Noralashinol A, a new norlignan from stem barks of <i>Syringa pinnatifolia</i>

<p>One new norlignan, namely noralashinol A (<b>1</b>), one known analogue (<b>2</b>), together with seven known lignans (<b>3</b>–<b>9</b>) were isolated from the stem barks of <i>Syringa pinnatifolia</i>. Their structures were elucidated extensively by spectroscopic methods, including mass spectrometry and 1D and 2D NMR spectroscopies. Compound <b>8</b> significantly inhibited NO production in LPS-induced BV-2 murine microglia cells with its IC₅₀ value of 20.7 μM, compared to a positive control quercetin with its IC₅₀ value of 15.3 μM.</p

QSYQ significantly decreased cell signal transduction pathway factors of pNFKB1 in rats with HF.

<p>pNFKB1 in model group increased compared with sham, while treated by QSYQ (H), (M) and (L) doses, the pNFKB1 level was significantly decreased. In captopril group, the level of pNFKB1 had no statistical significance compared to model group. n = 10∼14 for each group. Data were analyzed by one-way ANOVA, with p<0.05 indicating statistical significance. *Differed significantly from the model group (p<0.05), **Differed significantly from the model group (p<0.01).</p

Effects of QSYQ on MASSON results after occlusion of the left anterior descending (LAD) artery in rats.

<p>Representative results of Masson trichrome staining of the left ventrentricle in sham group (a).; model group (b).; QSYQ (H) (c).; QSYQ (M) (d).; QSYQ (L) (e).; Captopril group (f). Blue staining indicates myocardial fibrosis. Masson trichrome staining revealed different degree fibrosis in different groups. In sham group, there were almost no fibrosis region. While in model group, there were significant fibrosis region. the increase was significantly attenuated in different dosage of QSYQ groups and Captopril group by contrast with those in the model group. n = 10∼14 for each group.</p

QSYQ treatment significantly decreased cardiac MMP-2 and MMP-9 in rats with HF.

<p>MMP-2 and MMP-9 were remarkably up-regulated in model group, indicating elevated degree of remodeling changes. QSYQ (H) greatly suppressed myocardial hypertrophy and remodeling by MMP-2 and MMP-9. QSYQ (M) and QSYQ (L) can also play the same effect. The captopril only suppressed expression of MMP-2, without significant effect on MMP-9. n = 10∼14 for each group. Data were analyzed by one-way ANOVA, with p<0.05 indicating statistical significance. *p<0.05 and **p<0.01 vs. model group.</p

QSYQ treatment significantly decreased cardiac NADPHoxidase in rats with HF.

<p>The NADPHoxidase in model group was increased compared with sham group, while treated by QSYQ (H) and (M) doses, the levels showed 35.80% and 31.48% reduction, respectively. The treatment with QSYQ in low-dosage and captopril didn’t improve the NADPHoxidase significantly. The effect of QSYQ on NADPHoxidase showed a dosage-dependent manner. n = 10∼14 for each group. Data were analyzed by one-way ANOVA, with p<0.05 indicating statistical significance. *Differed significantly from the model group (p<0.05).</p

Levels of inflammation indicators in different groups (± s).

<p>Levels of inflammation indicators in different groups (± s).</p

Assessment of oxidative stress in different groups (± s).

<p>Assessment of oxidative stress in different groups (± s).</p

QSYQ significantly decreased cell signal transduction pathway factors of STAT3 and NF-κB in rats with HF.

<p>NF-κB in model group increased compared with sham, while treated by QSYQ (H) and (M) doses, the NF-κB level was significantly decreased. TheSTAT3 level in model group was up-regulated, while QSYQ at doses of 9.33 mg/kg (H) and 4.67 mg/kg (M) significantly decreased the STAT3 level respectively. After the administration of QSYQ (L) and captopril, the level of NF-κB and STAT3 had no statistical significance compared to model group. n = 10∼14 for each group. Data were analyzed by one-way ANOVA, with p<0.05 indicating statistical significance. *Differed significantly from the model group (p<0.05).</p

Protocol of the underlying mechanism of QSYQ in attenuating oxidative stress and inflammation signaling pathways in HF rats.

<p>QSYQ can reduce Left Ventricular Remodeling by Attenuating Inflammation and NADPH oxidase. It down-regulated the TNFα- NF-B and IL-6- STAT3 respectively to reduce the inflammation in heart failure. Futhermore, it also can supress the NADPH oxidase mediated oxidative stress injury to myocardial tissue. Finally, QSYQ can reduce the MMPs and collegen I and III in different degree and finally provide beneficial effects for clinical heart failure.</p

Results of Collagen I expression in different groups.

<p>The concentrations of collagens I in the model group (b) were obviously higher than those in sham group (a), indicating a cardiac remodeling in model rats. Whereas the levels of collagens I in high QSYQ (c), middle QSYQ (d) and low QSYQ groups (e) were remarkably lower than those in the model group. Captopril group (f) showed a same effect on suppressing the collagen synthesis. n = 10∼14 for each group. Quantitative analysis of collegen I was presented in (g). OD values represent the mean ± SD. *P<0.05 vs Model group, **P<0.01 vs Model group.</p