Folium Sennae and emodin reverse airway smooth muscle contraction.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

Polygonum aviculare L. extract and quercetin attenuate contraction in airway smooth muscle.

Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients that inhibit the precontraction of mouse and human airway smooth muscle (ASM). High K+-induced precontraction in ASM was completely inhibited by nifedipine, a selective blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only partially reduced the precontraction induced by acetylcholine chloride (ACH). Additionally, the ACH-induced precontraction was partly reduced by pyrazole-3 (Pyr3), a selective blocker of TRPC3 and stromal interaction molecule (STIM)/Orai channels. These channel-mediated currents were inhibited by the compounds present in P. aviculare extracts, suggesting that this inhibition was mediated by LVDCCs, TRPC3 and/or STIM/Orai channels. Moreover, these channel-mediated currents were inhibited by quercetin, which is present in P. aviculare extracts. Furthermore, quercetin inhibited ACH-induced precontraction in ASM. Overall, our data indicate that the ethyl acetate fraction of P. aviculare and quercetin can inhibit Ca2+-permeant LVDCCs, TRPC3 and STIM/Orai channels, which inhibits the precontraction of ASM. These findings suggest that P. aviculare could be used to develop new bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease.

Cortex phellodendri Extract Relaxes Airway Smooth Muscle.

Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component) was prepared, which completely inhibits high K(+)- and acetylcholine- (ACH-) induced precontraction of airway smooth muscle in tracheal rings and lung slices from control and asthmatic mice, respectively. The contraction induced by high K(+) was also blocked by nifedipine, a selective blocker of L-type Ca(2+) channels. The ACH-induced contraction was partially inhibited by nifedipine and pyrazole 3, an inhibitor of TRPC3 and STIM/Orai channels. Taken together, our data demonstrate that NBAECP can relax ASM by inhibiting L-type Ca(2+) channels and TRPC3 and/or STIM/Orai channels, suggesting that NBAECP could be developed to a new drug for relieving bronchospasm.

Picture representation during REM dreams: a redox molecular hypothesis.

A novel molecular hypothesis about visual perception and imagery has recently been proposed (Bókkon, 2009; BioSystems). Namely, external electromagnetic visible photons are converted into electrical signals in the retina and are then conveyed to V1. Next, these retinotopic electrical signals (spike-related electrical signals along classical axonal-dendritic pathways) can be converted into synchronized bioluminescent biophoton signals (inside the neurons) by neurocellular radical reactions (redox processes) in retinotopically organized V1 mitochondrial cytochrome oxidase-rich visual areas. The bioluminescent photonic signals (inside the neurons) generated by neurocellular redox/radical reactions in synchronized V1 neurons make it possible to produce computational biophysical pictures during visual perception and imagery. Our hypothesis is in line with the functional roles of reactive oxygen and nitrogen species in living cells and states that this is not a random process, but rather a strict mechanism used in signaling pathways. Here, we suggest that intrinsic biophysical pictures can also emerge during REM dreams.

Electroacupuncture (EA) modulates the expression of NMDA receptors in primary sensory neurons in relation to hyperalgesia in rats.

N-methyl-D-aspartate (NMDA) receptor on the central terminals of the dorsal root ganglion (DRG) appears to be playing an important role in the development of central sensitization related to persistent inflammatory pain. Acupuncture analgesia has been confirmed by numerous clinical observations and experimental studies to be a useful treatment to release different kinds of pains, including inflammatory pain and hyperalgesia. However, the underlying mechanisms of the analgesic effect of acupuncture are not fully understood. In the present study, using a rat model of inflammatory pain induced by complete Freund's adjuvant (CFA), we observed the effect of electroacupuncture (EA) on animal behavior with regard to pain and the expression of a subunit of NMDA receptor (NR1) and isolectin B4 (IB4) in the neurons of the lumbar DRG. Intraplantar injection of 50 microl CFA resulted in considerable changes in thermal hyperalgesia, edema of the hind paw and "foot-bend" score, beginning 5 h post-injection and persisting for a few days, after which a gradual recovery occurred. The changes were attenuated by EA treatment received on the ipsilateral "Huan Tiao" and "Yang Ling Quan" once a day from the first day post-injection of CFA. Using an immunofluorescence double staining, we found that the number of double-labeled cells to the total number of the IB4 and NR1-labeled neurons increased significantly on days 3 and 7 after CFA injection. The change was attenuated by EA treatment. These results suggest that EA affects the progress of experimental inflammatory pain by modulating the expression of NMDA receptors in primary sensory neurons, in particular, IB4-positive small neurons.

Electroacupuncture modulates cortical activities evoked by noxious somatosensory stimulations in human.

A noninvasive high-resolution imaging technique of cerebral electric activities has been developed to directly link scalp potential measurement with the magnetic resonance images of the subjects, which is very helpful for the elucidation of the cortical processing following various stimulations. Here, we used a 64-channel Neuroscan ESI-128 system to explore the specific cortical activities elicited by electroacupuncture (EA) acupoint in normal volunteers and the modulatory effect of EA on cortical activities evoked by noxious somatosensory stimulation. A specific later-latency somatosensory-evoked potential (SEP, P150) located in bilateral anterior cingulated cortex was observed after EA acupoint but not non-acupoint. Two pain-specific SEP components (P170 and N280), located in bilateral suprasylvian operculum and anterior cingulated cortex respectively were observed following painful median nerve stimulation. Binding EA acupoint with painful median nerve stimulation, the amplitudes of P170 and N280 appeared to be attenuated significantly, 2D topography exhibited tremendous decrease of cortical activation between 120 ms and 296 ms in latency, and visual analogue scale (VAS) changes also showed a similar pattern to the change of amplitude. The bilateral anterior cingulated cortex recruited following acupoint stimuli might, to some extent, suggest that EA has the specific physiological effects. Decrease of pain-induced cortical activation by EA acupoint was considered to be mainly due to an interaction of the signals in anterior cingulated cortex ascending from the pain stimulation and EA.