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阔叶十大功劳通过抑制巨噬细胞中 CCL-5 的表达来减轻肉芽肿性小叶性乳腺炎相关炎症。

Broadleaf Mahonia attenuates granulomatous lobular mastitis‑associated inflammation by inhibiting CCL‑5 expression in macrophages.

机构信息

Department of Mammary Disease, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.

Department of Breast Oncology, Sun Yat‑Sen Univeristy Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Guangzhou, Guangdong 510060, P.R. China.

出版信息

Int J Mol Med. 2018 Jan;41(1):340-352. doi: 10.3892/ijmm.2017.3246. Epub 2017 Nov 9.

Abstract

Granulomatous lobular mastitis (GLM) is a type of chronic mammary inflammation with unclear etiology. Currently systematic corticosteroids and methitrexate are considered as the main drugs for GLM treatment, but a high toxicity and risk of recurrence greatly limit their application. It is therefore an urgent requirement that safe and efficient natural drugs are found to improve the GLM prognosis. Broadleaf Mahonia (BM) is a traditional Chinese herb that is believed to have anti‑inflammatory properties according to ancient records of traditional Chinese medicine. The present study investigated this belief and demonstrated that BM significantly inhibited the expression of interleukin‑1β (IL‑1β), IL‑6, cyclooxygenase‑2 and inducible nitric oxide synthase in RAW264.7 cells, but had little influence on the cell viability, cell cycle and apoptosis. Meanwhile, the lipopolysaccharide‑induced elevation of reactive oxygen species and nitric oxide was also blocked following BM treatment, accompanied with decreased activity of nuclear factor‑κB and MAPK signaling. A cytokine array further validated that BM exhibited significant inhibitory effects on several chemoattractants, including chemokine (C‑C motif) ligand (CCL)‑2, CCL‑3, CCL‑5 and secreted tumor necrosis factor receptor 1, among which CCL‑5 exhibited the highest inhibition ratio in cell and clinical GLM specimens. Collectively, the results show that BM is a novel effective anti‑inflammatory herb in vitro and ex vivo, and that CCL‑5 may be closely associated with GLM pathogenesis.

摘要

肉芽肿性小叶性乳腺炎(GLM)是一种病因不明的慢性乳腺炎。目前,系统性皮质类固醇和甲氨蝶呤被认为是 GLM 治疗的主要药物,但高毒性和高复发率极大地限制了它们的应用。因此,迫切需要找到安全有效的天然药物来改善 GLM 的预后。阔叶十大功劳(BM)是一种传统的中国草药,根据中医古籍的记载,它具有抗炎作用。本研究调查了这一信念,并证明 BM 显著抑制了 RAW264.7 细胞中白细胞介素-1β(IL-1β)、IL-6、环氧化酶-2 和诱导型一氧化氮合酶的表达,但对细胞活力、细胞周期和细胞凋亡几乎没有影响。同时,BM 处理还阻断了脂多糖诱导的活性氧和一氧化氮的升高,伴随着核因子-κB 和 MAPK 信号通路活性的降低。细胞因子阵列进一步验证了 BM 对几种趋化因子,包括趋化因子(C-C 基序)配体(CCL)-2、CCL-3、CCL-5 和分泌型肿瘤坏死因子受体 1,具有显著的抑制作用,其中 CCL-5 在细胞和临床 GLM 标本中表现出最高的抑制率。综上所述,结果表明 BM 是一种新型有效的体外和体内抗炎草药,CCL-5 可能与 GLM 的发病机制密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f8d/5746325/6234c6351384/IJMM-41-01-0340-g00.jpg

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