Henan University of Chinese Medicine, 450046, Zhengzhou, China.
The Engineering and Technology Center for Chinese Medicine Development of Henan Province, 450046, Zhengzhou, China.
BMC Complement Med Ther. 2022 Feb 28;22(1):52. doi: 10.1186/s12906-022-03535-y.
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.
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会加重慢性肾脏病（CKD）的进程。鸡冠花（C. flabellata，CF）是中国民间常用的植物药，但关于其药理作用的研究较少。本研究旨在探讨 CF 乙醇提取物对 SAMP8 小鼠肾纤维化的影响，并鉴定潜在的活性化合物。
采用快速老化模型小鼠（SAMP8）作为动物模型，通过灌胃给予不同剂量的 CF 一个月。用β-半乳糖苷酶染色观察小鼠肾脏衰老程度。Masson 染色和 Col-I、α-SMA、FN 的表达水平评估小鼠的肾纤维化。测量肾脏中 Nrf2 通路和 Wnt/β-catenin/RAS 通路的蛋白表达水平。并采用β-半乳糖苷酶（β-gal）诱导的 NRK-52E 细胞作为体外模型筛选 CF 的活性成分。
CF 乙醇提取物可显著抑制 SAMP8 小鼠肾脏β-半乳糖苷酶的活性和 Col-I、α-SMA、FN 的表达水平，改善 SAMP8 小鼠的 Masson 染色。CF 显著降低 SAMP8 小鼠的尿蛋白、肌酐、尿素氮和血清 TNF-α、IL-1β 水平，显著提高 SOD 和 GSH-Px 水平。此外，CF 激活了小鼠肾脏中的 Nrf2 通路，并阻断了 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-反式咖啡酰基-β-D-阿洛呋喃糖基-(1→3)-β-D-吡喃葡萄糖基（1→6）]-β-D-吡喃葡萄糖苷（SDC-1-8），这两种化合物可减少 NRK-52E 细胞的衰老，可能是 CF 发挥抗衰老作用的活性成分。
本实验表明，CF 乙醇提取物可能通过 Wnt/β-catenin/RAS 通路改善 SAMP8 小鼠的肾纤维化。而 SDC-0-14,16 和 SDC-1-8 可能是 CF 发挥抗肾衰老相关作用的物质基础。
