Therapeutic effects of liver soothing pingchuan formula decoction on experimental asthma in BALB/c mice via regulation of nerve growth factor-tyrosine kinase A pathway.

The present study was designed to investigate the effects of liver soothing pingchuan formula decoction (LSPF) on experimental asthma in BALB/c mice and explore its potential molecular mechanisms. An animal model of asthma was established in BALB/c mice through sensitization and activation with intraperitoneal injection of 10% ovalbumin (OVA)/Al(OH)3 solution in addition to inhalation of a 5% OVA solution. LSPF (300 and 600 mg/kg/day) was initially administered orally prior to activation. Following this, bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histopathalogical examination. Levels of inflammatory cells and cytokines were determined in the BALF, and levels of nerve growth factor (NGF) and tyrosine kinase A (TrkA) in the lung tissues were determined. The results of the present study indicated that increased inflammatory reactions were observed following OVA sensitization (P<0.05), and the expression levels of NGF (P<0.05) and TrkA (P<0.05) were significantly increased, compared with normal mice. Notably, compared with the asthma model group, immunohistochemical results revealed that LSPF treatment suppressed OVA induced inflammatory reactions (P<0.05) and NGF (P<0.05) and TrkA expression levels (P<0.05). In addition, the NGF (P<0.05) and TrkA (P<0.05) were revealed to be downregulated with LSPF treatment from the results of the ELISA and western blotting assay. Overall, the results of the present study demonstrated that LSPF exhibits therapeutic effects on experimental asthma in mice, via downregulation of the NGF-TrkA pathway.

Effect of treatment with geraniol on ovalbumin-induced allergic asthma in mice.

BACKGROUND: Asthma, a complex highly prevalent airway disease, is a major public health problem for which current treatment options are inadequate. OBJECTIVE: To evaluate the antiasthma activity of geraniol and investigate its underlying molecular mechanisms. METHODS: In a standard experimental asthma model, Balb/c mice were sensitized with ovalbumin, treated with geraniol (100 or 200 mg/kg) or a vehicle control, during ovalbumin challenge. RESULTS: Treatment of ovalbumin-sensitized/challenged mice with geraniol significantly decreased airway hyperresponsiveness to inhaled methacholine. Geraniol treatment reduced eotaxin levels in bronchoalveolar lavage fluid and attenuated infiltration of eosinophils induced by ovalbumin. Geraniol treatment reduced TH2 cytokines (including interleukins 4, 5, and 13), increased TH1 cytokine interferon γ in bronchoalveolar lavage fluid, and reduced ovalbumin-specific IgE in serum. In addition, treatment of ovalbumin-sensitized/challenged mice with geraniol enhanced T-bet (TH1 response) messenger RNA expression and reduced GATA-3 (TH2 response) messenger RNA expression in lungs. Furthermore, treatment of ovalbumin -sensitized/challenged mice with geraniol further enhanced Nrf2 protein expression and activated Nrf2-directed antioxidant pathways, such as glutamate-cysteine ligase, superoxide dismutase, and glutathione S-transferase, and enhanced formation of reduced glutathione and reduced formation of malondialdehyde in lungs. CONCLUSION: Geraniol attenuated important features of allergic asthma in mice, possibly through the modulation of TH1/TH2 balance and activation the of Nrf2/antioxidant response element pathway.

[Effects of Chinese herbal medicine Pingchuan Formula on airway inflammation, interferon-γ and interleukin-4 in mice with asthma].

OBJECTIVE: To observe the changes of interferon-γ (IFN-γ) and interleukin-4 (IL-4), factors related to T helper 1/T helper 2 (Th1/Th2), in airway inflammation in an asthmatic model of mice and the effects of Pingchuan Formula (PCF), a compound traditional Chinese herbal medicine. METHODS: Eighty BALB/c mice were randomly divided into normal group, model group, dexamethasone group and PCF group, with 20 mice in each group. For inducing asthma, the BALB/c mice were sensitized by intraperitoneal injection of mixed ovalbumin, and then activated by inhaling ovalbumin. After 2 weeks of sensitizing, asthmatic mice were intragastrically administered with the drugs once a day for four weeks. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected respectively after 7-day activation or 2 weeks after activation. The general histological changes were observed by hematoxylin and eosin staining and collagen staining, meanwhile the levels of IFN-γ and IL-4 in BALF were detected by enzyme-linked immunosorbent assay. RESULTS: After 7 d of activation, compared with the normal group, significant decrease in IFN-γ and increase in IL-4 were detected in the model group; compared with the model group, IL-4 level of the two treated groups was decreased and the IFN-γ/IL-4 ratio was increased significantly; no significant difference was found between the two treated groups. Two weeks after activation, compared with the normal group, IFN-γ was decreased, IL-4 was increased, and the IFN-γ/IL-4 ratio was decreased in the model group; compared with the model group, IL-4 level in the dexamethasone group was significantly decreased and IFN-γ/IL-4 ratio was significantly elevated, while the level of IL-4 in the PCF group was significantly decreased, the level of IFN-γ was increased simultaneously, and the IFN-γ/IL-4 ratio was significantly elevated. There was no significant difference between the two treated groups in IFN-γ and IL-4 levels, nor in the IFN-γ/IL-4 ratio. The area of collagen fiber in airway wall epithelium in the model group was smaller than that in the normal group, and those in the treated groups were lower than that in the model group; there was no significant difference between the two treated groups. CONCLUSION: PCF has regulating function in correcting the imbalance of Th1/Th2 so as to improve airway inflammation. The therapeutic effects of PCF are basically similar to dexamethasone.

[Effects of Chinese herbal medicine Bushen Gubiao Recipe on toll-like receptor 4 and CD4(+)CD25(+)foxp3(+) regulatory T cells in mice with recurrent respiratory tract infections].

OBJECTIVE: To evaluate the effects of Bushen Gubiao Recipe (BGR), a compound traditional Chinese herbal medicine, on toll-like receptor 4 (TLR4) signaling pathway and CD4(+)CD25(+)foxp3(+)regulatory T cells (CD4(+)CD25(+)foxp3(+)Tregs) in mice with recurrent respiratory tract infections (RRTIs). METHODS: A mouse model of kidney-yang deficiency which simulated physical characteristics of RRTIs was established by intraperitoneal injection of hydrocortisone for 14 d. The model mice were divided into 4 groups, model group, high-dose BGR group, low-dose BGR group, and nucleic acid and casein oral solution group. They were administered respectively with distilled water, high-dose BGR (50 g/kg body weight), low-dose BGR (25 g/kg body weight) and nucleic acid and casein oral solution. Besides, a normal control group was set up and gastrogavage with distilled water. The effect of intervention was evaluated 4 weeks later by estimating the changes in behaviors of mice. Expressions of TLR4 and nuclear factor-kappa B (NF-κB) p65 in lung tissue were detected by immunohistochemical SABC method, the expression of TLR4 mRNA in lung tissue was detected by fluorescence quantitative-polymerase chain reaction (FQ-PCR), and the level of blood CD4(+)CD25(+)foxp3(+) Tregs was determined by flow cytometry. RESULTS: A kidney-yang deficiency mouse model with RRTIs was successfully established by intraperitoneal injection of hydrocortisone. BGR could improve the abnormal behavioral condition of the mice and enhance the expressions of TLR4 and NF-κB p65 in the lung tissue. Expression of TLR4 mRNA in high-dose BGR group was higher than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). Levels of CD4(+)CD25(+)foxp3(+)Tregs in high-dose BGR group and nucleic acid and casein oral solution group were lower than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). CONCLUSION: BGR can improve the behavior of the kidney-yang deficiency mice, and improve the innate immune function by up-regulating TLR/NF-κB signaling pathway. BGR can adjust the immune imbalance of T-helper cell (Th) 1/Th2 through reducing the activity of CD4(+)CD25(+)foxp3(+)Tregs and enhancing the immune response of Th1 type.

[Study on extracting process for Tiao ZhiAn mixture].

OBJECTIVE: To study the technology of optimal extraction for Tiao ZhiAn mixture. METHODS: Optimization of the influence of the mixed volatile oil extracting of Ligusticum chuanxiong Hort., Angelica sinensis (Oliv.) Diels and Curcuma longa L. was chosen by single-index test. Orthogonal test was employed for selecting the optimum of extraction technology by colligation score as the indexes of the contents of stilbene glucoside of Polygunum multiflorum Thunb, total solid matters in water extraction. RESULTS: The best technology for extracting Ligusticum chuanxiong Hort., Angelica sinensis (oliv.) Diels and Curcuma longa L. was to add water nine times within eight hours. The way of adding water six times to the medicine sediment and other herbs, extracting 3 times in one hour each time was considered the optimum extraction technology. CONCLUSION: The considerable extraction rate of active components in the drugs is achieved by applying the selected technology, and the simple method is fit for manufacturing Tiao ZhiAn mixture.

[Expression and significance of PTEN/PI3K signal transduction-related proteins in non-small cell lung cancer].

BACKGROUND & OBJECTIVE: PTEN/PI3K signal transduction pathway regulates cell proliferation and survival, and is closely associated with the development and progress of various tumors. However, the relationship between the function of this pathway with lung carcinoma has not been completely elucidated. This study was to investigate the expression and clinical significance of PTEN/PI3K signal transduction-related proteins, such as insulin-like growth factor-1 receptor (IGF-1R), PTEN and phosphatidylinositol 3-kinase (PI3K), in non-small cell lung carcinoma (NSCLC). METHODS: The expression of IGF-1R, PTEN, and PI3K in 59 specimens of primary NSCLC, 19 specimens of metastatic lymph nodes, 16 specimens of para-cancerous hyperplastic lung tissues, and 7 specimens of normal lung tissues were detected by SP immunohistochemistry. The difference of positive rates of IGF-1R,PTEN and PI3K was evaluated by Chi-square test and Fisher's exact test. RESULTS: The positive rates of IGF-1R, PTEN, and PI3K in NSCLC were 72.88%, 27.12%, and 84.75%, respectively. The positive rates of IGF-1R and PI3K were not associated with the clinicopathologic features of NSCLC (P>0.05). The positive rate of PTEN was highly associated with lymph node metastasis of NSCLC (P=0.009), but was not associated with pathologic type and differentiation grade of NSCLC (P>0.05). The positive rate of PTEN was significantly lower and that of PI3K was significantly higher in NSCLC and metastatic lymph node tissues than in para-cancerous hyperplastic and normal lung tissues (P<0.05). The expression of IGF-1R in NSCLC was positively correlated to that of PI3K (r=0.432, P=0.001); while the expression of PTEN was negatively correlated to that of PI3K (r=0.505, P<0.001). CONCLUSION: Overexpression of IGF-1R and PI3K, and low expression of PTEN are closely correlated to the development, invasion and metastasis of NSCLC.