Unconventional hcp/fcc Nickel Heteronanocrystal with Asymmetric Convex Sites Boosts Hydrogen Oxidation.

Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H2O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mgNi -1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites.

Enhanced Mitophagy in Cholesteatoma Epithelial Cells.

HYPOTHESIS: Mitophagy may have a potential role in the pathogenesis of acquired cholesteatoma. BACKGROUND: Enhanced mitophagy has been proven to be involved in various cancers. However, its role in the pathogenesis of cholesteatoma, which shares some common features with cancer, is controversial. This study investigated mitophagy in cholesteatoma epithelial cells. METHODS: The autophagy protein markers LC3-II and p62 and mitophagy proteins BNIP3, Parkin, and PINK1 were analyzed in cholesteatoma epithelial cells and external auditory canal epithelium cells by immunoblotting. The results were confirmed by immunohistochemistry. Adenovirus Ad-mCherry-GFP-LC3B and Ad-GFP-LC3B were used to evaluate autophagic activity. Transmission electron microscopy was used to observe and analyze autophagosomes. RESULTS: LC3-II expression was increased in cholesteatoma cells, whereas soluble and insoluble p62 levels were decreased. The expressions of BNIP3, Parkin, and PINK1 were higher in total protein and mitochondrial protein of cholesteatoma cells compared with normal external auditory canal epithelium cells. Autophagic activity was increased in cholesteatoma cells compared with normal external auditory canal epithelium cells. CONCLUSION: Mitophagy was enhanced in cholesteatoma epithelial cells and may have a potential role in the pathogenesis of acquired cholesteatoma.

A serum metabolomics study based on LC-MS: Chemosensitization effects of Rauvolfia vomitoria Afzel. combined with 5- fluorouracil on colorectal cancer mice.

Colorectal cancer (CRC) is one of the malignant tumors with high incidence, and is mainly treated by chemotherapy at present. However, during CRC treatment, long-term use of traditional chemotherapeutic drugs will reduce the sensitivity of chemotherapy. Our previous studies have shown that Rauvolfia vomitoria total alkaloids (RVA) played an important role in 5-fluorouracil (5-FU) chemosensitization in CRC therapy, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, LC-MS based metabolomics was employed to explore the mechanism of 5-FU chemosensitization in CRC induced by the combination of RVA and conventional chemotherapeutic with 5-FU. The results showed that the final tumor weight of the high-dose combined group was significantly different from that of the 5-FU alone group. To evaluate the chemosensitization effects of RVA, serum samples collected from six groups (six mice in each group) with different administration methods were analyzed by HPLC-Q-Exactive Orbitrap/MS. After multivariate statistical analysis and metabolites identification, 25 different metabolites were identified between the 5-FU treatment group and combined high-dose treatment group, among which lipid and fatty acid metabolism pathways were mostly affected. These results suggest that RVA may sensitize traditional chemotherapeutic drug 5-FU and exert anti-tumor activity through influencing lipid metabolism and cell energy metabolism. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine in treating colorectal cancer.

Identification of chemosensitizing agents of colorectal cancer in Rauvolfia vomitoria using an NMR-based chemometric approach.

Searching for new adjuvants of conventional chemotherapeutic approaches against colorectal cancer cells is extremely urgent. In current research, a non-targeted analytical approach was established by combining proton nuclear magnetic resonance spectroscopy with a chemometrics data mining tool to identify chemosensitizing agents from Rauvolfia vomitoria. This approach enabled the identification of potential active constituents in the initial fractionation process and provided their structural information. This strategy was validated by its application to Rauvolfia vomitoria extract exhibiting chemosensitizing activity on 5-fluorouracil against colorectal cancer cells. After the workflow, the biochemometrics analysis showed that at least 15 signals (Variable influence on projection (VIP) > 1) could have contributions in the differentiation of various fractions. Through systematic literature and database searches, we found that the most active fraction (fraction 7) exhibited the highest presence of sabazin-type and armaniline-type alkaloids, which were potential chemosensitizers as previously reported. To validate the results of the strategy, the effect of 5-FU and compounds isolated from fraction seven incubation on HCT-8 and LoVo cell vialibilty were evaluated. These results evidenced that compound ß-carboline (3), 1-methyl-ß-carboline (4), and lochnerine (6) could enhance the cytotoxicity of 5-fluorouracil against to Colorectal cancer cells. Besides, 21 compounds including two new compounds were isolated from Rauvolfia vomitoria. The experimental results verify the reliability of the method, and this approach provides a new and efficient tool to overcome some of the bottlenecks in natural products drug discovery.

Relationship between Tumor Infiltrating Immune Cells and Tumor Metastasis and Its Prognostic Value in Cancer.

Tumor metastasis is an important reason for the difficulty of tumor treatment. Besides the tumor cells themselves, the tumor microenvironment plays an important role in the process of tumor metastasis. Tumor infiltrating immune cells (TIICs) are one of the main components of TME and plays an important role in every link of tumor metastasis. This article mainly reviews the role of tumor-infiltrating immune cells in epithelial mesenchymal transformation, extracellular matrix remodeling, tumor angiogenesis and formation of pre-metastatic niche. The value of TIICs in the prognosis of cervical cancer, lung cancer and breast cancer was also discussed. We believe that accurate prognosis of cancer treatment outcomes is conducive to further improving treatment regimens, determining personalized treatment strategies, and ultimately achieving successful cancer treatment. This paper elucidates the relationship between tumor and TIICs in order to explore the function of immune cells in different diseases and provide new ideas for the treatment of cancer.

The effect of polysaccharides from Cibotium barometz on enhancing temozolomide-induced glutathione exhausted in human glioblastoma U87 cells, as revealed by 1H NMR metabolomics analysis.

Glioblastoma (GBM) is the most malignant central nervous system tumor, with poor prognosis. Temozolomide (TMZ) has been used as a first-line drug for the treatment of GBM for over a decade, but its treatment benefits are limited by acquired resistance. Polysaccharides from Cibotium barometz (CBPs) are polysaccharides purified from the root of Cibotium barometz (L.) J. Sm., possessing sensitizing activity. The purpose of this study was to investigate the anti-cancer effect of CBP from different processing methods on U87 cells using a 1H NMR-based metabolic approach, complemented with qRT-PCR and flow cytometry, to identify potential markers and discover the targets to explore the underlying mechanism. Cibotium barometz is usually processed under sand heating in clinical applications. Polysaccharides from both the processed (PCBP) and raw (RCBP) C. barometz were prepared, and the effect on enhancing the sensitivity to TMZ was investigated in vitro. CBP can significantly increase the toxicity of TMZ to the U87 cell line, promote apoptosis, enhance cell cycle changes, and arrest cells in S phase, and RCBP demonstrated better activity. Multivariate statistical analyses, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA), were used to identify metabolic biomarkers, and 12 metabolites in the cell extract samples were clearly identified as altered after RCBP exposure. NMR-based cell metabolomics provided a holistic method for the identification of CBP's apoptosis-enhancing mechanisms and the exploration of its potential applications in preclinical and clinical studies.

4ß-Hydroxywithanolide E from Goldenberry (Whole Fruits of Physalis peruviana L.) as a Promising Agent against Chronic Obstructive Pulmonary Disease.

Environmental toxicant- and oxidant-induced [e.g., cigarette smoke (CS)] respiratory oxidative stress and inflammatory response play a vital role in the onset and progression of COPD. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents an important mechanism for regulating intracellular oxidative stress and inflammatory response and is a promising target for developing agents against COPD. Herein, a bioactivity-guided purification of goldenberry (whole fruits of Physalis peruviana L.) led to the isolation of a novel and potent Nrf2 activator 4ß-hydroxywithanolide E (4ß-HWE). Our study indicated that (i) 4ß-HWE activated the Nrf2-mediated defensive response through interrupting Nrf2-Keap1 protein-protein interaction (PPI) via modification of Cys151 and Cys288 cysteine residues in Keap1 and accordingly suppressing the ubiquitination of Nrf2. (ii) 4ß-HWE enhanced intracellular antioxidant capacity and inhibited oxidative stress in normal human lung epithelial Beas-2B cells and wild-type AB zebrafish. (iii) 4ß-HWE blocked LPS-stimulated inflammatory response and inhibited LPS-stimulated NF-κB activation in RAW 264.7 murine macrophages. (iv) 4ß-HWE effectively suppressed oxidative stress and inflammatory response in a CS-induced mice model of pulmonary injury. Collectively, these results display the feasibility of using 4ß-HWE to prevent or alleviate the pathological progression of COPD and suggest that 4ß-HWE is a candidate or a leading molecule against COPD.

Trans-4,4'-dihydroxystilbene ameliorates cigarette smoke-induced progression of chronic obstructive pulmonary disease via inhibiting oxidative stress and inflammatory response.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease resulted from airflow obstructions, and there is a driving requirement for novel and effective preventive and therapeutic agents of COPD. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been regarded to be a promising therapeutic target for COPD. Resveratrol is a natural Nrf2 activator with antioxidant and anti-inflammatory properties, however, its application is limited by its relative low efficiency and poor bioavailability. Herein, based on the skeleton of resveratrol, trans-4,4'-dihydroxystilbene (DHS) has been firstly identified to be an Nrf2 activator, which is more potent than the well-known sulforaphane (SF) and resveratrol. Our results indicate that DHS blocks Nrf2 ubiquitylation through specifically reacting with Cys151 cysteine in Keap1 protein to activate Nrf2-regulated defensive response, and thus enhances intracellular antioxidant capability. Furthermore, DHS relieves lipopolysaccharide (LPS)-stimulated inflammatory response via inhibition of NF-κB. Importantly, DHS significantly ameliorates pathological alterations (e.g. infiltration of leukocytes and fibrosis), downregulates the levels of oxidant biomarkers malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'-deoxyguanosin (8-oxo-dG), and inhibits the overproductions of inflammatory mediators [e.g. tumor necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9)] in a cigarette smoke (CS)-induced pulmonary impairment mice model. Taken together, this study demonstrates that DHS attenuates the CS-induced pulmonary impairments through inhibitions of oxidative stress and inflammatory response targeting Nrf2 and NF-κB in vitro and in vivo, and could be developed into a preventive agent against pulmonary impairments induced by CS.

An isopentenyl-substituted flavonoid norartocarpin activates Nrf2 signalling pathway and prevents oxidative insults in human lung epithelial cells.

The nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in regulating the intracellular oxidative stress, and thus activation of Nrf2 by nature-derived molecules effectively alleviates the pathological process of oxidative stress-induced chronic diseases. The isopentenyl-substituted flavonoid norartocarpin (NOR) induced the activity of NAD(P)H: quinone reductase (QR), implying that it might be a potential Nrf2 activator. Further studies indicated that NOR upregulated the protein levels of Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (GCLM) through facilitating the nuclear translocation of Nrf2 and enhancing Nrf2 protein stability. NOR-induced activation of Nrf2 pathway was associated with multiple upstream kinases, including mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), protein kinase C (PKC), and protein kinase R-like endoplasmic reticulum kinase (PERK). Moreover, NOR protected human lung epithelial Beas-2B cells against sodium arsenite [As(III)]-induced cytotoxicity in an Nrf2-dependent manner. Collectively, NOR was firstly identified to be an Nrf2 activator, which demonstrated the capability of preventing oxidative insults in human lung epithelial cells.

Ingredients from Litsea garrettii as Potential Preventive Agents against Oxidative Insult and Inflammatory Response.

Oxidative stress and inflammation undoubtedly contribute to the pathogenesis of many human diseases. The nuclear transcription factor erythroid 2-related factor (Nrf2) and the nuclear factor κB (NF-κB) play central roles in regulation of oxidative stress and inflammation and thus are targets for developing agents against oxidative stress- and inflammation-related diseases. Our previous study indicated that the EtOH extract of Litsea garrettii protected human bronchial epithelial cells against oxidative insult via the activation of Nrf2. In the present study, a systemic phytochemical investigation of L. garrettii led to the isolation of twenty-one chemical ingredients, which were further evaluated for their inhibitions on oxidative stress and inflammation using NAD(P)H:quinone reductase (QR) assay and nitric oxide (NO) production assay. Of these ingredients, 3-methoxy-5-pentyl-phenol (MPP, 5) was identified as an Nrf2 activator and an NF-κB inhibitor. Further studies demonstrated the following: (i) MPP upregulated the protein levels of Nrf2, NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase regulatory subunit (GCLM); enhanced the nuclear translocation and stabilization of Nrf2; and inhibited arsenic [As(III)]-induced oxidative insult in normal human lung epithelial Beas-2B cells. And (ii) MPP suppressed the nuclear translocation of NF-κB p65 subunit; inhibited the lipopolysaccharide- (LPS-) stimulated increases of NF-κB p65 subunit, COX-2, iNOS, TNF-α, and IL-1ß; and blocked the LPS-induced biodegrade of IκB-α in RAW 264.7 murine macrophages. Taken together, MPP displayed potential preventive effects against inflammation- and oxidative stress-related diseases.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) participates in anti-lipopolysaccharide factors (ALFs) gene expression in mud crab.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a key cytoplasm signal adaptor that mediates signals activated by tumor necrosis factor receptor (TNFR) superfamily and the Interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily. The full-length 2492 bp TRAF6 (Sp-TRAF6) from Scylla paramamosain contains 1800 bp of open reading frame (ORF) encoding 598 amino acids, including an N-terminal RING-type zinc finger, two TRAF-type zinc fingers and a conserved C-terminal meprin and TRAF homology (MATH) domain. Multiple alignment analysis shows that the putative amino acid sequence of Sp-TRAf6 has highest identity of 88% with Pt-TRAF6 from Portunus trituberculatus, while the similarity of Sp-TRAF6 with other crustacean sequences was 54-55%. RT-PCR analysis indicated that Sp-TRAF6 transcripts were predominantly expressed in the hepatopancreas and stomach, whereas it was barely detected in the heart and hemocytes in our study. Moreover, Sp-TRAF6 transcripts were significantly up-regulated after Vibrio parahemolyticus and LPS challenges. RNA interference assay was carried out used by siRNA to investigate the genes expression patterns regulated by Sp-TRAF6. The qRT-PCR results showed that silencing Sp-TRAF6 gene could inhibit SpALF1, SpALF2, SpALF5 and SpALF6 expression in hemocytes, while inhibit SpALF1, SpALF3, SpALF4, SpALF5 and SpALF6 expression in hepatopancreas. Taken together, the acute-phase response to immune challenges and the inhibition of SpALFs gene expression indicate that Sp-TRAF6 plays an important role in host defense against pathogen invasions via regulation of ALF gene expression in S. paramamosain.

In Vivo and In Vitro Inhibitory Effects of Icariin on Angiogenesis.

OBJECTIVE: To investigate the inhibitory effects of icariin(ICA),an active ingredient of Herb Epimedii,on angiogenesis. METHODS: The chick chorioallantoic membrane(CAM)assay was adopted to evaluate the effects of various doses of the ICA on the angiogenesis. The cell growth inhibitory effect of ICA on human umbilical vein endothelial cells(HUVEC)was measured by MTT assay. Cell cycle arrest and the induction of apoptosis were evaluated by flow cytometry. The effect of ICA on the migration of HUVEC cells was measured on Transwell model. RESULTS: ICA remarkably inhibited angiogenesis in CAM in a concentration-dependent manner. The proliferation of HUVEC cells was inhibited by ICA, and the effect was time-and concentration-dependent. ICA-treated HUVEC cells showed cell cycle arrest;180 µg/ml of ICA decreased the percentage of migrating HUVEC cells by 78.0%. CONCLUSION: ICA can effectively suppress angiogenesis;however,its in vivo inhibitory effect on angiogenesis warrants further investigations.

Scapaundulin C, a novel labdane diterpenoid isolated from Chinese liverwort Scapania undulate, inhibits acetylcholinesterase activity.

In the present study, scapaundulin C (1), a new labdane diterpenoid, and four related known compounds scapaundulin A (2), 5α, 8α, 9α-trihydroxy-13E-labden-12-one (3), 5α, 8α-dihydroxy-13E-labden-12-one (4), and (13S)-15-hydroxylabd-8 (17)-en-19-oic acid (5), were isolated from the Chinese liverwort Scapania undulate (L.) Dum., using column chromatography. The structures of these compounds were determined on the basis of 1D- and 2D-NMR analyses. The acetylcholinesterase (AchE) inhibitory activity was evaluated using a bioautographic TLC assay and the cytotoxic activity was evaluated by the MTT method. All the compounds were reported for the first time to exhibit moderate AchE inhibitory activity with minimal inhibitory quantities ranging from 250 to 500 ng. All the compounds were tested for their cytotoxicity against five human tumor cell lines, A549, K562, A2780, Hela, and HT29, and compounds 3 and 4 exhibited moderate inhibitory effects on the growth of A2780 cells.

Diterpenoids from the Chinese liverwort Heteroscyphus tener and their antiproliferative effects.

Four new ent-labdane diterpenoids, heteroscyphins A-D (1-4), and four known diterpenoids (5-8) were isolated from the Chinese liverwort Heteroscyphus tener (Steph.) Schiffn. The absolute configuration of compound 1 was defined by single-crystal X-ray diffraction using Cu Kα radiation. Cytotoxicity tests revealed that compounds 3 and 5 exhibited modest activity against seven cancer cell lines. Compound 5 showed inhibitory effects on prostate cancer (PCa) cell proliferation but with less inhibition on non-neoplastic prostate epithelial cells. Compound 5 markedly caused cell growth arrest at the G0/G1 phase and induced cellular apoptosis through ROS-mediated DNA damage in PCa cells.

Antiproliferative activities of Garcinia bracteata extract and its active ingredient, isobractatin, against human tumor cell lines.

In our cell based screening of antitumor ingredients from plants, the EtOH extract of Garcinia bracteata displayed antiproliferative effect against human lung adenocarcinoma A549 cells, human breast cancer MCF-7 cells, and human prostate cancer PC3 cells. Phytochemical investigation of this active extract produced nine ingredients, and their structures were established by analysis of MS and NMR spectra. Antiproliferative evaluation of isolated ingredients on A549, MCF-7 and PC3 cells indicated that a xanthone named isobractatin (1) exhibited potent antiproliferative activity against the above three human cancer cell lines with IC50 values ranging from 2.90 to 4.15 µM. Treatment of PC3 cells with 1 led to an enhancement of the cell apoptosis, and arrested cell cycle in the G0/G1 phase. The G0/G1 phase cycle-related proteins analysis showed that the expressions of cyclins D1 and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activations of Bax, caspases 3 and 9, and by inhibition of Bcl-2. Our combined data illustrated that isobractatin (1) was the antiproliferative ingredient of G. bracteata against three human cancer cell lines, which exerted its antiproliferatrive effect via cell cycle arrest and induction of apoptosis.

Cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia balansae.

Ten new clerodane diterpenoids (1-10), caseabalansins A-G, 18-epicaseabalansin A, 2-epicaseabalansin B, and 2-epicaseabalansin C, one new triterpenoid, balansinone (11), and seven known diterpenoids (12-18) were obtained from the leaves and twigs of Casearia balansae. Compounds 1 and 2 are the first examples of clerodane diterpenoids with an oxygen bridge between C-2 and C-19, and compounds 5-7 are three new diterpenoid artifacts presumably formed during the extraction process. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 11 was verified by single-crystal X-ray crystallographic analysis. Compound 15 showed cytotoxic activity against the tumor cell lines PC3, DU145, SKOV3, and A549 with IC50 values of 4.5, 4.3, 5.1, and 5.7 µM, respectively. Compounds 1a, 2a, and 4 showed selective activity against PC3 tumor cells.

[Corynebacterium aquaticum infection: one case report and literature review].

OBJECTIVE: To study the diagnosis and treatment of Corynebacterium aquaticum infection. METHODS: A retrospective analysis of one case of Corynebacterium aquaticum infection and literature review were conducted. RESULTS: A 39-year old male patient was admitted because of cough, sputum production, fever and right chest pain for 10 days. Broad-spectrum antibiotic therapy had been given in another hospital, but the patient's condition had deteriorated.Nuclear magnetic resonance-guided percutancous transthoracic needle aspiration and lung tissue, pleural fluid and blood culture were performed after admission to our hospital. Corynebacterium aquaticum was grown from the lung tissue, the blood and the pleural effusion. Therefore the diagnosis of Corynebacterium aquaticum pneumonia complicated with pyothorax and septicemia was confirmed. After draining of pleural pus and intravenous vancomycin therapy, the patient recovered and was discharged from hospital. After literature search, we did not find reports on Corynebacterium aquaticum pneumonia complicated with pyothorax and septicemia. CONCLUSIONS: Corynebacterium aquaticum pneumonia complicated with pyothorax and septicemia is rare. The diagnosis could be confirmed by bacterial culture of lung tissue, pleural fluid and blood. Thoracic cavity draining and intravenous vancomycin are effective therapies for the disease.

Bioactive sesquiterpenoids and diterpenoids from the liverwort Bazzania albifolia.

One undescribed 6,7-secofusicoccane-type diterpene, albifolione (1), and one new aromadendrane-type sesquiterpenoid ketone, methyl 2-oxoaromadendra-1(10),3-dien-12-oate (2), along with four known compounds, δ-cuparenol (3), fusicoauritone (4), chiloscyphenols A and B (5 and 6, resp.), were isolated from the liverwort Bazzania albifolia Horik. The structures and relative configurations of 1 and 2 were established unequivocally on the basis of spectroscopic data analysis. Preliminary bioassay revealed that compound 5 showed quite strong cytotoxicity against the human tumor cell line MCF-7, with an IC(50) value of 5.6 µM.

Phenolic compounds with NF-κB inhibitory effects from the fungus Phellinus baumii.

Chemical investigation of the fungus Phellinus baumii has resulted in characterization of five previously undescribed hispidin derivatives, phellibaumins A-E (1-5), as well as two pairs of new non-equivalent epimeric benzyl dihydroflavones, methylphelligrin A (9), epi-methylphelligrin A (10), methylphelligrin B (11), and epi-methylphelligrin B (12), together with five known compounds, interfungin B (6), phelligridin H (7), phelligridimer A (8), phelligrin A (13), and epi-phelligrin A (14). Phellibaumin A (1) was a novel hispidin derivative with a unique 3,4-dihydroxybenzofuran unit. These compounds exhibited NF-κB inhibitory activity with IC(50) values of 52.96 µM (1), 41.40 µM (2), 52.92 µM (5), 36.44 µM (9 and 10), and 22.46 µM (11 and 12), respectively.