Solanum melongena L. Extract Promotes Intestinal Tight Junction Re-Assembly via SIRT-1-Dependent Mechanisms,Molecular Nutrition & Food Research

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Solanum melongena L. Extract Promotes Intestinal Tight Junction Re-Assembly via SIRT-1-Dependent Mechanisms
Molecular Nutrition & Food Research ( IF 4.5 ) Pub Date : 2024-07-31 , DOI: 10.1002/mnfr.202400230
Pichayapa Sukmak _{1,

2} , Purisha Kulworasreth ₁ , Supisara Treveeravoot _{1,

2} , Apiwan Arinno _{1,

2,

3} , Supitcha Anuwongworavet ₁ , Wanapas Wachiradejkul ₁ , Purit Kulworasreth ₁ , Natnicha Teansuk _{1,

2} , Laongdao Thongnak ₁ , Doungporn Amonlerdpison ₄ , Jakkapong Inchai ₅ , Chaiwet Jakrachai ₅ , Nattaphong Akrimajirachoote ₆ , Chanat Aonbangkhen ₃ , Chatchai Muanprasat ₇ , Wanangkan Poolsri ₈ , Chutima S Vaddhanaphuti ₅ , Pawin Pongkorpsakol _{1,

2}

Affiliation

Tight junction disruption can lead to pathogenesis of various diseases without therapeutic strategy to recover intestinal barrier integrity. The main objective of this study is to demonstrate the effect of Solanum melongena L. extract (SMLE) on intestinal tight junction recovery and its underlying mechanism. Intestinal barrier function is attenuated by Ca²⁺ depletion. SMLE treatment increased TER value across T84 cell monolayers. Permeability assay reveals that Ca²⁺ depletion promotes 4-kDa FITC-dextran permeability, but not 70-kDa FITC-dextran. SMLE suppresses the rate of 4-kDa FITC-dextran permeability, indicating that SMLE inhibits paracellular leak pathway permeability. SMLE-mediated TER increase and leak pathway suppression are abolished by neither calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor nor AMP-activated protein kinase (AMPK) inhibitor. Furthermore, mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) inhibitors have no effects on SMLE-mediated TER increase and leak pathway suppression. Interestingly, SMLE is unable to enhance TER value and diminish leak pathway permeability in T84 cell monolayers pre-treated with sirtuin-1 (SIRT-1) inhibitor. Immunofluorescence staining reveals that SMLE enhances re-assembly of tight junction proteins, including occludin and ZO-1 to intercellular space but this effect is abolished by SIRT-1 inhibitor. These data suggest that SMLE promotes intestinal tight junction re-assembly via SIRT-1-dependent manner.

中文翻译：

茄子提取物通过 SIRT-1 依赖性机制促进肠紧密连接重新组装

如果没有恢复肠道屏障完整性的治疗策略，紧密连接破坏可能导致各种疾病的发病机制。本研究的主要目的是证明茄果的功效。提取物（SMLE）对肠紧密连接恢复的影响及其潜在机制。 Ca ²⁺消耗会减弱肠道屏障功能。 SMLE 处理增加了 T84 单层细胞的 TER 值。渗透性测定表明，Ca ²⁺消耗可促进 4-kDa FITC-葡聚糖的渗透性，但不会促进 70-kDa FITC-葡聚糖的渗透性。 SMLE 抑制 4-kDa FITC-葡聚糖通透性，表明 SMLE 抑制细胞旁渗漏途径通透性。 SMLE 介导的 TER 增加和渗漏途径抑制均不能被钙/钙调蛋白依赖性蛋白激酶激酶 β (CaMKKβ) 抑制剂和 AMP 激活蛋白激酶 (AMPK) 抑制剂消除。此外，哺乳动物雷帕霉素靶点 (mTOR) 和细胞外信号调节激酶 (ERK) 抑制剂对 SMLE 介导的 TER 增加和渗漏途径抑制没有影响。有趣的是，在用 Sirtuin-1 (SIRT-1) 抑制剂预处理的 T84 细胞单层中，SMLE 无法提高 TER 值并降低渗漏途径通透性。免疫荧光染色显示，SMLE 增强了紧密连接蛋白（包括 occludin 和 ZO-1）在细胞间隙的重新组装，但这种作用被 SIRT-1 抑制剂消除。这些数据表明 SMLE 通过 SIRT-1 依赖性方式促进肠道紧密连接重新组装。

更新日期：2024-07-31

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