Background: Hyperuricemia is a common metabolic disease, which seriously affects the quality of life of patients. Salidroside (SAL) is a natural phenolic product extracted from Rhodiola rosea root, which is not only less toxic, but also beneficial for metabolic diseases. Purpose: To investigate SAL's role in regulating hyperuricemia and explore the potential mechanism. Methods: Molecular simulation was employed to predict the correlation between SAL and TLR4-NLRP3 pathway. The therapeutic effects of SAL were evaluated in cell model and hyperuricemia mice induced by potassium oxonate and hypoxanthine. Then, the mechanism was explored using Western blot assay. Results: Prediction results showed that SAL bond stably to target proteins TLR4, NLRP3, Caspase-1, and IL-1β involved in the classical pathway of hyperuricemia TLR4-NLRP3. Further hyperuricemia cell and mice model all showed SAL treatment did decrease the uric acid, creatinine and blood urea nitrogen level. Importantly, pathological observation demonstrated liver and kidney injuries were rescued using HE examination and renal fibrosis ameliorated by Masson staining, which was superior to the positive allopurinol. In terms of mechanism, proteins related to uric acid production (XOD) and excretion (ABCG2, OAT1, OCT1, URAT1 and GLUT9) as well as TLR4-NLRP3 pathway in cell model and hyperuricemia mice were all recovered after SAL administration, which were consistent with the molecular docking prediction. Conclusion: SAL may serve as a natural small molecule compound for improving hyperuricemia and its associated complications by inhibiting hepatic uric acid production and enhancing renal uric acid excretion. This discovery provides novel insights into hyperuricemia treatment.

As a traditional Tibetan medicine and health food, the fleshy roots of Sphallerocarpus gracilis were adopted to extract polyphenol powder(PP) in this research. Using a DSS-induced colitis mouse model combined with multi-omics analysis and experimental validation, we explored the protective effects and molecular mechanisms of PP against intestinal inflammation. PP mitigated colitis-related symptoms in a dose-dependent manner, inhibited pro-inflammatory cytokines and dose-dependently reversed elevated IL-10 levels to BC group. Multi-omics data revealed that PP intervention was associated with gut microbiota remodeling, enrichment of Akkermansia muciniphila, restoration of bacterial–fungal homeostasis, and improvement of tryptophan and biotin metabolism. By suppressing HMGB1 and RAGE expression, PP blocked the AGE-RAGE-mediated inflammatory cascade. In addition, PP maintained intestinal mucosal integrity through goblet cell protection, MDA reduction, and the regulation of BAX/Bcl-2, MMP3 and MMP9. Overall, PP relieves UC by regulating gut microecology, host metabolism and the AGE-RAGE pathway, which supports the translational potential of natural polyphenols for inflammatory bowel disease treatment as a gut microecological modulator.

Abstract Keratinocyte proliferation delay was a prominent clinical manifestation of diabetes, significantly impeding the wound healing process in diabetic mice. The potential therapeutic role of (−)-epigallocatechin gallate (EGCG) has been recognized due to its ability to enhance wound healing under diabetic conditions, but the underlying mechanism remained unclear. This study elucidates that EGCG expedited wound healing in diabetic mice by accelerating re-epithelialization and collagen deposition. Remarkably, we observed that EGCG promotes epidermal cell proliferation and enhances wound healing process in diabetic mice. We also discovered an overexpression of the Notch pathway in the epidermal cells of diabetic mice. Interestingly, EGCG effectively suppresses this overexpressed Notch pathway, suggesting a targeted mechanism for its therapeutic effects. Furthermore, the experiments with human immortalized keratinocytes (HaCaT) confirmed that high glucose levels activated the Notch signaling pathway, which was subsequently inhibited by EGCG treatment. In conclusion, our study reveals that EGCG improves wound healing in streptozotocin (STZ)-induced diabetic mice by targeting the Notch pathway in epidermal cells. These findings offered novel insights into therapeutic strategies for diabetic wounds and highlight EGCG as a promising candidate for treating chronic wounds.

Background: Potential acute and chronic oral toxic effects of Dendrobium officinale (DO) and black tea extract (BTE) mixture, a health-care food for osteoporosis, were evaluated to assess its suitability for therapeutic exploitation. Materials & Methods: Acute toxicity was examined via intragastric administration of DO-BTE twice within 24 h at 5 g/kg for a 14-day observation. In the subchronic toxicity test, normal rats were orally administered the combination at doses of 0.5, 1 and 2 g/kg twice daily for 90 days. Female ovariectomized (OVX) rats were intragastrically administered DO-BTE at 0.84 g/kg for 90 days. Results: Acute toxicity test disclosed no death or marked signs of toxicity, except lower activity in the combination treatment group. The maximal tolerance dose (MTD) of DO-BTE was 10 g/kg. In the chronic toxicity experiment, the rates of body weight growth in the combination treatment groups were slower than that in the control group. Plasma fibrinogen (FIB) and platelet (PLT) levels showed a decreasing trend. Conclusion: Acute and long-term toxicity tests revealed no toxic side-effects at the given doses in rodents, supporting further clinical investigation.

Background: Centranthera grandiflora Benth is commonly utilized in China to take advantage of its purported health benefits. Methods: Here, the chemical composition, nutritional value, and bioactivity of C. grandiflora Benth extract (CGE) are characterized, and the mechanisms through which it functions were explored. Results: CGE was found to exhibit a favorable nutritional and biosafety profile, especially due to its high amino acid and mineral contents. A UPLC-ESI-Q-TOF/MS approach identified 20 compounds. Through network pharmacology analyses, the antioxidant activity of CGE was found to be mediated through the PI3K/Akt pathway, with molecular docking results providing support for mussaenoside and azafrin as important bioactive compounds. At the cellular level, antioxidant activity of key protective antioxidants including GSH-Px and SOD while suppressing ROS accumulation, levels of damage-related factors (MDA, NO, TNF-α, IL-1β, and IL-6), and iNOS and COX-2 in RAW264.7 cells treated with LPS. These findings offer potential evidence for using CGE to lower oxidative stress and inflammation. Further analyses demonstrated the ability of CGE to promote Nrf2 and HO-1 upregulation, whereas Keap1 levels were suppressed, as were PI3K/Akt/NF-κB proteins. In light of these results, CGE appears to be able to act via simultaneously enhancing Nrf2/HO-1 activity and reducing that of PI3K/Akt/NF-κB. Conclusions: CGE, as a rich source of iridoid glycosides and other nutrients, may thus be a valuable dietary supplement for use in food applications.

EGFR is frequently overexpressed in non-small cell lung cancer, and EGFR plays a crucial role in the occurrence and progression of malignant tumors. Currently, drug resistance often develops following treatment with EGFR tyrosine kinase inhibitors, such as erlotinib and gefitinib. Therefore, It is essential to investigate new compounds that can effectively target EGFR overexpression. The polyphenols epigallocatechin-3-gallate (EGCG), found in tea, have demonstrated anti-cancer properties. In this study, we linked EGCG and erlotinib through a click reaction using polyglycol to form an EGCG-erlotinib conjugated compounds (EGCG-Erls). We then explored its biological activity through various experiments. The results indicated that the compound 10 exhibited a superior inhibitory effect on NCI-H1975 cells, reduced their cloning and migratory capabilities, promoted cell apoptosis, and inhibited cell cycle progression. Furthermore, it was observed that compound 10 can bind to the EGFR protein and effectively inhibit the expression of phosphorylated EGFR (p-EGFR) and its downstream signaling proteins. Overall, the study suggests that compound 10 may induce apoptosis and inhibit cell proliferation via the EGFR signaling pathway, providing a promising avenue for the development of new EGFR inhibitors.

Atherosclerosis is a chronic vascular disease characterized by the accumulation of cholesterol-rich lipids within the intima of large and medium-sized arteries. It is a leading cause of morbidity and mortality worldwide, contributing to the majority of myocardial infarctions and strokes. Ellagic acid (EA), a naturally occurring polyphenolic compound found in various plant species, exhibits promising potential in enhancing cholesterol metabolism and reducing the risk of atherosclerosis. However, the precise mechanisms and molecular targets underlying EA's cholesterol-regulating effects remain poorly understood. In this study, we demonstrate that EA effectively binds to the epidermal growth factor receptor (EGFR), exhibiting a dissociation constant (Kd) of 4.33 × 10-7 M and a binding energy of -7.1 kcal/mol. This binding activates EGFR and specifically engages the mitogen-activated protein kinase (MAPK) pathway, leading to the upregulation of low-density lipoprotein receptor (LDLR) expression in HepG2 cells. Furthermore, cetuximab, an EGFR-blocking antibody, inhibits the LDLR upregulation induced by EA, confirming EGFR as a key target in the regulation of LDLR expression. To evaluate the in vivo effects of EA on atherosclerosis, we encapsulated EA within human serum albumin to form nanoparticles (EA-NPs). This approach addresses poor water solubility and its tendency to convert into urolithin derivatives of EA following oral administration. In HepG2 cells, EA-NPs significantly enhanced LDLR expression, accompanied by increased phosphorylation of EGFR and extracellular signal-regulated kinase (ERK). In an ApoE-/- mouse model, EA-NPs exhibited potent anti-atherosclerotic effects mediated through the EGFR and MAPK pathways. Additionally, EA-NPs reduced hepatic lipid accumulation and attenuated the formation of aortic plaques. In conclusion, EA and its nanoparticle formulation effectively impede the progression of atherosclerosis, underscoring their therapeutic potential. These findings provide a robust foundation for the development of EA-based strategies as a viable daily therapeutic intervention for atherosclerosis management.

Tumor necrosis factor-α (TNF-α) is a key player in the pathogenesis of rheumatoid arthritis (RA) and considered a promising target for therapeutic drug development. Activation of the nuclear factor-kappa B (NF-κB) pathway upon TNF-α binding to its receptor is crucial for progression of RA. Stephanine (SA), an isoquinoline aporphine-type alkaloid recently identified in Stephania plants, exhibits anti-inflammatory properties, but its underlying mechanisms of action are unknown at present. In this study, we explored whether SA could ameliorate RA through inhibition of the NF-κB signaling pathway in association with TNF-α activity. Our experiments revealed a binding affinity (KD) of SA for TNF-α of 2.934 × 10−6 mol/L. Additionally, SA at a concentration of 10 μmol/L effectively hindered the binding of TNF-α to its receptors tumor necrosis factor receptor 1 (TNFR1) and TNFR2. In vitro, SA prevented TNF-α-induced death of L929 cells and blocked NF-κB activation triggered by TNF-α in 293-TNF-α responsive, as well as human fibroblast-like synoviocytes (HFLS) and human RA fibroblast-like synoviocytes (MH7A) cell lines. Furthermore, in a collagen-induced arthritis (CIA) mouse model, SA alleviated the symptoms of RA through suppression of NF-κB signaling. Our collective findings support the therapeutic efficacy of SA, a natural compound targeting TNF-α, in the management of RA.

Selenium-polysaccharides (SePs) are an emerging class of bioactive compounds formed by incorporating inorganic Se into polysaccharides, exhibiting enhanced biological activity compared to inorganic Se or isolated polysaccharides. The extraction of SePs from Se-enriched sources and the selenylation of polysaccharides are crucial for improving their biological activities, leading to structural variations that contribute to diverse biological effects. Structural variations in SePs, influenced by the incorporation of Se at specific positions or the formation of seleno-groups, play a key role in their biological effects. SePs have demonstrated antioxidant, anti-cancer, immune-regulating, anti-inflammatory, and other health benefits, making them promising candidates for nutraceutical applications. However, several areas remain underexplored in existing reviews, such as the dynamics of Se and its biosynthetic pathways in plants, as well as the structure-activity relationships and emerging applications of SePs. This study aims to investigate these biosynthetic pathways, structure-activity relationships, and the potential therapeutic and industrial applications of SePs. It highlights their potential in the food and health sectors, while also emphasizing the need for further research in these areas.

Excessive osteoclastogenesis-mediated osteoporosis has been recognized as a global health concern. Candidate compounds derived from medicinal plants or functional foods are promising to treat osteoporosis due to their high safety and efficiency. (−)-Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active polyphenol in green tea. It can inhibit osteoclastogenesis in vitro by blocking receptor activator of nuclear factor (NF) -κB (RANK) signaling pathways. This study used the ovariectomized (OVX) mouse model to estimate the therapeutic effect of EGCG on osteoporosis and verified the molecular mechanism in vivo. The results revealed that EGCG significantly inhibited the OVX-induced body weight gain. Moreover, no adverse effects were observed on blood glucose, histomorphological features, weights, as well as indices of liver and kidney in OVX mice. EGCG could significantly ameliorate bone loss in OVX mice by inhibiting osteoclastogenesis. This effect was evidenced by the reduced number of osteoclasts and the increased trabecular bone area in the femurs. Moreover, EGCG inhibited the activities of c-telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP-5b) and strengthened bone gla protein (BGP) and procollagen I N-terminal peptide (PINP) activities in OVX mice. Mechanistically, EGCG significantly downregulated the expression of osteoclastogenesis-related marker genes and proteins, including nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), c-Fos, tartrate-resistant acid phosphatase (TRAP), c-Src, and cathepsin K. In addition, the phosphorylation levels of p65, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and protein kinase B (AKT) were significantly suppressed in OVX mice. It was found that EGCG could alleviate OVX-induced bone loss in mice by suppressing osteoclastogenesis by blocking the NF-κB, mitogen-activated protein kinase (MAPK), and AKT signaling pathways. EGCG has the potential to prevent and treat osteoclast-related diseases such as osteoporosis.

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) hinders the clearance of low-density lipoprotein cholesterol (LDL-C) by promoting the degradation of the low-density lipoprotein receptor (LDLR), leading to the accumulation of LDL-C and thus becoming an important cause of atherosclerosis. Ellagic acid, a naturally occurring polyphenol widely present in fruits, vegetables, and nuts, has attracted significant attention due to its potential role in the prevention and treatment of cardiovascular diseases. However, the molecular mechanisms by which ellagic acid alleviates atherosclerosis by inhibiting PCSK9 are not fully understood. Materials and Methods: This study further validated the mechanism of action of ellagic acid through in vitro HepG2 cell experiments and a high-fat diet-induced ApoE-/- mouse model. Results: The results showed that ellagic acid significantly reduced the expression and secretion of PCSK9 while upregulating LDLR protein levels; its mechanism is related to the inhibition of hepatocyte nuclear factor 1a (HNF1a) expression and the promotion of forkhead box O3 (FoxO3) expression increase. Additionally, ellagic acid reduced aortic plaque deposition in mice induced by a high-fat diet; consistent with the in vitro experimental results, ellagic acid lowered the expression and secretion of PCSK9 and elevated LDLR protein levels by inhibiting HNF1a and increased FoxO3 expression. Conclusions: In summary, this study demonstrates that ellagic acid inhibits PCSK9 by regulating HNF1a and FoxO3, thereby increasing LDLR levels and alleviating atherosclerosis. This finding not only consolidates the scientific basis of plant-based diets for preventing cardiovascular diseases but also provides an important direction for developing functional foods and nutritional intervention strategies based on natural polyphenols. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND AND AIMS:Atherosclerosis (AS) is a complex and chronic vascular disease and elevated low-density lipoprotein cholesterol (LDL-C) level is one of its primary causative factors. As a key surface receptor, low-density lipoprotein receptor (LDLR) plays an essential role in LDL-C clearance. Resveratrol (RSV) has emerged as a promising compound for investigating potential therapeutic targets for AS due to its ability to lower cholesterol, reduce endothelial anti-inflammatory and suppress vascular smooth muscle cell proliferation. This study explored the effects of RSV on AS through upregulating LDLR and analyzed the mechanism through a combination of in vivo and vitro experiments. METHODS:HepG2 cells were exposed to varying concentrations of RSV. The effects of RSV on LDLR expression and cholesterol uptake were analyzed by western blot, RT-qPCR and DiI-LDL uptake assay. In vivo, C57BL/6J ApoE-/- mice were used and the experimental groups were treated with RSV, Lovastatin and Gefitinib. Plaque formation in the arteries and aortic roots was assessed by Oil Red O staining and plaque stability was evaluated using Hematoxylin-Eosin (H&E) and Elastic Van Gieson (EVG) staining. Western blot, RT-qPCR and immunohistochemical staining were employed to analyze the expression of LDLR in the livers of mice. RESULTS:RSV significantly enhanced the stability of LDLR mRNA and promoted LDLR protein expression. The inhibition experiments of EGFR signaling pathway (Cetuximab and Gefitinib) demonstrated that the efficacy of RSV was markedly weakened when this signaling pathway was inhibited. It indicated that RSV modulated LDLR gene expression by activating EGFR-ERK1/2 pathway. In ApoE-/- mice, RSV notably reduced arterial plaque formation, improved plaque stability and increased hepatic LDLR expression. CONCLUSION:This study elucidated the mechanism by which RSV upregulates LDLR gene expression through activating EGFR-ERK1/2 signaling pathway. In vivo experiments demonstrated its efficacy in reducing arterial plaque formation and stabilizing existing plaques. These results further indicated that RSV held potential therapeutic value for ameliorating atherosclerosis and cardiovascular diseases. Collectively, these findings provided novel theoretical support for RSV's potential role in cardiovascular therapy.

BACKGROUND:Hyperuricemia (HUA) is a chronic disease caused by abnormal purine metabolism with high prevalence. Dihydromyricetin (DMY) is a natural flavonoid that is abundant in plants, such as vine tea, grapes and bayberry. DMY has been shown to possess multiple biological properties, but its anti-HUA effect remains underexplored. In the present study, the regulatory effects of DMY on HUA and its complications and mechanism were investigated. RESULTS:DMY (10 and 20 μmol L-1) treatment significantly reduced xanthine oxidase (XOD) expression and uric acid (UA) synthesis in normal human liver cell strain cells, and intraperitoneal administration of DMY (100 mg kg-1) also significantly reduced serum UA and the expression of hepatic XOD in HUA mice. After DMY treatment for 12 consecutive days, the uricosuric protein, ATP-binding cassette subfamily G member 2, was upregulated, and reabsorption proteins, including urate transporter 1 and glucose transporter 9, were downregulated, which was consistent with the results of monosodium urate-induced HUA in human renal tubular epithelial cell line and human colon adenocarcinoma cell line cell models. In addition, DMY significantly ameliorated HUA-induced renal injury, and foot edema induced by monosodium urate. The nucleotide-binding oligomerization domain-like receptor family containing pyrin domain 3 (NLRP3) inflammasome was activated in HUA mice as evidenced by upregulation of NLRP3, caspase-1, ACS, TNF-α and IL-1β in the kidney and foot, which was significantly suppressed by DMY treatment. CONCLUSION:Collectively, these findings suggested that DMY may play important roles in experimental HUA. © 2025 Society of Chemical Industry.

Steroidal alkaloids are the main active components in many medicinal plants and exhibit diverse biological activities. Axillaridine A (AA) is a newly discovered steroidal alkaloid. However, whether AA could suppress osteoclastogenesis and alleviate ovariectomy-induced bone loss in mice remains unknown. In vitro, AA significantly suppressed the receptor activator of nuclear factor-‍κB (NF-‍κB) ligand (RANKL)‍-induced osteoclast differentiation via downregulating the expression of osteoclastogenesis-related marker genes, proteins, and transcriptional regulators, including tartrate-resistant acid phosphatase (TRAP), c-Src, matrix metallopeptidase-9 (MMP-9), cathepsin K, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and c-Fos. This was achieved by blocking RANKL-RANK interaction and inhibiting RANKL-mediated RANK signaling pathways, including NF‍-‍κB, AKT, and mitogen-activated protein kinases (MAPKs) in osteoclast precursors. In vivo, AA significantly inhibited the ovariectomized (OVX)‍-induced body weight gain and blood glucose increase in mice. AA did not adversely affect the histomorphologies, weights, and indices of the kidney and liver in OVX mice. AA effectively ameliorated bone loss in OVX mice by inhibiting osteoclastogenesis. AA significantly inhibited the serum levels of tartrate-resistant acid phosphatase 5b (TRACP-5b) and C-telopeptide of type I collagen (CTX-‍I). AA significantly inhibited the OVX-induced expression of osteoclastogenesis-related marker genes and proteins in the femur. In summary, AA alleviates ovariectomy-induced bone loss in mice by suppressing osteoclastogenesis via inhibition of RANKL-mediated RANK signaling pathways and could be potentially used for the prevention and treatment of osteoclast-related diseases such as osteoporosis.

The RSPO gene family, comprising RSPO1, RSPO2, RSPO3, and RSPO4, encodes cysteine-rich secreted glycoproteins. These proteins serve as key activators of the Wnt signaling pathway, a fundamental cascade critical for orchestrating developmental processes—such as embryogenesis and organ formation—and regulating essential cellular activities, including stem cell maintenance, proliferation, and differentiation. First identified in model organisms like mice and zebrafish, studies of the RSPO family have yielded foundational insights into developmental signaling. Yet, their evolutionary trajectory remains elusive, obscured by complex patterns of gene duplication, loss, and adaptation across divergent lineages, coupled with a scarcity of fossil and genomic data. Current research leverages comparative genomics, sophisticated phylogenetic reconstructions, and functional assays to unravel their enigmatic origin, trace their diversification, and pinpoint their specific roles across the tree of life. This review synthesizes recent advances in deciphering RSPO-mediated signaling, aiming to establish a robust framework for future investigations. Such work will encompass functional validation in non-model organisms and the intricate dissection of molecular mechanisms, ultimately striving to propel precision medicine targeting Wnt-related disorders.

Pu-erh tea polyphenol aggregates (PTPAs), macromolecular complexes analogous to theabrownin formed during microbial fermentation, are key bioactive components in this tea. Although their bioactivities are documented, critical gaps persist regarding both precise structural features and molecular mechanisms underlying the anti-inflammatory efficacy across biological models. To address these limitations, we systematically analyzed PTPAs using integrated methods, including alkaline hydrolysis, acid hydrolysis, and benzyl mercaptan-mediated degradation. The anti-inflammatory effects of PTPAs were then evaluated in LPS-induced RAW264.7 cells and DSS-induced colitis mice. Structural characterization revealed that the backbone of PTPAs consists primarily of catechin, epicatechin, and epicatechin gallate units, with flavan-3-ols, flavonols, and anthocyanins as the terminal units. Moreover, phenolic acids and amino acids are potentially integral components of PTPAs. Mechanistically, we demonstrated that PTPAs exert anti-inflammatory effects by inhibiting TLR4/MyD88-mediated NF-κB signaling pathway activation, thereby suppressing downstream inflammatory mediators including NO, TNF-α, IL-1β, and IL-6. Notably, in DSS-induced colitis, PTPAs demonstrated multimodal therapeutic effects by preserving intestinal barrier integrity, modulating systemic inflammation, and reshaping the gut microbiota composition. This study provides the first comprehensive evidence linking the structural complexity of PTPAs to pleiotropic anti-inflammatory actions via gut-immune axis regulation, elucidating Pu-erh tea's phytochemical basis and therapeutic potential.

Abstract Background: Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease. Previous research shows that Notch plays a role in the pathogenesis of UC and (−)-Epigallocatechin Gallate(EGCG) could attenuate colitis. However, the mechanism of EGCG to improve colitis remains unclear. Methods:The human epithelial colorectal adenocarcinoma Caco-2 cells were intervened with EGCG (10ug/ml or 30ug/ml) with or without Lipopolysaccharide. A mouse model of UC was induced by 3% dextran sulfate sodium and EGCG treatment was administered to mice at a dose of 10 and 20 mg/kg. The stool consistency, rectal bleeding and weight were recorded daily. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. Immunohistochemical analyses were performed for iNOS, F4/80, Notch1 and hes1. Inflammatory cytokines were detected using ELISA kits .Western blot assays were performed for TNF-α, IL-1β, , Notch1, Cleaved-Notch1, Notch2,, Hes-1, COX2, iNOS from colon tissues and Caco-2 cells. Results: In this study, we found that the cytokine secretion and inflammation protein expression were reduced with EGCG treatment in LPS induced Caco-2 cells. And the levels of Notch1, Cleaved-Notch1, and Hes-1 expression were decreased by EGCG administration in the cell. Moreover, we found the pro-inflammation cytokine secretion and the macrophages accumulation were reduced by oral EGCG in DSS-induced mice colon which indicates EGCG ameliorates colitis in vivo. And we also found the phenotype of macrophages could alter to M1 was inhibited by oral EGCG in vivo. In addition, we demonstrate that EGCG could attenuate the levels of Notch1, Cleaved-Notch1, and Hes-1 expression in the colon. Conclusion: This study demonstrates that colitis can be improved by EGCG through targeting Notch in DSS-induced UC mice. Key words: EGCG; Notch; colitis; inflammation

Gallic acid (GA) is a type of polyphenolic compound that can be found in a range of fruits, vegetables, and tea. Although it has been confirmed it improves non-alcoholic fatty liver disease (NAFLD), it is still unknown whether GA can improve the occurrence of NAFLD by increasing the low-density lipoprotein receptor (LDLR) accumulation and alleviating cholesterol metabolism disorders. Therefore, the present study explored the effect of GA on LDLR and its mechanism of action. The findings indicated that the increase in LDLR accumulation in HepG2 cells induced by GA was associated with the stimulation of the epidermal growth factor receptor–extracellular regulated protein kinase (EGFR-ERK1/2) signaling pathway. When the pathway was inhibited by EGFR mab cetuximab, it was observed that the activation of the EGFR-ERK1/2 signaling pathway induced by GA was also blocked. At the same time, the accumulation of LDLR protein and the uptake of LDL were also suppressed. Additionally, GA can also promote the accumulation of forkhead box O3 (FOXO3) and suppress the accumulation of hepatocyte nuclear factor-1α (HNF1α), leading to the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) mRNA expression and protein accumulation. This ultimately results in increased LDLR protein accumulation and enhanced uptake of LDL in cells. In summary, the present study revealed the potential mechanism of GA’s role in ameliorating NAFLD, with a view of providing a theoretical basis for the dietary supplementation of GA.

BACKGROUND High levels of plasma low-density lipoprotein (LDL) are a key risk factor for atherosclerosis. Low-density lipoprotein receptor (LDLR) mediates the degradation of plasma LDL. Therefore, it may be possible to prevent and treat atherosclerosis by increasing the levels of LDLR. The natural polyphenolic compound ellagic acid (EA) has various biological activities. In mice, EA alleviated the progression of atherosclerosis; however, the underlying mechanism remains unclear. METHODS Molecular interaction, cell, and animal experiments were used to explore the role and mechanism of EA in improving atherosclerosis. RESULTS EA binds to the extracellular domain of the epidermal growth factor receptor (EGFR), thus activating the EGFR-extracellular signal-regulated kinase (EGFR-ERK) signaling pathway, stabilizing LDLR mRNA, and promoting the expression of LDLR protein. The development of EA-loaded human serum albumin nanoparticles enabled intravenous administration in animal experiments. CONCLUSIONS The research verified the in vivo effects of EA on the EGFR-ERK signaling pathway, LDLR levels, and atherosclerosis. EA may assist in the prevention and treatment of atherosclerosis.

Epidermal growth factor receptor (EGFR) is a starring target for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat NSCLC patients with EGFR-activating mutations. However, most patients invariably develop resistance to these agents due to the occurrence of novel mutations at the EGFR kinase domain. There is an urgent need to develop more effective therapy strategies to provide more selection for patients with NSCLC. Coccinic acid was reported to exerts potential anti-tumor effects, but its mechanism has not been elucidated and warrants investigation. In this study, coccinic acid was shown to inhibit cell proliferation on cells harboring L858R/T790M mutant EGFR by suppressing p-EGFR and p-STAT3. It was also shown that coccinic acid promoted cell cycle distribution and showed a potent apoptosis-inducing efficacy. Further results in vivo assays demonstrated that coccinic acid reduced tumor growth of NCI-H1975 xenograft in nude mice via the EGFR/STAT3 signaling. Moreover, these effects are involving in the binding of coccinic acid to the EGFR extracellular domain. In conclusion, our finding demonstrated that coccinic acid may be utilized as a potential novel candidate for NSCLC with EGFR L858R/T790M mutation.