Palipoch Sarawoot, Punsawad Chuchard, Koomhin Phanit, Na-Ek Prasit, Poonsawat Wasinee, Kimseng Rungruedi, Chotipong Potiga, Bunluepuech Kingkan, Yusakul Gorawit, Suwannalert Prasit
School of Medicine, Walailak University, 222 Thaiburi, Thasala District, Nakhon Si Thammarat, 80161, Thailand.
Research Institute for Health Sciences, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
BMC Complement Med Ther. 2022 Mar 22;22(1):83. doi: 10.1186/s12906-022-03567-4.
Paraquat (PQ) has been reported to have a high mortality rate. The major target organ of PQ poisoning is the lungs. The pathogenesis of PQ-induced lung injury involves oxidative stress and inflammation. Unfortunately, there is still no effective antidote for PQ poisoning. We hypothesized that aqueous Thunbergia laurifolia (TL) leaf extract is a possible antidote for PQ-induced lung injury.
The total phenolic content and caffeic acid content of an aqueous extract of TL leaves were analyzed. Male Wistar rats were randomly divided into four groups (n = 4 per group): the control group (administered normal saline), the PQ group (administered 18 mg/kg body weight (BW) PQ dichloride subcutaneously), the PQ + TL-low-dose (LD) group (administered PQ dichloride subcutaneously and 100 mg/kg BW aqueous TL leaf extract by oral gavage) and the PQ + TL-high-dose (HD) group (administered PQ dichloride subcutaneously and 200 mg/kg BW aqueous TL leaf extract by oral gavage). Malondialdehyde (MDA) levels and lung histopathology were analyzed. In addition, the mRNA expression of NADPH oxidase (NOX), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) was assessed using reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of IL-1β and TNF-α was analyzed using immunohistochemistry.
The total phenolic content of the extract was 20.1 ± 0.39 μg gallic acid equivalents (Eq)/mg extract, and the caffeic acid content was 0.31 ± 0.01 μg/mg. The PQ group showed significantly higher MDA levels and NOX, IL-1β and TNF-α mRNA expression than the control group. Significant pathological changes, including alveolar edema, diffuse alveolar collapse, hemorrhage, leukocyte infiltration, alveolar septal thickening and vascular congestion, were observed in the PQ group compared with the control group. However, the aqueous TL leaf extract significantly attenuated the PQ-induced increases in MDA levels and NOX, IL-1β and TNF-α expressions. Moreover, the aqueous TL leaf extract ameliorated PQ-induced lung pathology.
This study indicates that aqueous TL leaf extract can ameliorate PQ-induced lung pathology by modulating oxidative stress through inhibition of NOX and by regulating inflammation through inhibition of IL-1β and TNF-α expressions. We suggest that aqueous TL leaf extract can be used as an antidote for PQ-induced lung injury.
据报道,百草枯(PQ)致死率很高。PQ中毒的主要靶器官是肺。PQ诱导的肺损伤发病机制涉及氧化应激和炎症。不幸的是,目前仍没有针对PQ中毒的有效解毒剂。我们推测毛叶千斤拔水提物可能是一种针对PQ诱导的肺损伤的解毒剂。
分析毛叶千斤拔叶水提物中的总酚含量和咖啡酸含量。将雄性Wistar大鼠随机分为四组(每组n = 4):对照组(给予生理盐水)、PQ组(皮下注射18 mg/kg体重的二氯化PQ)、PQ + 毛叶千斤拔低剂量(LD)组(皮下注射二氯化PQ并经口灌胃给予100 mg/kg体重的毛叶千斤拔叶水提物)和PQ + 毛叶千斤拔高剂量(HD)组(皮下注射二氯化PQ并经口灌胃给予200 mg/kg体重的毛叶千斤拔叶水提物)。分析丙二醛(MDA)水平和肺组织病理学。此外,使用逆转录-聚合酶链反应(RT-PCR)评估烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的mRNA表达,并使用免疫组织化学分析IL-1β和TNF-α的蛋白表达。
提取物的总酚含量为20.1±0.39 μg没食子酸当量(Eq)/mg提取物,咖啡酸含量为0.31±0.01 μg/mg。PQ组的MDA水平以及NOX、IL-1β和TNF-α的mRNA表达均显著高于对照组。与对照组相比,PQ组观察到明显的病理变化,包括肺泡水肿、弥漫性肺泡塌陷、出血、白细胞浸润、肺泡间隔增厚和血管充血。然而,毛叶千斤拔叶水提物显著减轻了PQ诱导的MDA水平升高以及NOX、IL-1β和TNF-α表达的增加。此外,毛叶千斤拔叶水提物改善了PQ诱导的肺部病理变化。
本研究表明,毛叶千斤拔叶水提物可通过抑制NOX调节氧化应激以及通过抑制IL-1β和TNF-α表达调节炎症,从而改善PQ诱导的肺部病理变化。我们建议毛叶千斤拔叶水提物可作为针对PQ诱导的肺损伤的解毒剂。