Antinociceptive activity of astragaloside IV in the animal model of chronic constriction injury.

To investigate the applicability of astragaloside IV (AG) for the treatment of refractory neuropathic pain, we systemically evaluated the antinociceptive activity of AG in the animal model of chronic constriction injury. We studied behaviors, electrophysiology, and biochemistry from day 2 to day 23 after the surgery. We found that when administered intraperitoneally at the dose of 60 mg/kg, AG caused significant inhibition of allodynia and hyperalgesia induced by mechanic and thermal stimuli as well as downregulation of the expressions of a series of proteins involved in mediating neuropathic pain in the dorsal root ganglia, such as P2X purinoceptor 3, glial cell-derived neurotrophic factor, glial cell-derived neurotrophic factor family receptor α1, and transient receptor potential cation channel subtypes A1 and V1. Further investigation showed that AG restored the nerve conduction velocity and the histological structure of the damaged sciatic nerve on day 23 after the surgery. Moreover, results from immunoelectron microscope showed that glial cell-derived neurotrophic factor family receptor α1 induced by AG could form a circular band in the myelin debris between the injured axons and Schwann cells, contributing toward restoration of the damaged nerve. In conclusion, in our animal model, AG effectively inhibited the neuropathic pain induced by chronic constriction injury.

Evaluation of the wound-healing activity and anti-inflammatory activity of aqueous extracts from Acorus calamus L.

In folklore medicine, Acorus calamus has been used as a wound-healing agent for thousands of years; however, there have been few scientific reports on this activity so far. Now, we explored deeply the wound-healing effect of aqueous extracts from the fresh roots and rhizomes of A. calamus in vivo, as well as anti-inflammatory activity in vitro, so as to provide scientific evidence for the traditional application. The wound-healing effect was determined by the image analysis techniques and the histological analysis in the excisional wounding test, and the anti-inflammatory activity was evaluated by the real-time RT-PCR techniques in the lipopolysaccharide-induced RAW 264.7 cells test. Aqueous extracts, administered topically at the dose range from twice to thrice in a day, could enhance significantly the rate of skin wound-healing. Moreover, the extracts could effectively inhibit the mRNA expressions of inflammatory mediators induced by lipopolysaccharide in RAW 264.7 cells. These results showed significantly the wound-healing activity of aqueous extracts in the animal model of excise wound healing, and anti-inflammatory activity in vitro.

Antibacterial, antifungal and cytotoxic isoquinoline alkaloids from Litsea cubeba.

Five novel isoquinoline alkaloids (+)-N-(methoxylcarbonyl)-N-nordicentrin (1), (+)-N-(methoxylcarbonyl)-N-norpredicentrine (2), (+)-N-(methoxylcarbonyl)-N-norbulbodione (3), and (+)-N-(methoxylcarbonyl)-N-norisocorydione (4), and (+)-8-methoxyisolaurenine-N- oxide (5) were isolated, together with one known compound, (+)-N-(methoxylcarbonyl)- N-norglaucine (6), from a 70% EtOH extract of the barks of Litsea cubeba. Structural elucidation of all the compounds were performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. Alkaloids 1, 2 and 6 showed antimicrobial activity against the bacterium S. aureus and two fungi (A. alternata and C. nicotianae). Compounds 3,4 exhibited significant cytotoxicity against all of six tested tumor cell lines.

Analgesic activity of the aqueous fraction from the ethanolic extract of Chrysanthemum indicum in mice.

The aqueous fraction (AF) of an ethanolic extract from Chrysanthemum indicum was evaluated for analgesic activity in mice using chemical and thermal models of nociception. Given orally, AF at doses of 300 and 600 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin/capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. In the pentobarbital sodium-induced sleeping time test and the open-field test, AF neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed analgesic activity was unlikely due to sedation or motor abnormality. In a measurement of core body temperature, AF did not affect temperature within 80 min. Moreover, the effective dose (600 mg/kg) also showed no toxicity within 7 days. These results suggested further that AF produced analgesic activity possibly related to the flavonoid glycosides and phenolic glycosides in this fraction.

Antitumor activity of two gelsemine metabolites in rat liver microsomes.

Gelsemine is one of the major alkaloids from Gelsemium elegans Benth., which has been used as an antitumor remedy in clinic. In this paper, metabolism of gelsemine has been investigated in vitro in phenobarbital-treated rat liver microsomes. The metabolites of gelsemine were separated and evaluated using the flash silica gel column, preparative HPLC, using NMR and MS methods. According to the spectral data, two metabolites, M1 and M2, were identified as 4-N-demethylgelsemine and 21-oxogelsemine, respectively. By the MTT method in vitro, the antitumor activities between gelsemine and its metabolites were compared in the HepG2 and HeLa cell lines. Moreover, the main metabolic pathway was further proposed.

Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention: A meta-analysis.

BACKGROUND: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. METHODS: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. RESULTS: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P < 0.00001) and an 18% reduction in RR (RR 0.82, 95% CI [0.73, 0.93], P = 0.002) in the subgroup without renal transplant recipients and patients undergoing regular hemodialysis separately. For the fatal stroke incidences, intensive-dose statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. CONCLUSION: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences.

The analgesic activity and possible mechanisms of deacetyl asperulosidic acid methyl ester from Ji shi teng in mice.

Deacetyl Asperulosidic Acid Methyl Ester (DAAME) from Ji shi teng was evaluated on analgesic activity in mice using chemical and thermal models of nociception. Given intraperitoneally, DAAME, at doses of 40 and 80 mg/kg, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin/capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. In the open-field test and the rotarod test, DAAME couldn't impair the motor performance, indicating that the observed antinociception was unlikely due to motor abnormality. In a measurement of core body temperature, DAAME (80 mg/kg) did not affect temperature within 80 min. Moreover, DAAME-induced antinociception in the capsaicin test and the hot plate test was significantly antagonized by glibenclamide. The results suggested that DAAME-produced antinociception was possibly involved in the ATP sensitive K+ channels in the capsaicin test and the hot plate test, which merited exploring further.

The influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles.

Currently, concerns of clopidogrel and proton pump inhibitors (especially omeprazole) interaction are raised, because they are both metabolized by CYP2C19. What is more, omeprazole can also inhibit the activity of CYP2C19. The study was to compare the influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles. One hundred forty-two consecutive patients undergoing elective coronary stenting received aspirin and clopidogrel, and were randomized to omeprazole or the placebo. Enrolled patients were analyzed for adenosine diphosphate-induced platelet aggregation (ADP-Ag), and CYP2C19*2 and CYP2C19*3 were identified by polymerase chain reaction-restriction fragment length polymorphism. Of the patients included, 47 (33.1%) belonged to homozygous extensive metabolizers (homEMs) (CYP2C19*1/*1), 70 (49.3%) belonged to heterozygous extensive metabolizers (hetEMs) (*1/*2 or *1/*3), and 25 (17.6%) belonged to poor metabolizers (PMs) (*2/*3 or *2/*2). ADP-Ag had a significant difference among the three genotypic groups (p<0.01). Moreover, the present study revealed that the degree of the interaction between clopidogrel and omeprazole was not homogeneous within the various genotypes of CYP2C19. The difference of ADP-Ag between the patients with and without omeprazole was significantly largest in homEMs (45.7%±14.2% vs. 35.5%±16.0%, p<0.05). However, any significant difference of ADP-Ag between the patients with and without omeprazole was not observed in other two genotypic groups (hetEMs and PMs, p>0.05). In conclusion, concomitant therapy with omeprazole appears to reduce the antiplatelet effect of clopidogrel most significantly in homEMs of CYP2C19.

Mechanisms involved in the antinociception of petroleum ether fraction from the EtOH extract of Chrysanthemum indicum in mice.

The petroleum ether fraction (PEF) from the EtOH extract of flowers and buds of Chrysanthemum indicum was evaluated on antinociception in mice using chemical and thermal models of nociception. PEF administered orally at doses of 188 and 376 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and the hot plate test. In the pentobarbital sodium-induced sleep time test and the open-field test, PEF neither enhanced the pentobarbital sodium-induced sleep time nor impaired the motor performance, indicating that the observed antinociception was unrelated to sedation or motor abnormality. In a measurement of core body temperature, PEF did not affect temperature within 80 min. Moreover, PEF-induced antinociception in the capsaicin test was insensitive to naloxone, yohimbine or methylene blue, but was significantly antagonized by atropine and glibenclamide. These results suggested that PEF-produced antinociception might be involvement in the ATP sensitive K+ channels and the mAChRs-ATP sensitive K+ channels pathway. In additional, the antinociception of PEF might attribute to the synergic effects of these two compounds, 2-[[2-[2-[(2-ethylcyclopropyl)methyl] cyclop Cyclopropaneoctanoic and n-hexadecanoic acid, or the property of a single compound, which merited exploring further.