Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India.
Inflammopharmacology. 2023 Apr;31(2):823-844. doi: 10.1007/s10787-022-01133-5. Epub 2023 Jan 20.
Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality in COVID-19 patients, due to limited therapeutic options. This prompted us to explore natural sources to mitigate this condition. Gymnema Sylvestre (GS) is an ancient medicinal plant known to have various therapeutic effects. This investigation examined the therapeutic effect of hydroalcoholic extract of Gymnema Sylvestre (HAEGS) against lipopolysaccharide (LPS)-induced lung injury and ARDS in in vitro and in vivo models. UHPLC-HRMS/GC-MS was employed for characterizing the HAEGS and identified several active derivatives including gymnemic acid, gymnemasaponins, gymnemoside, gymnemasin, quercetin, and long fatty acids. Gene expression by RT-qPCR and DCFDA analysis by flow cytometry revealed that several inflammatory cytokine/chemokine, cell injury markers, and reactive oxygen species (ROS) levels were highly upregulated in LPS control and were significantly reduced upon HAEGS treatment. Consistent with the in vitro studies, we found that in LPS-induced ARDS model, pre-treatment with HAEGS significantly suppressed the LPS-induced elevation of inflammatory cell infiltrations, cytokine/chemokine marker expression, ROS levels, and lung injury in a dose-dependent manner. Further mechanistic studies demonstrated that HAEGS suppressed oxidative stress by modulating the NRF2 pathway and ameliorated the ARDS through the NF-κB/MAPK signalling pathway. Additional fractionation results revealed that fraction 6 which has the exclusive composition of gymnemic acid derivatives showed better anti-inflammatory effects (inhibition of IL-6 and IL-1β) at lower concentrations compared to HAEGS. Overall, HAEGS significantly mitigated LPS-induced lung injury and ARDS by targeting the NF-κB/MAPK signalling pathway. Thus, our work unravels the protective role of HAEGS for the first time in managing ARDS.
急性呼吸窘迫综合征（ARDS）是 COVID-19 患者死亡的主要原因之一，由于治疗选择有限。这促使我们探索天然来源来减轻这种情况。匙羹藤（GS）是一种古老的药用植物，已知具有多种治疗作用。本研究探讨了匙羹藤水醇提取物（HAEGS）对体外和体内脂多糖（LPS）诱导的肺损伤和 ARDS 的治疗作用。采用 UHPLC-HRMS/GC-MS 对 HAEGS 进行了表征，鉴定出几种活性衍生物，包括匙羹酸、匙羹藤皂苷、匙羹藤苷、匙羹藤素、槲皮素和长脂肪酸。通过 RT-qPCR 进行基因表达和通过流式细胞术进行 DCFDA 分析表明，LPS 对照中几种炎症细胞因子/趋化因子、细胞损伤标志物和活性氧（ROS）水平高度上调，而 HAEGS 处理后显著降低。与体外研究一致，我们发现，在 LPS 诱导的 ARDS 模型中，HAEGS 预处理可显著抑制 LPS 诱导的炎症细胞浸润、细胞因子/趋化因子标志物表达、ROS 水平和肺损伤的升高，呈剂量依赖性。进一步的机制研究表明，HAEGS 通过调节 NRF2 通路抑制氧化应激，并通过 NF-κB/MAPK 信号通路改善 ARDS。进一步的分离结果表明，具有匙羹酸衍生物独特组成的第 6 馏分在较低浓度下显示出更好的抗炎作用（抑制 IL-6 和 IL-1β），优于 HAEGS。总体而言，HAEGS 通过靶向 NF-κB/MAPK 信号通路显著减轻 LPS 诱导的肺损伤和 ARDS。因此，我们的工作首次揭示了 HAEGS 在管理 ARDS 中的保护作用。
