Rhizoma Coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFκB-Dependent Pathway

Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFκB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. Results. Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP)-1 production in RAW cells. Activation of the transcription factors AP-1 and NFκB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. Conclusions. Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFκB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine

Autonomic effects of music in health and Crohn's disease:the impact of isochronicity, emotional valence, and tempo

BACKGROUND: Music can evoke strong emotions and thus elicit significant autonomic nervous system (ANS) responses. However, previous studies investigating music-evoked ANS effects produced inconsistent results. In particular, it is not clear (a) whether simply a musical tactus (without common emotional components of music) is sufficient to elicit ANS effects; (b) whether changes in the tempo of a musical piece contribute to the ANS effects; (c) whether emotional valence of music influences ANS effects; and (d) whether music-elicited ANS effects are comparable in healthy subjects and patients with Crohn´s disease (CD, an inflammatory bowel disease suspected to be associated with autonomic dysfunction). METHODS: To address these issues, three experiments were conducted, with a total of n = 138 healthy subjects and n = 19 CD patients. Heart rate (HR), heart rate variability (HRV), and electrodermal activity (EDA) were recorded while participants listened to joyful pleasant music, isochronous tones, and unpleasant control stimuli. RESULTS: Compared to silence, both pleasant music and unpleasant control stimuli elicited an increase in HR and a decrease in a variety of HRV parameters. Surprisingly, similar ANS effects were elicited by isochronous tones (i.e., simply by a tactus). ANS effects did not differ between pleasant and unpleasant stimuli, and different tempi of the music did not entrain ANS activity. Finally, music-evoked ANS effects did not differ between healthy individuals and CD patients. CONCLUSIONS: The isochronous pulse of music (i.e., the tactus) is a major factor of music-evoked ANS effects. These ANS effects are characterized by increased sympathetic activity. The emotional valence of a musical piece contributes surprisingly little to the ANS activity changes evoked by that piece

Stimuli and procedure of Experiment 1.

<p>A, B, and C show 30 second samples of a triplet of corresponding acoustic stimuli used. Notice that the isochronous tones in B and C have identical tempi as the stimulus in A. D demonstrates the sequence of one trial. Twenty-five such trials with different stimuli were presented. Before and after each auditory stimulus, short sinus tone sequences (indicated by the two notes in the figure) were used to notify the subjects that a trial will start, respectively the rating procedure will follow.</p

Heart rate variability results of Experiment 3.

<p>The acoustic stimuli decreased all heart rate variability parameters compared to silence except the LF/HF ratio, thus reproducing the results of Experiment 1 and 2. Note the generally similar results of healthy subjects and Crohn′s disease patients. This demonstrates that Crohn′s disease is not per se characterized by a different autonomic tone or autonomic reactivity. <i>Lg</i>: indicates logarithmized data where transformation was applied; <i>Pleasant</i>: pleasant music; <i>Unpleasant</i>: music-like noise; *: <i>p</i> < .05; **: <i>p</i> < .01; ***: <i>p</i> < .001. For description of HRV parameters see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126224#pone.0126224.t001" target="_blank">Table 1</a>.</p

Summary of heart rate and heart rate variability effects of pleasant music compared to silence.

<p>Summary of heart rate and heart rate variability effects of pleasant music compared to silence.</p

Clinical characteristics of Crohn′s disease patients of Experiment 3.

<p>Clinical characteristics of Crohn′s disease patients of Experiment 3.</p

Summary of heart rate and heart rate variability effects of isochronous tones, music-like noise, and unpleasant music compared to silence.

<p>Summary of heart rate and heart rate variability effects of isochronous tones, music-like noise, and unpleasant music compared to silence.</p

Characteristics of participants in Experiment 3.

<p>Characteristics of participants in Experiment 3.</p