Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing, Jiangsu Province 210009, China.
Suzhong Pharmaceutical Research Institute, 3-1 Xinjinhu Road, Jiangbei New Area, Nanjing, Jiangsu Province 210018, China.
Biomed Pharmacother. 2023 Dec 31;169:115899. doi: 10.1016/j.biopha.2023.115899. Epub 2023 Nov 18.
As a traditional Chinese medicine, Huangkui capsule (HKC) has been used to treat patients with kidney diseases, including diabetic nephropathy (DN). We have recently demonstrated that HKC could re-regulate the activities of solute carriers (SLC)s in proximal and distal convoluted tubules of kidneys in regression of the development of DN. The main active chemical constituents of HKC are the flavones of Abelmoschus manihot (L.). The current study aims to further evaluate the efficacy of total flavones of A. manihot (TFA) in the regression of DN by analyzing SLC activities in proximal and distal convoluted tubules of kidneys. TFA (0.076 g/kg/d) or vehicle was administered in db/db mice, the animal model of type 2 diabetes and DN, daily via oral gavage for four weeks. Blood glucose levels and urinary albumin-to-creatinine ratio (UACR) were measured and used for the determination of T2D and DN. Ten SLCs, including slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 were highly expressed in proximal and distinct convoluted tubules of kidneys. Their expression at mRNA and protein levels before and after TFA treatment were analyzed with real-time RT-PCR and immunohistochemistry. Data showed that UACR in the db/db mice after TFA treatment was significantly decreased. Compared with the group of non-diabetic control, slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 in the group of DN were down-regulated but up-regulated after TFA treatment. Further analyses of whole kidney sections indicated that the numbers and structures of the nephron in db/db mice was increased and improved after TFA treatment. Thereby, the current study provides further evidence that the flavones in A. manihot have pharmacological effects on the treatment of DN by improving the biological function of SLCs in kidneys.
作为一种传统中药，黄葵胶囊（HKC）已被用于治疗肾脏疾病患者，包括糖尿病肾病（DN）。我们最近证明，HKC 可以通过重新调节肾脏近端和远端曲管中的溶质载体（SLC）的活性来抑制 DN 的发展。HKC 的主要活性化学成分是黄蜀葵中的黄酮类化合物。本研究旨在通过分析肾脏近端和远端曲管中的 SLC 活性，进一步评估黄蜀葵花总黄酮（TFA）在抑制 DN 中的疗效。TFA（0.076 g/kg/d）或载体通过口服灌胃每天给予 db/db 小鼠，db/db 小鼠是 2 型糖尿病和 DN 的动物模型，持续四周。测量血糖水平和尿白蛋白与肌酐比（UACR），用于确定 T2D 和 DN。十个 SLC，包括 slc2a2、slc4A1、slc5a2、slc5A3、slc5a8、slc6a20、slc27a2、slc12a3、slc34a1 和 slc38a2，在肾脏的近端和远端曲管中高度表达。使用实时 RT-PCR 和免疫组织化学分析 TFA 治疗前后它们在 mRNA 和蛋白水平上的表达。结果显示，TFA 治疗后 db/db 小鼠的 UACR 显著降低。与非糖尿病对照组相比，DN 组的 slc2a2、slc4A1、slc5a2、slc5A3、slc5a8、slc6a20、slc27a2、slc12a3、slc34a1 和 slc38a2 的表达下调，但经 TFA 治疗后上调。对整个肾脏切片的进一步分析表明，TFA 治疗后 db/db 小鼠的肾单位数量和结构增加并得到改善。因此，本研究进一步证明，黄蜀葵中的黄酮类化合物通过改善肾脏中 SLC 的生物学功能对糖尿病肾病具有治疗作用。
