Oriental Hornet (Vespa orientalis) Larval Extracts Induce Antiproliferative,Antioxidant, Anti-Inflammatory,and Anti-Migratory Effects on MCF7 Cells

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.     

New chemical constituents from the fruits of Zanthoxylum armatum and its in vitro anti-inflammatory profile

Chemical investigations on the fruits of Zanthoxylum armatum Roxb. (Rutaceae) led to the isolation of two new constituents characterised as 2α-methyl-2β-ethylene-3β-isopropyl-cyclohexan-1β, 3α-diol (1) and phenol-O-β-D-arabinopyranosyl-4′-(3″, 7″, 11″, 15″-tetramethyl)-hexadecan-1″-oate (2) along with known compounds m-methoxy palmityloxy benzene (3), acetyl phenyl acetate (4), linoleiyl-O-α-D-xylopyranoside (5), m-hydroxyphenoxy benzene (6) and palmitic acid (7). The chemical structures were established with the help of physical, chemical and spectroscopic methods. The anti-inflammatory potential of isolated compounds 1 and 2 was evaluated using in vitro target-based anti-inflammatory activity in LPS-stimulated primary peritoneal macrophages isolated from mice. Production of pro-inflammatory cytokines (TNF-α and IL-6) was significantly inhibited by the treatment of isolated compounds 1 and 2 in a dose-dependent manner.     

Anti-inflammatory activity of 4′,6,7-trihydroxy-5-methoxyflavone from Fridericia chica (Bonpl.) L.G.Lohmann

Abstract

Fridericia chica, Bignoniaceae, is a tropical tree-creeper used as a traditional remedy for a number of diseases, highlighting inflammation. Our objective was to corroborate the popular anti-inflammatory use of the hydroethanolic extract from the leaves (HEFc) and of its isolated 4′,6,7-trihydroxy-5-methoxyflavone (5-O-methylscutellarein) [1], described here for the first time. Quantitative analysis indicated 8.77?±?0.23?mg/g of this compound in the extract. Neither HEFc nor [1] was cytotoxic in vitro. In LPS-induced peritonitis in mice, oral pre-treatment with HEFc or [1] led to decreased leukocyte migration to the peritoneal cavity and a reduction in the concentrations of pro-inflammatory cytokines (TNFα and IL-1β). Also, the anti-inflammatory cytokine IL-10 was enhanced following treatment with [1]. Overall, these results validate the traditional use of Fridericia chica as anti-inflammatory, and indicate that the compound 5-O-methylscutellarein may participate in this effect.     

The Effects of New Zealand Grown Ginseng Fractions on Cytokine Production from Human Monocytic THP-1 Cells

Pro-inflammatory cytokines and anti-inflammatory cytokines are important mediators that regulate the inflammatory response in inflammation-related diseases. The aim of this study is to evaluate different New Zealand (NZ)-grown ginseng fractions on the productions of pro-inflammatory and anti-inflammatory cytokines in human monocytic THP-1 cells. Four NZ-grown ginseng fractions, including total ginseng extract (TGE), non-ginsenoside fraction extract (NGE), high-polar ginsenoside fraction extract (HPG), and less-polar ginsenoside fraction extract (LPG), were prepared and the ginsenoside compositions of extracts were analyzed by HPLC using 19 ginsenoside reference standards. The THP-1 cells were pre-treated with different concentrations of TGE, NGE, HPG, and LPG, and were then stimulated with lipopolysaccharide (LPS). The levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and anti-inflammatory cytokines, such as interleukin-10 (IL-10), and transforming growth factor beta-1 (TGF-β1), were determined by enzyme-linked immunosorbent assay (ELISA). TGE at 400 µg/mL significantly inhibited LPS-induced TNF-α and IL-6 productions. NGE did not show any effects on inflammatory secretion except inhibited IL-6 production at a high dose. Furthermore, LPG displayed a stronger effect than HPG on inhibiting pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) productions. Particularly, 100 µg/mL LPG not only significantly inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, but also remarkably enhanced the production of anti-inflammatory cytokine IL-10. NZ-grown ginseng exhibited anti-inflammatory effects in vitro, which is mainly attributed to ginsenoside fractions (particularly less-polar ginsenosides) rather than non-saponin fractions.     

Asiatic Acid Glucosamine Salt Alleviates Ultraviolet B-induced Photoaging of Human Dermal Fibroblasts and Nude Mouse Skin

Herbal extracts including asiatic acid (AA) have become popular candidates of anti-photoaging agents due to their anti-inflammatory and antioxidant properties and minimal side effect. Nevertheless, low bioavailability due to poor solubility limits their practical application. In this study, a highly bioavailable form of AA called AAGS (compounded by asiatic acid and glucosamine) was investigated for its anti-photoaging effect using both in vitro and in vivo models along with UVB irradiation. The results showed that AAGS alleviated UVB-induced cell proliferation inhibition by reducing G2 phase arrest and cell apoptosis rate as well as the gene expressions of P53, BAX, CASPASE 3 and CASPASE 9, but enhancing BCL-2 expression. It also reduced the production of reactive oxygen species along with increased gene expression of GPX-1 and downregulated the gene expression of IL-1β, IL-6, IL-8, IL-17 and TNF-α compared to nontreated cells. In vivo results demonstrated the antiphotodamaging effects by restoring skin thickness, collagen content and reducing MMPs expression, which are also supported by reduced MMPs gene expression and enhanced collagen I and TGF-β1 gene expression in vitro. Thus, AAGS may become a potential anti-photoaging agent for topical use due to its capability of self-assembling into a water gel.     

Synthesis and Structural Study of Amidrazone Derived Pyrrole-2,5-Dione Derivatives: Potential Anti-Inflammatory Agents

1H-pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl-1H-pyrrole-2,5-dione derivatives 2a–2f in the reaction of N³-substituted amidrazones with 2,3-dimethylmaleic anhydride and evaluate their structural and biological properties. Compounds 2a–2f were studied by the ¹H-¹³C NMR two-dimensional techniques (HMQC, HMBC) and single-crystal X-ray diffraction (derivatives 2a and 2d). The anti-inflammatory activity of compounds 2a–2f was examined by both an anti-proliferative study and a production study on the inhibition of pro-inflammatory cytokines (IL-6 and TNF-α) in anti-CD3 antibody- or lipopolysaccharide-stimulated human peripheral blood mononuclear cell (PBMC) cultures. The antibacterial activity of compounds 2a–2f against Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Esherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Mycobacterium smegmatis and Nocardia corralina strains was determined using the broth microdilution method. Structural studies of 2a–2f revealed the presence of distinct Z and E stereoisomers in the solid state and the solution. All compounds significantly inhibited the proliferation of PBMCs in anti-CD3-stimulated cultures. The strongest effect was observed for derivatives 2a–2d. The strongest inhibition of pro-inflammatory cytokine production was observed for the most promising anti-inflammatory compound 2a.     

Nano Milk Protein-Mucilage Complexes: Characterization and Anticancer Effect

The anticancer activity of natural compounds has recently attracted multidisciplinary research. In this study, the complexation of milk proteins (MP) with Isabgol husk mucilage (IHM) and Ziziphus spina-christi mucilage (NabM) was investigated. In this context, the physicochemical properties of milk protein mucilage complexes (MPMC) including pH, Carr’s index, water solubility, and water absorption indices were measured, and the flow behavior was studied. In addition, the amino acid profile, protein digestibility, and phenolic and flavonoids content of MPMC were explored, and the microstructure of the complexes was visualized using transmission electron microscopy. The antioxidant and anticancer potencies of MPMC against two cancerous cell lines, human liver cancer HEPG-2 and breast cancer MCF-7, in comparison with two normal cell lines, namely, Bj-1 and MCF-12F, were tested using neutral red uptake assay. The results revealed that MPMC had scavenging activity against DPPH, ABTS, and HS radicals. Moreover, MPMC has the potential to prevent DNA damage induced by oxidative stress in Type-Fenton’s reaction. The results of the neutral red assay showed significant growth inhibition of both HEPG-2, MCF-7, whereas no significant cytotoxic effect was detected against Bj-1 and MCF-12F. RT-qPCR results indicated MPMC stimulated apoptosis as revealed by the upregulation of the pro-apoptosis gene markers Casepase-3, p53, Bax. Meanwhile, the anti-apoptosis Bcl-2 gene was downregulated. However, no significant difference was observed in normal cell lines treated with MPMC. In conclusion, MPMC can be considered as a promising anticancer entity that can be used in the development of novel cancer therapeutics with comparable activity and minimal side effects compared to conventional cancer chemotherapies.     

Synthesis,characterization and biological evaluation of a cobalt(II) complex with 5‐chloro‐8‐hydroxyquinoline as anticancer agent

A new cobalt(II) complex ( 1 ) of 5‐chloro‐8‐hydroxyquinoline was prepared and structurally characterized using infrared spectroscopy, electrospray ionization mass spectrometry, elemental analysis, single‐crystal X‐ray diffraction as well as powder X‐ray diffraction. Its biological activities including DNA binding and anticancer activity were investigated. The DNA binding study of complex 1 suggested that it interacted with calf thymus DNA mainly via an intercalative binding mode. The in vitro anticancer activity of complex 1 was screened against a series of tumor cell lines as well as the normal liver cell line HL‐7702 using MTT assay. complex 1 showed much higher cytotoxicity than corresponding metal salt and ligand towards the five tested tumor cell lines, in which T‐24 was the most sensitive tumor cell line towards 1, with IC₅₀ value of 7.04 ± 0.06 μM. complex 1 was found to greatly induce cell cycle arrest in T‐24 cells at S phase, and consequently to induce cell apoptosis in a dose‐dependent mode suggested by cell apoptosis analysis via Hoechst 33258 and acridine orange/ethidium bromide staining assays. The cell apoptosis mechanism of 1 was studied targeting the mitochondrion‐mediated pathway, since the apoptotic mechanism in the T‐24 cells treated by 1 was investigated by reactive oxygen species (ROS) detection, intracellular calcium concentration measurement and caspase‐9/3 activity assay. The results suggested that the cell apoptosis induced by 1 was closely related to the loss of mitochondrial membrane potential, ROS production and enhancement of intracellular [Ca²⁺], which would trigger the caspase‐9/3 activation via a mitochondrial dysfunction pathway. Copyright © 2016 John Wiley & Sons, Ltd.     

A new indole alkaloid with anti-inflammatory from the branches of Nauclea officinalis

Abstract

A new indole alkaloid, 17-oxo-19-(Z)-naucline, and six known alkaloids 2–7 were isolated from the branches of Nauclea officinalis. The structure of the new compound 1 was characterised mainly by analysing its physical data including IR, 1?D, 2?D NMR, and HR-ESI-MS. Other compounds were identified by comparisons their data with those reported in the literature. Compound1, 4, 5, 6, 7 showed in vitro anti-inflammatory activity decrease the LPS-stimulated production of nitric oxide in RAW264.7 cell, while all compounds exhibited weak cytotoxicity against human tumour cell lines (LOVO, A549 and HepG2).     

Synthesis,structural characterization and in vitro cytotoxicity of diorganotin complexes with Schiff base ligands derived from 3‐hydroxy‐2‐naphthoylhydrazide

A series of diorganotin complexes with Schiff base ligands, (E)‐N′‐(5‐bromo‐2‐hydroxybenzylidene)‐3‐hydroxy‐2‐naphthohydrazide, H₂L1, and (E)‐N′‐(5‐chloro‐2‐hydroxybenzylidene)‐3‐hydroxy‐2‐naphthohydrazide, H₂L2, were synthesized and characterized by elemental analysis, IR, ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy. The molecular structures of the complexes, [(5‐bromo‐2‐oxidobenzylidene)‐3‐hydroxy‐2‐naphthohydrazidato]di(o‐chlorobenzyl)tin(IV) 6 and [(5‐chloro‐2‐oxidobenzylidene)‐3‐hydroxy‐2‐naphthohydrazidato]dibutyltin(IV) 9, were determined through single‐crystal X‐ray diffraction and revealed a distorted trigonal‐bipyramidal configuration. The in vitro cytotoxic activity of the Schiff bases and their diorganotin complexes was also evaluated against several human carcinoma cell lines, namely HT29 (human colon carcinoma cell line), SKOV‐3 (human ovarian cancer cell line), MCF7 (hormone‐dependent breast carcinoma cell line) and MRC5 (non‐cancer human fibroblast cell line). [(5‐Bromo‐2‐oxidobenzylidene)‐3‐hydroxy‐2‐naphthohydrazidato]dibutyltin(IV) 2 and [(5‐bromo‐2‐oxidobenzylidene)‐3‐hydroxy‐2‐naphthohydrazidato]dibenzyltin(IV) 5 were the most active diorganotin complexes of H₂L1 ligand. Among the diorganotin complexes of H₂L2 ligand, [(5‐chloro‐2‐oxidobenzylidene)‐3‐hydroxy‐2‐naphthohydrazidato]dicyclohexyltin(IV) 11 showed good cytotoxic activity against all the tested cell lines. As such, the above compounds can be considered agents with potential anticancer activities, and can therefore be investigated further in in vitro or in vivo anticancer studies. Copyright © 2012 John Wiley & Sons, Ltd.     

Oxyresveratrol Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats by Suppressing Inflammation

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1β) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.     

Design,Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of α‐(Benzoylamino)‐β‐substituted Acrylic Amide Derivatives of Pyrazolo[1,5‐a]pyrimidine

A novel series of α‐(benzoylamino)‐β‐substituted acrylic amide derivatives of pyrazolo[1,5‐a]pyrimidine has been synthesized using a convergent multistep synthesis. The synthesized compounds were characterized by ¹H NMR, ¹³C NMR, ESI‐MS, and IR analyses. Those new compounds were screened for their in vitro antiproliferative activity using an MTT assay analysis. Out of nine derivatives synthesized in the current study, compounds 13g , 13d , 13h , and 13i exhibited the greatest anticancer activities in HeLa and HepG₂ cell lines. The in vitro anticancer activity of compound 13g against HeLa, HepG₂, and MCF‐7 cell lines is superior to the marketed drugs paclitaxel and SAHA.     

Evening Primrose Oil Enhances Tamoxifen’s Anticancer Activity against Breast Cancer Cells by Inducing Apoptosis,Inhibiting Angiogenesis,and Arresting the Cell Cycle

Background: Despite advancements in cancer treatment, breast cancer (BC) is still one of the leading causes of death among women. The majority of anti-breast-cancer medications induce serious side effects and multidrug resistance. Although several natural compounds, such as evening primrose oil (EPO), have been shown to have anticancer properties when used alone, their combination with the anticancer medicine tamoxifen (TAM) has yet to be investigated. The present study aimed to investigate the anticancer efficacy of EPO, alone or in combination with TAM, in the BC cell lines MCF-7 and MDA-MB-231, as well as to elucidate the mechanism of action. Methods: The MTT assay was used to investigate the cytotoxic effect of EPO on the two cell lines, and we discovered an acceptable IC₅₀ that was comparable to TAM. The ELISA, qRT-PCR, flow cytometry and colorimetric techniques were used. Results: The combination of EPO and TAM suppressed the VEGF level, VEGF gene expression and Cyclin D1 signaling pathways, arrested the cell cycle, and induced the apoptotic signaling pathways by increasing the Bax/Bcl-2 ratio and caspase 3 activity; this revealed significant anti-tumor activity. Conclusions: The most significant finding of this study was the confirmation of the anticancer activity of the natural product EPO, which potentiated the activity of the anticancer drug TAM against MCF-7 and MDA-MB-231 BC cell lines through the induction of apoptosis, inhibiting angiogenesis and halting cell proliferation.     

pH‐responsive near‐infrared emitting conjugated polymer nanoparticles for cellular imaging and controlled‐drug delivery

In this article, pH‐responsive near‐infrared emitting conjugated polymer nanoparticles (CPNs) are prepared, characterized, and their stabilities are investigated under various conditions. These nanoparticles have capacity to be loaded with water insoluble, anticancer drug, camptothecin (CPT), with around 10% drug loading efficiency. The in vitro release studies demonstrate that the release of CPTs from CPNs is pH‐dependent such that significantly faster drug release at mildly acidic pH of 5.0 compared with physiological pH 7.4 is observed. Time and dose‐dependent in vitro cytotoxicity tests of blank and CPT‐loaded nanoparticles are performed by real‐time cell electronic sensing (RT‐CES) assay with hepatocellular carcinoma cells (Huh7). The results indicate that CPNs can be effectively utilized as vehicles for pH‐triggered release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 114–122     

Synthesis and biological evaluation of some novel thiadiazole-benzofuran hybrids as potential antitumor agents

Two series of novel 1,3,4-thiadiazole-benzofuran and 1,3,4-thiadiazole-furochromene derivatives were synthesized through heterocyclization of alkyl 2-(1-(6-hydroxy-4,7-dimethoxybenzofuran-5-yl)ethylidene)hydrazine-1-carbodithioate 3a–f and 2-(1-(5-methoxy-8-methyl-2,6-dioxo-2,6-dihydropyrano[3,2-g]chromen-3-yl)ethylidene)hydrazinecarbothioamide 9a,b with various hydrazonoyl halides, respectively. The structure of the newly synthesized products was elucidated through elemental analysis, spectral data and alternative routes whenever possible. Ten new compounds were evaluated for their anticancer activity against the human breast carcinoma (MCF-7) cell lines in comparison with reference doxorubicin using MTT assay. The results showed that some new compounds have promising anticancer activity.     

Synthesis,characterization and biological evaluation of some novel sulfonylthiosemicarbazides

Abstract

A series of thiosemicarbazides were synthesized and structurally characterized by spectroscopic techniques (NMR, FT-IR) besides elemental analysis. These compounds were evaluated for their cytotoxicity against human breast cancer cell line MCF7 and prostate cancer cell line PC3 and nonmalignant fibroblast L929 cell line by MTT assay. Among the compounds, N-[2-(4-chlorophenyl)ethyl]-2-[(4-methylphenyl)sulfonyl]hydrazinecarbothioamide (3d) and 2-[(4-methylphenyl)sulfonyl]-N-[4-(trifluoromethoxy)phenyl]hydrazinecarbothioamide (3f) were found to display significant cytotoxicity with IC₅₀ of 13.87?μM (against PC3 cell line) and 1.47?μM (against MCF7 cell line), respectively. These compounds were non-cytotoxic to normal cell line with IC₅₀>100?μM. Western blotting studies demonstrated that compound 3f induced apoptosis and caused cell death in the MCF7 and PC3 cell lines via an increase in Bax protein expression and a slight decrease in Bcl-2 protein expression. The gene expression ratio Bax/Bcl-2 showed the induction of mitochondrial apoptosis in cancer cell lines. All of synthesized compounds have also been tested for antioxidant activity and all compounds achieved strong inhibition of the DPPH radical. These findings showed that compound 3f, displays potential to be further explored in the development of new anticancer agents.     

Design,Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of Imidazolone Fused Pyrazolo[1,5‐a]pyrimidine Derivatives

A novel series of imidazolone fused pyrazolo[1,5‐a]pyrimidine derivatives has been designed and synthesized using a convergent approach, and the structures of these compounds were confirmed by ¹H NMR, ¹³C NMR, ESI‐MS, and IR analyses. These new compounds were tested for their in vitro antiproliferative activity using an 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. Out of the 20 derivatives prepared in the current study, compounds 8h , 8n , and 8r exhibited good anticancer activities tested against HeLa cells and HepG₂ cells. However, the in vitro anticancer activity of compound 8r against HeLa, HepG₂, and MCF‐7 cell lines is superior to the marketed drugs Paclitaxel and SAHA.     

Anti-inflammatory effects of Scutellaria baicalensis water extract in LPS-induced THP-1 Macrophages through metabolomics study

(1) Background: Scutellaria baicalensis (Huang Qin) is a traditional Chinese Medicine possess beneficial effects of anti-inflammation in various diseases. In this study, we aimed to use untargeted metabolomics approach to investigate the possible underlying metabolic mechanisms of anti-inflammation effects of Scutellaria baicalensis in LPS-induced macrophages.; (2) Methods: Scutellaria baicalensis water extract (SBE) were applied to the THP-1 cells which were induced by phorbol 12-myristate 13-acetate (PMA) into macrophages under the LPS treated conditions. The cell lysate were collected and metabolites were extracted before characterizing by ultra-performance liquid chromatography (UPLC) combined with Q-Exactive mass/mass spectrometry (LC-MS/MS). The differential accumulated metabolites and related metabolism pathways affected by SBE in LPS-induced macrophages were identified. Further investigation of the secretion and expression of inflammatory cytokines IL-1β, TNF-ɑ and VEGFR were tested by real-time polymerase chain reaction (RT-PCR). (3) Results: The metabolome profile have indicated that retinol metabolism, arachidonic acid metabolism and linoleic acid metaoblism pathways were the most significantly enriched pathways response to SBE in LPS induced inflammatory model. Besides, SBE could inhibit the expression of the pro-inflammatory cytokines IL-1β and TNF-ɑ, and downregulation of the macrophage migration accelerator VEGFR1 in a dose dependent manner; (4) Conclusions: These findings indicated that SBE may exerted anti-inflammatory ability by regulating multiple fatty acids metabolism pathways as well as inhibiting the secretion of pro-inflammatory cytokines and VEGFR. This study provides evidences for Scutellaria baicalensis as the material for developing natural, effective anti-inflammatory products.     

Synthesis and Anticancer Evaluation of Some Novel Thiophene,Thieno[3,2‐d]pyrimidine,Thieno[3,2‐b]pyridine,and Thieno[3,2‐e][1,4]oxazepine Derivatives Containing Benzothiazole Moiety

In an attempt to establish novel candidate with promising anticancer activity, two derivatives of (benzo[d]thiazol‐2‐yl)thiophene backbone 1 and 14 were synthesized, and they further reacted with various chemical reagents to afford the corresponding substituted thiophene derivatives 6 , 8 , 10 , 15 , 17 , and 20 , thieno[3,2‐d]pyrimidine derivatives 2 – 5 , 7 , 9 , 16 , 21 , 23 , and 24 , thieno[3,2‐b]pyridine derivatives 11 – 13 , and thieno[3,2‐e][1,4]oxazepine derivative 18 . Structures of prepared compounds were affirmed via spectral and elemental data. Among the obtained compounds, seven derivatives 2 , 3 , 4 , 5 , 11 , 12 , and 13 were chosen by National Cancer Institute, USA. Such compounds were screened for their antitumor activity versus 60 cancer cell lines in one‐dose (10 μmol) screening assay. The outcomes showed that all selected compounds exhibited moderate to high anticancer activity towards many cancer cell lines among which compounds 5 and 11 exerted potent antitumor activity against numerous malignant growth cell lines particularly Ovarian Cancer IGROV1.     

Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.