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库姆阿卡黑米富含花青素的组分在体内外均可减轻NLRP3炎性小体驱动的肺部炎症。

Anthocyanin-Rich Fraction from Kum Akha Black Rice Attenuates NLRP3 Inflammasome-Driven Lung Inflammation In Vitro and In Vivo.

作者信息

Umsumarng Sonthaya, Semmarath Warathit, Arjsri Punnida, Srisawad Kamonwan, Intanil Intranee, Jamjod Sansanee, Prom-U-Thai Chanakan, Dejkriengkraikul Pornngarm

机构信息

Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.

Lanna Rice Research Center, Chiang Mai University, Chiang Mai 50200, Thailand.

出版信息

Nutrients. 2025 Mar 28;17(7):1186. doi: 10.3390/nu17071186.

Abstract

BACKGROUND/OBJECTIVES: Chronic lower respiratory tract inflammation can result from exposure to bacterial particles, leading to the activation of the NLRP3 inflammasome pathway. These effects may cause irreversible respiratory damage, contributing to persistent lung injury and chronic obstructive pulmonary disease (COPD), as observed in long COVID or bacterial pneumonia in older adults' patients. Given its profound impact, the NLRP3 inflammasome has emerged as a key therapeutic target for mitigating aberrant inflammatory responses.

METHODS

In this study, we investigated the anti-inflammatory effects of Kum Akha black rice, a functional food, on the attenuation of NLRP3 inflammasome pathway using lipopolysaccharide-induced A549 lung epithelial cells and a C57BL/6NJcl mouse model. The anthocyanin-rich fraction from Kum Akha black rice germ and bran extract (KA1-P1) was obtained using a solvent-partitioned extraction technique.

RESULTS

KA1-P1 exhibited a high anthocyanin content (74.63 ± 1.66 mg/g extract) as determined by the pH differential method. The HPLC analysis revealed cyanidin-3-O-glucoside (C3G: 45.58 ± 0.48 mg/g extract) and peonidin-3-O-glucoside (P3G: 6.92 ± 0.29 mg/g extract) as its anthocyanin's active compounds. Additionally, KA1-P1 demonstrated strong antioxidant activity, as assessed by DPPH and ABTS assays. KA1-P1 (12.5-100 μg/mL) possessed inhibitory effects on LPS + ATP-induced A549 lung cells inflammation through the significant suppressions of , and mRNA levels and the inhibition of cytokine secretions in a dose-dependent manner ( < 0.05). Mechanistic analysis revealed that KA1-P1 downregulated key proteins in the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). Furthermore, in vivo studies demonstrated that KA1-P1 significantly diminished LPS-induced lower respiratory inflammation in C57BL/6NJcl mice, as evidenced by the reduced bronchoalveolar lavage fluid and blood levels of inflammatory cytokines (IL-6, IL-1β, and IL-18) and diminished histopathological inflammatory lung lesions.

CONCLUSIONS

Overall, our findings suggest that the anti-inflammatory properties of KA1-P1 may support its application as a functional supplement or promote the consumption of pigmented rice among the elderly to mitigate chronic lower respiratory tract inflammation mediated by the NLRP3 inflammasome pathway.

摘要

背景/目的:暴露于细菌颗粒可导致慢性下呼吸道炎症,进而激活NLRP3炎性小体途径。这些影响可能会造成不可逆的肺部损伤,导致持续性肺损伤和慢性阻塞性肺疾病(COPD),就像在老年患者的长期新冠或细菌性肺炎中所观察到的那样。鉴于其深远影响,NLRP3炎性小体已成为减轻异常炎症反应的关键治疗靶点。

方法

在本研究中,我们使用脂多糖诱导的A549肺上皮细胞和C57BL/6NJcl小鼠模型,研究了功能性食品库姆阿卡黑米对NLRP3炎性小体途径的抗炎作用。采用溶剂分配萃取技术从库姆阿卡黑米胚芽和麸皮提取物中获得富含花青素的部分(KA1-P1)。

结果

通过pH差值法测定,KA1-P1显示出高花青素含量(74.63±1.66mg/g提取物)。高效液相色谱分析表明,矢车菊素-3-O-葡萄糖苷(C3G:45.58±0.48mg/g提取物)和芍药素-3-O-葡萄糖苷(P3G:6.92±0.29mg/g提取物)是其花青素活性成分。此外,通过DPPH和ABTS测定评估,KA1-P1表现出强大的抗氧化活性。KA1-P1(12.5~100μg/mL)通过显著抑制、和mRNA水平以及剂量依赖性抑制细胞因子分泌,对脂多糖+ATP诱导的A549肺细胞炎症具有抑制作用(<0.05)。机制分析表明,KA1-P1下调了NLRP3炎性小体途径中的关键蛋白(NLRP3、ASC、前半胱天冬酶-1和裂解的半胱天冬酶-1)。此外,体内研究表明KA1-P1显著减轻了C57BL/6NJcl小鼠中脂多糖诱导的下呼吸道炎症,支气管肺泡灌洗液和血液中炎症细胞因子(IL-6、IL-1β和IL-18)水平降低以及组织病理学肺部炎症损伤减轻证明了这一点。

结论

总体而言,我们的研究结果表明,KA1-P1的抗炎特性可能支持其作为功能性补充剂的应用,或促进老年人食用有色米,以减轻由NLRP3炎性小体途径介导的慢性下呼吸道炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bf4/11990836/82c193b3e304/nutrients-17-01186-g001.jpg

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