Therapeutic mechanism and clinical application of Chinese herbal medicine against diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is the major complications of type 1 and 2 diabetes, and is the predominant cause of chronic kidney disease and end-stage renal disease. The treatment of DKD normally consists of controlling blood glucose and improving kidney function. The blockade of renin-angiotensin-aldosterone system and the inhibition of sodium glucose cotransporter 2 (SGLT2) have become the first-line therapy of DKD, but such treatments have been difficult to effectively block continuous kidney function decline, eventually resulting in kidney failure and cardiovascular comorbidities. The complex mechanism of DKD highlights the importance of multiple therapeutic targets in treatment. Chinese herbal medicine (active compound, extract and formula) synergistically improves metabolism regulation, suppresses oxidative stress and inflammation, inhibits mitochondrial dysfunction, and regulates gut microbiota and related metabolism via modulating GLP-receptor, SGLT2, Sirt1/AMPK, AGE/RAGE, NF-κB, Nrf2, NLRP3, PGC-1α, and PINK1/Parkin pathways. Clinical trials prove the reliable evidences for Chinese herbal medicine against DKD, but more efforts are still needed to ensure the efficacy and safety of Chinese herbal medicine. Additionally, the ideal combined therapy of Chinese herbal medicine and conventional medicine normally yields more favorable benefits on DKD treatment, laying the foundation for novel strategies to treat DKD.

Characteristics of elderly diabetes patients: focus on clinical manifestation, pathogenic mechanism, and the role of traditional Chinese medicine

“…TCM had the effect of modulating gut microbiota and improving glucose metabolisms in T2DM patients and pre-clinical experiments ( Zheng et al, 2021b ). Numerous studies reviewed the efficacy and mechanisms of Chinese herbal medicine on DKD, DR, and DPN, which have been reported to be critical for diabetes in the elderly ( Lu et al, 2019 ; Ai et al, 2020 ; Chen et al, 2022b ; Liu et al, 2022 ). Whlie TCM could give full play to the advantages of multiple targets and intervene in many important mechanisms of elderly diabetes.…”

Emerging Role of Ferroptosis in Diabetic Kidney Disease: Molecular Mechanisms and Therapeutic Opportunities

“…Previous studies have demonstrated that Nrf2 plays a crucial role in responding to antioxidative stress and maintaining redox homeostasis. In the mechanism of DKD, in addition to Kelch-1ike ECH-associated protein l (Keap1)/Nrf2/antioxidant response element (ARE) signaling, Nrf2 can inhibit inflammation to relieve kidney damage by suppressing NF-κB, Sirtuin1 (SIRT1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) 104 , 126 . Controversially, Nrf2 seems to have a dual effect in DKD.…”

Role of Gut Microbiota, Immune Imbalance, and Allostatic Load in the Occurrence and Development of Diabetic Kidney Disease

“…Extensive research findings indicate that the utilization of natural medications exhibits a positive impact on the management of DKD by restraining inflammation and oxidative stress. In addition, these drugs help modulate the gut microbiota and related metabolic processes [ 194 , 195 ].…”