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绵枣儿果实提取物对系膜细胞中棕榈酸酯诱导的脂毒性的保护作用。

Protective Effects of Siebold Fruit Extract against Palmitate-Induced Lipotoxicity in Mesangial Cells.

作者信息

Kim Donghee, Kim Hyo-Jin, Cha Seon-Heui, Jun Hee-Sook

机构信息

Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea.

College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea.

出版信息

Evid Based Complement Alternat Med. 2019 Jan 8;2019:4509403. doi: 10.1155/2019/4509403. eCollection 2019.

DOI:10.1155/2019/4509403
PMID:30728845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6341277/
Abstract

Diabetic nephropathy is one of the most serious complications of diabetes. Lipotoxicity in glomerular mesangial cells is associated with the progression of diabetic nephropathy. Paper mulberry, Siebold (BK), has been used in oriental medicine for human health problems. However, to date, the beneficial effect of BK fruit has not been studied. In this study, we investigated the protective effect of an ethanolic extract of BK fruit (BKFE) against palmitate- (PA-) induced toxicity in mesangial cells. BKFE significantly increased the viability of PA-treated SV40 MES13 cells. BKFE significantly inhibited PA-induced apoptosis and decreased the expression of apoptotic genes, cleaved caspase-3, and cleaved PARP. Moreover, BKFE inhibited the expression of endoplasmic reticulum (ER) stress-related genes, such as BiP, phosphorylated eIF2, cleaved ATF6, and spliced XBP-1, in PA-treated SV40 MES13 cells. BKFE decreased PA-induced ROS production. In addition, BKFE activated the transcription factor Nrf2 and increased the expression of antioxidant enzymes. However, knockdown of Nrf2 using siRNA suppressed this BKFE-induced increase in antioxidant enzyme expression. Furthermore, the protective effect of BKFE on PA-induced apoptosis was significantly reduced by Nrf2 knockdown. In conclusion, BKFE induced the expression of antioxidant enzymes via activation of Nrf2 and protected against PA-induced lipotoxicity in mesangial cells.

摘要

糖尿病肾病是糖尿病最严重的并发症之一。肾小球系膜细胞中的脂毒性与糖尿病肾病的进展相关。构树，学名楮实子（BK），在东方医学中被用于解决人类健康问题。然而，迄今为止，构树果实的有益作用尚未得到研究。在本研究中，我们调查了构树果实乙醇提取物（BKFE）对棕榈酸（PA）诱导的系膜细胞毒性的保护作用。BKFE显著提高了PA处理的SV40 MES13细胞的活力。BKFE显著抑制PA诱导的细胞凋亡，并降低凋亡基因、裂解的半胱天冬酶-3和裂解的聚（ADP-核糖）聚合酶的表达。此外，BKFE抑制了PA处理的SV40 MES13细胞中内质网（ER）应激相关基因的表达，如结合免疫球蛋白重链结合蛋白（BiP）、磷酸化真核翻译起始因子2（eIF2）、裂解的活化转录因子6（ATF6）和剪接的X盒结合蛋白1（XBP-1）。BKFE减少了PA诱导的活性氧（ROS）产生。此外，BKFE激活了转录因子核因子E2相关因子2（Nrf2）并增加了抗氧化酶的表达。然而，使用小干扰RNA（siRNA）敲低Nrf2可抑制BKFE诱导的抗氧化酶表达增加。此外，Nrf2敲低显著降低了BKFE对PA诱导的细胞凋亡的保护作用。总之，BKFE通过激活Nrf2诱导抗氧化酶的表达，并保护系膜细胞免受PA诱导的脂毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/0e26f0134ca7/ECAM2019-4509403.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/439020f7b250/ECAM2019-4509403.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/469793094068/ECAM2019-4509403.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/43b64726e2d7/ECAM2019-4509403.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/28b0dc67bdd8/ECAM2019-4509403.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/00e523ab7aec/ECAM2019-4509403.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/5de2de10c05a/ECAM2019-4509403.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/0e26f0134ca7/ECAM2019-4509403.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/439020f7b250/ECAM2019-4509403.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/469793094068/ECAM2019-4509403.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/43b64726e2d7/ECAM2019-4509403.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/28b0dc67bdd8/ECAM2019-4509403.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/00e523ab7aec/ECAM2019-4509403.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/5de2de10c05a/ECAM2019-4509403.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9407/6341277/0e26f0134ca7/ECAM2019-4509403.007.jpg

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