Fatima Mobeen, Khan Kashif Ur Rehman, Al-Joufi Fakhria A, Hussain Musaddique
Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
J Ethnopharmacol. 2025 Apr 25;346:119689. doi: 10.1016/j.jep.2025.119689. Epub 2025 Mar 29.
ARDS (Acute Respiratory Distress Syndrome) and ALI (Acute Lung Injury) are severe pulmonary alterations manifested by amplified inflammatory and oxidative responses contributing to high mortality rates. ALI triggered by various provoking factors, including cigarette smoke (CS), or pathogens (Lipopolysaccharide or SARS-CoV-2), cause severe life-threatening morbidities. Salvadora persica has been used across various countries for cough and asthma, however; there is a paucity of data on its use in ALI.
This research explores signaling pathways and the potential of S-persica in treating ALI, emphasizing the feasibility of its compounds being advanced into therapeutic agents via pre-clinical trials and computational approaches.
In-vitro, GC-MS, phytochemicals, antioxidants (Phosphomolybdenum, DPPH, ABTS, and FRAP), and enzyme inhibition (AChE & BChE) assays were performed. 60 rats were divided into 12 groups (n = 5 each), and assigned to SP-mx (100, 200, and 300 mg/kg), Dexa (1 mg/kg), Control (NS), LPS-challenged and CS-exposed groups, to establish in-vivo models. After 24 h (LPS-challenged) and day 10th (CS-exposure), oxygen saturation, inflammatory cells, lung weight, histopathology, MDA, TOS, TAC, and mRNA expression of IL-1β, TNF-α, IL-6, NF-κβ, COX-2, IL-4 and IL-10 were evaluated. Further, in-silico studies were conducted via Docking, Swiss ADME, Molinspiration, and ProTox-III.
In both models, SP-mx reduced edema, inflammatory cells infiltration, histopathological alterations, oxidative stress, expression of pro-inflammatory cytokines, COX-2 and NF-κB, while elevating TAC and anti-inflammatory cytokines. Its high phenolic contents along with antioxidant and anticholinesterase activities, endorsed SP-mx remarkable ability to combat oxidative stress. In-silico studies confirmed its interactions with AChE, BChE, COX-2, TNF-α, IL-1β, and NF-κB, as well as its favorable ADMET, and drug-likeness properties.
These findings highlight that SP-mx is a potential therapeutic candidate for treating ALI by possibly modulating COX-2/NF-κB signaling pathways, warranting further research for clinical translation.
急性呼吸窘迫综合征（ARDS）和急性肺损伤（ALI）是严重的肺部病变，表现为炎症和氧化反应增强，导致高死亡率。由各种诱发因素引发的ALI，包括香烟烟雾（CS）或病原体（脂多糖或SARS-CoV-2），会导致严重的危及生命的疾病。然而，各地都有使用佩兰治疗咳嗽和哮喘的情况；但关于其在ALI治疗中的应用数据却很匮乏。
本研究探索佩兰治疗ALI的信号通路和潜力，强调其化合物通过临床前试验和计算方法推进成为治疗药物的可行性。
进行体外气相色谱 - 质谱联用（GC-MS）、植物化学分析、抗氧化剂（磷钼酸、二苯基苦味酰基自由基（DPPH）、2,2'-联氮-双-3-乙基苯并噻唑啉-6-磺酸（ABTS）和铁还原抗氧化能力（FRAP））测定以及酶抑制（乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE））测定。将60只大鼠分为12组（每组n = 5），并分为佩兰提取物高剂量组（SP-mx，100、200和300mg/kg）、地塞米松组（Dexa，1mg/kg）、对照组（NS）、脂多糖攻击组和香烟烟雾暴露组，以建立体内模型。在24小时（脂多糖攻击组）和第10天（香烟烟雾暴露组）后，评估氧饱和度、炎症细胞、肺重量、组织病理学、丙二醛（MDA）、总氧化应激（TOS）、总抗氧化能力（TAC）以及白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、核因子-κB（NF-κβ）、环氧化酶-2（COX-2）、白细胞介素-4（IL-4）和白细胞介素-10（IL-10）的mRNA表达。此外，通过分子对接、瑞士药物代谢和药代动力学预测平台（Swiss ADME）、Molinspiration和ProTox-III进行计算机模拟研究。
在两种模型中，佩兰提取物高剂量组均减轻了水肿、炎症细胞浸润、组织病理学改变、氧化应激、促炎细胞因子、COX-2和NF-κB 的表达，同时提高了TAC和抗炎细胞因子水平。其高酚类含量以及抗氧化和抗胆碱酯酶活性，证明了佩兰提取物高剂量组对抗氧化应激的显著能力。计算机模拟研究证实了其与AChE、BChE、COX-2、TNF-α和IL-1β以及NF-κB的相互作用，以及其良好的药物代谢动力学、药物毒性和类药性质。
这些发现突出表明，佩兰提取物高剂量组可能通过调节COX-2/NF-κB信号通路成为治疗ALI的潜在候选药物，值得进一步开展临床转化研究。
