EPA and DHA Alleviated Chronic Dextran Sulfate Sodium Exposure-Induced Depressive-like Behaviors in Mice and Potential Mechanisms Involved.

Patients with ulcerative colitis (UC) have higher rates of depression. However, the mechanism of depression development remains unclear. The improvements of EPA and DHA on dextran sulfate sodium (DSS)-induced UC have been verified. Therefore, the present study mainly focused on the effects of EPA and DHA on UC-induced depression in C57BL/6 mice and the possible mechanisms involved. A forced swimming test and tail suspension experiment showed that EPA and DHA significantly improved DSS-induced depressive-like behavior. Further analysis demonstrated that EPA and DHA could significantly suppress the inflammation response of the gut and brain by regulating the NLRP3/ASC signal pathway. Moreover, intestine and brain barriers were maintained by enhancing ZO-1 and occludin expression. In addition, EPA and DHA also increased the serotonin (5-HT) concentration and synaptic proteins. Interestingly, EPA and DHA treatments increased the proportion of dominant bacteria, alpha diversity, and beta diversity. In conclusion, oral administration of EPA and DHA alleviated UC-induced depressive-like behavior in mice by modulating the inflammation, maintaining the mucosal and brain barriers, suppressing neuronal damage and reverting microbiota changes.

[Role and mechanism of non-coding RNA in the pathogenesis of acute kidney injury].

Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.

Recovery of brain DHA-containing phosphatidylserine and ethanolamine plasmalogen after dietary DHA-enriched phosphatidylcholine and phosphatidylserine in SAMP8 mice fed with high-fat diet.

BACKGROUND: Glycerophospholipids were the main components of cerebral cortex lipids, and there was a close association between lipid homeostasis and human health. It has been reported that dietary DHA-enriched phosphatidylcholine (DHA-PC) and phosphatidylserine (DHA-PS) could improve brain function. However, it was unclear that whether supplementation of DHA-PC and DHA-PS could change lipid profiles in the brain of dementia animals. METHODS: SAMP8 mice was fed with different diet patterns for 2 months, including high-fat diet and low-fat diet. After intervention with DHA-PC and DHA-PS for another 2 months, the lipid profile in cerebral cortex was determined by lipidomics in dementia mice. RESULTS: High-fat diet could significantly decrease the levels of DHA-containing PS/pPE, DPA-containing PS, and AA-containing PE, which might exhibit the potential of lipid biomarkers for the prevention and diagnosis of AD. Notably, DHA-PC and DHA-PS remarkably recovered the lipid homeostasis in dementia mice. These might provide a potential novel therapy strategy and direction of dietary intervention for patients with cognitive decline. CONCLUSIONS: DHA-PC and DHA-PS could recover the content of brain DHA-containing PS and pPE in SAMP8 mice fed with high-fat diet.

Lewis Acidic PSbP Pincer Ligand in Pt-Catalyzed 1,6-Enyne Cycloisomerization: A Theoretical Study.

The progressively improved heterobimetallic antimony transition metal complex PSbP-Pt (I1) provides superior activity in catalyzed 1,6-enyne cycloisomerization. Our DFT calculations demonstrate that the noninnocent character of the antimony ligand enhances the self-activation of the catalyst precursor through a substrate-aided intramolecular chloride migration, which triggers subsequent reaction. Designed alternative redox noninnocent active species with strong electron-withdrawing groups also show promising catalytic ability due to an electron-deficient antimony ligand, which lowers the typical reaction barrier for the cycloisomerization of 1,6-enyne.

Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine.

BACKGROUND: Phosphatidylcholine (PC), the major source of dietary choline, has been demonstrated to improve the capability of learning and memory in rodent and the amelioration of long-chain n-3 polyunsaturated fatty acids (PUFA) on anti-aging and anti-oxidation is widely known as well. In this study, three kinds of PC were chose to demonstrate the role of different fatty acids composition on glycerol backbone in improving the brain function of mice induced by scopolamine which was used to impair cholinergic system and cause oxidative stress. METHODS: Male BALB/c mice were randomly divided into 5 groups: model (M) group, control (Con) group, egg yolk lecithin (EL) group, squid PC (SQ-PC) group and sea cucumber PC (SC-PC) group. The intraperitoneal injection of scopolamine hydrobromide (5 mg/kg) was carried out on the 8(th) of group feeding and sustained daily until the end of test. Morris water maze test was used to evaluate the improvement of cognitive decline and the activity of acetylcholinesterase (AchE), superoxide dismutase (SOD) and monoamine oxidase (MAO) and malondialdehyde (MDA) content in brain were measured to assess the physiological changes. RESULTS: In behavior test, the latency of PC groups was significantly reduced, while number of crossing the platform and time in target quadrant were increased in comparison with M group and the improvements of SQ-PC and SC-PC were better than that of EL (P < 0.05). Similar trend was observed in physiological changes. The AchE activity was effectively decreased and the SOD activity increased in hippocampus, cortex and white matter when comparing PC groups with M group. SQ-PC, SC-PC and EL respectively showed 22.82, 28.80 and 11.81 % decrease in MDA level in brain compared with M group. The MAO activity in white matter of SQ-PC, SC-PC and EL group separately depressed 33.05, 33.64 and 19.73 % in comparison with M group. No significance between SQ-PC and SC-PC was found in these indicators except the SOD activity in hippocampus and white matter. SQ-PC group had a higher SOD activity in hippocampus (103.68U/mg · prot.) and lower in white matter (120.57 U/mg · prot.) than SC-PC group (95.53 U/mg · prot. in hippocampus, 134.49 U/mg · prot. in white matter). PC rich in n-3 PUFA acted more ameliorative effects than that barely contained on the indicators above. CONCLUSIONS: Different fatty acids composition of PC all could diminish the cognitive decline and biological damage and protect the brain. EPA and DHA partly enhaced to the advantageous effects.

Prognostic value of grading masticator space involvement in nasopharyngeal carcinoma according to MR imaging findings.

PURPOSE: To derive a suitable method for grading masticator space invasion in nasopharyngeal carcinoma on the basis of magnetic resonance (MR) images and to determine its prognostic value in patients undergoing intensity-modulated radiation therapy. MATERIALS AND METHODS: After institutional review board approval and informed consent were acquired, 808 patients with nasopharyngeal carcinoma who were treated with definitive intensity-modulated radiation therapy were analyzed retrospectively. The anatomic sites of masticator space involvement were identified with MR imaging. Overall survival, local relapse-free survival, and distant metastasis-free survival were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. Potential prognostic factors were identified by means of multivariate analysis. RESULTS: Masticator space involvement was diagnosed in 163 of 808 patients (20.2%). Patients with lateral invasion (involvement of the lateral pterygoid muscle of the masticator space and beyond) had significantly poorer overall survival and distant metastasis-free survival than those with medial invasion (involvement of the medial pterygoid muscle of the masticator space) (P = .035 and P = .026, respectively). Furthermore, their overall survival, local relapse-free survival, and distant metastasis-free survival were significantly poorer compared with patients with stage T2 or T3 disease (all P ≤ .023) but similar to patients with stage T4 disease. The grade of masticator space involvement was an independent prognostic factor for overall survival, local relapse-free survival, and distant metastasis-free survival (all P ≤ .023). CONCLUSION: Masticator space involvement in nasopharyngeal carcinoma should be graded as medial (stage T2 disease) or lateral (stage T4 disease). This can facilitate staging of nasopharyngeal carcinoma and may be a suitable prognostic indicator of survival.

Effects of Dietary Supplementation with EPA-enriched Phosphatidylcholine and Phosphatidylethanolamine on Glycerophospholipid Profile in Cerebral Cortex of SAMP8 Mice fed with High-fat Diet.

The destruction of lipid homeostasis is associated with nervous system diseases such as Alzheimer's disease (AD). It has been reported that dietary EPA-enriched phosphatidylcholine (EPA-PC) and phosphatidylethanolamine (EPA-PE) could improve brain function. However, it was unclear that whether EPA-PC and EPA-PE intervention could change the lipid composition of cerebral cortex in AD mice. All the senescence-accelerated mouse-prone 8 (SAMP8) mice were fed with a high-fat diet for 8 weeks. After another 8 weeks of intervention with EPA-PC and EPA-PE (1%, w/w), the cerebral cortex lipid levels were determined by lipidomics. Results demonstrated that dietary supplementation with EPA-PE and EPA PC for 8 weeks significantly increased the amount of choline plasmalogen (pPC) and Lyso phosphatidylethanolamine (LPE) in the cerebral cortex of SAMP8 mice fed with high fat diet. Meanwhile, administration with EPA-PE and EPA-PC could significantly decrease the level of docosapentaenoic acid (DPA)-containing phosphatidylserine (PS) as well as increase the levels of arachidonic acid (AA)-containing phosphatidylethanolamine and PS in cerebral cortex. EPA-PE and EPA-PC could restore the lipid homeostasis of dementia mice to a certain degree, which might provide a potential novel therapy strategy and direction of dietary intervention in patients with cognitive impairment.

Establishment and characterization of a lactating bovine mammary epithelial cell model for the study of milk synthesis.

This study sought to establish an in vitro lactating BMEC (bovine mammary epithelial cell) model, which may maintain the native function for a period of time. Mammary tissues of midlactation Holstein dairy cows were dispersed and cultured in a medium containing insulin, prolactin, hydrocortisone, transferrin, epidermal growth factor and fetal calf serum. After the cells migrating from the tissue reached approximately 80% of confluency, the tissues were removed, and secretory epithelial cells were enriched by digesting with 0.25% trypsin repeatedly to remove fibroblasts. The BMEC cells plated on plastic dishes displayed a monolayer, cobblestone, epithelial-like morphology and formed alveoli-like structures and island monolayer aggregates which are the typical characteristics of the mammary epithelial cells. The isolated cells were identified as of epithelial origin by staining with antibody against cytokeratin 18. A one-half logarithmically growth curve and abundant microvilli and cytoplasmic lipid droplets were observed in these cells. The transcription of the alphas1 casein gene and synthesis of alphas caseins were also detected in the model. Thus, our lactating BMEC model can be an effective model in vitro for studies of milk synthesis in the bovine mammary gland.

Enantioselective hydrosilylation of unsaturated carbon-heteroatom bonds (C[double bond, length as m-dash]N, C[double bond, length as m-dash]O) catalyzed by [Ru-S] complexes: a theoretical study.

A detailed theoretical study on the mechanism of enanthioselective hydrosilylation of imines and ketones catalyzed by the ruthenium(ii) thiolate catalyst [Ru-S] ([L*-Ru(SDmp)]+[BAr4 F]-) with a chiral monodentate phosphine ligand is carried out in this work. We elucidate all the pathways leading to the main products or by products mediated by the [Ru-S] complex in order to have deep understanding of the chemoselectivity and enantioselectivity. The DFT (Density Functional Theory) calculations show that the reaction mechanism including: (1) Si-H bond cleavage by the dual activity of Ru-S bond; (2) the generation of a sulfur-stabilized silane cation; (3) the electrophilic attack of silane cation to N[double bond, length as m-dash]C/O[double bond, length as m-dash]C; (4) hydrogen transfer from Ru to carbon cation. The hydrosilylation products are found to be the final products rather than the dehydrogenative ones, which is consistent with the experimental results. The dehydrogenative silylation reaction pathways which give N- or O-silylated enamine/enol ether are reversible according to our calculations. The computational results also show that the electrophilic attack of silicon to N[double bond, length as m-dash]C/O[double bond, length as m-dash]C is the rate-determining step and the ee value can be improved significantly with more bulky model phosphine ligand based on the same calculation methods.

Chlorophyll-Based Near-Infrared Fluorescent Nanocomposites: Preparation and Optical Properties.

Near-infrared (NIR) fluorescence has attracted much attention in biomedical fields because it offers deep tissue penetration and high spatial resolution. Herein, a method is developed for the preparation of NIR fluorescent nanocomposites (NCs) by encapsulating natural chlorophyll (Chl) into the micelles of octylamine-modified poly(acrylic acid) (OPA). Both femtosecond transient absorption spectra and isothermal titration calorimetry thermogram reveal that the micelles of OPA provide a hydrophobic environment for the improved fluorescence efficiency. Hence the resulted Chl NCs possess unique properties such as ultrasmall size, outstanding photostability, good biocompatibility, and superbright NIR fluorescence emission. In vivo imaging of sentinel lymph node is achieved in nude mice, demonstrating the potential of Chl NCs in biomedical applications. This work provides a new strategy for the preparation of highly biocompatible NIR fluorescence labeling nanocomposites.

Toonasindiynes A-F, new polyacetylenes from Toona sinensis with cytotoxic and anti-inflammatory activities.

The plants of genus Toona are well known for diverse limonoid secondary metabolites, while polyacetylenes are rarely found from Toona species. In this work, six new polyacetylenes toonasindiynes A-F (1-6) and six known analogues (7-12) were isolated from the root bark of Toona sinensis. Their structures and absolute configurations were elucidated by HRESIMS, 1D and 2D NMR spectroscopic analysis, modified Mosher's method, and biosynthetic consideration. These polyacetylenes share the same 4,6-diyne moiety with different side chain length and different oxidation degree. Bioactivity screening revealed the cytotoxic activity of 3, 5, 9, and 11 against U2OS cells, and the inhibitory effects on nitric oxide (NO) production of 1, 2, 5, 8, 9, and 11 in lipopolysaccharide-induced RAW 264.7 cells.

Comparative studies of DHA-enriched phosphatidylcholine and recombination of DHA-ethyl ester with egg phosphatidylcholine on ameliorating memory and cognitive deficiency in SAMP8 mice.

Docosahexaenoic acid-enriched phospholipids (DHA-PLs) are important bioactive components from marine foods, and are barely obtained by people living inland due to limited sources of commercial DHA-PLs compared to commercial DHA-TG and DHA-EE fish oil. Therefore, it is of significance to develop substitutions of DHA-PLs. In the present study, we comparatively investigated the effects of DHA-phosphatidylcholine (PC) and the recombination of DHA-ethyl ester (EE) with egg PC on improving the dysfunction of memory and cognition in senescence-accelerated prone 8 (SAMP8) mice and illustrated the possible underlying mechanisms. Results showed that DHA-PC exhibited stronger effects than the recombination of DHA-EE with egg PC on improving the dysfunction of memory and cognition via suppressing Aß generation, neuro-inflammation and apoptosis, and improving neurotrophins. These findings suggested that DHA-PLs (DHA-PC) could not be substituted by the recombination of commercial fish oil with DHA-free PC in alleviating age-related memory loss and cognitive deficiency in SAMP8 mice, which provided a reference for the prevention and treatment of neurodegenerative diseases.

Mechanisms of DHA-enriched phospholipids in improving cognitive deficits in aged SAMP8 mice with high-fat diet.

Recent studies have shown that a high-fat diet (HFD) is involved in both metabolic dysfunction and cognitive deficiency and that docosahexaenoic-acid-enriched phospholipids (DHA-PLs) have beneficial effects on obesity and cognitive impairment. However, there are only a few studies comparing differences between DHA-PC and DHA-PS in HFD-induced Alzheimer's disease (AD) models. After 8 weeks feeding with HFD, 10-month-old SAMP8 mice were fed with 1% (w/w) DHA-PC or 1% DHA-PS (biosynthesized from DHA-PC) for 8 weeks; we then tested the behavioral performances in the Barnes maze test and Morris maze test. The changes of the generation and accumulation of Aß, oxidative stress, apoptosis, neuroinflammation and neurotrophic factors were also measured. The results indicated that both DHA-PC and DHA-PS significantly improved the metabolic disorders and cognitive deficits. Both DHA-PC and DHA-PS could ameliorate oxidative stress, and DHA-PS presented more notable benefits than DHA-PC on Aß pathology, mitochondrial damage, neuroinflammation and neurotrophic factors; DHA-PS was for the first time found to increase the production of insoluble Aß (less pathogenic) in this AD model. These data suggest that DHA-PLs can significantly improve cognitive deficiency, and the molecular mechanisms for this closely relate to the phospholipid polar groups.

Comparative Study of Different Polar Groups of EPA-Enriched Phospholipids on Ameliorating Memory Loss and Cognitive Deficiency in Aged SAMP8 Mice.

SCOPE: Recent studies have shown that omega-3 PUFAs enriched phospholipids (n-3 PUFA-PLs) have beneficial effects on memory and cognition. However, most reports only attribute the benefit to docosahexaenoic acid (DHA) and pay little attention to eicosapentaenoic acid (EPA). METHODS AND RESULTS: We investigate the effect of EPA-enriched phospholipids on cognitive deficiency in senescence-accelerated prone 8 (SAMP8) mouse. Ten-month-old SAMP8 mice are fed with 2% (w/w) EPA-enriched phosphatidylcholine/phosphatidyl ethanolamine (EPA-PC/PE; EPA:DHA = 46.8:3.01) or 2% EPA-enriched phosphatidylserine (EPA-PS; biosynthesized from EPA-PC/PE) for 8 weeks; we then test the behavioral performances in the Barnes maze test and Morris maze test; the changes of oxidative stress, apoptosis, neurotrophic factors, tau phosphorylation, and Aß pathology are also measured. The results of behavior tests indicate that both EPA-PC/PE and EPA-PS significantly improve memory and cognitive deficiency. It is found that remarkable amelioration of oxidative stress and apoptosis occurs in both EPA-PC/PE and EPA-PS groups. EPA-PS shows more ameliorative effects than EPA-PC/PE on neurotrophic activity by decreasing hyper-phosphorylation of tau and depressing the generation and accumulation of ß-amyloid peptide (Aß). CONCLUSION: These data suggest that EPA-PS exhibits better effects than EPA-PC/PE on ameliorating memory and cognitive function, which might be attributed to the phospholipid polar groups.

Visible-Light-Driven Hydrogen Production and Polymerization using Triarylboron-Functionalized Iridium(III) Complexes.

The development of novel iridium(III) complexes has continued as an important area of research owing to their highly tunable photophysical properties and versatile applications. In this report, three heteroleptic dimesitylboron-containing iridium(III) complexes, [Ir(p-B-ppy)2 (N^N)]+ {p-B-ppy=2-(4-dimesitylborylphenyl)pyridine; N^N=dipyrido[3,2-a:2',3'-c]phenazine (dppz) (1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (2), and 1,10-phenanthroline (phen) (3)}, were prepared and fully characterized electrochemically, photophysically, and computationally. Altering the conjugated length of the N^N ligands allowed us to tailor the photophysical properties of these complexes, especially their luminescence wavelength, which could be adjusted from λ=583 to 631 nm in CH2 Cl2 . All three complexes were evaluated as visible-light-absorbing sensitizers for the photogeneration of hydrogen from water and as photocatalysts for the photopolymerization of methyl methacrylate. The results showed that all of them were active in both photochemical reactions. High activity for the photosensitizer (over 1158 turnover numbers with 1) was observed, and the system generated hydrogen even after 20 h. Additionally, poly(methyl methacrylate) with a relatively narrow molecular-weight distribution was obtained if an initiator (i.e., ethyl α-bromophenylacetate) was used. The living character of the photoinduced polymerization was confirmed on the basis of successful chain-extension experiments.

Anti-inflammatory activity of Khayandirobilide A from Khaya senegalensis via NF-κB, AP-1 and p38 MAPK/Nrf2/HO-1 signaling pathways in lipopolysaccharide-stimulated RAW 264.7 and BV-2 cells.

BACKGROUND: Immunocytes-involved inflammation is considered to modulate the damage in various diseases. Herein, novel therapeutics suppressing over-activation of immunocytes could prove an effective strategy to prevent inflammation-related diseases. PURPOSE: The objective of this study is to evaluate the anti-inflammatory activity of Khayandirobilide A (KLA), a new andirobin-type limonoid with modified furan ring isolated from the Khaya senegalensis (Desr.) A. Juss., and to explore its potential underlying mechanisms in LPS-stimulated inflammatory models. METHODS: The structure of KLA was elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS. As for its anti-inflammatory effect, the production of pro-inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 and BV-2 cells were measured by Griess reagent, ELISA and qRT-PCR. The relevant proteins including nuclear factor κB (NF-κB), p-AKT, p-p38 and Nrf2/HO-1 were investigated by western blot. Nuclear localisations of NF-κB, activator protein-1 (AP-1) and Nrf2 were also examined by western blot and immunofluorescence. RESULTS: KLA could inhibit the production of LPS-induced NO with IC50 values of 5.04 ±â€¯0.14 µM and 4.97 ±â€¯0.5 µM in RAW 264.7 and BV-2 cells, respectively. KLA also attenuated interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels. Further mechanistic studies demonstrated the activation of NF-κB and AP-1 were reduced by KLA. Moreover, KLA elevated expression of heme oxygenase-1(HO-1) via inducing Keap1 autophagic degradation and promoting Nrf2 nuclear translocation. Despite KLA induced the phosphorylation of mitogen-activated protein kinases (MAPKs) family, inhibiting the phosphorylation of p38 by its specific inhibitor SB203580 attenuated the degradation of KLA-induced Keap1, and then reduced KLA-induced Nrf2 nuclear translocation and HO-1 expression. Furthermore, SB203580, Brusatol (a Nrf2 specific inhibitor) and ZnPP (a HO-1 specific inhibitor) could partly reverse the suppressive effects of KLA on LPS-induced NO production and mRNA levels of pro-inflammatory genes. CONCLUSION: These data displayed that KLA possessed anti-inflammatory activity, which was attributed to inhibit the release of LPS-stimulated inflammatory mediators via suppressing the activation of NF-κB, AP-1, and upregulating the induction of p38 MAPK/Nrf2-mediated HO-1.

Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo.

BACKGROUND: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (ß5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. METHODS: In this study, we investigated the role of ß5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo. RESULTS: We showed that 6-OHDA upregulated ß5i expression in DA neurons in a concentration- and time-dependent manner. Inhibition and downregulation of ß5i induced the expression of glucose-regulated protein (Bip) and exacerbated 6-OHDA neurotoxicity in DA neurons. The inhibition of ß5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA. ß5i also activated transporter associated with antigen processing 1 (TAP1) and promoted MHC-I expression on DA neurons. CONCLUSION: Taken together, our data suggest that ß5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.

The Anti-inflammatory Activities of Two Major Withanolides from Physalis minima Via Acting on NF-κB, STAT3, and HO-1 in LPS-Stimulated RAW264.7 Cells.

Physalis minima has been traditionally used as a folk herbal medicine in China for the treatment of many inflammatory diseases. However, little is known about its anti-inflammatory constituents and associated molecular mechanisms. In our study, withaphysalin A (WA) and 2, 3-dihydro-withaphysalin C (WC), two major withanolide-type compounds, were obtained from the anti-inflammatory fraction of P. minima. Both WA and WC significantly inhibited the production of nitrite oxide (NO), prostaglandin E2 (PGE2), and several pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Further research indicated that they downregulated the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, they also suppressed nuclear translocation of NF-κB p65, phosphorylation of STAT3, and upregulated HO-1 expression. Intriguingly, the activation of MAPKs was suppressed by WA but was not altered by WC. Taken together, these data provide scientific evidence for elucidating the major bioactive constituents and related molecular mechanisms for the traditional use of P. minima and suggest that WA and WC can be attractive therapeutic candidates for various inflammatory diseases.

Walrobsins A and B, Two Anti-inflammatory Limonoids from Root Barks of Walsura robusta.

Walrobsins A (1) and B (2), two limonoids featuring an unprecedented 5-oxatricyclo[5.4.11,4]hendecane ring system, were isolated from the root barks of Walsura robusta. Their structures, including their absolute configurations, were determined by analyses of HR-ESIMS, 1D/2D NMR, and X-ray crystallography. Compounds 1 and 2 possessed a stable hemiketal structure formed between the OH-11 and 3-carbonyl group in the hexatomic oxoheterocyclic ring. Compound 1 showed significant anti-inflammatory activity with an IC50 value of 7.8 µM and inhibited the expression of iNOS and IL-1ß in a dose-dependent manner.

Anti-proliferation of triple-negative breast cancer cells with physagulide P: ROS/JNK signaling pathway induces apoptosis and autophagic cell death.

Physagulide P (PP), a new natural compound, was isolated from Physalis angulate L. in our laboratory. In this study, we demonstrated that PP potently suppressed cell proliferation by inducing G2/M phase arrest in MDA-MB-231 and MDA-MB-468 cells. Moreover, PP provoked apoptosis by decreasing the mitochondrial membrane potential and elevating the Bax/Bcl-2 protein expression ratio. The caspase inhibitor Z-VAD-FMK partly restore cell viability, suggesting that apoptosis plays as an important role in the anti-proliferative effect of PP. PP-treated cells also underwent autophagy, as evidenced by the formation of autophagosomes and the accumulation of LC3BII. Furthermore, the knockdown of LC3B reduced PP-induced cytotoxicity, indicating that autophagy played an anticancer effect. PP also induced the generation of reactive oxygen species (ROS) and resulted in c-Jun N-terminal kinases (JNK) activation. Accordingly, JNK siRNA significantly attenuated PP-triggered apoptosis and autophagy, and ROS scavengers almost completely reverse this apoptosis and autophagy. The ROS scavenger also blocked PP-induced G2/M phase arrest and the phosphorylation of JNK. Our results revealed that PP induced G2/M phase arrest, apoptosis and autophagy via the ROS/JNK signaling pathway in MDA-MB-231 and MDA-MB-468 cells. Therefore, PP is a promising candidate for the development of antitumor drugs for the treatment of triple-negative breast cancer.