Total flavonoids of Abelmoschus manihot (L.) medic attenuate early renal injury in diabetic kidney disease by modulating the LINC00665/miR-379-5p axis.
Nan Li, Yuhe Zeng, Yaohui Fang, Jie Wu, Harvest F Gu, Ying Wang
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Abstract
Context: Huangkui capsule (HKC), derived from Abelmoschus manihot (L.) Medic, is clinically utilized for diabetic kidney disease (DKD) treatment. Its primary bioactive components are the total flavonoids of A. manihot (L.) (TFA). Evidence has implicated the negative interaction between long non-coding RNA LINC00665 and miR-379-5p in DKD pathogenesis.
Objective: To investigate the therapeutic effects of TFA on early DKD renal injury and its mechanism involving LINC00665/miR-379-5p axis modulation.
Materials and Methods: Db/db mice and non-diabetic controls received TFA or vehicle. Urinary albumin/creatinine ratio (UACR) was measured with ELISA; renal histopathology was assessed with H&E staining. SV40-MES-13 and HK-2 cells were treated with TFA-intestinal absorption fluid (TFA-IAF). LINC00665 and miR-379-5p expression analyzed with RT-qPCR and Western blot. LINC00665/miR-379-5p interaction validated with dual-luciferase reporter assays. Functional effects assessed using LINC00665 siRNA silencing and miR-379-5p mimics.
Results: TFA administration reduced UACR in db/db mice compared to vehicle-treated controls and ameliorated renal histological damage. Renal miR-379-5p expression was decreased in db/db mice versus non-diabetic controls, while TFA treatment in vivo upregulated miR-379-5p expression. TFA-IAF treatment in vitro modulated the expression of genes implicated in DKD progression, specifically affecting cell proliferation and ECM accumulation pathways in SV40-MES-13 and HK-2 cells. TFA-IAF downregulated LINC00665 expression in the cultured cells. Furthermore, dual-luciferase assays confirmed miR-379-5p binding to LINC00665, as miR-379-5p mimics suppressed wild-type LINC00665 reporter activity. Silencing LINC00665 increased miR-379-5p expression, potentiating by co-treatment with TFA.
Conclusions: The LINC00665/miR-379-5p axis contributes to DKD pathogenesis. TFA exerts therapeutic effects against early renal injury in DKD by suppressing LINC00665 and consequently upregulating miR-379-5p activity.
期刊介绍：
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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