A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1.

Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs).

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy.

To find inhibitors against skeletal muscle loss, we isolated a lignan compound ((-)-(2,3-1,4-O-diferuloylsecoisolarciresinol, DFS) from the stem of . C2C12 myoblasts were treated with DFS during differentiation. To induce an atrophic condition, differentiated myotubes were treated with dexamethasone (a synthetic glucocorticoid).

Sesquiterpenes from regulate inflammatory responses in RAW 264.7 macrophages.

Four sesquiterpenoids were isolated from an ethyl acetate-soluble fraction of ethanolic extract: seco-tanapartholide B (5-epi-seco-tanapartholide A) (), 4-epi-seco-tanapartholide A (), 11,13-dehydrodesacetylmatricarin () and desacetylmatricarin (). Compounds  -  dose-dependently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. These compounds also decreased mRNA and protein expression levels of inducible NO synthase and cyclooxygenase-2 as well as mRNA levels of pro-inflammatory cytokines (interleukin-1β and tumour necrosis factor-α) in LPS-stimulated RAW 264.

Kazinol C from stimulates autophagy via endoplasmic reticulum stress-mediated signaling.

Autophagy modulators are considered putative therapeutic targets because of the role of autophagy in cancer progression. Kazinol C, a 1,3-diphenylpropane from the plant , has been shown to induce apoptosis in colon cancer cells through the activation of AMPK at high concentrations. In the present study, we found that Kazinol C induced autophagy through endoplasmic reticulum stress-mediated unfolded protein response signaling in several normal and cancer cell lines at low concentrations of Kazinol C that did not induce apoptosis.

Urushiol V Suppresses Cell Proliferation and Enhances Antitumor Activity of 5-FU in Human Colon Cancer Cells by Downregulating FoxM1.

Colorectal cancer (CRC) is one of the most common malignant tumor. 5-FU is commonly used for the treatment of CRC. However, the development of drug resistance in tumor chemotherapy can seriously reduce therapeutic efficacy of 5-FU.

Antiobesity therapeutics with complementary dual-agonist activities at glucagon and glucagon-like peptide 1 receptors.

Aim: To develop more effective and long-lasting antiobesity and antidiabetic therapeutics by employing novel chemical modifications of glucagon-like peptide-1 receptor (GLP-1R) agonists.

Methods: We constructed novel unimolecular dual agonists of GLP-1R and glucagon receptor prepared by linking sEx-4 and native glucagon (GCG) via lysine or triazole [sEx4-GCG(K) and sEx4-GCG(T), respectively] and evaluated their antiobesity and antidiabetic efficacy in the diabetic and obese mouse model.

Results: Both sEx4-GCG(K) and sEx4-GCG(T) showed the beneficial metabolic effects of GLP-1 and glucagon: they promoted weight loss and ameliorated insulin resistance and hepatic steatosis.

Beam stability of buried-heterostructure quantum cascade lasers employing HVPE regrowth.

Measurements of beam stability for mid-infrared (IR)-emitting quantum cascade lasers (QCLs) are important for applications that require the beam to travel through air to remote targets, such as free-space communication links. We report beam-quality measurement results of narrow-ridge, 4.6 µm-emitting buried-heterostructure (BH) QCLs fabricated using ICP etching and HVPE regrowth.

Structure-Activity Relationship of Phytoestrogen Analogs as ERα/β Agonists with Neuroprotective Activities.

A set of isoflavononid and flavonoid analogs was prepared and evaluated for estrogen receptor α (ERα) and ERβ transactivation and anti-neuroinflammatory activities. Structure-activity relationship (SAR) study of naturally occurring phytoestrogens, their metabolites, and related isoflavone analogs revealed the importance of the C-ring of isoflavonoids for ER activity and selectivity. Docking study suggested putative binding modes of daidzein 2 and dehydroequol 8 in the active site of ERα and ERβ, and provided an understanding of the promising activity and selectivity of dehydroequol 8.

Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton's Tyrosine Kinase.

As a member of the tyrosine protein kinase Tec (TEC) family, Bruton's tyrosine kinase (BTK) is considered a promising therapeutic target due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic warhead for targeting Cys481.

Discovery of Tricyclic Pyranochromenone as Novel Bruton's Tyrosine Kinase Inhibitors with in Vivo Antirheumatic Activity.

Bruton's tyrosine kinase (BTK) is an attractive target for treating patients with B cell malignancies and autoimmune diseases. Many BTK inhibitors have been identified; however, like other kinase inhibitors, they lack diversity in their core structures. Therefore, it is important to secure a novel scaffold that occupies the adenine-binding site of BTK.

Tussilagone promotes osteoclast apoptosis and prevents estrogen deficiency-induced osteoporosis in mice.

Osteoporosis is a degenerative disease characterized by reduced bone mass, in which deregulated bone remodeling by osteoclasts and osteoblasts is a main pathogenesis. Although recently tussilagone, a major active component of flower buds of Tussilago farfara, has been shown to inhibit osteoclastogenesis, its effect on estrogen deficiency-induced osteoporosis remains unknown. This study examined the effect of tussilagone on bone loss in ovariectomized mice and further explored its impact on osteoclast apoptosis and osteoblast formation in addition to osteoclastogenesis.

A novel nucleolin-binding peptide for Cancer Theranostics.

Cancer-specific ligands have been of great interest as pharmaceutical carriers due to the potential for site-specific delivery. In particular, cancer-specific peptides have many advantages over nanoparticles and antibodies, including high biocompatibility, low immunogenicity, and the formation of nontoxic metabolites. The goal of the present study was the development of a novel cancer-specific ligand.

Lignan from Inhibits Adipocyte Differentiation via Cell Cycle and FOXO1 Regulation.

In the present study, we isolated a lignan ((-)-(2,3)-1,4--diferuloylsecoisolariciresinol, DFS) from and evaluated its antiobesity potential in vitro. We also determined its mechanism of action in a mouse pre-adipocyte 3T3-L1 cell line. DFS dose- and day-dependently inhibited adipogenesis by downregulation of adipogenic factors and lipid metabolism-regulating factors during adipocyte differentiation.

Broussoflavonol B from Siebold Exerts Anti-Pancreatic Cancer Activity through Downregulating FoxM1.

Pancreatic cancer has a high mortality rate due to poor rates of early diagnosis. One tumor suppressor gene in particular, p53, is frequently mutated in pancreatic cancer, and mutations in p53 can inactivate normal wild type p53 activity and increase expression of transcription factor forkhead box M1 (FoxM1). Overexpression of FoxM1 accelerates cellular proliferation and cancer progression.

Inhibition of autophagy sensitizes lignan-induced endoplasmic reticulum stress-mediated cell death.

Relationship between autophagy and endoplasmic reticulum (ER) stress and their application to treat cancer have been actively studied these days. Recently, a lignan [(-)-(2R, 3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica has been found to reduce the viability of colon cancer cells. In this study, we have observed DFS-induced autophagy in a variety of cancer cell lines.

Solution structure and functional analysis of HelaTx1: the first toxin member of the κ-KTx5 subfamily.

Scorpion venom comprises a cocktail of toxins that have proven to be useful molecular tools for studying the pharmacological properties of membrane ion channels. HelaTx1, a short peptide neurotoxin isolated recently from the venom of the scorpion Heterometrus laoticus, is a 25 amino acid peptide with two disulfide bonds that shares low sequence homology with other scorpion toxins. HelaTx1 effectively decreases the amplitude of the K+ currents of voltage-gated Kv1.

Corylifol A from L. Enhances Myogenesis and Alleviates Muscle Atrophy.

Inflammatory conditions caused by cancer, chronic diseases or aging can lead to skeletal muscle atrophy. We identified myogenic compounds from (PC), a medicinal plant that has been used for the treatment of inflammatory and skin diseases. C2C12 mouse skeletal myoblasts were differentiated in the presence of eight compounds isolated from PC to evaluate their myogenic potential.

Z-Ajoene Inhibits Growth of Colon Cancer by Promotion of CK1α Dependent β-Catenin Phosphorylation.

Aberrant activation of a Wnt/β-catenin pathway results in nuclear accumulation of β-catenin in colon cancer. Inhibiting β-catenin is one strategy for treating colon cancer. Here, we identified Z-ajoene, a sulfur containing compound isolated from crushed garlic, as an inhibitor of colon cancer cell growth.

Correction to: Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1.

Following publication of the original article [1], the authors have re-evaluated the authorship for this article. The updated author group is.

Z-ajoene from Crushed Garlic Alleviates Cancer-Induced Skeletal Muscle Atrophy.

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (), one of the world's most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy.

A Chalcone from Ashitaba () Stimulates Myoblast Differentiation and Inhibits Dexamethasone-Induced Muscle Atrophy.

Ashitaba, Koidzumi (AK), as a traditional medicine in Korea, Japan, and China, has been known as an elixir of life having therapeutic potential. However, there is no scientific evidence to support that Ashitaba can enhance or maintain muscle strength. To find a new therapeutic agent from the medicinal plant, we evaluated the anti-myopathy effect of chalcones from ethanol extract of AK (EAK) in cellular and animal models of muscle atrophy.

Ajoene, a Major Organosulfide Found in Crushed Garlic, Induces NAD(P)H:quinone Oxidoreductase Expression Through Nuclear Factor E2-related Factor-2 Activation in Human Breast Epithelial Cells.

Background: NAD(P)H:quinone oxidoreductase-1 (NQO1) is a widely-distributed flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes. This reduces quinone levels and thereby minimizes generation of excess reactive oxygen species (ROS) formed by redox cycling, and concurrent depletion of intracellular thiol pools. Ajoene is derived from crushed garlic.

Anti-Inflammatory Compounds from .

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from ; , 2-[(2)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; , 1-acetoxy-tetradeca-6,12-diene-8, 10-diyne-3-ol; , 1,3-diacetoxy-tetradeca-6, 12-diene-8, 10-diyne. Compounds - showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E (PGE) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages.