Tingli Dazao Xiefei Decoction Ameliorates Asthma by Modifying Lung and Intestinal No-Co Metabolism Mediatedinflammation, Immune Imbalance, Cellular Barrier Damage, Oxidative Stress and Intestinal Bacterial Disorders To Achieve Co-Regulation of Lung and Intestine in Vivo and in Vitro

Ethnopharmacological relevance: Asthma is a chronic airway inflammatory disease. Current treatment with 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 lungs and intestines. 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 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 and OVA nebulized excitation, 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 enterocytes NCM-460 were used to establish a model of lung injury-induced intestinal injury using LPS and co-culture chambers, and lung cells or enterocytes 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 and enterocytes 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 P < 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 P < 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 enterocytes NCM-460 (P < 0.01). The ameliorative effect on enterocytes 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.