Anti-inflammatory and antioxidant activities of methanol extract of Piper betle Linn. (Piper betle L.) leaves and stems by inhibiting NF-κB/MAPK/Nrf2 signaling pathways in RAW 264.7 macrophages,Biomedicine & Pharmacotherapy

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Anti-inflammatory and antioxidant activities of methanol extract of Piper betle Linn. (Piper betle L.) leaves and stems by inhibiting NF-κB/MAPK/Nrf2 signaling pathways in RAW 264.7 macrophages
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2022-09-21 , DOI: 10.1016/j.biopha.2022.113734
Jihye Seo ₁ , Unju Lee ₁ , Sumin Seo ₂ , Agung Eru Wibowo ₃ , Olivia Bunga Pongtuluran ₄ , KyuJong Lee ₅ , Sang Beom Han ₂ , Sayeon Cho ₁

Affiliation

Oxidative stress and chronic inflammation are closely linked to various diseases. However, previous studies have demonstrated that plant extracts could prevent and alleviate these adverse outcomes. Piper betle Linn. (Piper betle L.) is a cosmopolitan plant that belongs to the Piperaceae family, whose leaves are edible and possess several health benefits. This study sought to characterize the anti-inflammatory and antioxidant effects of a methanol extract of Piper betle L. leaves and stems (MPBLLS). MPBLLS was found to have a dose-dependent radical scavenging effect, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl assay. Additionally, MPBLLS inhibited the lipopolysaccharide (LPS)-stimulated production of nitric oxide and prostaglandin E₂ by reducing the expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages without affecting cell viability. Furthermore, our findings suggested that the inhibitory effects of MPBLLS on pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 were due to the inhibition of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-treated RAW 264.7 macrophages. MPBLLS and hydroxychavicol, a major constituent of MPBLLS, suppressed LPS-induced translocation of NF-κB p65 from cytoplasm to nucleus. Interestingly, MPBLLS increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and transcription levels of Nrf2 target genes in a dose-dependent manner. Collectively, our findings suggest that MPBLLS could serve as a basis for the development of novel orally-administered therapies due to its inhibitory effects on oxidative and inflammatory stress.

Data Availability

The data presented in this study are available on request from the corresponding author.

中文翻译：

Piper betle Linn甲醇提取物的抗炎和抗氧化活性。(Piper betle L.) 通过抑制 RAW 264.7 巨噬细胞中的 NF-κB/MAPK/Nrf2 信号通路来叶和茎

氧化应激和慢性炎症与各种疾病密切相关。然而，先前的研究表明，植物提取物可以预防和减轻这些不良后果。派珀贝特林恩。( Piper betle L.) 是一种属于胡椒科的世界性植物，其叶子可食用并具有多种健康益处。本研究旨在描述蒌蒻叶和茎 (MPBLLS)甲醇提取物的抗炎和抗氧化作用。发现 MPBLLS 具有剂量依赖性自由基清除作用，如 2,2-diphenyl-1-picrylhydrazyl 测定所示。此外，MPBLLS 抑制脂多糖 (LPS) 刺激的一氧化氮和前列腺素 E _2的产生通过降低 RAW 264.7 巨噬细胞中诱导型一氧化氮合酶和环氧合酶 2 的表达而不影响细胞活力。此外，我们的研究结果表明，MPBLLS 对促炎细胞因子如肿瘤坏死因子-α、白细胞介素 1β 和白细胞介素 6 的抑制作用是由于抑制了核因子-κB (NF-κB) 和有丝分裂原。 LPS 处理的 RAW 264.7 巨噬细胞中的活化蛋白激酶 (MAPK) 信号通路。MPBLLS 和 MPBLLS 的主要成分 hydroxychavicol 抑制 LPS 诱导的 NF-κB p65 从细胞质到细胞核的易位。有趣的是，MPBLLS 以剂量依赖性方式增加了核因子红细胞 2 相关因子 2 (Nrf2) 蛋白水平和 Nrf2 靶基因的转录水平。集体，