Neferine alleviates ovalbumin-induced asthma via MAPK signaling pathways in mice.

PURPOSE: To investigate the role of neferine in ovalbumin (OVA)-induced asthma, and to reveal the possible mechanism. METHODS: In OVA-induced asthmatic mice, enzyme-linked-immunosorbent serologic assay was performed to evaluate the level of interleukin (IL)-4, IL-5, IL-13, immunoglobulin E (IgE) in serum and tumor necrosis factor-α (TNF-α), IL-6, IL-1ß, and monocyte chemoattractant protein-1 (MCP-1) in bronchoalveolar lavage fluid (BALF). Eosinophil, neutrophil, and lymphocyte counts in BALF were calculated to assess inflammation. The pulmonary function was measured by airway resistance, peak expiratory flow (PEF) and forced expiratory volume/forced vital capacity (FEV0.4/FVC) ratio, and respiratory rate. Hematoxylin and eosin staining and Masson staining were used to evaluate lung injury. Further, Western blot analysis was conducted to detect phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 of mitogen-activated protein kinase (MAPK) signaling pathways. RESULTS: Neferine, 20 mg/kg or 40 mg/kg, could significantly decrease the levels of IL-4, IL-5, IL-13, and IgE in OVA-induced serum, and that of TNF-α, IL-6, IL-1ß, and MCP-1 in OVA-induced BALF. Moreover, neferine could significantly decline eosinophil, neutrophil, and lymphocyte counts in BALF. Neferine contributed to improve OVA-induced airway resistance, promoted the value of PEF and FEV0.4/FVC ratio, and recovered the respiratory rate. It also reduced mucus secretion, distribution of inflammatory and goblet cells around bronchi, and attenuated collagen deposition in lung tissues. Furthermore, neferine reduced the phosphorylation of p38, JNK, and ERK to inhibit MAPK signaling pathways. CONCLUSION: Neferine relieves asthma-induced inflammatory reaction, airway resistance, and lung injury by inhibiting MAPK signaling pathways. This could serve neferine as a novel therapeutic candidate for treating asthma.

Neferine alleviates ovalbumin-induced asthma via MAPK signaling pathways in mice

Purpose: To investigate the role of neferine in ovalbumin (OVA)-induced asthma, and to reveal the possible mechanism. Methods: In OVA-induced asthmatic mice, enzyme-linked-immunosorbent serologic assay was performed to evaluate the level of interleukin (IL)-4, IL-5, IL-13, immunoglobulin E (IgE) in serum and tumor necrosis factor-α (TNF-α), IL-6, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) in bronchoalveolar lavage fluid (BALF). Eosinophil, neutrophil, and lymphocyte counts in BALF were calculated to assess inflammation. The pulmonary function was measured by airway resistance, peak expiratory flow (PEF) and forced expiratory volume/forced vital capacity (FEV0.4/FVC) ratio, and respiratory rate. Hematoxylin and eosin staining and Masson staining were used to evaluate lung injury. Further, Western blot analysis was conducted to detect phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 of mitogen-activated protein kinase (MAPK) signaling pathways. Results: Neferine, 20 mg/kg or 40 mg/kg, could significantly decrease the levels of IL-4, IL-5, IL-13, and IgE in OVA-induced serum, and that of TNF-α, IL-6, IL-1β, and MCP-1 in OVA-induced BALF. Moreover, neferine could significantly decline eosinophil, neutrophil, and lymphocyte counts in BALF. Neferine contributed to improve OVA-induced airway resistance, promoted the value of PEF and FEV0.4/FVC ratio, and recovered the respiratory rate. It also reduced mucus secretion, distribution of inflammatory and goblet cells around bronchi, and attenuated collagen deposition in lung tissues. Furthermore, neferine reduced the phosphorylation of p38, JNK, and ERK to inhibit MAPK signaling pathways. Conclusion: Neferine relieves asthma-induced inflammatory reaction, airway resistance, and lung injury by inhibiting MAPK signaling pathways. This could serve neferine as a novel therapeutic candidate for treating asthma (AU)

Beneficial effects of estrogens in obstructive sleep apnea hypopnea syndrome.

Epidemiological studies showing the higher frequency of obstructive sleep apnea hypopnea syndrome in men, polycystic ovary syndrome (PCOS), and in post-menopausal women suggest the beneficial role of estrogen. These findings are well supported by the pre-clinical studies (ten research studies described in this review) showing that estrogen and phytoestrogens attenuate the deleterious effects of chronic intermittent hypoxia (obstructive apnea in animals) on the genioglossal muscles and on other organs (co-morbidities) in ovariectomized rodents. Moreover, clinical studies (four research studies described in this review) have also shown the beneficial role of estrogen therapy on the parameters of obstructive apnea in post-menopausal women. The beneficial effects of estrogen and phytoestrogens on obstructive sleep apnea and its co morbidities have been attributed to increase in thioredoxin, Nrf-2, activation of p38 MAP kinases, inhibition of vagal C fibers, and attenuation of HIF-1α. It is possible that estrogen-mediated activation of p38 MAP kinase may inhibit HIF-1α to attenuate lung inflammation, which may inhibit the activation of vagal C fibers to attenuate bronchoconstriction and prevent obstruction during sleep. Moreover, estrogen-mediated increase in thioredoxin and Nrf-2 may also contribute in increasing antioxidant defense and attenuating inflammation.

Dioscin Attenuates Myocardial Damages in Diabetic Rats maybe by Regulating NO-sGC-cGMP-PKG Pathway.

PURPOSE: The objective of this research was to explore the effect of dioscin on myocardium in streptozotocin (STZ)-induced diabetic rats and the underlying mechanisms. METHODS: Diabetic rat model was established by a single intravenous injection of streptozocin (STZ). The rats were divided into 5 groups: control group, control+dioscin group, model group (diabetes), DDL group (diabetic rats treated with 100 µg/kg/day dioscin) and DDH group (diabetic rats treated with 200 µg/kg/day dioscin). Each group was continuously intervened for 6 weeks. Hemodynamic parameters were detected and pathological alterations of myocardium were observed by hematoxylin-eosin (HE) staining. Inflammatory response and related proteins in the NO-sGC-cGMP-PKG pathway were detected by western blot. RESULTS: Dioscin treatment can increase ejection fraction (EF) and decrease left ventricular end-diastolic pressure (LVEDP) as well as time constant of left ventricular pressure decay (Tau) parameters in diabetic rats, suggesting the improvement of left ventricular function. By histopathology observation, we found that dioscin treatment can also improve myocardial histological lesions caused by diabetes. In addition, the levels of inflammatory cytokines TGF-ß1, TNF-α and IL-1ß of the model group were remarkably higher than those in the control group (p<0.01), while after being treated with dioscin these cytokines were obviously decreased (p<0.05). The levels of PDE-5, PKG and p-VASP in the diabetic rats were significantly declined after being treated by dioscin in a dose-dependent manner (p<0.05). CONCLUSION: Dioscin may prevent the myocardial injury in diabetic rats by up-regulating NO-sGC-cGMP-PKG pathway.