Extract of Corallodiscus flabellata attenuates renal fibrosis in SAMP8 mice via the Wnt/β-catenin/RAS signaling pathway.
Extract of Corallodiscus flabellata attenuates renal fibrosis in SAMP8 mice via the Wnt/β-catenin/RAS signaling pathway.
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DOI：
10.1186/s12906-022-03535-y
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发表时间：
2022-02-28
影响因子：
3.9
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Cao B;Zeng M;Si Y;Zhang B;Wang Y;Xu R;Huang Y;Feng W;Zheng X
纤维化是肾脏衰老过程中最常见的病理特征之一，衰老肾脏中的纤维化也加剧了慢性肾脏病（CKD）的过程。扇形珊瑚盘B. L. Burtt（C.荷叶（flabellata，CF）是我国民间常用的植物药。然而，很少有研究报道其药理作用。本研究旨在探讨CF乙醇提取物对SAMP 8小鼠肾纤维化的影响并鉴定潜在的活性化合物。以加速衰老小鼠8（SAMP 8）为模型，灌胃给予不同剂量的CF，连续1个月。采用β-半乳糖苷酶染色法观察小鼠肾脏衰老程度。采用Masson染色及免疫组织化学方法检测Col-Ⅰ、α-SMA、FN的表达水平。检测肾脏Nrf 2通路和Wnt/β-catenin/RAS通路蛋白表达水平。以β-半乳糖苷酶（β-gal）诱导的NRK-52 E细胞为模型，筛选CF的活性成分。CF乙醇提取物显著抑制SAMP 8小鼠肾脏β-半乳糖苷酶活性和Col-I、α-SMA和FN表达水平，改善SAMP 8小鼠Masson染色。CF能显著降低SAMP 8小鼠尿蛋白、肌酐、尿素氮及血清TNF-α、IL-1β水平，显著升高SOD、GSH-Px水平。此外，CF激活小鼠肾脏中的Nrf 2通路并阻断Wnt/β-catenin/RAS通路。此外，从CF中分离得到3，4-二羟基苯乙醇（SDC-0-14，16）和（3，4-二羟基苯乙醇-8-O-[4-O-反式-咖啡酰-β-D-阿皮呋喃糖基-（1→3）-β-D-吡喃葡萄糖基（1→6）]-β-D-吡喃葡萄糖苷（SDC-1-8），它们具有延缓NRK-52 E细胞衰老的作用，可能是CF发挥抗衰老作用的活性成分。本实验提示，CF乙醇提取物可通过Wnt/β-catenin/RAS途径改善SAMP 8小鼠肾纤维化。SDC-0- 14、16和SDC-1-8可能是CF发挥抗肾衰老作用的物质基础。在线版本包含补充材料，可通过10.1186/s12906-022-03535-y获得。
Fibrosis is one of the most common pathological features of the aging process of the kidney, and fibrosis in aging kidneys also aggravates the process of chronic kidney disease (CKD). Corallodiscus flabellata B. L. Burtt (C. flabellata, CF) is a commonly used botanical drug in Chinese folklore. However, few studies have reported its pharmacological effects. This study aimed to explore the effect of CF ethanol extract on renal fibrosis in SAMP8 mice and identify potentially active compounds. Senescence-accelerated mouse-prone 8 (SAMP8) were used as animal models, and different doses of CF were given by gavage for one month. To observe the degree of renal aging in mice using β-galactosidase staining. Masson staining and the expression levels of Col-I, α-SMA, and FN were used to evaluate the renal fibrosis in mice. The protein expression levels of Nrf2 pathway and Wnt/β-catenin/RAS pathway in the kidney were measured. And β-galactosidase (β-gal) induced NRK-52E cells as an in vitro model to screen the active components of CF. The CF ethanol extract significantly inhibited the activity of renal β-galactosidase and the expression levels of Col-I, α-SMA, and FN in SAMP8 mice, and improved Masson staining in SAMP8 mice. CF remarkably reduced urinary protein, creatinine, urea nitrogen and serum levels of TNF-α and IL-1β in SAMP8 mice, and significantly increased the levels of SOD and GSH-Px. Moreover, CF activated the Nrf2 pathway and blocked the Wnt/β-catenin/RAS pathway in the kidneys of mice. Besides, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)]-β-D-glucopyranoside (SDC-1-8) were isolated from CF, which reduced the senescence of NRK-52E cells, and maybe the active ingredients of CF playing the anti-aging role. Our experiments illuminated that CF ethanol extract may ameliorate renal fibrosis in SAMP8 mice via the Wnt/β-catenin/RAS pathway. And SDC-0-14,16 and SDC-1-8 may be the material basis for CF to exert anti-renal senescence-related effects. The online version contains supplementary material available at 10.1186/s12906-022-03535-y.
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影响因子：
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