Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway.
10.19540/j.cnki.cjcmm.20221111.703
- Author:
Yu WANG
1
;
Dong-Wei CAO
2
;
Yi-Gang WAN
3
;
Geng-Lin MU
4
;
Wei WU
3
;
Qi-Jun FANG
3
;
Ya-Jing LI
5
;
Si-Yu CHA
5
;
Yue TU
6
;
Zi-Yue WAN
7
Author Information
1. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing 210008,China Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School Nanjing 210008,China Institute of Chinese Medicine,Nanjing University Nanjing 210008,China.
2. Department of Nephrology,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine Shanghai 200071,China.
3. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School Nanjing 210008,China.
4. Institute of Chinese Medicine,Nanjing University Nanjing 210008,China.
5. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing 210008,China.
6. Department of Traditional Chinese Medicine Health Preservation,Acupuncture,Moxibustion and Massage College,Health Preservation and Rehabilitation College,Nanjing University of Chinese Medicine Nanjing 210023,China.
7. Graduate School of Social Sciences,Faculty of Social Sciences,Hitotsubashi University Tokyo 186-8601,Japan.
- Publication Type:Journal Article
- Keywords:
IRS1/PI3K/Akt pathway;
diabetic kidney disease;
insulin resistance;
podocyte epithelial-mesenchymal transition;
total flavones of Abelmoschus manihot
- MeSH:
Rats;
Animals;
Diabetic Nephropathies/drug therapy*;
Proto-Oncogene Proteins c-akt/metabolism*;
Phosphatidylinositol 3-Kinases/metabolism*;
Abelmoschus/chemistry*;
Podocytes;
Rats, Sprague-Dawley;
Epithelial-Mesenchymal Transition;
Flavones/pharmacology*;
Insulin Resistance;
Reactive Oxygen Species;
Diabetes Mellitus
- From:
China Journal of Chinese Materia Medica
2023;48(10):2646-2656
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
