Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology

Abstract

Aims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients.Methods: We searched for available randomized controlled studies on DKD patients’ treatment with CaD through open databases. Continuous variables were expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). The putative targets and possible pathways of CaD on DKD were analyzed by network pharmacology. Molecular docking was employed to verify the match between CaD and the target genes.Results: In the meta-analysis, 42 trials were included, involving 3,671 DKD patients, of which 1,839 received CaD treatment in addition to conventional treatment, while 1,832 received conventional treatment. Compared with routine therapy, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) significantly decreased in the CaD treatment (early stage of DKD, Scr: p < 0.00001; BUN: p < 0.0001; clinical stage of DKD, Scr: p < 0.00001; BUN: p < 0.00001; kidney failure stage, Scr: p = 0.001; BUN: p = 0.004). The levels of serum cystatin C (Cys-C), urine levels of molecules reflecting kidney function (urinary albumin excretion rate (UAER) and micro glycoprotein), and inflammatory factors [hypersensitive c-reactive protein (hs-CRP)] were reduced compared with control groups, while glomerular filtration rate (GFR) was increased in patients treated with CaD for 12 weeks. CaD also showed a better effect on improving endothelial function. Network pharmacology results showed that the interaction pathway between CaD and DKD was mainly enriched in MAPK and chemokine signaling pathways. AKT1, CASP3, IGF1, MAPK8, and CCL5 might be the key targets for CaD in treating DKD.Conclusion: Combination with CaD is effective and safe in patients with DKD. Inhibition of MAPK and chemokine signaling pathways might be vital in treating CaD in DKD patients.

Huajuxiaoji Formula Alleviates Phenyl Sulfate‐Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis

“…PS plays a role in cellular injury, specifically targeting podocyte integrity and function [ 40 ]. In vivo experiments demonstrated that the DKD mice exhibited elevated levels of CRE, BUN, urine protein, and endotoxin, which are important indicators for evaluating kidney function [ 41 , 42 ]. After treating the mice with HJXJ, their behavior and symptoms saw a significant improvement overall, which is consistent with previous studies [ 31 ].…”

Pharmacokinetics and Bioequivalence of Amlodipine Besylate Tablet in Healthy Chinese Volunteers Under Fasting and Fed Conditions

“…The AUC from time 0 to infinity and AUC from 0 to 144 hours were slightly higher than the fasting test, and the postprandial AUC of the test preparation and the reference drug were higher than that of the fasting test, but the difference was not significant. 17,18…”