Disruption of bioenergetics enhances the radio-sensitivity of patient-derived glioblastoma tumorspheres.

Background: Despite available treatment approaches, including surgical resection along with chemotherapy and radiotherapy, glioblastoma (GBM), the most prevalent primary brain tumor, remains associated with a grim prognosis. Although radiotherapy is central to GBM treatment, its combination with bioenergetics regulators has not been validated in clinical practice. Here, we hypothesized that bioenergetics regulators can enhance the radio-sensitivity of GBM tumorspheres (TSs).

Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres.

Background: Glioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs).

Methods: The biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis.

Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres.

Introduction: The importance of fatty acid oxidation (FAO) in the bioenergetics of glioblastoma (GBM) is being realized. Etomoxir (ETO), a carnitine palmitoyltransferase 1 (CPT1) inhibitor exerts cytotoxic effects in GBM, which involve interrupting the FAO pathway. We hypothesized that FAO inhibition could affect the outcomes of current standard temozolomide (TMZ) chemotherapy against GBM.

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).

Prediction and identification of synergistic compound combinations against pancreatic cancer cells.

Resistance to current therapies is common for pancreatic cancer and hence novel treatment options are urgently needed. In this work, we developed and validated a computational method to select synergistic compound combinations based on transcriptomic profiles from both the disease and compound side, combined with a pathway scoring system, which was then validated prospectively by testing 30 compounds (and their combinations) on PANC-1 cells. Some compounds selected as single agents showed lower GI50 values than the standard of care, gemcitabine.

Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways.

Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood.

Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone.

Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution.

BACE1 molecular docking and anti-Alzheimer's disease activities of ginsenosides.

Ethnopharmacological Relevance: Ginsenosides are natural product steroid glycosides and triterpene saponins obtained from the Panax species. Panax ginseng has been widely used as a traditional Chinese medicine (TCM) for around a thousand years, especially in East Asian countries. Ginseng, the root and rhizome of the most popular species P.

Anti-Alzheimer's disease potential of coumarins from Angelica decursiva and Artemisia capillaris and structure-activity analysis.

Objective: To use structure-activity analysis to study the anti-Alzheimer's disease (anti-AD) activity of natural coumarins isolated from Angelica decursiva and Artemisia capillaris, along with one purchased coumarin (daphnetin).

Methods: Umbelliferone, umbelliferone 6-carboxylic acid, scopoletin, isoscopoletin, 7-methoxy coumarin, scoparone, scopolin, and esculetin have been previously isolated; however 2'-isopropyl psoralene was isolated from Angelica decursiva for the first time to evaluate their inhibitory effects against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) enzyme activity. We scrutinized the potentials of coumarins as cholinesterase and BACE1 inhibitors via enzyme kinetics and molecular docking simulation.

Attenuation of neuropathic pain and neuroinflammatory responses by a pyranocoumarin derivative, anomalin in animal and cellular models.

The present study investigated the neuropathic pain, anti-neuroinflammatory and neuroprotective properties of a pyranocoumarin derivative (anomalin) in in vivo and in vitro models. An in vivo streptozotocin (STZ)-induced diabetic neuropathic pain model demonstrated that anomalin significantly suppressed neuropathic pain in mice. To identify the molecular mechanism of the anti-neuropathic pain activity of anomalin, sodium-nitroprusside (SNP)-induced neuroinflammation in neuro-2a (N2a) cells was further investigated in signaling pathways.

Promising anti-diabetic potential of capillin and capillinol isolated from Artemisia capillaris.

Caffeoylquinic acids, flavonoids, and coumarins isolated from Artemisia capillaris have recently emerged as therapeutic candidates for diabetes and diabetic complications; however, there have been very few studies of the anti-diabetic potential of polyacetylenes. In the present study, we investigated the anti-diabetic potential of two polyacetylenes isolated from A. capillaris, namely capillin and capillinol by investigating their ability to inhibit α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and rat lens aldose reductase (RLAR).

Kinetics and molecular docking studies of fucosterol and fucoxanthin, BACE1 inhibitors from brown algae Undaria pinnatifida and Ecklonia stolonifera.

Since the action of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is strongly correlated with the onset of Alzheimer's disease (AD), the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. In our ongoing research aimed at identifying anti-AD remedies derived from maritime plants, we evaluated the BACE1 inhibitory activities of fucosterol and fucoxanthin from Ecklonia stolonifera and Undaria pinnatifida. In vitro anti-AD activities were performed via BACE1 inhibition assays, as well as enzyme kinetic and molecular docking predictions.

Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitrite oxide production in RAW 264.7 cells.

Angelica decursiva has long been used in Korean traditional medicine as an antitussive, analgesic, antipyretic, and cough remedy. In this study, the anti-inflammatory activity of 9 coumarin derivatives isolated from a 90 % methanol fraction was evaluated via inhibition of production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.

Health benefit of fucosterol from marine algae: a review.

Seaweeds belong to a group of marine plants known as algae, which are consumed as sea vegetables in several Asian countries. Recent studies have focused on the biological and pharmacological activities of seaweeds and their highly bioactive secondary metabolites because of their potential in the development of new pharmaceutical agents. Although several varieties of bioactive novel compounds such as phlorotannins, diterpenes and polysaccharides from seaweeds have already been well scrutinized, fucosterol as a phytosterol still needs to reinvent itself.

Anti-adipogenic effect of epiberberine is mediated by regulation of the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways.

It has been reported that alkaloids derived from Coptis chinensis exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating peroxisome proliferation-activity receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein-α (C/EBP-α). However, the signaling-based mechanism of the inhibitory role of epiberberine in the early stages of 3T3-L1 adipocyte differentiation is uncharacterized. Here, we show that epiberberine had inhibitory effects on adipocyte differentiation and significantly decreased lipid accumulation by downregulating an adipocyte-specific transcription factor, sterol regulatory element-binding protein-1 (SREBP-1).

Protein tyrosine phosphatase 1B inhibitory activity of alkaloids from Rhizoma Coptidis and their molecular docking studies.

Ethnopharmacologic Relevance: Rhizoma Coptidis (the rhizome of Coptis chinensis Franch) has commonly been used for treatment of diabetes mellitus in traditional Chinese medicine due to its blood sugar-lowering properties and therapeutic benefits which highly related to the alkaloids therein. However, a limited number of studies focused on the Coptis alkaloids other than berberine.

Materials And Methods: In the present study, we investigated the anti-diabetic potential of Coptis alkaloids, including berberine (1), epiberberine (2), magnoflorine (3), and coptisine (4), by evaluating the ability of these compounds to inhibit protein tyrosine phosphatase 1B (PTP1B), and ONOO(-)-mediated protein tyrosine nitration.

Desoxyrhapontigenin up-regulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury.

Heme oxygenase-1 (HO-1) is an important anti-inflammatory, antioxidative and cytoprotective enzyme that is regulated by the activation of the major transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In the present study, six stilbene derivatives isolated from Rheum undulatum L. were assessed for their antioxidative potential.

Anti-hyperalgesic and anti-allodynic activities of capillarisin via suppression of inflammatory signaling in animal model.

Ethnopharmacological Relevance: Artemisia capillaris has widespread traditional and pharmacological applications such as analgesic, anti-inflammatory, anti-pyretic, enhance immunity and anti-tumor activity properties. To evaluate the pharmacological activities of this plant, capillarisin, one of the potent constituent of Artemisia capillaris was studied based on anti-hyperalgesic and anti-allodynic effects with detailed mechanism. It can be assumed that measurement of anti-nociceptive effects of capillarisin is one of the parameter for the evaluation of this herb.

Desoxyrhapontigenin, a potent anti-inflammatory phytochemical, inhibits LPS-induced inflammatory responses via suppressing NF-κB and MAPK pathways in RAW 264.7 cells.

This study investigates the anti-inflammatory effects of a stilbene compound, desoxyrhapontigenin, which was isolated from Rheum undulatum. To determine the anti-inflammatory effects of this compound, lipopolysaccharide (LPS)-induced RAW 264.7 macrophages were treated with different concentrations of six stilbene derivatives.

Anti-inflammatory activity of edible brown alga Saccharina japonica and its constituents pheophorbide a and pheophytin a in LPS-stimulated RAW 264.7 macrophage cells.

Anti-inflammatory activity of Saccharina japonica and its active components was evaluated via in vitro inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression in RAW 264.7 murine macrophage cells. Since the methanolic extract of S.