AIMTo develop a HPLC-ESI-MS assay for determination of eperisone hydrochloride in human plasma and investigate the pharmacokinetics and bioequivalence of two eperisone hydrochloride tablets in human.

METHODSBuflomedil hydrochloride was used as the internal standard. After alkalized with saturated sodium bicarbonate solution, plasma was extracted with diethylether-cyclohexane (1:1) and separated using HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 3.88 with acetic acid)-methanol (20:80). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 260 for eperisone and m/z 308 for the internal standard. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer.

RESULTSCalibration curve was linear over the range of 0.02-20 microg x L(-1). The limit of quantification for eperisone hydrochloride in plasma was 0.02 microg x L(-1). The main pharmacokinetics parameters T1/2, Tmax and Cmax were (2.7 +/- 0.4) h, (1.1 +/- 0.5) h and (2.8 +/- 2.8) microg x L(-1) for the reference tablet; (2.8 +/- 0.5) h, (1.1 +/- 0.4) h and (3 +/- 4) microg x L(-1) for the test tablet, respectively. The relative bioavalability of the test tablet was (101 +/- 13)%.

CONCLUSIONThe assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.

Adult ; Chromatography, High Pressure Liquid ; Humans ; Male ; Propiophenones ; administration & dosage ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Therapeutic Equivalency

Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully.
Female ; Humans ; Hypersensitivity/*etiology ; Middle Aged ; Muscle Relaxants, Central/*adverse effects ; Propiophenones/adverse effects ; Quinazolines/adverse effects

Eperisone hydrochloride is an antispasmodic drug, decreasing spasticity of skeletal muscle and alleviating stiffness, and as a consequence, controlling pain. It is preferably prescribed with other analgesics, beneficially less decreasing alertness compared with other antispasmodics. Its fatal drug adverse reactions were rarely reported. A 70 year-old female with hives, swollen face, hoarse voice, and near fainting admitted via emergency department. She suffered from the series of the fatal symptoms after administration of the pills, prescribed for her neck pain. Two months before, she had experienced hives on similar medications. At presentation, she revealed hypoxemia and hypotension, and treated with epinephrine, glucocorticoids and antihistamines. Among the medicines she took, eperisone hydrochloride was proven as the causative medicine and others were excluded in oral provocation tests. The positive result in intradermal test with eperisone hydrochloride suggested immediate-type hypersensitivity reaction. We report a case of anaphylaxis to eperisone hydrochloride, one of the widely prescribed medicines in clinical practice, previously without awareness of drug adverse reaction.
Analgesics ; Anaphylaxis ; Anoxia ; Drug Hypersensitivity ; Emergencies ; Epinephrine ; Female ; Glucocorticoids ; Histamine Antagonists ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Hypotension ; Intradermal Tests ; Muscle Spasticity ; Muscle, Skeletal ; Muscles ; Neck Pain ; Parasympatholytics ; Propiophenones ; Syncope ; Urticaria ; Voice

OBJECTIVETo compare clinical effects of spinal leveraging manipulation and medicine for the treatment of degenerative scoliosis in pain and function.

METHODSFrom July 2010 to June 2013, 38 patients with degenerative scoliosis were randomly divided into spinal leveraging manipulation group and medicine group by coin tossing. In manipulation group, there were 9 males and 11 females aged from 58 to 74 years old with an average of (66.63±7.73), the courses of diseases ranged from 3 to 8 months with an average of (5.65±2.58), spinal leveraging manipulation(following meridian to straighten tendon,relieving spasm, osteopathy and massage, clearing and activating the channels and collaterals) were performed for 30 min, once a day, 4 days for a period treatment, totally 9 courses. In medicine group, there were 8 males and 10 females aged from 57 to 70 years old with an average of (63.51±6.61) the courses of diseases ranged from 3 to 5 months with an average of (4.82±1.43), celecoxib with eperisone hydrochloride were orally taken, 4 days for a period treatment, totally 9 courses. VAS score, Cobb angle and ODI score were measured.

RESULTSAfter treatment, VAS score in manipulation group was (5.38±0.99), (6.36±1.31) in medicine group,and had significant meaning (t=2.618, P<0.05); there was significant differences in Cobb angle between manipulation group (16.51±4.89)° and medicine group (19.85±5.03) °(t=2.074,P<0.05); and had obviously meaning in ODI score between manipulation group (20.20±2.93) and medicine group (26.01±3.11) (t=5.592, P<0.05).

CONCLUSIONSpinal leveraging manipulation for degenerative scoliosis could regulate muscle balance on both side of spine, correct coronal imbalances in spine, recover normal sequence of spine, reduce and remove opperssion and stimulation of nerve root, relieve pain in leg and waist and further improve quality of life.

Aged ; Case-Control Studies ; Celecoxib ; Female ; Humans ; Lumbar Vertebrae ; surgery ; Male ; Manipulation, Spinal ; Middle Aged ; Propiophenones ; administration & dosage ; Pyrazoles ; administration & dosage ; Scoliosis ; drug therapy ; therapy ; Sulfonamides ; administration & dosage ; Treatment Outcome

Xanthohumol (XH), the principal prenylflavonoid of the hop plant (Humulus lupulus L.), dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis in B16 melanoma cells, with little cytotoxicity at the effective concentrations. Decreased melanin content was accompanied by reduced tyrosinase enzyme activity, protein and mRNA expression. The levels of tyrosinase-related protein 1 and 2 mRNAs were decreased by XH. XH also inhibited alpha-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. XH downregulated the protein and mRNA expression of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of key melanogenic enzymes. These results suggest that XH might act as a hypo-pigmenting agent through the downregulation of MITF in the cAMP-dependent melanogenic pathway.
1-Methyl-3-isobutylxanthine/pharmacology ; Animals ; Cell Line ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; Drug Antagonism ; Forskolin/pharmacology ; *Humulus ; Intramolecular Oxidoreductases/antagonists & inhibitors/biosynthesis ; Melanins/antagonists & inhibitors/*biosynthesis ; Melanocytes/*drug effects/*metabolism ; Melanoma, Experimental ; Membrane Glycoproteins/antagonists & inhibitors/biosynthesis ; Mice ; Microphthalmia-Associated Transcription Factor/antagonists & inhibitors ; Monophenol Monooxygenase/antagonists & inhibitors/biosynthesis/genetics ; Oxidoreductases/antagonists & inhibitors/biosynthesis ; Propiophenones/*pharmacology ; Signal Transduction/drug effects ; alpha-MSH/metabolism

OBJECTIVETo investigate the anti-HIV constituents from the root of Polygonatum kingianum.

METHODThe compounds were isolated by column chromatography on silica gel, Sephadex LH-20, MCI-gel CHP-20P and their structures were determined on the basis of their spectroscopic evidence including IR, MS and NMR data.

RESULT13 compounds were isolated, of which nine compounds were identified as liquiritigenin, isoliquiritigenin, 4', 7-dihydroxy-3'-methoxyisoflavone, (6aR, 11aR)-10-hydroxy-3, 9-dimethoxypterocarpan, 5-hydroxymethyl-2-furancarboxaldehyde, salicylic acid, n-butyl-beta-D-fructopyranoside, n-butyl-beta-D-fructofuranoside, n-butyl-alpha-D-fructofuranoside.

CONCLUSIONCompounds 1-6 were obtained from this plant for the first time.

Chalcone ; analogs & derivatives ; chemistry ; isolation & purification ; Chalcones ; Flavanones ; Flavonoids ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Polygonatum ; chemistry ; Salicylic Acid ; chemistry ; isolation & purification

Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TI-I-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-kappaB (NF-kappaB) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation.
Cell Survival ; Chalcone* ; Chalcones ; Chemokine CCL2 ; Chemokines ; Gene Expression ; Inflammation ; Luciferases ; Macrophages* ; Phosphorylation ; Reactive Oxygen Species ; RNA, Messenger ; Transcription Factor AP-1 ; Transcriptional Activation

Propafenone (Rythmonorm) was administered intravenously at a dose of 5mg/kg/3h to treat an atrial fibrillation case. Synal rhythm was restored in 2.30 hours with a QRS complex enlargement. 3 hours later on, a blood pressure drop as well as a cerebral and myocardial ischemia lasting 2 days were noted and were managed effectively with isoproterenol and dopamine. These drugs administered orally in divided doses up to 450 mg/day can put an end to the atrial fibrillation paroxysm while the maintenance dose of 450mg/day in fractional doses can prevent atrial fibrillation recurrence
Anti-Arrhythmia Agents ; Propafenone ; Overdose ; Accidents

Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-alpha), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-kappaB (NF-kappaB) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.
Chalcone* ; Chalcones ; Cyclooxygenase 2 ; Down-Regulation ; Gene Expression ; Genes, Reporter ; Heme Oxygenase-1* ; Inflammation ; Interleukin-6 ; Luciferases ; Macrophages* ; Nitric Oxide Synthase Type II ; Nitric Oxide* ; Phosphotransferases ; RNA, Messenger ; RNA, Small Interfering ; Transcription Factor AP-1* ; Transfection ; Tumor Necrosis Factor-alpha

AIMTo study the chemical constituents of Caragana intermedia.

METHODSThe compounds were separated by chromatography methods, their structures were identified by spectral analysis.

RESULTSTen compounds were isolated and identified as 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (1), 3,5,7,8,4'-pentahydroxy-3'-methoxyflavone(2), puercetin(3), limocitrin(4), 5,7,3',4'-tetrahydroxy-3-methoxyflavone(5), 7,3',5'-trihydroxyflavanone(6), 5,7,3',4'-tetrahydroxy-3,8-dimethoxyflavone(7), butein(8), liquiritigenin(9) and 5,7,4'-trihydroxy-3,8-dimethoxyflavone(10).

CONCLUSIONCompound 6 is a new compound and the others were obtained from this plant for the first time.

Caragana ; chemistry ; Chalcone ; analogs & derivatives ; chemistry ; isolation & purification ; Chalcones ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flavanones ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Molecular Structure ; Plants, Medicinal ; chemistry ; Quercetin ; chemistry ; isolation & purification