Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis.
10.19540/j.cnki.cjcmm.20230216.702
- Author:
Bing-Ying WAN
1
;
Dong-Wei CAO
2
;
Yi-Gang WAN
3
;
Dai CHEN
4
;
Wei WU
3
;
Qi-Jun FANG
3
;
Si-Yi LIU
5
;
Yue TU
5
;
Yu WANG
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 Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine Changzhou 213000,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. Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine Changzhou 213000,China.
5. 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.
6. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing 210008,China.
7. Graduate School of Social Sciences,Faculty of Social Sciences,Hitotsubashi University Tokyo 186-8601,Japan.
- Publication Type:Journal Article
- Keywords:
PERK-eIF2α-ATF4-CHOP signaling pathway;
cell apoptosis;
diabetic tubulopathy;
endoplasmic reticulum stress;
total flavones of Abelmoschus manihot
- MeSH:
Rats;
Animals;
Abelmoschus;
Reactive Oxygen Species/metabolism*;
Flavones/pharmacology*;
Endoplasmic Reticulum Stress;
Diabetic Nephropathies/drug therapy*;
Apoptosis;
Diabetes Mellitus
- From:
China Journal of Chinese Materia Medica
2023;48(10):2657-2666
- CountryChina
- Language:Chinese
-
Abstract:
Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
