NXC736 Attenuates Radiation-Induced Lung Fibrosis via Regulating NLRP3/IL-1β Signaling Pathway.

Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown.

Sphingosine 1-Phosphate Receptor 4 Promotes Nonalcoholic Steatohepatitis by Activating NLRP3 Inflammasome.

Background & Aims: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear.

Methods: We investigated which type of S1PR isoforms is activated in various murine models of NASH.

Exposure assessment of epidermal growth factor to various tissues in mice after intravenous and subcutaneous administration.

Objectives: This study was conducted to examine the tissue distribution of human recombinant epidermal growth factor (EGF) after multiple intravenous and subcutaneous injections in mice.

Methods: Male BALB/c mice were divided into (1) EGF 1 mg/kg intravenous dose, (2) EGF 5 mg/kg intravenous dose, (3) drug-free intravenous control, (4) EGF 1 mg/kg subcutaneous dose, (5) EGF 5 mg/kg subcutaneous dose and (6) drug-free subcutaneous control groups. EGF and drug-free dosing solutions were injected by intravenous and subcutaneous injections once a day for 3 days.

Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation.

In this study, the synergistic effect of 6-[4-(1-cyclohexyl- 1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H )-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice.

Anti-inflammatory and analgesic activities of SKLJI, a highly purified and injectable herbal extract of Lonicera japonica.

The parenteral route has many merits over the oral route, including greater predictability, reproducibility of absorption, and rapid drug action, but injectable phytomedicines are uncommon due to protein precipitating tannin and hemolytic saponin components. In this study, in an effort to develop a safe injectable analgesic phytomedicine, we prepared a tannin and saponin-free Lonicera japonica extract, SKLJI, through fractionation and column purification, and evaluated its anti-inflammatory and analgesic activities in in vivo experimental models of inflammation and pain. The removal of tannin and saponin resulted in loganin and sweroside-enriched SKLJI and it showed reduced hemolysis and protein precipitation.

Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons.

Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied.

Enhancement of gastric ulcer healing and angiogenesis by cochinchina Momordica seed extract in rats.

Cochinchina momordica seed is the dried ripe seed of Momordica cochinchinensis, a perennial vine. The antiulcer effect of an extract from cochinchina momordica seeds (SK-MS10) was evaluated in a rat model of acetic acid-induced gastric ulcers. Gastric ulcers were produced by subserosal injection of acetic acid.

Pharmacokinetics of mirodenafil, a new erectogenic, and its metabolite, SK3541, in rats: involvement of CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 for the metabolism of both mirodenafil and SK3541.

Purpose: This study was performed to find which types of hepatic CYP isoforms are responsible for the metabolism of mirodenafil (a new erectogenic) and one of its metabolite, SK3541, using various hepatic CYP inducers and inhibitors in rats.

Methods: Mirodenafil at a dose of 20 mg/kg was administered intravenously to control rats and rats pretreated with various CYP inducers and inhibitors. The disappearance of SK3541 was also measured in vitro hepatic microsomes of rats with and without CYP inducer and inhibitors.

Pharmacodynamic (hemodynamic) and pharmacokinetic comparisons of S-amlodipine gentisate and racemate amlodipine besylate in healthy Korean male volunteers: two double-blind, randomized, two-period, two-treatment, two-sequence, double-dummy, single-dose crossover studies.

Background: S-amlodipine gentisate, consisting entirely of the (S)-enantiomer, was developed to increase the potency and improve the safety profile of amlodipine. Regulatory requirements for marketing of S-amlodipine gentisate in Korea require comparison of this agent versus amlodipine racemate.

Objective: This study was conducted to compare the pharmacodynamic (PD) and pharmacokinetic (PK) characteristics of the S-amlodipine formulation (S-amlodipine gentisate) and amlodipine racemate (amlodipine besylate).

Influence of alcohol on the hemodynamic effects and pharmacokinetic properties of mirodenafil: a single-dose, randomized-sequence, open-label, crossover study in healthy male volunteers in Korea.

Background: Mirodenafil is a phosphodiesterase type 5 (PDE-5) inhibitor developed for the treatment of erectile dysfunction. Mirodenafil has the possibility of being administered with alcohol.

Objective: This study assessed the hemodynamic effects and pharmacokinetic properties of mirodenafil administered with alcohol.

Ginkgo biloba extract enhances antiplatelet and antithrombotic effects of cilostazol without prolongation of bleeding time.

Thrombosis and thromboembolic occlusions of major and minor blood vessels are a major complication in various peripheral vascular diseases. Antiplatelet agents (APA), key tools in the treatment of atherothrombosis, therefore became a mainstay medication for a wide range of vascular diseases. Cilostazol and Ginkgo biloba extract (GB), commonly used remedies for peripheral arterial disease, inhibit platelet aggregation with distinct therapeutic mechanisms.

Gastroprotective action of Cochinchina momordica seed extract is mediated by activation of CGRP and inhibition of cPLA(2)/5-LOX pathway.

Cochinchina momordica seed extract (SKMS10), which is composed of the major compounds momordica saponins, has been evaluated for its gastroprotective effects in rat models of acute gastric mucosal damage. Ethanol and water immersion restraint stress (WRS) induced gastric damage, including hemorrhages and edema, was significantly attenuated by pretreatment with SK-MS10. In addition, SK-MS10 reduced increases of mucosal myeloperoxidase (MPO), IL-1β, and TNFα levels and the expression of cPLA(2), and 5-LOX induced by ethanol or WRS.

Determination of mirodenafil and sildenafil in the plasma and corpus cavernous of SD male rats.

The purpose of the present study was to determine sildenafil and a novel PDE-5 inhibitor, mirodenafil in the plasma and corpus cavernosum tissue of rats to compare their pharmacokinetic properties. The concentrations of mirodenafil and sildenafil in the rat plasma and corpus cavernosum tissue samples were analyzed using LC-MS/MS after a single oral administration at a dose of 40mg/kg to rats. Although the T(max), Tlambda(1/2) and MRT were not different between mirodenafil and sildenafil, the C(max) and AUC of mirodenafil were significantly higher than those of sildenafil in the plasma and corpus cavernosum tissue.

LC-MS/MS method for determination of hederacolchiside E, a neuroactive saponin from Pulsatilla koreana extract in rat plasma for pharmacokinetic study.

A simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to pharmacokinetic study of a neuroactive oleanolic-glycoside saponin, hederacolchiside E from SK-PC-B70M, a standardized extract of Pulsatilla koreana in rat. Rat plasma samples were pretreated by protein precipitation with acetonitrile, eluted from C(18) column, and analyzed using electrospray ionization (ESI)-MS/MS in negative ion mode. Digoxin was used as an internal standard.