墨旱莲甲醇提取物通过抑制NF-kappa-B途径降低慢性过敏性哮喘小鼠模型炎症
2023/10/25
摘要
背景：墨旱莲是多个巴西民族用来治疗呼吸道疾病、肝炎和有毒动物咬伤的药用植物。墨旱莲甲醇提取物（MEEP）的主要成分是蟛蜞菊内酯（WED）和去甲基蟛蜞菊内酯，在急性哮喘模型中表现抗炎活性，但MEEP对肺部炎症的影响以及在慢性哮喘模型中的作用机制尚不清楚。
目的：本研究旨在通过慢性卵蛋白（OVA）诱导的小鼠过敏性哮喘模型研究MEEP在体内的作用。
材料和方法：通过液相色谱法和串联质谱确定WED和DMW在MEEP中存在并测定其浓度。雄性Balb/c小鼠用OVA致敏和激发，实验组动物用MEEP（100、250或500 mg/kg）治疗，而对照组动物用地塞米松（2 mg/kg）或生理盐水治疗。评估支气管高反应性、支气管肺泡灌洗液（BAL）中的细胞总数和细胞分类计数以及肺匀浆中Th2细胞因子的产生情况。通过组织学分析评估肺部炎症和粘液生成情况，同时通过免疫组化评估核因子κB（NF-κB）的激活情况。
结果：WED和DMW在MEEP中的浓度分别为5.12%和1.04%。MEEP（250或500 mg/kg）可显著降低支气管高反应性，降低BAL中的细胞总数和嗜酸性粒细胞计数以及肺匀浆中的IL-4浓度，并抑制NF-κB激活。500mg/kg的MEEP可降低肺匀浆中IL-5的水平，但并未降低IL-13浓度或粘液生成。
结论：在小鼠慢性哮喘模型中，MEEP可减轻支气管高反应性，减少肺部和气道内炎症。其作用机制涉及抑制NF-κB活化，很可能与香豆素类WED和DMW存在有关。上述结果提供了应用旱墨莲治疗哮喘和其他呼吸道炎症疾病的民族药理学证据。
A methanolic extract of Eclipta prostrata (L.) L. decreases inflammation in a murine model of chronic allergic asthma via inhibition of the NF-kappa-B pathway
Morel LJF, Carmona F, Guimarães CC, Moreira LGQ, Leão PDS, Crevelin EJ, Batah SS, Fabro AT, França SC, Borges MC, Pereira AMS. Epub 2023 Jul 23. PMID: 37487966.
Abstract
BACKGROUND:Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known.
OBJECTIVE:To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice.
METHODS:The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa-B (NF-κB) activation was assessed immunohistochemically.
RESULTS:Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production.
CONCLUSION:MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases.
背景：墨旱莲是多个巴西民族用来治疗呼吸道疾病、肝炎和有毒动物咬伤的药用植物。墨旱莲甲醇提取物（MEEP）的主要成分是蟛蜞菊内酯（WED）和去甲基蟛蜞菊内酯，在急性哮喘模型中表现抗炎活性，但MEEP对肺部炎症的影响以及在慢性哮喘模型中的作用机制尚不清楚。
目的：本研究旨在通过慢性卵蛋白（OVA）诱导的小鼠过敏性哮喘模型研究MEEP在体内的作用。
材料和方法：通过液相色谱法和串联质谱确定WED和DMW在MEEP中存在并测定其浓度。雄性Balb/c小鼠用OVA致敏和激发，实验组动物用MEEP（100、250或500 mg/kg）治疗，而对照组动物用地塞米松（2 mg/kg）或生理盐水治疗。评估支气管高反应性、支气管肺泡灌洗液（BAL）中的细胞总数和细胞分类计数以及肺匀浆中Th2细胞因子的产生情况。通过组织学分析评估肺部炎症和粘液生成情况，同时通过免疫组化评估核因子κB（NF-κB）的激活情况。
结果：WED和DMW在MEEP中的浓度分别为5.12%和1.04%。MEEP（250或500 mg/kg）可显著降低支气管高反应性，降低BAL中的细胞总数和嗜酸性粒细胞计数以及肺匀浆中的IL-4浓度，并抑制NF-κB激活。500mg/kg的MEEP可降低肺匀浆中IL-5的水平，但并未降低IL-13浓度或粘液生成。
结论：在小鼠慢性哮喘模型中，MEEP可减轻支气管高反应性，减少肺部和气道内炎症。其作用机制涉及抑制NF-κB活化，很可能与香豆素类WED和DMW存在有关。上述结果提供了应用旱墨莲治疗哮喘和其他呼吸道炎症疾病的民族药理学证据。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(J Ethnopharmacol. 2024 Jan 10;318(Pt B):116930. doi: 10.1016/j.jep.2023.116930.)
(J Ethnopharmacol. 2024 Jan 10;318(Pt B):116930. doi: 10.1016/j.jep.2023.116930.)
A methanolic extract of Eclipta prostrata (L.) L. decreases inflammation in a murine model of chronic allergic asthma via inhibition of the NF-kappa-B pathway
Morel LJF, Carmona F, Guimarães CC, Moreira LGQ, Leão PDS, Crevelin EJ, Batah SS, Fabro AT, França SC, Borges MC, Pereira AMS. Epub 2023 Jul 23. PMID: 37487966.
Abstract
BACKGROUND:Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known.
OBJECTIVE:To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice.
METHODS:The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa-B (NF-κB) activation was assessed immunohistochemically.
RESULTS:Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production.
CONCLUSION:MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases.
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