Mishra Priyanka, Pandey Ratna, Pandey Nikhil, Tripathi Suyash, Tripathi Yamini Bhusan
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Front Cell Dev Biol. 2022 Oct 13;10:1003767. doi: 10.3389/fcell.2022.1003767. eCollection 2022.
Acute lung injury (ALI) is a lethal respiratory disorder; directed uncontrolled inflammation, sloughing of the alveolar cells and their diffusion, and altered cardiorespiratory parameters with a global mortality rate of 40%. This study was designed to assess the preventive effect of a polyherbal decoction (Bronco T, 1.5 g/kg b. w.) on cardiorespiratory variables in oleic acid-induced ALI in rats. Oleic acid increases the level of neutrophil infiltration leading to pulmonary edema and alters the cardiorespiratory dynamics. The adult male rats were surgically cannulated and treated with intravenous oleic acid (0.38 ml/kg b. w.) to establish the ALI model. Bronco T was pre-administered orally 3 hours before oleic acid. The biophysical, histological, biochemical, and molecular effects were compared with dexamethasone (5 mg/kg b. w. i. p.). The animals were randomly divided into control, lethal, standard, and treatment groups. Respiratory frequency (RF), heart rate (HR), and mean arterial pressure (MAP) were recorded on a computerized chart recorder; arterial blood sample was collected to determine PaO/FiO, TNF-α, and MPO. Lipid peroxidation, superoxide dismutase, and catalase activity were evaluated to measure oxidative stress in bronchoalveolar lavage. Additionally, the pulmonary water content, COX-2 expression and histological examination were determined in the lung. A molecular docking study of the active phytoconstituent of BT obtained from HR-LCMS analysis against reported targets (IL-6, COX-2, TNFα, MPO and ENaC) of ALI was carried out. The B.T. pretreatment prevents mortality in comparison to the oleic acid group. It protects the lungs and heart from the detrimental effect of oleic acid, on par with dexamethasone. COX-2 mRNA expression was significantly down-regulated in the treatment group. The reduced level of TNF-α, MPO, SOD and catalase supported the protective effect of B.T. The study revealed strong binding interaction between the phytoconstituent (Galangin 3- [galactosyl-(1-4)-rhamnoside and Beta solamarine] of BT and the reported target. The B.T. pre-administration attenuates the oleic acid-induced mortality and cardiorespiratory toxicity.
急性肺损伤(ALI)是一种致命的呼吸系统疾病;其特征为炎症失控、肺泡细胞脱落及扩散,以及心肺参数改变,全球死亡率达40%。本研究旨在评估一种多草药煎剂(Bronco T,1.5 g/kg体重)对油酸诱导的大鼠ALI心肺变量的预防作用。油酸会增加中性粒细胞浸润水平,导致肺水肿并改变心肺动力学。成年雄性大鼠通过手术插管,静脉注射油酸(0.38 ml/kg体重)以建立ALI模型。在注射油酸前3小时口服给予Bronco T。将其生物物理、组织学、生化和分子效应与地塞米松(5 mg/kg体重,腹腔注射)进行比较。动物被随机分为对照组、致死组、标准组和治疗组。通过计算机化图表记录仪记录呼吸频率(RF)、心率(HR)和平均动脉压(MAP);采集动脉血样以测定动脉血氧分压/吸入氧分数值(PaO/FiO)、肿瘤坏死因子-α(TNF-α)和髓过氧化物酶(MPO)。评估脂质过氧化、超氧化物歧化酶和过氧化氢酶活性以测量支气管肺泡灌洗中的氧化应激。此外,测定肺组织中的肺含水量、环氧合酶-2(COX-2)表达并进行组织学检查。对通过高分辨液相色谱-质谱联用(HR-LCMS)分析从Bronco T中获得的活性植物成分针对ALI的报告靶点(白细胞介素-6、COX-2、肿瘤坏死因子α、MPO和上皮钠通道(ENaC))进行分子对接研究。与油酸组相比,Bronco T预处理可预防死亡。它与地塞米松一样,保护肺和心脏免受油酸的有害影响。治疗组中COX-2 mRNA表达显著下调。TNF-α、MPO、超氧化物歧化酶和过氧化氢酶水平降低支持了Bronco T的保护作用。该研究揭示了Bronco T的植物成分(高良姜素3 - [半乳糖基-(1-4)-鼠李糖苷和番茄碱])与报告靶点之间有强烈的结合相互作用。预先给予Bronco T可减轻油酸诱导的死亡率和心肺毒性。