Protective Effect of Bojungikki-Tang against Radiation-Induced Intestinal Injury in Mice: Experimental Verification and Compound-Target Prediction.

Bojungikki-tang (BJIT) is a traditional herbal medicine used in Korea, Japan, and China to treat gastrointestinal disorders. In this study, we aimed to investigate whether BJIT has protective effects against radiation-induced intestinal injury and to predict the underlying therapeutic mechanisms and related pathways via network pharmacological analyses. BJIT was injected intraperitoneally (50 mg/kg body weight) to C3H/HeN mice at 36 and 12 h before exposure to partial abdominal irradiation (5 Gy and 13 Gy) to evaluate the apoptotic changes and the histological changes and variations in inflammatory cytokine mRNA levels in the jejunum, respectively. Through in silico network analysis, we predicted the mechanisms underlying BJIT-mediated regulation of radiation-induced intestinal injury. BJIT reduced the level of apoptosis in the jejunal crypts 12 h post 5-Gy irradiation. Histological assessment revealed intestinal morphological changes in irradiated mice 3.5 days post 13-Gy irradiation. Furthermore, BJIT decreased inflammatory cytokine levels following radiation exposure. Apoptosis, TNF, p53, VEGF, toll-like receptor, PPAR, PI3K-Akt, and MAPK signaling pathways, as well as inflammatory bowel disease (IBD), were found to be linked to the radioprotective effects of BJIT against intestinal injury. According to our results, BJIT exerted its potential protective effects by attenuating histopathological changes in jejunal crypts and suppressing inflammatory mediator levels. Therefore, BJIT is a potential therapeutic agent that can treat radiation-induced intestinal injury and its associated symptoms.

Chemical Constituents from the Aerial Parts of Agastache rugosa and Their Inhibitory Activities on Prostaglandin E2 Production in Lipopolysaccharide-Treated RAW 264.7 Macrophages.

A new flavone glucoside, acacetin-7-O-(3″-O-acetyl-6″-O-malonyl)-ß-d-glucopyranoside (1), two new phenolic glucosides, (3R,7R)-tuberonic acid-12-O-[6'-O-(E)-feruloyl]-ß-d-glucopyranoside (14) and salicylic acid-2-O-[6'-O-(E)-feruloyl]-ß-d-glucopyranoside (15), and two new phenylpropanoid glucosides, chavicol-1-O-(6'-O-methylmalonyl)-ß-d-glucopyranoside (17) and chavicol-1-O-(6'-O-acetyl)-ß-d-glucopyranoside(18), as well as 26 known compounds, 2-13, 16, and 19-31, were isolated from the aerial parts of Agastache rugose. The structures of the new compounds were established by spectroscopic/spectrometric methods such as HRESIMS, NMR, and ECD. The anti-inflammatory effect of the isolated compounds was evaluated by measuring their inhibitory activities on prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. New compounds 1, 15, 17, and 18 inhibited LPS-induced PGE2 production with IC50 values of 16.8 ± 0.8, 33.9 ± 4.8, 14.3 ± 2.1, and 48.8 ± 4.4 µM, respectively. Compounds 5, 7, 9-11, 13, 19, 20, 22, and 27-30 showed potent inhibitory activities with IC50 values of 1.7-8.4 µM.

Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton.

Semaphorins are implicated in glioma progression, although little is known about the underlying mechanisms. We have reported plexin-B3 expression in human gliomas, which upon stimulation by Sema5A causes significant inhibition of cell migration and invasion. The concomitant inactivation of Rac1 is of mechanistic importance because forced expression of constitutively active Rac1 abolishes these inhibitory effects. Furthermore, Sema5A induces prominent cell collapse and ramification of processes reminiscent of astrocytic morphology, which temporally associate with extensive disassembly of actin stress fibers and disruption of focal adhesions, followed by accumulation of actin patches in protrusions. Mechanistically, Sema5A induces transient protein kinase C (PKC) phosphorylation of fascin-1, which can reduce its actin-binding/bundling activities and temporally parallels its translocation from cell body to extending processes. PKC inhibition or fascin-1 knockdown is sufficient to abrogate Sema5A-induced morphological differentiation, whereas the process is hastened by forced expression of fascin-1. Intriguingly, Sema5A induces re-expression of glial fibrillary acidic protein (GFAP), which when silenced restricts differentiation of glioma cells to bipolar instead of multipolar morphology. Therefore, we hypothesize complementary functions of fascin-1 and GFAP in the early and late phases of Sema5A-induced astrocytic differentiation of gliomas, respectively. In summary, Sema5A and plexin-B3 impede motility but promote differentiation of human gliomas. These effects are plausibly compromised in high-grade human astrocytomas in which Sema5A expression is markedly reduced, hence leading to infiltrative and anaplastic characteristics. This is evident by increased invasiveness of glioma cells when endogenous Sema5A is silenced. Therefore, Sema5A and plexin-B3 represent potential novel targets in counteracting glioma progression.

Autologous epidermal grafting with PUVA-irradiated donor skin for the treatment of vitiligo.

BACKGROUND: Epidermal autografting has been used to treat vitiligo. The pigmentation achieved at the recipient site can be variegated and incomplete compared with that of the surrounding normal skin, and sometimes remains that way for a fairly long time. OBJECTIVE: We investigated whether the clinical results from epidermal autografting are related to a change in the number of melanocytes. This was performed by counting the number of melanocytes in the epidermis obtained from biopsy and suction with and without psoralen plus UVA (PUVA) exposure of the donor sites before grafting. METHODS: The numbers of melanocytes in the epidermis were counted after staining with dopa. The epidermis from suction and biopsy was included. The biopsied specimen was treated with NaBr for dermo-epidermal separation before staining, whereas the epidermis obtained from suction was stained directly. RESULTS: The epidermis obtained from suction contained 40-60% of the number of melanocytes found in the biopsied epidermis. Melanocytes around the hair follicles seemed to be omitted. Treatment with PUVA 10-21 times caused the number of melanocytes to increase by 1.5-2 times the normal level with a promising clinical result. CONCLUSIONS: The preparation of donor sites with PUVA before the treatment of vitiligo by epidermal autografting induced an increased number of melanocytes and improved the clinical result.

177 cardiovascular risk factors, classified in 10 categories, to be considered in the prevention of cardiovascular diseases: an update of the original 1982 article containing 96 risk factors.

The first comprehensive listing of cardiovascular risk factors was presented in this journal in 1982 in the article, "96 Cardiovascular Risk Factors" (by Y. Omura & S. Heller), which was the most extensive list of cardiovascular risk factors written on the subject at that time. Since then, much research has been carried out to identify cardiovascular risk factors; according to the authors' most recent computer search, close to 9,000 articles appeared between 1982 and 1996. Upon initial review of most of the abstracts of these articles, we were surprised to find that the number of cardiovascular risk factors has increased significantly (79 new factors in addition to those we published in 1982). With a few exceptions (7 risk factors are now considered to be questionable), those we listed in 1982 are still valid today, and have been further confirmed with additional data and improved technology. Through reviewing the abstracts of these articles, we found about 177 cardiovascular risk factors, including most of the 96 previously listed. Of the original 96, we have identified those now considered to be questionable, e.g. taking oral contraceptives, which today contain significantly lower doses of estrogen than in the past and are therefore much safer. All 177 cardiovascular risk factors are classified into the following 10 major categories, with the 11th category listing those factors now considered to be questionable: 1) Nutrition-Related Cardiovascular Risk Factors (33 risk factors) 2) Internal Cardiovascular Risk Factors Identifiable by Laboratory Tests: Abnormal Blood & Tissue Chemistry Findings Related to Cardiovascular Diseases (35 risk factors) 3) Drug, Chemical, Hormonal, and Nutritional Supplement Intake (Including Drug-Drug Interaction and Drug-Food Interaction) As Cardiovascular Risk Factors (34 risk factors) 4) Signs and Symptoms Associated With a High Incidence of Cardiovascular Diseases (33 risk factors) 5) Non-Invasively Detectable Abnormal Laboratory Findings Associated With Cardiovascular Diseases (13 risk factors) 6) Hereditary Cardiovascular Risk Factors (5 risk factors) 7) Environmental Cardiovascular Risk Factors, Including Air Pollution, Electromagnetic Fields, Materials that Contact the Body Surface, Poisonous Venoms, and Insertion of Needle into Infected Body Tissue by Acupuncture of Injection (14 risk factors) 8) Socioeconomic and Demographic Cardiovascular Risk Factors (7 risk factors) 9) Cardiovascular Risk Factors Related to Medical Care (2 risk factors) 10) Co-existence of Multiple Cardiovascular Risk Factors (1 risk factor) 11) Factors Previously Regarded As Cardiovascular Risk Factors, But Now in Question (7 risk factors) While a few factors, like hereditary characteristics, age, and sex, generally cannot be changed, most of the cardiovascular risk factors can be controlled by changing one's lifestyle, maintaining proper dietary intake, and correcting any existing abnormalities once each individual's unique constellation of cardiovascular risk factors is recognized. Some factors can be recognized by individuals themselves, but many other factors require physical examinations and laboratory tests by a physician or properly trained paramedical to be recognized. Medical examinations and blood chemistry and other laboratory tests may be necessary to establish baselines and measure changes over time. Once abnormal parameters are identified, periodic examinations should follow with proper corrective measures monitored by a qualified medical professional.

Chlorosilphanol A and silphanepoxol, labdane diterpenes from Silphium perfoliatum.

Two carterochaetols, chlorosilphanol A and silphanepoxol, isolated from the leaves of Silphium perfoliatum were assigned structures 1 and 3, respectively, from spectral studies and with absolute stereochemistry established by X-ray crystallography of 1. Complete 1H- and 13C-nmr assignments for the parent compounds and their acetates 2 and 4 were made at high-field using 1D and 2D methods, and chlorosilphanol A was chemically converted via its acetate to silphanepoxol. Revision of structure for related carterochaetols in the literature is required, in particular with respect to the stereochemistry at C-12 and that of the side-chain.

Antiarrhythmic action of naloxone. Suppression of picrotoxin-induced cardiac arrhythmias in the rat.

The antiarrhythmic properties of the opiate antagonist naloxone have been reported in a variety of models of arrhythmia. To determine the generality and the possible central involvement of its antiarrhythmic activity, the effects of naloxone were assessed against cardiac arrhythmias induced by intravenous bolus injections of picrotoxin. Naloxone at doses of 0.33 and 1 mg/kg significantly reduced the incidence and severity of picrotoxin-induced arrhythmias in a dose-related manner, without alteration of blood pressure and heart rate. The results demonstrate the antiarrhythmic efficacy of naloxone in an additional animal model. They further suggest that the antiarrhythmic actions of naloxone may be mediated by the central nervous system via both the autonomic and GABAergic pathways.

Cardiovascular effects of central administration of beta-endorphin in rats receiving neonatal injection of monosodium glutamate.

1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.) injection of beta-endorphin on arterial blood pressure (BP) in rats that received five intraperitoneal injections of monosodium glutamate (MSG) on alternate days in the first 10 days of life were studied. 2. beta-endorphin administered into the lateral ventricles caused a prolonged elevation in BP, whereas i.c. injection of the peptide resulted in an even longer lasting reduction in BP. In the MSG-treated rat, the prolonged hypertensive effect of i.c.v. injection of beta-endorphin was completely abolished, but the effect of i.c. injection of the peptide was the same as that in the control. Since MSG treatment destroyed selectively the structures around the third ventricle, it is suggested that these structures, including the arcuate nucleus, may be responsible for mediating the cardiovascular effects of beta-endorphin. 3. The effects of central administration of beta-endorphin were completely blocked by naloxone, which mainly antagonizes the actions of mu-receptor agonists and has no cardiovascular effects itself. The results suggest that mu-receptors may be involved in mediation of the effects of beta-endorphin on the cardiovascular system and that beta-endorphin in the brain may not exert a tonic influence on the cardiovascular functions.

A cardiac antiarrhythmic screening test using the isolated ischaemic perfused rat heart preparation.

Ventricular fibrillation was induced by myocardial ischaemia and reperfusion in the isolated perfused rat heart. The dose-response effectiveness for the prototype antiarrhythmic drugs, propranolol, quinidine and lidocaine in converting the induced ventricular fibrillation to sinus rhythm was determined. The test is easy to perform and does not require skillful surgical procedure and long time for observation. In addition, no arrhythmogenic drugs are used and the amount of substance needed for the test is very small. It is suggested that this simple test be used as a cardiac antiarrhythmic screening test for antiarrhythmic drugs.