<br>十味龙胆花方对脂多糖所致气道粘液高分泌、咳嗽过敏、氧化应激及肺部炎症的影响,Biomedicine & Pharmacotherapy

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十味龙胆花方对脂多糖所致气道粘液高分泌、咳嗽过敏、氧化应激及肺部炎症的影响
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2023-04-28 , DOI: 10.1016/j.biopha.2023.114793
Liu Wei ₁ , Hou Hongping ₂ , Li Chufang ₃ , Mingji Cuomu ₄ , Li Jintao ₅ , Cai Kaiyin ₆ , Chen Lvyi ₇ , Chen Weiwu ₈ , Ye Zuguang ₉ , Zhong Nanshan ₁

Affiliation

Guangzhou Laboratory, Guangzhou, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Guangzhou Laboratory, Guangzhou, China.
The University of Tibetan Medicine, Lhasa, China.
Beijing International Science and Technology Cooperation Base of Antivirus Drug, Beijing University of Technology, Beijing, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China; Tibet Cheezheng Tibet Medicine Co.,Ltd., Beijing, China.
School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
Tibet Cheezheng Tibet Medicine Co.,Ltd., Beijing, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

十味龙胆花颗粒（SWLDH）是处方使用率排名前20名的中成药经典藏药，用于治疗肺炎、急慢性气管支气管炎、慢性阻塞性肺病急性加重期、支气管哮喘等呼吸系统疾病，解决炎症、咳嗽等问题。临床上主要以痰瘀证为主。然而，其系统药理机制尚未阐明。在此，我们通过综合分析气道炎症、氧化应激、粘液分泌过多、咳嗽过敏以及与慢性疾病发生相关的指标，研究SWLDH治疗BALB/c小鼠急性呼吸道疾病的治疗效果。我们的结果表明，SWLDH 可能通过干扰花生四烯酸 (AA) 代谢途径来发挥对肺部炎症的抑制作用。 SWLDH处理后可通过增强谷胱甘肽氧化还原系统、硫氧还蛋白系统的还原活性以及过氧化氢酶和超氧化物歧化酶(SOD)的催化活性来缓解与组织损伤程度高度相关的氧化应激。此外，SWLDH 可以通过灭活球细胞并减少病理条件下形成凝胶的粘蛋白（MUC5AC 和 MUC5B）的分泌来显着消除粘液分泌过多引起的细支气管阻塞，这证明了其粘液活性效力。 SWLDH 还显示出对导致气道感觉超敏反应的神经肽释放的逆转作用。同时观察到的钙内流抑制、体内乙酰胆碱生物合成的减少和环磷酸腺苷 (cAMP) 含量的恢复可能共同导致气道平滑肌细胞 (ASMC) 舒张。这些发现表明 SWLDH 可能通过抑制咳嗽冲动和 ASMC 收缩来发挥镇咳功效。此外，SWLDH 可能会影响气道重塑。我们发现 SWLDH 可以延缓 TGF-β1 和 α-SMA 的升高，而 TGF-β1 和 α-SMA 是慢性阻塞性肺病和哮喘等慢性气道炎症性疾病进展过程中增生和收缩的重要指标。

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Effects of Shiwei Longdanhua formula on LPS induced airway mucus hypersecretion, cough hypersensitivity, oxidative stress and pulmonary inflammation

Shiwei Longdanhua Granule (SWLDH) is a classic Tibetan medicine (TM) ranking in the top 20 Chinese patent medicines in prescription rate to treat respiratory diseases like pneumonia, acute and chronic tracheobronchitis, acute exacerbation of COPD and bronchial asthma in solution of inflammation, cough and phlegm obstruction in clinical practice. However, its systematic pharmacological mechanisms have not been elucidated yet. Here, we studied the therapeutic efficacy of SWLDH in treatment of acute respiratory diseases in BALB/c mice by comprehensive analysis of airway inflammation, oxidative stress, mucus hypersecretion, cough hypersensitivities and indicators associated with the development of chronic diseases. Our results show that SWLDH might exhibit its inhibitory effects on pulmonary inflammation by interference with arachidonic acid (AA) metabolism pathways. Oxidative stress that highly related to the degree of tissue injury could be alleviated by enhancing the reductive activities of glutathione redox system, thioredoxin system and the catalytic activities of catalase and superoxide dismutase (SOD) after SWLDH treatment. In addition, SWLDH could significantly abrogate the mucus hypersecretion induced bronchiole obstruction by inactivate the globlet cells and decrease the secretion of gel-forming mucins (MUC5AC and MUC5B) under pathological condition, demonstrating its mucoactive potency. SWLDH also showed reversed effects on the release of neuropeptides that are responsible for airway sensory hypersensitivity. Simultaneously observed inhibition of calcium influx, reduction in in vivo biosynthesis of acetylcholine and the recovery of the content of cyclic adenosine monophosphate (cAMP) might collaboratively contribute to cause airway smooth muscle cells (ASMCs) relexation. These findings indicated that SWLDH might exhibited antitussive potency via suppression of the urge to cough and ASMCs contraction. Moreover, SWLDH might affect airway remodeling. We found SWLDH could retard the elevation of TGF-β1 and α-SMA, which are important indicators for hyperplasia and contraction during the progression of the chronic airway inflammatory diseases like COPD and asthma.

更新日期：2023-04-28

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