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Background: With the changes in lifestyle and diet structure, the incidence of obesity has increased year by year, and obesity is one of the inducements of many chronic metabolic diseases. Epigallocatechin gallate (EGCG), which is the most abundant component of tea polyphenols, has been used for many years to improve obesity and its complications. Though it has been reported that EGCG can improve obesity through many molecular mechanisms, EGCG may have many mechanisms yet to be explored. In this study, we explored other possible mechanisms through molecular docking and in vitro experiments. Methods: AutoDock Vina was selected for conducting the molecular docking analysis to elucidate the interaction between EGCG and Notch1, while molecular dynamics simulations were employed to validate this interaction. Then, the new regulation mechanism of EGCG on obesity was verified with in vitro experiments, including a Western blot experiment, immunofluorescence experiment, oil red O staining, and other experiments in 3T3-L1 adipocytes. Results: The molecular docking results showed that EGCG could bind to Notch1 protein through hydrogen bonding. In vitro cell experiments demonstrated that EGCG can significantly reduce the sizes of lipid droplets of 3T3-L1 adipocytes and promote UCP-1 expression by inhibiting the expression of Notch1 in 3T3-L1 adipocytes, thus promoting mitochondrial biogenesis. Conclusions: In this study, molecular docking and in vitro cell experiments were used to explore the possible mechanism of EGCG to improve obesity by inhibiting Notch1. [ABSTRACT FROM AUTHOR]

The phytochemical investigation of Veratrum mengtzeanum Loes. roots resulted in the isolation and characterization of two novel, namely Mengtzeanines A (1), Mengtzeanines B (2), and eight known steroidal alkaloids (3–10). Their structural properties were assessed though extensive spectroscopic techniques. All constituents 1–10 were analyzed for suppression of NO formation in LPS-induced RAW264.7 macrophages. Among them, constituent 6 (Verazine) showed inhibition against LPS-induced NO production (IC50 = 20.41 μM). Additionally, compound 6 could inhibit the secretion of IL1β, IL6, and TNFα, and downregulate the productions of iNOS and COX2 in LPS-induced RAW264.7 macrophages. Further experiments revealed that 6 exhibited a potent anti-inflammatory level in LPS-stimulated RAW264.7 macrophages via inhibiting NF-κB, and triggering of Keap1/Nrf2/HO-1 axis, implying that compound 6 may be a promising candidate for treating inflammatory disorders. [ABSTRACT FROM AUTHOR]

Inhibiting the tyrosine kinase activity of epidermal growth factor receptor (EGFR) using small-molecule tyrosine kinase inhibitors (TKIs) or monoclonal antibodies is often ineffective in treating cancers harboring wild-type EGFR. Given the fact that EGFR possesses a kinase-independent pro-survival function, more effective inhibition of EGFR-mediated signals is therefore necessary. In this study, we investigated the effects of using a combination of low-dose nimotuzumab and theasinensin A to evaluate whether the inhibitory effect of nimotuzumab on NCI-H441 cancer cells was enhanced. Here, theasinensin A, a novel epigallocatechin-3-gallate (EGCG) derivative, was identified and its potent anticancer activity against wild-type EGFR NSCLC was demonstrated in vitro; the anticancer activity was induced through degradation of EGFR. Mechanistic studies further revealed that theasinensin A bound directly to the EGFR extracellular domain, which decreased interaction with its ligand EGF in combination with nimotuzumab. Theasinensin A significantly promoted EGFR degradation and repressed downstream survival pathways in combination with nimotuzumab. Meanwhile, treatment with theasinensin A and nimotuzumab prevented xenograft growth, whereas the single agents had limited effect. Thus, the combination therapy of theasinensin A with nimotuzumab is a powerful candidate for treatment of wild-type EGFR cancers. [ABSTRACT FROM AUTHOR]

Coffee fermentation is crucial for flavor and aroma, as microorganisms degrade mucilage and produce metabolites. This study aimed to provide a basis for understanding the impact of microorganisms on Coffea arabica from Yunnan, China, during washed processing. The microbial community structure and differentially changed metabolites (DCMs) of C. arabica beans during washed processing were analyzed. The results indicated that the top five predominant microorganisms at the genera level were Achromobacter, Tatumella, Weissella, Streptococcus, and Trichocoleus for bacteria and Cystofilobasidium, Hanseniaspora, Lachancea, Wickerhamomyces, and Aspergillus for fungi. Meanwhile, the relative content of 115 DCMs in 36 h samples decreased significantly, compared to non-fermentation coffee samples (VIP > 1, p < 0.05, FC < 0.65), and the relative content of 28 DCMs increased significantly (VIP > 1, p < 0.05, FC > 1.5). Furthermore, 17 DCMs showed a strong positive correlation with microorganisms, and 5 DCMs had a strong negative correlation (p < 0.05, |r| > 0.6). Therefore, the interaction and metabolic function of microbiota play a key role in the formation of coffee flavor, and these results help in clarifying the fermentation mechanisms of C. arabica and in controlling and improving the quality of coffee flavor. [ABSTRACT FROM AUTHOR]

The primary processing method of coffee plays a crucial role in determining its flavor profile. In this study, roasted coffee beans were subjected to three primary processing methods, i.e., natural processing (SC), washed processing (WC), and honey processing (MC), that were analyzed by LC-MS/MS and GC-MS metabolomics. Additionally, sensory evaluation was conducted by the Specialty Coffee Association of America (SCAA) to assess coffee flavor characteristics. The results showed that 2642 non-volatile compounds and 176 volatile compounds were detected across the three primary processing methods. Furthermore, significant differentially changed non-volatile compounds (DCnVCs) and volatile compounds (DCVCs) were detected among SC/WC (137 non-volatile compounds; 32 volatile compounds), MC/SC (103 non-volatile compounds; 25 volatile compounds), and MC/WC (20 non-volatile compounds; 9 volatile compounds). Notable compounds, such as lichenin, 6-gingerdiol 5-acetate, 3-fluoro-2-hydroxyquinoline, and 4-(4-butyl-2,5-dioxo-3-methyl-3-phenyl-1-pyrrolidiny)benzenesulfonamide, were identified as important DCnVCs, while ethyl alpha-D-glucopyranoside, 2,3-butanediol, maltol, and pentane-1,2,5-triol were identified as significant DCVCs in SC/WC. In MC/SC, 3-fluoro-2-hydroxyquinoline, etimicin, lichenin, and imazamox were important DCnVCs, whereas ethyl alpha-D-glucopyranoside, 2-pyrrolidinone, furfuryl alcohol, and pentane-1,2,5-triol were import DCVCs. Lastly, MC/WC samples exhibited notable DCnVCS, such as (S)-2-hydroxy-2-phenylacetonitrile O-[b-D-apiosyl-1->2]-b-D-glucoside], CMP-2-aminoethyphosphonate, talipexole, and neoconvallatoxoloside, along with DCVCS including citric acid, mannonic acid, gamma-lactone, 3-(1-hydroxy-1-methylethyl)benzonitrile, and maltol. Therefore, the primary processing method was a useful influence factor for coffee compositions. [ABSTRACT FROM AUTHOR]

Spirocyclic frameworks could enhance the drug‐like properties of planar bioactive molecules by increasing their three‐dimensionality, making the development of synthetic methodology and bioactivity assays for spiro compounds highly attractive. This work reported the silver‐catalyzed tandem cycloisomerization/Povarov reaction between β‐alkynyl ketones and hexahydro‐1,3,5‐triazines, access to spiro[isochromene‐1,4'‐quinoline]. This synthetic protocol was characterized by remarkable efficiency, low catalyst‐loading and high diastereoselectivity. Moreover, the spirocyclic quinolines exhibited good cytotoxicity in U937 cells by activating the Notch‐signaling pathway exclusively. [ABSTRACT FROM AUTHOR]

Dendrobiumofficinale is one of the most valuable Dendrobium species and has been widely used in traditional Chinese medicine (TCM). Dendrocandins (DDCDs) are characteristic chemical structures of D.officinale and have various biological activities. Herein, we report the anticancer effects of DDCD in HepG2 cells using MTT assay. Furthermore, the mechanism of action of DDCD was determined by molecular docking and quantum chemical studies. The results showed that DDCD demonstrated significant anticancer activity against HepG2 cells by inducing apoptosis and attenuating the levels of p-AKT. Molecular modeling studies suggested the DDCD bound to the active site of AKT by the formation of four hydrogen bonds, two hydrophobic interactions, and one π-alky interaction. Quantum chemical studies were carried out on DDCD to understand the structural features essential for bioactivity. Thus, DDCD with a novel structure has the potential to be developed as an anticancer agent for liver cancer. [ABSTRACT FROM AUTHOR]

Quantum-chemical calculations based on the density functional theory (DFT) at the B3LYP/6–311 + + G(2d,2p)//B3LYP/6–31G(d,p) level were employed to study the relationship between the antioxidant properties and chemical structures of six dendrocandin (DDCD) analogues in the gas phase and two solvents (methanol and water). The hydrogen atom transfer (HAT), electron-transfer-proton-transfer (ET-PT), and sequential proton-loss-electron-transfer (SPLET) mechanisms are explored. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), reactivity indices (η, μ, ω, ω+, and ω–), and molecular electrostatic potentials (MEPs) were also evaluated. The results suggest that the D ring plays an important role in mediating the antioxidant activity of DDCDs. For all the studied compounds, indicating that HAT was identified as the most favorable mechanism, whereas the SPLET mechanism was the most thermodynamically favorable pathway in polar solvents. The results of our study should aid in the development of new or modified antioxidant compounds. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant tumours in the world. Recent reports have revealed natural products displayed inhibition on colon cancer potential by suppressing transforming growth factor‐β/Smads induced epidermal‐mesenchymal transition (EMT). In this article, 12 kinds of natural berberine analogues were screened for their effects on the inhibition of the colon cancer cells, the results showed that demethyleneberberine (DM‐BBR) exhibited an interesting and potential effect on inducing the apoptosis of HCT‐116 cells with drug concentrations of 6, 12 and 18 μM. Particularly, DM‐BBR reversed the EMT process by inhibiting the expression of p‐Smad2 and p‐Smad3 in the transforming growth factor‐β/Smads signal pathway, up‐regulated pro‐apoptotic protein cleaved caspase‐9, and blocked cell cycle at the S phase and increasing the expression of cyclin proteins P27 and P21. Taken together, these findings suggested that DM‐BBR could promote apoptosis and suppress TGF‐β/Smads induced EMT in the colon cancer cells HCT‐116. [ABSTRACT FROM AUTHOR]

Background: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The inhibition of epidermal growth factor receptor (EGFR) signaling by tyrosine kinase inhibitors or monoclonal antibodies plays a key role in NSCLC treatment. Unfortunately, these treatment strategies are limited by eventual resistance and cell lines with differential EGFR status. Therefore, new therapeutic strategies for NSCLC are urgently required. Methods: To improve the stability and absorption of (−)-epigallocatechin-3-gallate (EGCG), we synthesized a series of EGCG derivatives. The antitumor activities of EGCG derivatives with or without cisplatin were investigated in vitro and vivo. Cell proliferation, cell cycle distribution and apoptosis were measured in NSCLC cell lines and in vivo in a NCI-H441 xenograft model. Results: We found that the EGCG derivatives inhibited cell viability and colony formation, caused cell cycle redistribution, and induced apoptosis. More importantly, the combination of the EGCG derivative and cisplatin led to increased growth inhibition, caused cell cycle redistribution, and enhanced the apoptosis rate compared to either compound alone. Consistent with the experiments in vitro, EGCG derivatives plus cisplatin significantly reduced tumor growth. Conclusions: The combination treatment was found to inhibit the EGFR signaling pathway and decrease the expression of p-EGFR, p-AKT, and p-ERK in vitro and vivo. Our results suggest that compound 3 is a novel potential compound for NSCLC patients. [ABSTRACT FROM AUTHOR]