ECH intervention partially reversed the elevated expression levels of p-p65 NF-κB and TNF-α in liver and pancreatic tissue. In addition, the expression levels of MyD88, p-IκBα, p-IKKα, and p-p65 were upregulated in liver tissue of rats with acute pancreatitis, which could be partially reversed after ECH intervention. Conclusion　Echinacoside can alleviate liver and pancreatic injury induced by acute pancreatitis by inhibiting the TLR4/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

A phenylethanoid glycoside known as echinacoside has demonstrated promising anticancer properties against numerous cancer cell types. However, its pharmacokinetics or anticancer mechanism has remained unclear. Herein, the interaction of the echinacoside with human serum albumin (HSA) was explored by intrinsic/extrinsic fluorescence spectroscopy, circular dichroism (CD) spectroscopy as well as molecular docking simulation. Also, the anticancer effects and possible mechanism of action of the echinacoside against hepatocellular carcinoma (HCC) cells, MHCC-97-H with high tumorgenicity and metastasis, were assessed by cell viability, flow cytometry, qRT-PCR, and western blot assays. The results showed a static quenching mechanism in the formation of echinacoside-HSA complex, one binding site on HSA for echinacoside, contribution of hydrophobic interactions (PHE157, GLU188 and PRO447), and slight conformational changes of HSA in the complex form. Cellular assays disclosed that treatment with echinacoside concentration-dependently mitigated the proliferation of MHCC97-H cells in vitro with an IC50 concentration of around 30 µM. Also, echinacoside triggered apoptosis through the regulation of caspase-3 at mRNA and protein levels. Moreover, echinacoside reduced the expression of astrocyte elevated gene-1 (AEG-1) and N-cadherin, while enhancing the expression of E-cadherin, as the main hallmarks of epithelial–mesenchymal transition (EMT) in tumorigenicity and metastasis. Therefore, these data indicated that echinacoside with a promising binding affinity with HSA in a mimicking physiological condition may inhibit the proliferation and metastatic activity of MHCC97-H cells mediated by manipulation of the AEG-1/EMT pathway.

Background: Lower urinary tract symptoms commonly occur in the elderly population and seriously constrain the quality of life. Glandular fibrosis is an important pathobiological process in benign prostatic hyperplasia and is also a main inducing factor for benign prostatic hyperplasia-associated lower urinary tract symptoms. Cistanches species is an important herbal medicine resource and is traditionally used in ameliorating renal and prostatic defects. Methods: This study was to investigate the potential protective function of echinacoside (a bioactive compound from Cistanches) against prostatic fibrosis in mice and human benign prostatic hyperplasia epithelial-1 cell models. Results: It was found that echinacoside attenuated testosterone-induced prostatic hyperplasia and collagen deposition in mice, relieved prostate local inflammation and oxidative damage, and ameliorated prostatic epithelial-mesenchymal transition. Additionally, echinacoside inhibited the activation of the MKK6/MK2 signaling pathway both in vivo and in vitro. Conclusion: This study added new evidence for the anti-fibrotic function of echinacoside on the prostate and provided new insights for understanding its possible pharmacological mechanisms. [ABSTRACT FROM AUTHOR]

Echinacoside (ECH) is a prominent naturally occurring bioactive compound with effects of alleviating myocardial damage. We aimed to explore the beneficial effects of ECH against sepsis-induced myocardial damage and elucidate the potential mechanism. Echocardiography and Masson staining demonstrated that ECH alleviates cardiac function and fibrosis in the cecal ligation and puncture (CLP) model. Transcriptome profiling and network pharmacology analysis showed that there are 51 overlapping targets between sepsis-induced myocardial damage and ECH. Subsequently, chemical carcinogenesis-reactive oxygen species (ROS) were enriched in multiple targets. Wherein, SOD2 may be the potential target of ECH on sepsis-induced myocardial damage. Polymerase chain reaction results showed that ECH administration could markedly increase the expression of SOD2 and reduce the release of ROS. Combined with injecting the inhibitor of SOD2, the beneficial effect of ECH on mortality, cardiac function, and fibrosis was eliminated, and release of ROS was increased after inhibiting SOD2. ECH significantly alleviated myocardial damage in septic mice, and the therapeutic mechanism of ECH is achieved by upregulating SOD2 which decreased the release of ROS. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogenic bacterium responsible for a range of severe infections, such as skin infections, bacteremia, and pneumonia. Due to its antibiotic-resistant nature, current research focuses on targeting its virulence factors. Sortase A (SrtA) is a transpeptidase that anchors surface proteins to the bacterial cell wall and is involved in adhesion and invasion to host cells. Through fluorescence resonance energy transfer (FRET), we identified echinacoside (ECH), a natural polyphenol, as a potential SrtA inhibitor with an IC50 of 38.42 μM in vitro. It was demonstrated that ECH inhibited SrtA-mediated S. aureus fibrinogen binding, surface protein A anchoring, and biofilm formation. The fluorescence quenching assay determined the binding mode of ECH to SrtA and calculated the KA-binding constant of 3.09 × 105 L/mol, demonstrating the direct interaction between the two molecules. Molecular dynamics simulations revealed that ECH–SrtA interactions occurred primarily at the binding sites of A92G, A104G, V168A, G192A, and R197A. Importantly, the combination of ECH and vancomycin offered protection against murine models of MRSA-induced pneumonia. Therefore, ECH may serve as a potential antivirulence agent against S. aureus infections, either alone or in combination with vancomycin. [ABSTRACT FROM AUTHOR]

Currently, the treatment for sepsis-induced acute lung injury mainly involves mechanical ventilation with limited use of drugs, highlighting the urgent need for new therapeutic options. As a pivotal aspect of acute lung injury, the pathologic activation and apoptosis of endothelial cells related to oxidative stress play a crucial role in disease progression, with NOX4 and Nrf2 being important targets in regulating ROS production and clearance. Echinacoside, extracted from the traditional Chinese herbal plant Cistanche deserticola, possesses diverse biological activities. However, its role in sepsis-induced acute lung injury remains unexplored. Moreover, although some studies have demonstrated the regulation of NOX4 expression by SIRT1, the specific mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the effects of echinacoside on sepsis-induced acute lung injury and oxidative stress in mice and to explore the intricate regulatory mechanism of SIRT1 on NOX4. We found that echinacoside inhibited sepsis-induced acute lung injury and oxidative stress while preserving endothelial function. In vitro experiments demonstrated that echinacoside activated SIRT1 and promoted its expression. The activated SIRT1 was competitively bound to p22 phox, inhibiting the activation of NOX4 and facilitating the ubiquitination and degradation of NOX4. Additionally, SIRT1 deacetylated Nrf2, promoting the downstream expression of antioxidant enzymes, thus enhancing the NOX4-Nrf2 axis and mitigating oxidative stress-induced endothelial cell pathologic activation and mitochondrial pathway apoptosis. The SIRT1-mediated anti-inflammatory and antioxidant effects of echinacoside were validated in vivo. Consequently, the SIRT1-regulated NOX4-Nrf2 axis may represent a crucial target for echinacoside in the treatment of sepsis-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Context: Stp1 is a new potential target closely related to the pathogenicity of Staphylococcus aureus (S. aureus). In this study, effective Stp1 inhibitors were screened via virtual screening and enzyme activity experiments, and the inhibition mechanism was analyzed using molecular dynamics simulation. Methods: AutoDock Vina 4.0 software was used for virtual screening. The molecular structures of Stp1 and ligands were obtained from the RCSB Protein Data Bank and Zinc database, respectively. The molecular dynamics simulation used the Gromacs 4.5.5 software package with the Amberff99sb force field and TIP3P water model. AutoDock Tools was used to add polar hydrogen atoms to Stp1 and distribute part of the charge generated by Kollman's combined atoms. The binding free energies were calculated using the Amber 10 package. Results: The theoretical calculation results are consistent with the experimental results. We found that echinacoside (ECH) substantially inhibits the hydrolytic activity of Stp1. ECH competes with the substrate by binding to the active center of Stp1, resulting in a decrease in Stp1 activity. In addition, Met39, Gly41, Asp120, Asn162, and Ile163 were identified to play key roles in the binding of Stp1 to ECH. The benzene ring of ECH also plays an important role in complex binding. These findings provide a robust foundation for the development of innovative anti-infection drugs. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) affects approximately 800,000 individuals globally each year. Despite advancements in HCC treatments, there is still a pressing need to identify new drugs that can combat resistance. One potential option is echinacoside, a natural caffeic acid glycoside with antioxidant, anti-inflammatory, antidepressant, and antidiabetic properties. Therefore, we aimed to investigate the ability of echinacoside to exhibit antitumor activity against HCC in rats through ameliorating hepatic fibrosis and tumor invasion. Rats were given thioacetamide to induce HCC, and some were given 30 mg/kg of echinacoside twice a week for 16 weeks. The liver impairment was assessed by measuring serum α-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-transforming growth factor (TGF)-β1 antibodies. The hepatic expression of mRNA and protein levels of TGF-β1, β-catenin, SMAD4, matrix metalloproteinase-9 (MMP9), phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR), connective tissue growth factor 2 (CCN2), E-Cadherin, platelets derived growth factor (PDGF)-B and fascin were also analyzed. Echinacoside improved the survival rate of rats by decreasing serum AFP and the number of hepatic nodules. Examination of micro-images indicated that echinacoside can reduce fibrosis. It also significantly decreased the expression of TGF-β1, β-catenin, SMAD4, MMP9, PI3K, mTOR, CCN2, PDGF-B, and fascin while enhancing the expression of E-Cadherin. In conclusion, echinacoside exhibits a protective effect against HCC by increasing survival rates and decreasing tumor growth. It also acts as an inhibitor of the hepatic tissue fibrosis pathway by reducing the expression of TGF-β1, β-catenin, SMAD4, PI3K, CCN2, PDGF-B and mTOR. Additionally, it prevents tumor invasion by suppressing MMP9 and fascin, and increasing the expression of E-Cadherin.

Possible complications, such as intestinal obstruction and inflammation of the intestinal tract, can have a detrimental effect on the prognosis after surgery for Hirschsprung disease. The aim of this study was to investigate the potential targets and mechanisms of action of echinacoside to improve the prognosis of Hirschsprung disease. Genes related to the disease were obtained through analysis of the GSE96854 dataset and four databases: OMIM, DisGeNET, Genecard and NCBI. The targets of echinacoside were obtained from three databases: PharmMapper, Drugbank and TargetNet. The intersection of disease genes and drug targets was validated by molecular docking. The valid docked targets were further explored for their expression by using immunohistochemistry. In this study, enrichment analysis was used to explore the mechanistic pathways involved in the genes. Finally, we identified CA1, CA2, CA9, CA12, DNMT1, RIMS2, RPGRIP1L and ZEB2 as the core targets. Except for ZEB2, which is predominantly expressed in brain tissue, the remaining seven genes show tissue specificity and high expression in the gastrointestinal tract. RIMS2 possesses a high mutation phenomenon in pan-cancer, while a validated ceRNA network of eight genes was constructed. The core genes are involved in several signaling pathways, including the one-carbon metabolic process, carbonate dehydratase activity and others. This study may help us to further understand the pharmacological mechanisms of echinacoside and provide new guidance and ideas to guide the treatment of Hirschsprung disease.

Clinically, neuropathic pain treatment remains a challenging issue because the major therapy, centred around pharmacological intervention, is not satisfactory enough to patient by reason of low effectiveness and more adverse reaction. Therefore, it is still necessary to find more effective and safe therapy to ameliorate neuropathic pain. The purpose of this study was to explore the antinociceptive effect of Echinacoside (ECH), an active compound of Cistanche deserticola Ma, on peripheral neuropathic pain induced by chronic constriction injury (CCI) in mice, and to demonstrate its potential mechanism in vivo and vitro. In the present study, results showed that intraperitoneal administration of ECH (50, 100, and 200 mg/kg) could alleviate mechanical allodynia, cold allodynia and thermal hyperalgesia via behavioural test. Moreover, the structure and function of injured sciatic nerve by CCI were taken a turn for the better to a certain extent after ECH treatment using histopathological and electrophysiological test. Furthermore, ECH repressed the expression of the P2X7R and FKN and reduced the expression and release of the IL-1β, IL-6 and TNF-α. Besides, ECH could decrease Ca2+ influx and Cats efflux and inhibit phosphorylation of p38MAPK. To sum up, the present study illustrated that ECH could alleviate peripheral neuropathic pain by inhibiting microglia overactivation and inflammation through P2X7R/FKN/CX3CR1 signalling pathway in spinal cord. This study would provide a new perspective and strategy for the pharmacological treatment on neuropathic pain.

Echinacoside, a natural phenylethanoid glycoside, was discovered and isolated from the garden plant Echinacea angustifolia DC., belonging to the Compositae family, approximately sixty years ago. Extensive investigations have revealed that it possesses a wide array of pharmacologically beneficial activities for human health, particularly notable for its neuroprotective and anticancer activity. Several crucial concerns surfaced, encompassing the recognition of active metabolites that exhibited inadequate bioavailability in their prototype form, the establishment of precise molecular signal pathways or targets associated with the aforementioned effects of echinacoside, and the scarcity of dependable clinical trials. Hence, the question remains unanswered as to whether scientific research can effectively utilize this natural compound. To support future studies on this natural product, it is imperative to provide a systematic overview and insights into potential future prospects. The current review provides a comprehensive analysis of the existing knowledge on echinacoside, encompassing its wide distribution, structural diversity and metabolism, diverse therapeutic applications, and improvement of echinacoside bioavailability for its potential utilization.

Copyright of Detergent & Cosmetics is the property of Detergent & Cosmetics Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper presents raw plant materials and their characteristic compounds which may affect the immune system. Plant-derived agents in specific doses affect the body's non-specific, antigen-independent defense system. They have immunostimulatory effects on the entire immune regulatory system. They can enhance the immune response through various factors such as macrophages, leukocytes, and granulocytes, as well as through mediators released by the cellular immune system. This paper was inspired by the threats caused by the COVID-19 pandemic. The proper functioning of the immune system is important in limiting the effects of viral infection and restoring the normal functioning of the body. This paper also emphasizes the importance of the skillful use of plant immunostimulants by potential patients, but also by those who prescribe drugs. It is important not only to choose the right plant drug but above all to choose the correct dose and duration of treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocellular carcinoma (HCC) is among the most common and malignant cancers with no effective therapeutic approaches. Echinacoside (ECH), a phenylethanoid glycoside isolated from Chinese herbal medicine, Cistanche salsa, can inhibit HCC progression; however, poor absorption and low bioavailability limit its biological applications. Methods To improve ECH sensitivity to HepG2 cells, we developed a mesoporous silica nanoparticle (MSN)-based drug delivery system to deliver ECH to HepG2 cells via galactose (GAL) and poly(ethylene glycol) diglycidyl ether (PEGDE) conjugation (ECH@Au@MSN-PEGDE-GAL, or ECH@AMPG). Gain- and loss-of-function assays were conducted to assess the effects of UBR5 on HCC cell apoptosis and glycolysis. Moreover, the interactions among intermediate products were also investigated to elucidate the mechanisms by which UBR5 functions. Results The present study showed that ubiquitin protein ligase E3 component N-recognin 5 (UBR5) acted as an oncogene in HCC tissues and that its expression was inhibited by ECH. AMPG showed a high drug loading property and a slow and sustained release pattern over time. Moreover, owing to the valid drug accumulation, ECH@AMPG promoted apoptosis and inhibited glycolysis of HepG2 cells in vitro. In vivo experiments demonstrated that AMPG also enhanced the antitumor effects of ECH in HepG2 cell-bearing mice. Conclusions Our results indicated the clinical significance of UBR5 as a therapeutic target. On the basis of the nontoxic and high drug-loading capabilities of AMPG, ECH@AMPG presented better effects on HCC cells compared with free ECH, indicating its potential for the chemotherapy of HCC.

Cistanche tubulosa (Schrenk) Wight, named Guan hua Rou Cong‐Rong in Chinese, is a traditional plant with liver, kidney, and intestine protective effects. Echinacoside (ECH) is its active constituent and has been found to have various biological effects, including antioxidative stress and anti‐inflammatory effects. Liver injury caused by acetaminophen or CCL4 has been proven to benefit from ECH; however, the effects of ECH against alcoholic liver disease (ALD) remain unclear. This study was used to estimate the effect of echinacoside on nuclear factor erythroid 2‐related factor 2 (Nrf2), which ameliorates ALD by inhibiting oxidative stress and cell apoptosis through affecting Nrf2.A mouse model of ALD was established with ethanol using hematoxylin and eosin (HE) staining, oiled staining, and biochemical indices. Alpha Mouse Liver 12 (AML‐12) cells were induced with ethanol in vitro and analyzed using western blotting, flow cytometry, and biochemical assays. In the animal model of ALD, ECH dramatically reduced liver damage, as proven by the downregulation of aspartate aminotransferase (AST) and HE staining. In vitro, ECH distinctly reduced the damage caused by ethanol through the decreased expression of cleaved caspase‐3 measured by western blotting. ECH significantly increased the activity of Nrf2 in vivo and in vitro. Nrf2 knockout may diminish the influence of ECH on ALD. Meanwhile, ECH also increased the expression of haem oxygenase‐1 (HO‐1) and glutamate‐cysteine ligase catalytic subunit (GCLC), while it inhibited levels of oxidative stress and cell apoptosis. Our findings suggest that ECH protects against ethanol‐induced liver injuries by alleviating oxidative stress and cell apoptosis by increasing the activity of Nrf2. Therefore, ECH is promising for the treatment of ALD. [ABSTRACT FROM AUTHOR]

The present study was performed to investigate the antidepressant effect of echinacoside (ECH) using chronic unpredictable mild stress (CUMS) induced depression mice and lipopolysaccharide (LPS)-stimulated N9 microglial cells. CUMS treatment was performed on C57BL/6 mice for 28 days, followed by gavaging with different doses of echinacoside (15 and 60 mg/kg) for 21 consecutive days. Sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were measured to assess the effects of echinacoside on CUMS-Induced Depressive-Like Behaviors. After that, the pathological changes of hippocampus were determined by Hematoxylin and eosin (HE) staining and Nissl staining; the neurotransmitters, pro-inflammatory cytokines and indoleamine 2,3- dioxygenase (IDO) levels, and the hypothalamic--pituitary--adrenal (HPA) axis activity were determined by enzyme linked immunosorbent assay (ELISA); Iba 1were evaluated by Immunofluorescence assay; Key protein expression levels of CREB/BDNF signal pathway were measured by western blotting. Subsequently, N9 cells were stimulated with 1 μg/ml LPS to induce N9 microglia activation, and were treated with 5--20 μM of echinacoside for 24 h. After that, the levels of NO, interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), IL-4, IL-10, and transforming growth factor beta (TGF-β) in N9 cell culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA) kits; morphology and Iba 1 expression level were observed by high-content screening assay; the M1 markers of CD11b, CD86 and M2 markers of CD206 were analyzed by imaging flow cytometry. Results show that treatment with echinacoside reversed CUMS-increased immobility time in OFT, TST, FST and reversed CUMS-reduced sucrose preference in SPT. In addition, echinacoside reduced the levels of proinflammatory cytokines and Iba 1. Moreover, echinacoside significantly increased p-CREB/CREB ratio and BDNF level in hippocampus. Furthermore, echinacoside reduced the secretion of inflammatory factors and inhibited microglia M1 polarization in N9 cells. In conclusion, echinacoside may be beneficial for the treatment of depression diseases through regulating the microglia balance by inhibiting the polarization of microglia to M1 phenotype, and improving hippocampal neurogenesis by the CREBBDNF signaling pathway. [ABSTRACT FROM AUTHOR]

Currently, the treatment for sepsis-induced acute lung injury mainly involves mechanical ventilation with limited use of drugs, highlighting the urgent need for new therapeutic options. As a pivotal aspect of acute lung injury, the pathologic activation and apoptosis of endothelial cells related to oxidative stress play a crucial role in disease progression, with NOX4 and Nrf2 being important targets in regulating ROS production and clearance. Echinacoside, extracted from the traditional Chinese herbal plant Cistanche deserticola, possesses diverse biological activities. However, its role in sepsis-induced acute lung injury remains unexplored. Moreover, although some studies have demonstrated the regulation of NOX4 expression by SIRT1, the specific mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the effects of echinacoside on sepsis-induced acute lung injury and oxidative stress in mice and to explore the intricate regulatory mechanism of SIRT1 on NOX4. We found that echinacoside inhibited sepsis-induced acute lung injury and oxidative stress while preserving endothelial function. In vitro experiments demonstrated that echinacoside activated SIRT1 and promoted its expression. The activated SIRT1 was competitively bound to p22 phox, inhibiting the activation of NOX4 and facilitating the ubiquitination and degradation of NOX4. Additionally, SIRT1 deacetylated Nrf2, promoting the downstream expression of antioxidant enzymes, thus enhancing the NOX4-Nrf2 axis and mitigating oxidative stress-induced endothelial cell pathologic activation and mitochondrial pathway apoptosis. The SIRT1-mediated anti-inflammatory and antioxidant effects of echinacoside were validated in vivo. Consequently, the SIRT1-regulated NOX4-Nrf2 axis may represent a crucial target for echinacoside in the treatment of sepsis-induced acute lung injury.

Wan Shu, Ziwei Wang, Rong Zhao, Rui Shi, Jun Zhang, Wei Zhang, Hongbo Wang Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Hongbo Wang, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email hb_wang1969@sina.comBackground: Endometrial cancer (EC) is one of the most common gynecological malignancies, especially in postmenopausal women. Echinacoside (ECH) is a major natural bioactive ingredient derived from Cistanches Herba and Echinacea that has a variety of pharmacological effects. However, the efficacy and the mechanism of ECH against EC have not been elucidated yet.Purpose: A compound-target-disease network was constructed to explore the potential targets and mechanism of ECH against EC. Molecular docking and in vitro experiments further verified the effect of ECH against EC.Methods: The potential targets of ECH against EC were retrieved from multiple public databases. Then, the protein–protein interaction (PPI) network was constructed to screen hub targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to discover the potential mechanism. Molecular docking was utilized to verify the binding affinity between hub targets and ECH. Finally, in vitro experiments were conducted to demonstrate the anti-EC effect of ECH.Results: A total of 110 genes were identified as potential targets of ECH against EC. The GO enrichment analysis found that targets were primarily related to oxygen species, apoptosis, and other physiological processes. KEGG pathway analysis showed that PI3K/Akt signaling pathways might play an important role in ECH against EC. Molecular docking indicated that ECH had a significant binding ability with the EGFR, AKT1, ESR1, CASP3, HSP90AA1and MMP9 targets. Results from in vitro experiments revealed that ECH induced apoptosis of Ishikawa and HEC-1-B cells by promoting the arrest of the G2M phase, increasing ROS levels, and decreasing mitochondrial membrane potential (MMP) levels. Furthermore, treatment of ECH significantly reduced the expression levels of PI3K and p-AKT, and the combination of the PI3K inhibitor (LY294002) further enhanced the effects of ECH against EC. The findings suggested that ECH exerted an inhibitory effect on EC cells by inhibiting the PI3K/AKT pathway.Conclusion: Based on network pharmacology, molecular docking technology and in vitro experiments, we comprehensively clarified the anti-EC efficacy of ECH through multiple targets and signal pathways. Furthermore, we provided a novel idea of Traditional Chinese medicine (TCM) against EC.Keywords: endometrial carcinoma, echinacoside, network pharmacology, mechanism, molecular docking

Osteoarthritis (OA) is a progressive disease characterized by degeneration of cartilage and echinacoside (Ech) has anti-inflammatory and antioxidant effects in various human diseases. This study aimed to reveal the effect and potential mechanism of Ech on OA. The in vitro OA model was established by rat chondrocytes treated with IL-1β, and the in vivo OA model was established by anterior cruciate ligament transaction. The effect of Ech on the viability, inflammatory response, extracellular matrix (ECM) degradation, and oxidative stress of IL-1β-treated rat chondrocytes were evaluated by Cell Counting Kit-8 assay, enzyme-linked immunosorbent assay, quantitative real-time PCR, Western blot, and immunofluorescence assay. Meanwhile, the mechanism of Ech was assessed using Western blot, Cell Counting Kit-8 assay, enzyme-linked immunosorbent assay, and immunofluorescence analysis. Moreover, the function of Ech in vivo was analyzed in rat models of OA. Functionally, Ech enhanced the viability of rat chondrocytes, repressed the inflammatory response and ECM degradation of rat chondrocytes induced by IL-1β with restrained oxidative stress. Mechanically, Ech repressed IL-1β-induced chondrocyte injury by activating the Nrf2/HO-1 signaling pathway. Meanwhile, Ech alleviated the degree of articular cartilage injury in rats and exerted protective effects on the rat model of OA in vivo. Ech alleviated OA in rats by activating the Nrf2-HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Prevalence of heart failure (HF) continues to rise over time and is a global difficult problem; new drug targets are urgently needed. In recent years, pyroptosis is confirmed to promote cardiac remodelling and HF. Echinacoside (ECH) is a natural phenylethanoid glycoside and is the major active component of traditional Chinese medicine Cistanches Herba, which is reported to possess powerful anti‐oxidation and anti‐inflammatory effects. In addition, we previously reported that ECH reversed cardiac remodelling and improved heart function, but the effect of ECH on pyroptosis has not been studied. So, we investigated the effects of ECH on cardiomyocyte pyroptosis and the underlying mechanisms. In vivo, we established HF rat models induced by isoproterenol (ISO) and pre‐treated with ECH. Indexes of heart function, pyroptotic marker proteins, ROS levels, and the expressions of NOX2, NOX4 and ER stress were measured. In vitro, primary cardiomyocytes of neonatal rats were treated with ISO and ECH; ASC speckles and caspase‐1 mediated pyroptosis in cardiomyocytes were detected. Hoechst/PI staining was also used to evaluate pyroptosis. ROS levels, pyroptotic marker proteins, NOX2, NOX4 and ER stress levels were all tested. In vivo, we found that ECH effectively inhibited pyroptosis, down‐regulated NOX2 and NOX4, decreased ROS levels, suppressed ER stress and improved heart function. In vitro, ECH reduced cardiomyocyte pyroptosis and suppressed NADPH/ROS/ER stress. We concluded that ECH inhibited cardiomyocyte pyroptosis and improved heart function via suppressing NADPH/ROS/ER stress. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is among the most common and malignant cancers with no effective therapeutic approaches. Echinacoside (ECH), a phenylethanoid glycoside isolated from Chinese herbal medicine, Cistanche salsa, can inhibit HCC progression; however, poor absorption and low bioavailability limit its biological applications. Methods: To improve ECH sensitivity to HepG2 cells, we developed a mesoporous silica nanoparticle (MSN)-based drug delivery system to deliver ECH to HepG2 cells via galactose (GAL) and poly(ethylene glycol) diglycidyl ether (PEGDE) conjugation (ECH@Au@MSN-PEGDE-GAL, or ECH@AMPG). Gain- and loss-of-function assays were conducted to assess the effects of UBR5 on HCC cell apoptosis and glycolysis. Moreover, the interactions among intermediate products were also investigated to elucidate the mechanisms by which UBR5 functions. Results: The present study showed that ubiquitin protein ligase E3 component N-recognin 5 (UBR5) acted as an oncogene in HCC tissues and that its expression was inhibited by ECH. AMPG showed a high drug loading property and a slow and sustained release pattern over time. Moreover, owing to the valid drug accumulation, ECH@AMPG promoted apoptosis and inhibited glycolysis of HepG2 cells in vitro. In vivo experiments demonstrated that AMPG also enhanced the antitumor effects of ECH in HepG2 cell-bearing mice. Conclusions: Our results indicated the clinical significance of UBR5 as a therapeutic target. On the basis of the nontoxic and high drug-loading capabilities of AMPG, ECH@AMPG presented better effects on HCC cells compared with free ECH, indicating its potential for the chemotherapy of HCC. [ABSTRACT FROM AUTHOR]

[Objectives] To establish a HPLC-UV method for the determination of Cistanches Herba in Zhenrongdnn mixture. [Methods] According to the content determination method of Cistanches Herba in the 2020 edition of Chimese Pharmacopoeia, using HPLC-UV method, the content determination method of Cistanches Herba in Zhenrongdan mixture was established, and the content of echinacoside was determined. The related chromatographic conditions were explored, and the methodological investigation was caried out. [Results] The chromatographic conditions were determined as flows: octadecylsilane bonded silica gel a filler (C18) ; 80% acetonitrile solution (containing 0. 2% phosphoric acid) -0.2% phosphoric acid aqueous solution (15:85) a mobile phase; detection wavelength was 330 nm. The number of theoretical plates should not be lees than 3 000 according to the peak of echinacoside. The methodological investigation showed that the method had better precision, accuracy and repeatability. Under the conditions of this study, echinacoside had better linear relationship in the range of 74.9 - 1 498 ng, and the average recovery was 99. 1 %, RSD = 0.5% (n = 6). [Conclusions ] A method for the determination of Cistanches Herba in Zhenrongdan mixture by HPLC-UV was established. The method is sensitive, rapid, accurate and suitable for the determination of Cistanches Herba in Zhenrongdan mixture. [ABSTRACT FROM AUTHOR]

Copyright of Pamukkale Medical Journal is the property of Pamukkale Journal of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Several natural products have been demonstrated to be effective in the treatment of depressive disorders. Echinacoside, a naturally occurring phenol extracted from Cistanche tubulosa, Echinacea angustifolia, and Cistanche spp, has a wide range of physiological effects, such as antioxidation, neuroprotection, anti-inflammatory, and immunoregulation, which are closely related to depression. In addition, echinacoside can activate protein kinase B (Akt), extracellular signal–regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) in the brain. A key downstream event of the Akt, ERK, and BDNF signaling pathways, namely mechanistic target of rapamycin (mTOR) signaling, plays a crucial role in generating an rapid antidepressant effect. Thus, echinacoside is a promising therapeutic agent for depression. However, research regarding the role of echinacoside in antidepressant effect and brain mTOR activation remains lacking. Materials and methods The forced swimming test and Western blot analysis in C57BL/6 mice was used to investigate the antidepressant-like activities of echinacoside and the underlying mechanism involved inα-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)–Akt/ERK–mTOR pathway. Results We confirmed the suggestions by previous reports that echinacoside activates Akt/ERK signaling and further demonstrated that echinacoside could provide antidepressant-like effects in mice via the activation of AMPAR–Akt/ERK–mTOR pathway in the hippocampus. Conclusions To the best of our knowledge, our study is the first to reveal that echinacoside is a potential treatment for depressive disorders. Moreover, the present study suggests a mechanism for the neuroprotective effect of echinacoside.

A phenylethanoid glycoside known as echinacoside has demonstrated promising anticancer properties against numerous cancer cell types. However, its pharmacokinetics or anticancer mechanism has remained unclear. Herein, the interaction of the echinacoside with human serum albumin (HSA) was explored by intrinsic/extrinsic fluorescence spectroscopy, circular dichroism (CD) spectroscopy as well as molecular docking simulation. Also, the anticancer effects and possible mechanism of action of the echinacoside against hepatocellular carcinoma (HCC) cells, MHCC-97-H with high tumorgenicity and metastasis, were assessed by cell viability, flow cytometry, qRT-PCR, and western blot assays. The results showed a static quenching mechanism in the formation of echinacoside-HSA complex, one binding site on HSA for echinacoside, contribution of hydrophobic interactions (PHE157, GLU188 and PRO447), and slight conformational changes of HSA in the complex form. Cellular assays disclosed that treatment with echinacoside concentration-dependently mitigated the proliferation of MHCC97-H cells in vitro with an IC 50 concentration of around 30 µM. Also, echinacoside triggered apoptosis through the regulation of caspase-3 at mRNA and protein levels. Moreover, echinacoside reduced the expression of astrocyte elevated gene-1 (AEG-1) and N-cadherin, while enhancing the expression of E-cadherin, as the main hallmarks of epithelial–mesenchymal transition (EMT) in tumorigenicity and metastasis. Therefore, these data indicated that echinacoside with a promising binding affinity with HSA in a mimicking physiological condition may inhibit the proliferation and metastatic activity of MHCC97-H cells mediated by manipulation of the AEG-1/EMT pathway. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats. Methods: The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively. Results: ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01). Conclusion: ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats. [ABSTRACT FROM AUTHOR]

Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer's disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice treated with ECH in 50 mg/kg/day for 3 months. Morris water maze, nesting test, and immunofluorescence staining used to observe whether ECH could improve AD pathology. Western blot used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress, and inflammatory response in AD. Therefore, we suggest that ECH may considered as a potential drug for AD treatment. [ABSTRACT FROM AUTHOR]

Copyright of Xinjiang Agricultural Sciences is the property of Xinjiang Agricultural Sciences Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Interstitial cystitis (IC) is featured by apoptosis and chronic inflammation in bladder tissue. We aimed to evaluate the effect of echinacoside (ECH), which is known to modulate inflammation and apoptosis on IC using relevant models. We established a mouse model of cystitis using cyclophosphamide (CYP) and treated human urothelium cells (SV-HUC-1) with lipopolysaccharide (LPS) + ATP as in vitro model. The bladder function was tested by urodynamics. Apoptosis of bladder cells was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Expressions of apoptosis-associated and inflammation-related proteins were assessed using western blotting. Treatment with ECH significantly improved bladder function, reduced inflammatory damage, and decreased apoptosis in the models. Furthermore, ECH decreased the phosphorylation levels of IκB and NF-κB(p65), and upregulated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), which are related to apoptosis and inflammation in CYP-induced mouse cystitis. Moreover, ECH did not reduce apoptosis of urothelial cells after treatment with PPARγ antagonist GW9662. Our findings suggest that ECH might have protective effect against IC in bladder and be mediated through modulation of the PPARγ/NF-κB pathway. [ABSTRACT FROM AUTHOR]

The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it an attractive target for antiviral drug development. In this study, the natural products from Echinacea angustifolia were retrieved for structure-based virtual screening against JEV–RdRp. The top six compounds (Echinacoside, Echinacin, Rutin, Cynaroside, Quercetagetin 7-glucoside, and Kaempferol-3-glucoside) were obtained based on the highest negative docking score, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and molecular interaction. The computational analysis of these selected compounds against the co-crystallized ligands, i.e., ATP and GTP, were performed. Further, 100 ns molecular dynamic simulation and post-free binding energy calculation of all the selected compounds complexed with JEV–RdRP were performed to check the stability of the complexes. The obtained results showed considerable stability and intermolecular interaction with native ligand-binding site residues of JEV–RdRp. Hence, selected natural compounds are admissible inhibitors of JEV–RdRp protein and can be considered for future antiviral drug development studies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the protective effect of echinacoside (Ech) on carbon tetrachloride (CCL4)-induced chronic liver injury in rats and its potential mechanisms. Thirty Sprague-Dawley (SD) rats were randomly divided into five groups: the Control group, the CCL4 group, the CCL4 + Ech 25 mg/kg group, the CCL4 + Ech 50 mg/kg group, and the CCL4 + Ech 100 mg/kg group. The rats were injected intraperitoneally with CCL4 solution twice a week to induce chronic liver injury, and Ech intervention lasted for 4 weeks. After the intervention, the liver and blood samples from rats were collected for subsequent analysis. Ech effectively reduced the levels of serum liver injury markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, alkaline phosphatase, and total bilirubin), attenuated the hepatocyte degeneration and necrosis, improved the severity of liver fibrosis, and inhibited the local inflammatory response of the liver in a dose-dependent manner. Ech effectively mitigated CCL4-induced chronic liver injury in rats by downregulating the NF-κB/NLRP3 inflammasome pathway., (© 2024 John Wiley & Sons A/S.)

Background and Aim: Pathological changes in the central nervous system (CNS) begin before the clinical symptoms of Alzheimer's Disease (AD) manifest, with the hippocampus being one of the first affected structures. Current treatments fail to alter AD progression. Traditional Chinese medicine (TCM) has shown potential in improving AD pathology through multi-target mechanisms. This study investigates pathological changes in AD hippocampal tissue and explores TCM active components that may alleviate these changes., Methods: GSE5281 and GSE173955 datasets were downloaded from GEO and normalized to identify differentially expressed genes (DEGs). Key functional modules and hub genes were analyzed using Cytoscape and R. Active TCM components were identified from literature and the Pharmacopoeia of the People's Republic of China. Enrichment analyses were performed on target genes overlapping with DEGs., Result: From the datasets, 76 upregulated and 363 downregulated genes were identified. Hub genes included SLAMF, CD34, ELN (upregulated) and ATP5F1B, VDAC1, VDAC2, HSPA8, ATP5F1C, PDHA1, UBB, SNCA, YWHAZ, PGK1 (downregulated). Literature review identified 33 active components from 23 herbal medicines. Target gene enrichment and analysis were performed for six components: dihydroartemisinin, berberine, naringenin, calycosin, echinacoside, and icariside II., Conclusion: Mitochondrial to synaptic vesicle dysfunction pathways were enriched in downregulated genes. Despite downregulation, UBB and SNCA proteins accumulate in AD brains. TCM studies suggest curcumin and echinacoside may improve hippocampal pathology and cognitive impairment in AD. Further investigation into their mechanisms is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhiyan, Min, Yida, Chunying, Xiaohua, Yutong, Huan and Linjuan.)

Inflammatory immune response plays a key role in exercise-induced injury and healing; however, the relevant regulatory mechanisms of immune infiltration in exercise-induced injuries remain less studied. In the present study, a highly efficient system for screening immunity-related biomarkers and immunomodulatory ability of natural nutritional supplements was developed by integrating intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. The findings demonstrated that resting natural killer cells showed a higher rate of infiltration after exercise, whereas naive B cells and activated dendritic cells showed higher rate of infiltration before exercise. Four key genes, namely PRF1, GZMB, CCL4, and FASLG, were associated with exercise-induced injuries and inflammatory immune response. In total, 26 natural compounds including echinacoside, eugenol, tocopherol, and casuariin were predicted by using the HERB databases. Molecular docking analysis showed that GZMB, FASLG, and CCL4 bound to echinacoside. In vivo experiments in mice showed that after 30 min swimming, natural killer (NK) cells showed high infiltration rates, and the key genes (GZMB, PRF1, FASLG, and CCL4) were highly expressed; however, echinocandin significantly reduced the level of NK cells and decreased the expression of the four key genes post exercise. This natural nutritional supplement may act to protect against inflammatory injury after exercise by suppressing specific immune infiltration.

Naoqingzhiming, whose active ingredient is echinacoside, is the first new Class I natural medicine approved for clinical trials for the therapeutic potential of vascular dementia in China. We report randomized, double-blind, placebo-controlled trials to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of Naoqingzhiming tablet after oral administration in healthy Chinese subjects. The single ascending dose of Naoqingzhiming tablet (180–2160 mg) were well tolerated in all enrolled subjects, without serious adverse events and adverse events leading to withdrawal from the study. The most common drug-related treatment-emergent adverse events were elevated blood bilirubin and serum uric acid. No clinically significant findings were found in the physical examinations, vital signs or electrocardiograms. After single-dose administration of Naoqingzhiming tablet, echinacoside was absorbed with a Tmax at 1.25–1.75 h and declined with a t1/2 of 2.42–3.33 h. However, the proportionality coefficients for Cmax, AUC0−t and AUC0-∞ of echinacoside were not fully contained in the pre-defined 90 % CI criterion (0.91–1.09). As a result, the dose proportionality could not be concluded statistically within the dosage range of this study. Overall, the safety profile and PK properties support further development and use of Naoqingzhiming in vascular dementia.

Infected osteolysis as a common secondary osteoporosis is associated with excessive osteoclastogenesis and bone resorption. The inhibition of osteoclastogenesis and bone resorption have been demonstrated an effective approach in the treatment of osteolytic diseases. Echinacoside (ECH) is a natural phenylethanoid glycoside with multiple biological functions, including anti-inflammatory, antioxidant, and osteoblast differentiation promotion. However, the effects of ECH on osteoclast differentiation and bone resorption function remain unknown. In vitro , we investigated the effects of ECH on osteoclast differentiation and bone resorption induced by RANKL and its potential mechanisms. In vivo , we established a periprosthetic joint infection (PJI) rat model and demonstrated the changes of infected osteolysis and osteoclasts activities in surgical sites. ECH (20 mg/kg) was injected intraperitoneally after debridement for 4 weeks. Radiological evaluation and bone histomorphometric analysis was performed to assess the efficacy of ECH. The results showed that ECH inhibited osteoclast differentiation, F-actin belts formation, bone resorption function and osteoclast-specific gene expression by preventing NFATc1 translocation, down-regulating its expression and affecting the PI3K/Akt/c-Fos pathway in vitro. ECH also alleviated in vivo PJI-induced osteolysis and maintained bone mass by inhibiting osteoclast activity. Our study indicated that ECH attenuated RANKL-induced osteoclastogenesis and PJI-induced bone loss and was shown as a potentially effective therapeutic agent for osteoclast-related bone diseases. [ABSTRACT FROM AUTHOR]

A creative dual-template molecularly imprinted polymer (Fe 3 O 4 @MCM-41-MIPs) with good magnetic properties and specific recognition of echinacoside and acteoside was prepared by surface imprinting. Echinacoside and acteoside served as dual templates, 4-vinylpyridine (4-VP) was used as a functional monomer, the cross-linker was ethylene glycol dimethacrylate (EGDMA), and the selected initiator was azobisisobutyronitrile (AIBN). The prepared Fe 3 O 4 @MCM-41-MIPs were applied to the selective separation and enrichment of echinacoside and acteoside from Cistanche deserticola Y. C. Ma (C. deserticola). The resulting Fe 3 O 4 @MCM-41-MIPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), laser particle size scanning and vibration sample magnetometry (VSM). The results of the isotherm adsorption experiment showed that the maximum adsorption capacities of Fe 3 O 4 @MCM-41-MIPs for echinacoside and acteoside were 6.02 and 1.63 mg·g-1, respectively, at 298 K. The pseudo-second-order reaction mechanism showed that the equilibrium adsorption capacities of Fe 3 O 4 @MCM-41-MIPs for echinacoside and acteoside were 4.81 and 0.93 mg·g-1, respectively. The characterization of Fe 3 O 4 @MCM-41-MIPs showed that the imprinted layer with dual-template molecules was wrapped on the outside of the carrier, and the obtained Fe 3 O 4 @MCM-41-MIPs showed good saturation magnetization, desirable capacity for echinacoside and acteoside adsorption, and satisfactory reuse (echinacoside and acteoside maintained relative adsorption rates of 97.5% and 95.8% after five cycles). After separation, the purities of echinacoside and acteoside were 33.50% and 27.00%, respectively. In addition, in the selective adsorption experiment, the synthesized Fe 3 O 4 @MCM-41-MIPs showed better selectivity for echinacoside and acteoside than their structural analogs. Therefore, this method proved to be sustainable, rapid and highly efficient for the separation and enrichment of echinacoside and acteoside. [Display omitted] • Fe 3 O 4 @MCM-41-MIPs based on dual-molecular was prepared and characterized. • Fe 3 O 4 @MCM-41-MIPs showed good selective extraction and enrichment for target compounds. • Fe 3 O 4 @MCM-41-MIPs exhibited a good magnetic property for rapid extraction. • Fe 3 O 4 @MCM-41-MIPs was proved to be simple, selective and recyclable material. [ABSTRACT FROM AUTHOR]

The current study aimed to examine the effects of echinacoside on cognitive impairment in mice after exposure to sevoflurane. To examine the role of FOXO1, si-FOXO1 and si-con were injected into the hippocampus through the left lateral cerebral ventricles. Sevoflurane-induced mice had serious cognitive dysfunction. However, pretreatment with echinacoside alleviated the cognitive dysfunction, as measured by a shortened escape latency time, and increased platform crossing times, the percentage of distance in the target quadrant and Y-maze spontaneous alternations. In addition, we found that echinacoside elevated FOXO1 expression in the hippocampus; increased the expression of autophagy-related proteins including Beclin 1, ATG5, ATG7, and LC3; and reduced P62 expression. Silencing of FOXO1 aggravated the cognitive deficits and reduced expression of the autophagy-related markers, whereas the effects of si-FOXO1 on memory were abrogated by echinacoside. Echinacoside attenuated the cognitive impairment in sevoflurane-induced mice through FOXO1-mediated autophagy. [ABSTRACT FROM AUTHOR]

Dysfunction at various levels of spermatogenesis (SD) is one of the important causes of infertility in men of reproductive age and requires advanced treatment strategies. Increasing evidence suggests that the therapeutic effects of echinacoside (ECH) mainly depend on their capacity to inhibit cell death. This study aimed to explore the therapeutic potential of ECH in SD rat models. Treatment with ECH reverted the morphological changes observed in testes with spermatogenesis dysfunction. It improved total sperm number, decreased the sperm deformity rate, and increased the sperm forward motility rate. The level of glutathione (GSH) was significantly higher in ECH-treated mice, whereas the lactate dehydrogenase (LDH) and SOD activities were improved compared with those in the spermatogenesis dysfunction model. Moreover, the increased expression of p38 and JNK was partially reversed by ECH. The number of normal TM3 cells increased gradually in an Echinacea dosage-dependent manner, suggesting that ECH promoted the proliferation of TM3 cells. In addition, treatment with ECH partially reversed the increased expression of p38 and JNK in TM3 cells. ECH protects against oxidative stress damage by activating antioxidant enzymes and MAPK signaling-related factors (p38 and JNK). It suggested that treatment with ECH alleviated spermatogenetic dysfunction of testes in male mice and it could be a promising strategy for patients suffering severe SD. [ABSTRACT FROM AUTHOR]

Echinacoside is a group of natural compounds extracted from medicinal plants Cistanche and Echinacea, which has neuroprotective, antiaging, immunomodulatory and anticancer effects, but its specific role and mechanism in tumor remains partially unclear. To our knowledge, it was the first time to reported the effect of Echinacoside in ovarian cancer. Colony formation, TUNEL staining, Transwell and tube formation assays were conducted to analyze the proliferation, apoptosis, invasion and tube formation abilities of serous ovarian carcinoma cells (SKOV3 and OVCAR-3), respectively. The expressions of apoptosis-, invasion- and PI3K/AKT pathway-related proteins were measured by western blotting. In addition, PI3K agonist (740Y-P) was used to assess the regulatory effect of Echinacoside on PI3K/AKT signaling in ovarian cancer. Finally, the anti-tumor effect of Echinacoside on SKOV3-xenografted mice was evaluated by xenograft tumor mouse model. Our results demonstrated Echinacoside concentration-dependently reduced the proliferation, migration and angiogenesis of ovarian cancer cells, whereas promoted apoptosis. Moreover, western blotting revealed that Echinacoside suppressed the growth of ovarian cancer cells by downregulating the phosphorylation levels of PI3K, AKT and mTOR, which could be partially reversed by 740Y-P. Further, in vivo results showed that Echinacoside could effectively alleviate the tumor growth of xenograft mice, accompanied by the decrease of PI3K/AKT signaling. In general, our results demonstrate that Echinacoside could reduce the ovarian cancer progression through inhibition of PI3K/AKT pathway, suggesting that Echinacoside may be a new treatment option for ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Echinacoside (ECH) is the main active ingredient of Cistanches Herba, which is known to have therapeutic effects on metastatic tumors. However, the effects of ECH on liver cancer are still unclear. This study was to investigate the effects of ECH on the aggression of liver cancer cells. Methods Two types of liver cancer cells Huh7 and HepG2 were treated with different doses of ECH at different times and gradients. MTT and colony formation assays were used to determine the effects of ECH on the viability of Huh7 and HepG2 cells. Transwell assays and flow cytometry assays were used to detect the effects of ECH treatment on the invasion, migration, apoptosis and cell cycle of Huh7 and HepG2 cells. Western blot analysis was used to detect the effects of ECH on the expression levels of TGF-β1, smad3, smad7, apoptosis-related proteins (Caspase-3, Caspase-8), and Cyto C in liver cancer cells. The relationship between miR-503-3p and TGF-β1 was detected using bioinformatics analysis and Luciferase reporter assay. Results The results showed that ECH inhibited the proliferation, invasion and migration of Huh7 and HepG2 cells in a dose- and time-dependent manner. Moreover, we found that ECH caused Huh7 and HepG2 cell apoptosis by blocking cells in S phase. Furthermore, the expression of miR-503-3p was found to be reduced in liver tumor tissues, but ECH treatment increased the expression of miR-503-3p in Huh7 and HepG2 cells. In addition, we found that TGF-β1 was identified as a potential target of miR-503-3p. ECH promoted the activation of the TGF-β1/Smad signaling pathway and increased the expression levels of Bax/Bcl-2. Moreover, ECH could trigger the release of mitochondrial Cyto C, and cause the reaction Caspases grade. Conclusions This study demonstrates that ECH exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer, and provides a safe and effective anti-tumor agent for liver cancer.

Zhen-Nian Zhang,1,* Zhen Hui,1,* Chang Chen,1 Yan Liang,1 Li-Li Tang,1 Su-Lei Wang,1 Cheng-Cheng Xu,1 Hui Yang,1 Jing-Si Zhang,2 Yang Zhao1 1Department of Neurology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, People’s Republic of China; 2Department of Neurology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang ZhaoDepartment of Neurology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157 of Daming Road, Qinhuai District, Nanjing, 210022, People’s Republic of ChinaTel/Fax +86 13851498418Email zhao_dr66@163.comObjective: To explore the neuroprotective effect and the related mechanisms of echinacoside (ECH) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mice.Methods: Parkinson’s disease is induced in mice by MPTP and the neurobehaviors of mice in different groups are observed. Then, immunohistochemistry and Western blot analysis are adopted to measure the expression of tyrosine hydroxylase (TH) and α-synuclein in the substantia nigra (SN). The content of dopamine (DA) and other neurotransmitters in the brain is detected by high-performance liquid chromatography. The expression of nerve growth factors and inflammatory factors in SN in mice in each group is measured by quantitative polymerase chain reaction. Finally, the expression of oxidative stress-related parameters in each group is measured.Results: Compared with the model group, the pole-climbing time among mice in the moderate and high-dose ECH groups is significantly reduced (P < 0.01). The rotarod staying time, as well as fore and hind-limb strides, shows a significant increase (P < 0.01), as does spontaneous activity (P < 0.01). Moreover, the expression levels of TH, DA, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor in SN in mice show significant increases in these two groups (P < 0.01). The content of superoxide dismutase, catalase, and glutathione peroxidase indicates significant increases in the low, moderate, and high-dose ECH groups (P < 0.01), and the content of MDA was reduced (P < 0.01). In the high-dose ECH group, the expression of interleukin (IL) 6 and tumor necrosis factor-α is significantly reduced (P < 0.01), while the expression of IL-10 shows a marked increase (P < 0.01) alongside a decrease in the expression of α-synuclein (P < 0.01).Conclusion: Echinacoside improves neurobehavioral symptoms in PD mice and significantly increases the expression of TH and DA. The neuroprotective effect potentially correlates with anti-inflammation and anti-oxidation actions, promotes the expression of nerve growth factor, and reduces the accumulation of α-synuclein.Keywords: Parkinson’s disease, MPTP, echinacoside, α-synuclein, oxidative stress, neuroprotection, BDNF, GDNF, IL-6, TNF-α, IL-10

Zhen-Nian Zhang,1,* Zhen Hui,1,* Chang Chen,1 Yan Liang,1 Li-Li Tang,1 Su-Lei Wang,1 Cheng-Cheng Xu,1 Hui Yang,1 Yang Zhao,1 Jing-Si Zhang2 1Department of Neurology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, People’s Republic of China; 2Department of Neurology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing-Si ZhangDepartment of Neurology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 of Zhangheng Road, Pudong New Area, Shanghai, 201203, People’s Republic of ChinaTel/Fax +86 13127823579Email zhangzn88_dr@163.comObjective: The present study aimed to investigate the effect of echinacoside on autophagy-related indicators through the mTOR signaling pathway, especially the effect on the clearance of autophagy substrate P62 and α-synuclein, the core pathological products of Parkinson’s disease (PD), to provide new strategies for the treatment of PD.Methods: A mouse model of subacute PD was established by the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). First, the neurobehavioral symptoms in mice of each group were evaluated, and the monoamine neurotransmitters in the striatum in each group were measured with a high-performance liquid phase. Immunofluorescence double staining was adopted to observe the expression of tyrosine hydroxylase (TH), α-synuclein, and LC3. The transmission electron microscope was used to observe the changes of ultrastructure in substantia nigra and the formation of autophagosomes. Then, the expressions of TH, α-synuclein, Beclin 1, LC3, P62, mTOR, and the up-stream protein AKT were detected by Western blot.Results: When compared with the model group, the neurobehavioral function significantly improved in the echinacoside group (P < 0.01), together with increased expression of TH, DA, and DOPAC in the brain (P < 0.01). In the echinacoside group, while the expressions of Beclin 1 and LC3-II increased (P < 0.01), the expression levels of P62 and α-synuclein decreased significantly (P < 0.01). Echinacoside could up-regulate the expression level of the survival signal p-AKT/AKT and decrease the expression of mTOR.Conclusion: Echinacoside could increase autophagy by inhibiting the expression of mTOR, thereby promoting the clearance of α-synuclein and the degradation of the autophagy substrate P62 and exerting the neuroprotective effect.Keywords: Parkinson’s disease, MPTP, echinacoside, α-synuclein, P62, autophagy, mTOR