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Ulcerative colitis (UC) is a relapsing inflammatory disease with an unknown precise etiology. The purpose of this study is to investigate the protective effects of Gardenia jasminoides Ellis fruit extracts (GFE) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. GFE (50 mg/kg, 100 mg/kg) were administered orally for 7 days after induction. Meanwhile, the chemical components of GFE were performed by UPLC-QTOF-MS/MS. GFE significantly decreased DAI scores and ameliorated macroscopic and histologic damage. It also reduced the levels of MPO, NO, MDA, IL-1β, TNF-α, and IL-6, while increasing the level of SOD. Moreover, 56 components were identified in GFE using a UPLC-QTOF-MS/MS method, which can be categorized into six structural groups. Our results indicated that GFE has an ameliorative effect on TNBS-induced colitis in rats, which may further verify its anti-inflammatory and antioxidative properties. Therefore, GFE can be a promising protective agent of colitis that deserves further investigation. [ABSTRACT FROM AUTHOR]

Val‐Val‐Tyr‐Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride‐induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non‐alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L‐02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine‐choline‐deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non‐esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis‐related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24‐7 and Bacteroidia in high‐fat diet (HFD)‐fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)‐associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut‐liver axis activation. VVYP might be a promising drug candidate for NASH. [ABSTRACT FROM AUTHOR]

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0–2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction). [ABSTRACT FROM AUTHOR]

A trimeric tri-Tb3+-including antimonotungstate (AMT) hybrid Na17{(WO4)[Tb(H2O)(Ac)(B-α-SbW9O31(OH)2)]3}·50H2O (Tb3W28) was successfully synthesized, in which the capped tetrahedral {WO4} group plays a significant template role in directing the aggregation of three [B-α-SbW9O33]9− fragments and three Tb3+ ions. Eu3+/Tb3+/Dy3+/Gd3+-codoped AMT materials based on Tb3W28 were firstly prepared and their luminescence properties were investigated. The red emitter Eu3+, yellow emitter Dy3+, and nonluminous Gd3+ ions were codoped into Tb3W28 to substitute Tb3+ ions for investigating the energy transfer (ET) mechanism among Eu3+, Tb3+, and Dy3+ ions. Upon the 6H15/2 → 4I13/2 excitation at 389 nm of the Dy3+ ion, the ET1 mechanism (Dy3+ → Tb3+) was confirmed as a non-radiative dipole–dipole interaction. Under the 7F6 → 5L10 excitation at 370 nm of the Tb3+ ion, the ET2 mechanism (Tb3+ → Eu3+) was identified as a non-radiative quadrupole–quadrupole interaction. Under excitation at 389 nm, the two-step successive Dy3+ → Tb3+ → Eu3+ ET3 process was proved in Dy1.2Tb3zEu0.03Gd1.77−3zW28. Through changing the excitation wavelengths, the emission color of Dy1.2Tb1.2Eu0.03Gd0.57W28 can vary from blue to yellow, in which a near-white-light emission case was observed upon excitation at 378 nm. This work not only provides a systematic ET mechanism study of hetero-Ln-codoped AMTs, but also offers some useful guidance for designing novel performance-oriented Ln-codoped polyoxometalate-based materials. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) has a high mortality rate due to liver metastasis. The insulin‐like growth factor‐1 receptor (IGF‐1R) is highly expressed in UM and has been shown to be associated with hepatic metastases. Targeting IGF signalling may be considered as a promising approach to inhibit the process of metastatic UM cells. Pristimerin (PRI) has been demonstrated to inhibit the growth of several cancer cells, but its role and underlying mechanisms in the IGF‐1‐induced UM cell proliferation are largely unknown. The present study examined the anti‐proliferative effect of PRI on UM cells and its possible role in IGF‐1R signalling transduction. MTT and clonogenic assays were used to determine the role of PRI in the proliferation of UM cells. Flow cytometry was performed to detect the effect of PRI on the cell cycle distribution of UM cells. Western blotting was carried out to assess the effects of PRI and IGF‐1 on the IGF‐1R phosphorylation and its downstream targets. The results indicated that IGF‐1 promoted the UM cell proliferation and improved the level of IGF‐1R phosphorylation, whereas PRI attenuated the effect of IGF‐1. Interestingly, PRI could not only induce the G1 phase accumulation and reduce the G2 phase induced by IGF‐1, but also could stimulate the expression of p21 and inhibit the expression of cyclin D1. Besides, PRI could attenuate the phosphorylations of Akt, mTOR and ERK1/2 induced by IGF‐1. Furthermore, the molecular docking study also demonstrated that PRI had potential inhibitory effects on IGF‐1R. Taken together, these results indicated that PRI could inhibit the proliferation of UM cells through down‐regulation of phosphorylated IGF‐1R and its downstream signalling. [ABSTRACT FROM AUTHOR]

A tetrahedral {HPO 3 } and {WO 4 } group simultaneously directing acetate-decorated tri-Tb(III)-containing antimonotungstate was prepared and characterized. • Inorganic-organic hybrid trimer antimonotungstate. • Tetrahedral {HPO 3 } and tetrahedral {WO 4 } group directing tri-Tb(III)-containing antimonotungstate. • Photoluminescence properties. A tetrahedral {HPO 3 } and {WO 4 } group simultaneously directing tri-Tb(III)-containing antimonotungstate (AT) K 3 Na 21 H[Tb 3 (Ac) 3 (HPO 3)(WO 4)][B- α -SbW 9 O 33 ] 3 ·36H 2 O (1) has been triumphantly isolated by the aqueous reaction of Na 9 [B- α -SbW 9 O 33 ]·19·.5H 2 O, Na 2 WO 4 ·2H 2 O, H 3 PO 3 and Tb(NO 3) 3 ·6H 2 O. Notably, tetrahedral {HPO 3 } and {WO 4 } groups may play the template-directing function in the formation of polyoxoanion of 1. Under the excitation at 380 nm, the emission spectrum and the decay lifetime curve of 1 have been measured. Upon the O → W LMCT excitation at 260 nm, energy transfer from AT fragments to Tb3+ ions has occurred because Tb3+ ions can absorb energy from the O → W LMCT emission of AT fragments. By switching the excitation wavelength from 250 to 390 nm, it's available to tune the emission color of 1 from blue to green. [ABSTRACT FROM AUTHOR]

• The authors designed novel GPR119 agonists bearing various core moiety from lipophilic cycloolefin fused pyrimidines to polar tetrahydropyridopyrimidines and found that the less polar cyclohexene fused compounds displayed the most potent activity. A novel series of fused pyrimidine derivatives were designed, synthesized and evaluated as GPR119 agonists. Among them, cyclohexene fused compounds (tetrahydroquinazolines) showed greater GPR119 agonistic activities than did dihydrocyclopentapyrimidine and tetrahydropyridopyrimidine scaffolds. Analogues (16 , 19 , 26 , 28 , 42) bearing endo - N -Boc-nortropane amine and fluoro-substituted aniline exhibited better EC 50 values (0.27–1.2 μM) though they appeared to be partial agonists. [ABSTRACT FROM AUTHOR]

We described the discovery and optimization of a novel series of pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119) agonists against type 2 diabetes. Most designed compounds displayed significant GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly potent agonistic activities with single digit EC 50 values (2.2 nM and 8.1 nM, respectively). Therefore, 15a and 21e were evaluated for their oral glucose tolerance test (oGTT) in C57BL/6N mice. Compound 15a reduced the blood glucose area of under curve from 0 to 2 h (AUC 0–2h ) to 13.5% at the dose of 15 mg/kg comparing with Metformin reduced 18% of AUC 0–2h at the dose of 300 mg/kg. [ABSTRACT FROM AUTHOR]

A class of senkyunolide analogues bearing benzofuranone fragment were designed, synthesized and evaluated for their neuroprotective effect in models of oxygen glucose deprivation (OGD) and oxidative stress. All tested compounds showed neuroprotection profile based on the cell viability assay. In particular, derivatives 1f – 1i possessing furoxan-based nitric oxide releasing functionality exhibited significant biological activities in OGD models. More importantly, compound 1g containing short linker with furoxan displayed the most potent neuroprotection at the concentration of 100 μM (cell survival up to 145.2%). Besides, 1g also showed the middle level neuroprotective effect in model of oxidative stress. [ABSTRACT FROM AUTHOR]

A terbium-antimony-oxo-cluster bridging antimonotungstate comprising divacant and tetravacant Keggin segments was prepared and characterized. • Tetramer bridging antimonotungstate. • Terbium-antimony-oxo-cluster bridging antimonotungstate. • Photoluminescence properties. • Energy transfer. A terbium-antimony-oxo-cluster bridging antimonotungstate (AT) [H 2 N(CH 3) 2 ] 8 Na 6 H 8 {[Tb 4 (H 2 O) 6 Sb 6 O 4 ](SbW 10 O 37) 2 (B- α -SbW 8 O 31) 2 }·24H 2 O (1) was successfully prepared by reaction of Na 9 [B- α -SbW 9 O 33 ]·19·.5H 2 O, SbCl 3 , Tb(NO 3) 3 ·6H 2 O and dimethylamine hydrochloride (DMA·HCl) in acidic aqueous solution. Its tetramer polyanion consists of two divacant [SbW 10 O 37 ]11− and two tetravacant [B- α -SbW 8 O 31 ]11− fragments linked by two [Tb 2 (H 2 O) 3 Sb 3 O 2 ]11+ clusters. The photoluminescence emission spectra and lifetime decay curves of 1 are collected respectively under the most f−f excitation at 368 nm and O → W LMCT excitation at 268 nm. The sensitization of AT fragments can enhance the f−f transition emission intensity of Tb3+ ions and prolong the lifetime of Tb3+ ions. The time-resolved emission spectrum of 1 reveals that the decay rate of characteristic emission peaks of Tb3+ ions has been inhibited because of the sensitization effect of AT fragments to Tb3+ ions. The emission spectra under different excitation wavelengths indicate that the excitation at 268 nm from O → W LMCT is the most suitable excitation and can obtain the strongest emission spectrum of 1. Their corresponding CIE coordinates demonstrate that the emission colors of 1 can be tuned by changing different excitation wavelengths. [ABSTRACT FROM AUTHOR]