Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro / 中西医结合学报

<p><b>OBJECTIVE</b>Anti-asthma herbal medicine intervention (ASHMI(TM)), a combination of three traditional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMI(TM) exhibited synergy.</p><p><b>METHODS</b>Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme-linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters.</p><p><b>RESULTS</b>Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC25) values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50 values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-1. The interaction indices at IC50 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC50 values. All interaction indices were below 1 which indicated synergy.</p><p><b>CONCLUSION</b>By comparing the interaction index values, we find that constituents in ASHMI(TM) synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.</p>

Clinical effect of chaipo granule combined with routine treatment on refractory asthma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of Chaipo Granule (CPG) combined with routine treatment on refractory asthma.</p><p><b>METHODS</b>Sixty patient with refractory asthma were assigned equally in a double-blind, randomized way to the treatment group and the control group. Routine treatment (including regular inhalation of salmeterol and fluticasone propionate 50/250 microg, and if necessary, inhalation of salbutamol + ipratropium bromide) were given to all patients. CPG (3 pouches every time, twice a day) were administered to the treatment group in addition, while to the control group, placebo with similar appearance in equal volume was given. The therapeutic course for all was 24 weeks. Asthma control test (ACT) scoring and lung function tests (FEV1 and PEF) were performed before treatment and at the end of the 4th, 12th and 24th week; daily records of asthma, dose of hormone used, withdrawal reaction and adverse reaction occurred were monitored, and serum levels of cortisol, total IgE and cytokines (IL-4, IL-5, IL-13 and IFN-gamma) were measured before treatment and at terminating the 24-week treatment.</p><p><b>RESULTS</b>Symptoms and lung function were significantly improved after treatment in both groups, but the improvements were better in the treatment group than the control group at all time points, the difference between groups was statistically significant (P < 0.05). Levels of IL-5, IL-13, total IgE decreased, IFN-gamma and Cor increased in all patients after 24-week treatment, but the improvements in the treatment group was more significant, with statistical difference between groups (P < 0.05); the mean hormone withdrawal time in the treatment group was (14.6 +/- 5.1) days, with the incidence of systemic withdrawal reactions of 20%, while those in the control group was (22.1 +/- 6.8) days and 36.7% correspondingly, the difference between groups was statistically significant (P < 0.05). However, one patient in the treatment group quit the trial due to a severe seizure of asthma. No obvious treatment-related side effects appeared in the treatment group, except that 3 patients suffered from slight abdominal pain.</p><p><b>CONCLUSIONS</b>CPG could improve the clinical symptoms and lung function, facilitate to Th1/Th2 balance and enhance the secretion of adrenal cortex. It is an effective and safe Chinese herbal remedy for treatment of refractory asthma.</p>

Effects of dihydroxy-stilbene compound Vam3 on airway inflammation, expression of ICAM-1, activities of NF-kappaB and MMP-9 in asthmatic mice / 药学学报

The aim of the present study is to investigate the effects of Vam3 which is one of the dihydroxystilbene compounds on expressions of ICAM-1 in the lungs of OVA-induced asthmatic mice and the mechanisms of anti-airway inflammation. Balb/c mice were challenged with OVA inhalation. Lung tissues were stained with Mayer's hematoxylin and eosin for histopathologic examination. The expression of ICAM-1 in the lungs of mice was analyzed by Western blotting and immunohistochemistry method. The NF-kappaB activities were detected by NF-kappaB-luc reporter genetic transient transfection method. The activities of MMP-9 induced by LPS, TNF-alpha and PMA in THP-1 cells were determined by gelatin zymography method. The results showed that Vam3 could inhibit the expression of ICAM-1 in the OVA-induced mouse model. In addition, Vam3 could significantly suppress the activities of NF-kappaB in A549 cells and MMP-9 in THP-1 cells induced by LPS, TNF-alpha and PMA. These results suggested that Vam3 could alleviate the asthmatic inflammation by decreasing ICAM-1 expression in asthmatic mice, down regulating NF-kappaB and MMP-9 activities. Compound Vam3 showed inhibitory effects on inflammatory signal pathways involved in asthma.