Qi Peng, Wei Chunhua, Kou Dianbo
Department of Respiratory and Critical Care Treatment, Weifang Wei 'en Hospital, Weifang, Shandong 261031, China.
Korean J Physiol Pharmacol. 2021 Nov 1;25(6):555-564. doi: 10.4196/kjpp.2021.25.6.555.
We investigated the effects of naringenin and morin on IL-5 and ROS production in PMA+ionomycin-treated EL-4 cells with the corroboration of their antioxidant and anti-inflammatory properties using an asthma-induced mouse model. The EL-4 cell line was used to study the outcomes of naringenin or morin, followed by cell viability studies. Western blot analysis and ELISA test were used to determine Th2 mediated cytokines. studies were carried out on BALB/c mice to induce allergic asthma using ovalbumin administered intraperitoneally. Intracellular ROS was determined using 2',7'-dichlorodihydrofluorescein diacetate, followed by serum enzymatic (AST and ALT) estimations and inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and lung tissues. Histopathological studies were conducted to examine lung tissue-stained architecture. Our findings suggested that naringenin and morin significantly suppressed IL-5 and ROS production various pathways. Interestingly, by reducing NFAT activity, naringenin and morin stimulated HO-1 expression, thereby suppressing IL-5 secretion due to regulating the transcription factor Nrf2 P13/Akt or ERK/JNK signalling pathways in EL-4 cells, demonstrating the involvement of HO-1 expression in inhibiting asthmatic inflammation. The increased inflammatory cells in the BALF were substantially decreased by both naringenin and morin, followed by inhibition in the elevated Th-2 cytokines levels. The TNF-α protein levels in an allergic asthma mouse model were significantly reduced by suppressing Akt phosphorylation and eosinophil formation. Recent findings confirmed that naringenin and morin possess the potential to control asthma-related immune responses through antioxidant and anti-inflammatory properties, indicating potential therapeutic agents or functional foods.
我们使用哮喘诱导小鼠模型,在证实柚皮素和桑色素具有抗氧化和抗炎特性的情况下,研究了它们对佛波酯(PMA)+离子霉素处理的EL-4细胞中白细胞介素-5(IL-5)和活性氧(ROS)产生的影响。使用EL-4细胞系研究柚皮素或桑色素的作用效果,随后进行细胞活力研究。采用蛋白质免疫印迹分析和酶联免疫吸附测定(ELISA)来确定Th2介导的细胞因子。对BALB/c小鼠腹腔注射卵清蛋白以诱导过敏性哮喘。使用2',7'-二氯二氢荧光素二乙酸酯测定细胞内ROS,随后进行血清酶(谷草转氨酶和谷丙转氨酶)测定以及支气管肺泡灌洗液(BALF)和肺组织中的炎性细胞计数。进行组织病理学研究以检查肺组织染色结构。我们的研究结果表明,柚皮素和桑色素通过多种途径显著抑制IL-5和ROS的产生。有趣的是,通过降低活化T细胞核因子(NFAT)活性,柚皮素和桑色素刺激血红素加氧酶-1(HO-1)表达,从而在EL-4细胞中通过调节转录因子核因子E2相关因子2(Nrf2)/磷脂酰肌醇-3激酶(PI3)/蛋白激酶B(Akt)或细胞外信号调节激酶(ERK)/应激活化蛋白激酶(JNK)信号通路抑制IL-5分泌,证明HO-1表达参与抑制哮喘炎症。柚皮素和桑色素均使BALF中增加的炎性细胞显著减少,随后抑制升高的Th2细胞因子水平。通过抑制Akt磷酸化和嗜酸性粒细胞形成,过敏性哮喘小鼠模型中的肿瘤坏死因子-α(TNF-α)蛋白水平显著降低。最近的研究结果证实,柚皮素和桑色素具有通过抗氧化和抗炎特性控制哮喘相关免疫反应的潜力,表明它们可能是潜在的治疗药物或功能性食品。