Anti-obesity effects of a standardized ethanol extract of by regulating the AMPK signaling pathway in 3T3-L1 cells and HFD-induced mice.

Obesity requires treatment to mitigate the potential development of further metabolic disorders, including diabetes, hyperlipidemia, tumor growth, and non-alcoholic fatty liver disease. We investigated the anti-obesity effect of a 30% ethanol extract of (Kjellman) Setchell (EEB) on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese C57BL/6 mice. Adipogenesis transcription factors including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein-alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1) were ameliorated through the AMP-activated protein kinase (AMPK) pathway by EEB treatment in differentiated 3T3-L1 cells.

Anti-Metastatic Effects of Standardized Polysaccharide Fraction from Leaves via GSK3β/β-Catenin and JNK Inactivation in Human Colon Cancer Cells.

A polysaccharide fraction from (PLE0) leaves was previously reported to possess immunostimulatory, anti-osteoporotic, and TGF-β1-induced epithelial-mesenchymal transition inhibitory activities. Although a few beneficial effects against colon cancer metastasis have been reported, we aimed to investigate the anti-metastatic activity of PLE0 and its underlying molecular mechanisms in HT-29 and HCT-116 human colon cancer cells. We conducted a wound-healing assay, invasion assay, qRT-PCR analysis, western blot analysis, gelatin zymography, luciferase assay, and small interfering RNA gene silencing in colon cancer cells.

Discovery of N-benzylbenzamide-based allosteric inhibitors of Aurora kinase A.

Aurora kinases (AurkA/B/C) regulate the assembly of bipolar mitotic spindles and the fidelity of chromosome segregation during mitosis, and are attractive therapeutic targets for cancers. Numerous ATP-competitive AurkA inhibitors have been developed as potential anti-cancer agents. Recently, a few allosteric inhibitors have been reported that bind to the allosteric Y-pocket within AurkA kinase domain and disrupt the interaction between AurkA and its activator TPX2.

Deficiency of thioredoxin-interacting protein results in age-related thrombocytopenia due to megakaryocyte oxidative stress.

Background: Platelets are generated from megakaryocytes (MKs), mainly located in the bone marrow (BM). Megakaryopoiesis can be affected by genetic disorders, metabolic diseases, and aging. The molecular mechanisms underlying platelet count regulation have not been fully elucidated.

Ethanol Extracts from the Aerial Parts of and Alleviate Airway Inflammation in Mice That Inhaled Particulate Matter 10 and Diesel Particulate Matter.

Air pollution causes various airway diseases. However, many commonly used treatments can have high risks of side effects or are costly. To examine the anti-inflammatory properties of Thunb.

Therapeutic role of 2-stearoxyphenethyl phosphocholine targeting microtubule dynamics and Wnt/β-catenin/EMT signaling in human colorectal cancer cells.

The inhibition of cell death, perturbation of microtubule dynamics, and acceleration of Wnt/β-catenin/epithelial-mesenchymal transition (EMT) signaling are fundamental processes in the progression and metastasis of colorectal cancer (CRC). To explore the role of 2-stearoxyphenethyl phosphocholine (stPEPC), an alkylphospholipid-based compound, in CRC, we conducted an MTT assay, cell cycle analysis, western blot analysis, immunoprecipitation, immunofluorescence staining, Annexin V/propidium iodide double staining, small interfering RNA gene silencing, a wound-healing assay, an invasion assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the human CRC cell lines HT29 and HCT116. stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20).

Protective effect of hydrangenol on lipopolysaccharide-induced endotoxemia by suppressing intestinal inflammation.

Hydrangenol, a dihydroisocoumarin, isolated from the leaves of Hydrangea serrata, possesses anti-inflammatory, anti-obesity, and anti-photoaging activities. In this study, we investigated the protective effects of hydrangenol (HG) against lipopolysaccharide (LPS)-induced endotoxemia and elucidated the underlying molecular mechanisms of action in C57BL/6 mice. Oral administration of HG (20 or 40 mg/kg) significantly restored the survival rate and population of macrophages, T helper cells (CD3/CD4), and Th17 cells (CD3/CD4/CCR6) in the spleens of mice with LPS-induced endotoxemia.

Hydrangenol, an active constituent of (Thunb.) Ser., ameliorates colitis through suppression of macrophage-mediated inflammation in dextran sulfate sodium-treated mice.

Ulcerative colitis (UC) is a chronic disease of the colon characterized by mucosal damage and relapsing gastrointestinal inflammation. (Thunb.) Ser.

Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase.

Phenethyl-based edelfosine-analogs with saturated, monounsaturated, or polyunsaturated alkoxy substituents on phenyl ring were designed as novel antitumor lipids modulating p38 MAPK. Evaluation of the synthesised compounds against nine panels of diverse cancer cells presented saturated and monounsaturated alkoxy-substituted derivatives as the most active than other derivatives. In addition, -substituted compounds were more active than - or -substituted compounds.

In vitro modeling of liver fibrosis with 3D co-culture system using a novel human hepatic stellate cell line.

Hepatic stellate cells (HSCs) play an important role in liver fibrosis; however, owing to the heterogeneity and limited supply of primary HSCs, the development of in vitro liver fibrosis models has been impeded. In this study, we established and characterized a novel human HSC line (LSC-1), and applied it to various types of three-dimensional (3D) co-culture systems with differentiated HepaRG cells. Furthermore, we compared LSC-1 with a commercially available HSC line on conventional monolayer culture.

3',4'-Dihydroxyflavone mitigates inflammatory responses by inhibiting LPS and TLR4/MD2 interaction.

Background: We previously reported the potential inhibitory activity of 3',4'-dihydroxyflavone (DHF) on nitric oxide (NO) and prostaglandin E (PGE) production in lipopolysaccharide (LPS)-stimulated macrophages.

Purpose: We investigated the underlying molecular mechanisms of DHF in LPS-activated macrophages and evaluated its effect on LPS-induced septic shock in mice.

Methods: To explore the anti-inflammatory effect of DHF, nitrite, PGE, and cytokines were measured in vitro and in vivo experiments.

Dieckol Isolated from Ameliorates Wrinkling and Improves Skin Hydration via MAPK/AP-1 and TGF-β/Smad Signaling Pathways in UVB-Irradiated Hairless Mice.

Repetitive exposure to ultraviolet B (UVB) is one of the main causes of skin photoaging. We previously reported that dieckol isolated from extract has potential anti-photoaging effects in UVB-irradiated Hs68 cells. Here, we aimed to evaluate the anti-photoaging activity of dieckol in a UVB-irradiated hairless mouse model.

Protective effect of 7-hydroxyl-1-methylindole-3-acetonitrile on the intestinal mucosal damage response to inflammation in mice with DSS-induced colitis.

Ulcerative colitis (UC), a pathological condition of inflammatory bowel disease, is a chronic inflammatory disorder that involves an abnormal immune response and epithelial barrier dysfunction. Although we have previously reported the anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile (7-HMIA), a synthesized analog of arvelexin on macrophages and paw edema, its anti-colitis effect and its mechanism are not known. In this study, colitis was induced in mice model by 4% (w/v) dextran sodium sulfate (DSS) solution in drinking water for 9 days.

Establishment of a human induced pluripotent stem cell line, KRIBBi006-A, from peripheral blood mononuclear cells derived from a healthy male donor.

Given the advantage of being able to be extracted by a minimally invasive method, blood is regarded as a suitable cell source for reprogramming to establish induced pluripotent stem cells (iPSCs). Therefore, iPSCs established from patient derived peripheral blood mononuclear cells (PBMCs) is widely used to develop disease modeling to elucidate disease development. Here, PBMCs from a healthy man were reprogrammed into iPSCs using the Sendai virus.

A Botanical Mixture Consisting of and Relieves Obesity via the AMPK Signaling Pathway in 3T3-L1 Adipocytes and HFD-Fed Obese Mice.

Excessive lipid accumulation in white adipose tissue (WAT) is the major cause of obesity. Herein, we investigated the anti-obesity effect and molecular mechanism of a botanical mixture of 30% EtOH extract from the leaves of and (EEIP) in 3T3-L1 preadipocytes and high-fat diet (HFD)-fed obese mice. In vitro, EEIP prevented lipid accumulation by downregulating the expression of lipogenesis-related transcription factors such as CCAAT/enhancer binding protein (C/EBP)α, peroxisome proliferator-activated receptor (PPAR)γ, and sterol regulatory element binding protein (SREBP)-1 via AMP-activated protein kinase (AMPK) activation and G/G cell cycle arrest by regulating the Akt-mTOR pathways without inducing cytotoxicity.

Anti-Colitic Effect of an Exopolysaccharide Fraction from KFT-18 on Dextran Sulfate Sodium-Induced Colitis through Suppression of Inflammatory Mediators.

We previously reported the immunostimulatory effect of an exopolysaccharide fraction from KFT18 (PE-EPS), a lactic acid bacterium, in macrophages and primary splenocytes, as well as in cyclophosphamide-induced immunosuppressed mice. In this study, the anti-colitic activity of PE-EPS was investigated in a dextran sulfate sodium (DSS)-induced colitis animal model. PE-EPS relieved DSS-induced colitis symptoms, such as stool blood, decreased colon length, crypt disruption, and mucus layer edema.

In vitro and in vivo neuroprotective effect of novel mPGES-1 inhibitor in animal model of Parkinson's disease.

mPGES-1 is found to be up-regulated in the dopaminergic neurons of the substantia nigra pars compacta (SNpc) of postmortem brain tissue from Parkinson's disease (PD) patients and neurotoxin 6-hydroxydopamine (6-OHDA)-induced PD mice. Since the genetic deletion of mPGES-1 abolished 6-OHDA-induced PGE production and 6-OHDA-induced dopaminergic neurodegeneration in vitro and in vivo models, mPGES-1 enzyme has the potential to be an important target for PD therapy. In the present work, we investigated whether a small organic molecule as mPGES-1 inhibitor could exhibit the neuroprotective effects against 6-OHDA-induced neurotoxicity in in vitro and in vivo models.

Pennogenin-3--α--Rhamnopyranosyl-(1→2)-[α--Rhamnopyranosyl-(1→3)]-β--Glucopyranoside (Spiroconazol A) Isolated from L. var. Induces Autophagic Cell Death by p38 MAPK Activation in NSCLC Cells.

In our previous study, we reported the isolation of pennogenin-3--α--rhamnopyranosyl-(1→2)-[α--rhamnopyranosyl-(1→3)]-β--glucopyranoside (spiroconazol A), a steroidal saponin, from the flowers of L. var. .

Mosloflavone-Resveratrol Hybrid TMS-HDMF-5z Exhibits Potent and Anti-Inflammatory Effects Through NF-κB, AP-1, and JAK/STAT Inactivation.

TMS-HDMF-5z is a hybrid of the natural products mosloflavone and resveratrol. It was discovered to show potent inhibitory effects against lipopolysaccharide (LPS)-induced production of inflammatory mediators in RAW 264.7 macrophages.

Identification of highly selective type II kinase inhibitors with chiral peptidomimetic tails.

Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor potently inhibited Lck kinase with great selectivity (IC of 23.