Tingli Dazao Xiefei Decoction ameliorates asthma in vivo and in vitro from lung to intestine by modifying NO-CO metabolic disorder mediated inflammation, immune imbalance, cellular barrier damage, oxidative stress and intestinal bacterial disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is a chronic airway inflammatory disease. Current treatment of mainstream medications has significant side effects. There is growing evidence that the refractoriness of asthma is closely related to common changes in the lung and intestine. The lungs and intestines, as sites of frequent gas exchange in the body, are widely populated with gas signaling molecules NO and CO, which constitute NO-CO metabolism and may be relevant to the pathogenesis of asthma in the lung and intestine. The Chinese herbal formula Tingli Dazao Xiefei Decoction (TD) is commonly used in clinical practice to treat asthma with good efficacy, but there are few systematic evaluations of the efficacy of asthma on NO-CO metabolism, and the mode of action of its improving effect on the lung and intestine is unclear. AIM OF THE STUDY: To investigate the effect of TD on the lung and intestine of asthmatic rats based on NO-CO metabolism. MATERIALS AND METHODS: In vivo, we established a rat asthma model by intraperitoneal injection of sensitizing solution with OVA atomization, followed by intervention by gavage administration of TD. We simultaneously examined alterations in basal function, pathology, NO-CO metabolism, inflammation and immune cell homeostasis in the lungs and intestines of asthmatic rats, and detected changes in intestinal flora by macrogenome sequencing technology, with a view to multi-angle evaluation of the treatment effects of TD on asthmatic rats. In vitro, lung cells BEAS-2B and intestinal cells NCM-460 were used to establish a model of lung injury causing intestinal injury using LPS and co-culture chambers, and lung cells or intestinal cells TD-containing serum was administered to intervene. Changes in inflammatory, NO-CO metabolism-related, cell barrier-related and oxidative stress indicators were measured in lung cells and intestinal cells to evaluate TD on intestinal injury by way of amelioration and in-depth mechanism. RESULTS: In vivo, our results showed significant basal functional impairment in the lung and intestine of asthmatic rats, and an inflammatory response, immune cell imbalance and intestinal flora disturbance elicited by NO-CO metabolic disorders were observed (P < 0.05 or 0.01). The administration of TD was shown to deliver a multidimensional amelioration of the impairment induced by NO-CO metabolic disorders (P < 0.05 or 0.01). In vitro, the results showed that LPS-induced lung cells BEAS-2B injury could cause NO-CO metabolic disorder-induced inflammatory response, cell permeability damage and oxidative stress damage in intestinal cells NCM-460 (P < 0.01). The ameliorative effect on intestinal cells NCM-460 could only be exerted when TD-containing serum interfered with lung cells BEAS-2B (P < 0.01), suggesting that the intestinal ameliorative effect of TD may be exerted indirectly through the lung. CONCLUSION: TD can ameliorate NO-CO metabolism in the lung and thus achieve the indirectly amelioration of NO-CO metabolism in the intestine, ultimately achieving co-regulation of lung and intestinal inflammation, immune imbalance, cellular barrier damage, oxidative stress and intestinal bacterial disorders in asthma in vivo and in vitro. Targeting lung and intestinal NO-CO metabolic disorders in asthma may be a new therapeutic idea and strategy for asthma.

[Active components of Descurainia sophia improve lung permeability in rats with allergic asthma by regulating airway inflammation and epithelial damage].

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial-Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36.

Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial-mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 µmol/L sodium oleate were given 10 µmoL/L moracin-P-2″-O-ß-d-glucopyranoside (Y-1), moracin-P-3'-O-ß-d-glucopyranoside (Y-2), moracin-P-3'-O-α-l-arabinopyranoside (Y-3), and moracin-P-3'-O-[ß-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1ß), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-ß, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-ß-d-glucopyranoside and moracin-P-3'-O-ß-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.

[Spatial structure and distribution simulation of Aphis gossipii Glover population based on GIS].

Based on geographic information system (GIS) and geostatistical analysis, this paper studied the spatial structure of Aphis gossipii Glover population in Xiangshan District of Zhongwei City, Ningxia Province, with the spatial distribution of the population simulated by ordinary Kriging interpretation. The spatial structure of A. gossipii population varied with its occurrence stage (initial, blossom, and final stage). The semivariograms of A. gossipii could be described by exponential or Gaussian model, indicating that A. gossipii had an aggregated spatial arrangement. The aggregation degrees at different occurrence stages were all beyond 45%, and the spatial correlation ranged from 10.37 km to 29.11 km. The spatial variance was greatly affected by spatial autocorrelation. The population dynamics of A. gossipii at its different occurrence stages could be easily analyzed and intuitively simulated from the two aspects of time and space by spatial distribution simulation, and thus, the occurrence position and degree of A. gossipii could be easily determined.