Panax notoginseng root extract induces nuclear translocation of CRTC1 and Bdnf mRNA expression in cortical neurons.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is deeply involved in the development and higher function of the nervous system, including learning and memory. By contrast, a reduction in BDNF levels is associated with various neurological disorders such as dementia and depression. Therefore, the inducers of Bdnf expression might be valuable in ameliorating or protecting against a decline in brain functions.

Female and male obese Zucker rats display differential inflammatory mediator and long non-coding RNA profiles.

Aims: The goal of this study was to identify mediators in peri-lymphatic adipose tissue (PLAT) that are altered in obese versus lean Zucker rats, with focus on potential sex differences MAIN METHODS: Mesenteric PLAT was analyzed with protein and lncRNA arrays. Additional RT-PCR confirmation was performed with epididymal/ovarian fat.

Key Findings: MCP-1, TCK-1, Galectin-1, Galectin-3, and neuropilin-1 were elevated in PLAT from obese rats of both sexes.

Design and structural optimization of thiadiazole derivatives with potent GLS1 inhibitory activity.

GLS1 is an attractive target not only as anticancer agents but also as candidates for various potential pharmaceutical applications such as anti-aging and anti-obesity treatments. We performed docking simulations based on the complex crystal structure of GLS1 and its inhibitor CB-839 and found that compound A bearing a thiadiazole skeleton exhibits GLS1 inhibition. Furthermore, we synthesized 27 thiadiazole derivatives in an effort to obtain a more potent GLS1 inhibitor.

Design, synthesis, structure-activity relationship studies, and evaluation of novel GLS1 inhibitors.

Glutaminase converts glutamine into glutamic acid and has two isoforms: glutaminase 1 (GLS1) and glutaminase 2 (GLS2). GLS1 is overexpressed in several tumors, and research to develop glutaminase inhibitors as antitumor drugs is currently underway. The present study examined candidate GLS1 inhibitors using in silico screening and attempted to synthesize novel GLS1 inhibitors and assess their GLS1 inhibitory activities in a mouse kidney extract and against recombinant mouse and human GLS1.

The Microvascular-Lymphatic Interface and Tissue Homeostasis: Critical Questions That Challenge Current Understanding.

Lymphatic and blood microvascular networks play critical roles in the clearance of excess fluid from local tissue spaces. Given the importance of these dynamics in inflammation, tumor metastasis, and lymphedema, understanding the coordinated function and remodeling between lymphatic and blood vessels in adult tissues is necessary. Knowledge gaps exist because the functions of these two systems are typically considered separately.

Impact of Goreisan components on rat mesenteric collecting lymphatic vessel pumping.

Background: Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function.

Methods: Mesenteric collecting lymphatics were isolated from anesthetized Sprague-Dawley rats and mounted on resistance-matched glass micropipettes in a 37°C physiological salt solution bath for studies.

Immunostimulatory effects of cell wall-based nanoparticles in boiled radix water extracts involves TLR4.

A number of immunostimulant effects of herbal medicines have been reported; however, the underlying mechanisms of their immunostimulatory effects have not been elucidated in detail. Our previous study showed that sugar-based nanoparticles derived from cell walls acted as the immunostimulatory component of boiled radix water extracts. Therefore, the aim of the present study was to clarify the molecular mechanisms by which these cell wall-based nanoparticles functioned as immunostimulants.

Rhynchophylline promotes stem cell autonomous metabolic homeostasis.

Rhynchophylline (Rhy) effectively obstructs the expansive signaling pathways of degenerative diseases, including Alzheimer disease, Parkinson disease, epilepsy and amyotrophic lateral sclerosis, and stimulates neurogenesis. Maintenance of stemness and cell proliferation requires sophisticated intracellular environments to achieve pluripotency via specific expression of genes and proteins. We examined whether Rhy promotes this regulation in bone marrow human mesenchymal stromal cells (BM-hMSCs).

Screening inducers of neuronal BDNF gene transcription using primary cortical cell cultures from BDNF-luciferase transgenic mice.

Brain-derived neurotrophic factor (BDNF) is a key player in synaptic plasticity, and consequently, learning and memory. Because of its fundamental role in numerous neurological functions in the central nervous system, BDNF has utility as a biomarker and drug target for neurodegenerative and neuropsychiatric disorders. Here, we generated a screening assay to mine inducers of Bdnf transcription in neuronal cells, using primary cultures of cortical cells prepared from a transgenic mouse strain, specifically, Bdnf-Luciferase transgenic (Bdnf-Luc) mice.

Evidence of functional ryanodine receptors in rat mesenteric collecting lymphatic vessels.

In the current study, the potential contributions of ryanodine receptors (RyRs) to intrinsic pumping and responsiveness to substance P (SP) were investigated in isolated rat mesenteric collecting lymphatic vessels. Responses to SP were characterized in lymphatic vessels in the absence or presence of pretreatment with nifedipine to block L-type Ca channels, caffeine to block normal release and uptake of Ca from the sarcoplasmic reticulum, ryanodine to block all RyR isoforms, or dantrolene to more selectively block RyR1 and RyR3. RyR expression and localization in lymphatics was also assessed by quantitative PCR and immunofluorescence confocal microscopy.

Efficient Use of a Crude Drug/Herb Library Reveals Ephedra Herb As a Specific Antagonist for TH2-Specific Chemokine Receptors CCR3, CCR4, and CCR8.

Chemokine receptors CCR3 and CCR4 are preferentially expressed by TH2 cells, mast cells, and/or eosinophils, all of which are involved in the pathogenesis of allergic diseases. Therefore, CCR3 and CCR4 have long been highlighted as potent therapeutic targets for allergic diseases. Japanese traditional herbal medicine Kampo consists of multiple crude drugs/herbs, which further consist of numerous chemical substances.

Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents.

Novel urea derivatives of alkynes have been designed, synthesized, and evaluated as potential cancer therapeutics leads. The most active 1-((3-chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against HELA and MCF-7 cell lines with IC(50) values of 1.55 μM and 1.

Calpain 1 and -2 play opposite roles in cord formation of lymphatic endothelial cells via eNOS regulation.

Calpains are a family of calcium-dependent proteases. Two isoforms, calpain 1 and 2, have been implicated in angiogenesis and endothelial cell adhesion and migration. Calpains regulate the function of eNOS;however, the relation of calpains and eNOS to lymphangiogenesisis still unclear.

Traditional Japanese formula kigikenchuto accelerates healing of pressure-loading skin ulcer in rats.

We evaluated the effect of kigikenchuto (KKT), a traditional Japanese formula, in a modified rat pressure-loading skin ulcer model. Rats were divided into three groups, KKT extract orally administered (250 or 500 mg/kg/day for 35 days) and control. KKT shortened the duration until healing.

Effect of Hachimijiogan against Renal Dysfunction and Involvement of Hypoxia-Inducible Factor-1α in the Remnant Kidney Model.

In chronic renal failure, hypoxia of renal tissue is thought to be the common final pathway leading to end-stage renal failure. In this study the effects of hachimijiogan, a Kampo formula, were studied with respect to hypoxia-inducible factor (HIF). Using remnant kidney rats, we studied the effects of hachimijiogan on renal function in comparison with angiotensin II receptor blocker.

Keishibukuryogan reduces renal injury in the early stage of renal failure in the remnant kidney model.

The effects of keishibukuryogan on the early stage of progressive renal failure were examined in rats subjected to 5/6 nephrectomy. Keishibukuryogan, one of the traditional herbal formulations, was given orally at a dose of 1% (w/w) and 3% (w/w) in chow. Administration of keishibukuryogan was started at 1 week after 5/6 nephrectomy and was continued for 4 weeks.

Inhibitory effect of Yunnan traditional medicines on hepatitis C viral polymerase.

For the purpose of developing novel anti-hepatitis C virus (HCV) agents from natural resources, 93 Yunnan crude drugs were screened for their inhibitory effects on RNA-dependent RNA polymerase (RdRp) of HCV. Although 71 methanol extracts and 50 water extracts inhibited HCV-RdRp by more than 50% at a concentration of 50 μg/ml, the majority of them contained a high percentage of tannins. However, methanol extracts of Plumbago zeylanica (branch), Maytenus fookerii (leaf) and Huashidancha (Y61, branch and leaf), and water extracts of Potentilla griffithii (whole plant) and Salvia yunnanensis (underground part), having IC values of less than 10 μg/ml, showed less than 10% tannin content.

Synthesis and evaluation of anti-HIV-1 and anti-HSV-1 activities of 4H-[1,2,4]-triazolo[1,5-a]pyrimidin-5-one derivatives.

In a one pot procedure, 18 compounds of 7-(substituted phenyl)-2-substituted-6,7-dihydro-4H-[1,2,4]triazolo[1,5-a] pyrimidin-5-one derivatives (16-33) have been synthesized. 3(5)-Amino-5(3)-substituted-1,2,4-triazole derivatives (7-12) were used as synthomes which were cyclo-condensed by fusion with substituted methyl cinnamate esters (13-15) to afford the target compounds (16-33). In an effort to develop new non-nucleoside antiviral agents, compounds 16-33 were evaluated for their anti-HIV-1 and anti-HSV-1 activities.